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Pharma Guide®
1't

Mind-Matp
Pharmacology Fast Review

Dhshan Hassan Dhshan

IJ /Dr.Dhshan IJ /Pharma.Guide.book
~ /DhshanPharma ~ Dr.Dhshan@Gmail.com
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 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
1ot PanEffedorPresystemicMetabolism
•Firstpasseffectisaphenomenonofdrugmetabolismwherebytheconcentrationofadrugisgreatlyreducedbeforeil
reachesthesystemiccirculation.
General Pharmacology
• WhenadrugisabsorbedfromtheGitract,itenterstheportalcirculationbeforeenteringthesystemiccirtulation.
-lfthedrugisrapidlymetabolizedintheliverorgutwatlduringthisinitialpassage,theamountofunchangeddrugentering pHChangeofUrine

thesystemiccirculationisdecreased
1)Gut-firstpasseffect:
-GastricacidityQBenzylpenicillin
-Digestiveenzyme~lnsulin.
-Mucosalenzyme~Tyramine.
2)Hepaticfirstpasseffect:
-Complete.::>Nilroglycerinand l idocaine
-Partiai ¢ PropranololandMorphine
-Minimai¢AtenololandNadolol.
<rToovercomehepatictirJtpaSJetrect:
-lfpartial¢1ncreasethedoseofthedrug
-lfcomptete<=>UseanotherroutessuchasiVandsublingual.
VolumeofDistributlon(Vd)
• Volume of distribution (Vd), is a fluid volume that would
berequiredtocontaintheamountofdrugpresentinthe
bodyatthesameconcentrationasintheplasma
• Vdhasnophysiologicorphysicalbasis,itcanbeusefulto
comparethedistributionofadrugw~hthevolumesofthe
watercompartmentsin thebody
Vd =a (Total amount of drug) I Cp (Plasma concentration of
•t-h
e-drug
_)_ _ _ _ _ _ _ ___,
Bioavailabllity(BA)
-Bioavailabilityisthefraction(%)ofanadministereddose thatisabsorbedfromits
siteofadministrationandreaches(inanunchangedfOITTI)thesystemiccirculatioo.
Oralbioavailability(F)=AUCom iAUC~v X100
· Factorsaffectingb/oavallsbiflty:·
•Firstpasseffect<=:>Decreasebioavailability.
•Physicochemicalpropertiesofthedrug(Polarity-Solubility-Particlesize)
•Natureofformulation<=:>(Solution>Suspension> Tablet)
I
Blood Brain Barrier (BBB) -Acidification~. furine.(YitC)~.
lncreaseexcre!lonofbas1cdrugs
-BBBisahighlyselectivepeiTTieabilitybarrierthatseparatesthecirculatingbloodfromthebrain
- Alkalization of urine {NaHC03) ~
extracellularfluid(BECF)inthecentralnervoussystem{CNS).Vv'hichareconnectedbytightjunctions.
1ncreaseexcret1onofac1dicdrugs
-BBBallowsthepassageofwater,somegases,and f/pJdsolubfemo/ecu/es.
FactorsAffectingOraiAbsorption Note ...
1: PresenceoffoodandotherdrugsintheGIT:
-Amioo acids.::::> compete for the samecarrierofl-dopa
-Ca2+ (frommilk)<=:>decreaseabsorptionoftetracycline
Metabolism Enzymes
-Tannicacid {from tea}ortetracycline<=:>decreaseabsorptionofiron
-VitaminC~enhancestheabsorptionofiron
Majority of drug Some of drug biotransformation
-Fooddi!utessomedrugs~decreaseabsorptionthisdrugs. Majority
biotransformationreactioos reactions
2: StateofheatthofGIT: Presenceofdiseasee.g.Malabsorptionsyndrome <=:>decreasesabsorption
Site Smooth endoplasmic reticulum. Cytoplasmandm~ochondria.
3: Gastric emptying rate: {process of emptying food from the stomach into the ducxlenum) May be Clearance(CI):isthevolumeofplasmawhichdrugis
Mainlyinliverlhenkidney, Hepaticcellsaswellasinother completely cleared from the drug per unit time {mVmin)
increaseordecreaseabsorptionofthedrug{dependonthedrug):ForExample:1)Metoclopramide~ Organs
lungs, intestinal mucosa tissues including plasma Cl~.., = a (blood flow in organ) X ER (Extraction Ration)
1'gastricemptyingrate,soabsorptionof Paracetamolis1"butabsorptionofDigoxinis"- Catalysefewoxidative,ano.ot
Calalyseoxidative(CYP450), ERo (CA-CV)/CA
2)Atropine OD gastricemptyingrate(Reversingthepreviousexample). Phase I
reductive&hydrolylicreactions reductive&hydrolyticreactions.
4 : G1Motillty(Mo~llty) : -CA(drugenteringtheorganarterialside)
Also conjugation reaction other
- l ncreaseMotility(Diarrhea)~decreaseabsorptionofsomedrugs Phase II Glucuronidationreactionsonly. -CV(drugleavingtheorganvenousside)
thanglucuronidation
- Decrease Motility (Constipation) ~ Increase absorption of some drugs. Clto~a~ =CI ~* +CIFI81a~ +CIPWrnu•l'f +Cioo-
Activity Canbeinducedandinhibited Can'tbeinducedandinhibited
5: PHofGIT:
-Weakaciddrugs (Aspirin)<=:>absorbedinatidicmedium(Stomach) Drug binding to Plasma Proteins
-Weakbasedrugs(Ephedrine)<=:>absortledinbasicmedium(lntestine) Hepatic Microsomal Enzyme
-Aibuministhemajordrug-bindingproteinandmayactasadrugreservoir
6: Firstpasseffeet:e> Decreasebioavailability - Inhibition of microsomal enzymes: Certain drugs inhibits the activity of microsomal
-Boundfractionofthedrug ~notactive (not distributed )
enzyme .::::> decrease metabolism rate .::::> leading to prolongation the action of other
-Freefractionofthedrug~active(distributed)
drugs~increaseactivityandmayleadingtotoxicityofotherdrugs.Hepatic
Hypersusceptibllity(Supersensitivity)(Orug -Theconcentrationoffreedrugdecreasesduetoelimination~ · thebound drug
intolerance) Microsomal Enzyme {HME) inhibitors (examples) E.g. Cimetidine, Chloramphenicol,
dissociates from theprotein{to maintain equilibrium between free-drug and
-Thegreaterresponsetoadrenalineinthyrotoxic
bound-drug) Omeprazole,ErythromycinandKetoconazole
patient
-Factorsaffectingpfasmaproteinbinding: ·lnduction of microsomalenzymes:Certaindrugsincreasetheactivityof
-Drug intoleranceiscommonlyobservedininfant
1: 0isplacementofonedrugbyanotherdrug : microsomal enzyme .::::> leading to increase metabolism rate .::::> decrease activity of
Hypersensitivity(Drugallergy)
rr E .g.AspirinandWarfarin(Anticoagulant)~Aspirindisplaceswarfarindueto other drugs. Hepatic Microsomal Enzyme (HME) inducers (examples) E.g
-Antibody-antigeninteractioo <=:>increaserelease
high affinity to plasma proteins~ 1" free active Warfarin~ 1' toxicity of warfarin
of histamine. Cartlamazepine,Phenytoin,PhenobarbitalandRifampicin
2:"-inalbominorplasmaproteinspiverdiseases) .::::> "f"freeactivedrugs

==iii~EI;am;as;uoi''Niild~ULi
~
i ii.iii~
Elimination of the drug which
is lndependenlly of the drug
Def. cone. For example: 1.2 mg
are etiminated every hour
Rate Elimination rate saturates w~h
higherdrugconcentration.
Bimination of the drug which is
dependently ci the drug cone.
For example: increase drug
cone. lead to increase rate of
drug elimination
Eliminalioo rate is proportional
todrugconcentration
G·Protein-Coupled Receptors (GPCRs)
-Also known as .::::> seven-transmembrane domain (7TM) receptors, heptahelical receptors, TypesofAgonists
Competedwiththeagoniston Actonthedifferents~eoothe
serpentine receptor and G protein--linked receptors (GPLR) 1)Fui/Agonist: receptorand disp/aced by receptOfand notdlsp/aced by
- GPCRs are integral membrane proteins with seven membrane spanning helices ~ - lfadrugbilldstoareceptorandproducesamaximal
upon binding to a ligand ~ activate second messenger ~ alter in cell activity increasethedoseofagonist increasethedoseofagonist
response that mimics the response to the
- GPCRs Structures ~ The extracellular domain of this receptor contains the ligand- endogenous ligand Parallel shifttotherightinthe
bindingarea,andtheintracellulardomaininteracts(whenactivated)withaGproteinor -Example: phenylephrine is a full agonist at 01- curve
effector molecule adrenoceptors,becauseitproducesthesameEmaxas .VPotency~1'ECso
> Second Messenger System: doestheendogenousligand, norepinephrine Sameefficacy~SameEm;ox
-Are intracellular signalling molecules released by the cell to trlgger physiological 2)Partia1Agonist:

,. &·-··
Term Non-linear(Saturation) Unear E.g.AtropineinmuscarinicAch
changes(oneofintracellularsignaltransductioncascades) -Producesapartialresponsethatmimicstheresponse
receptors
- Examples .::::> Cyclic AMP, Cyclic GMP, Inositol Triphosphate, Diacylglycerol, and

~-
· - -... '
totheendogeoousligand
Calcium -Example: Aripiprazole, an antipsychotic drug, is a
> Main Types of GPCRs: partialagonistatdopaminereceptors
Curve :;- . - TherearemanykindsotGproteinsforexample,G.,G;andGq - N.S: Partialagonistmayhaveanaffinitythatisgreater
i' ' l: 1) G, (Stimulatory) .::::> Activate adenytate cyclase~ Increase cyclic adenosine than,lessthan,Ofequivalenttothatofafullagonist
r: ._ .
·-~": ..
monophosphate (cAMP) .::::> open Ca2• channels and Increase Ca2• influx from Whenareceptorisexposedtobothapartialagonist
sarcoplasmic reticulum (SR) .::::> Contraction. Example .::::> ~1 and fh adrenoceptors andalullagonist,thepartialagonistmayactasan
l •• ' I ~ ' ·-.;
2) G, {Inhibitory) .::::> Inhibits adenylate cyclase~ Decrease cAMP.::::> Decrease Ca2• ~ antagonistolthefullagonist
Pharmacodynamic Drug Interactions
1}/fincreasaindrugeffects:
A few substances are 95%oflhedrugsinuseat t nhibition . Example~a2adrenoceptors 3)/nverseAgonist
-Addition(Summation): Aigebraicsumofthe2drugseffect
eliminatedbyzero.order therapeutic concentrations are 3) Gq (Stimulatory) ~ Activate phospholipase-C {PLC) .::::> PLC break -Produce a response below the baseline response
(1 +1 =2)E.g.Acetylcholine+Histamineincontradionofintestine
elimination kinetics, because eliminated by first order phosphatidylinositol bisphosphate (PIP2) into toositol triphosphate {IPJ) arw:l measuredintheabsenceofdrug
-Synergism: Thecombinationeffectmorethanalgebraicsum
Example their elimination process is elimination kinetics Diacylglycerol (DAG) ~ IP3 increase Ca 2• influx from sarcoplasmic reticulum (SR) ~ -Decreasesthenumberofactivated receptors
Contraction. Example~a1adrenoceptors
(1+1=>2)E.g.Ethanoland8arbiturates<=:>Sever<=:>CNS
saturated. Examples are -Potentiation: Drugwhichincreasetheeffectofotherdrug.(0+1 = >1) E.g
Ethaooi,Pilenyto;n, Tolerance(Orugdesensitization)Failureofresponsivenesstotheusualdose Drug Dependence Physostigmine+Acetylcholine
Salicylates,andOmeprazole A) Congenital Tolerance 2)/fdecreaseindrogeffects(Antagonism):
- Husuallyoccursw~h CNSactingdrugs
~: EphedrineisnotmydriaticinNegroes • Chemical antagonism: Chemical interaction between 2 drugs ~ decrease
1)Habituation: MilddegreeofdrugdependenceandPsychic
- Therapeutic index (Measure of drug safety) is the ratio of the dose that ~: Rabbitsistoleratedlargeamountofbelladonnaduetoatropineesterase absorption.E.g.Heparin+Protaminesulfate
dependence
producestoxicilyinhalfthepopulation(T~)tothedosethatproducesa enzymeinrabbilliverandplasmawhichrapidlydetoxificationofatropine -Physiologicai{Functional)antagonism: 2drugsacton2different
-Whendrugstopped~developsomeemotionaldistressfora
clinicallydesiredoreffectiveresponse{EDso) inhalfthepopulation Jllndlviduai:Geneticfactorsarepossiblyinvolved receptors<=:>Differenteffect.E.g.AdrenalineandHistamine
relativeshortperiod. E.g.smokingandcoffee.
S)AcquiredTo/erance: (lncreasethedosetoobtaintheoriginaleffect)
2)Addiction: Moreseriousformofdrugdependence -Pharmacologicalantagonism: 2drugsadonthesamereceptorbutone
GeneticabnormaHty(Drugldiosyncrasy) 11Cross-tolerancee.g.antianxiety drugsalldsedativehypnotics.
-Psychicandphysicaldependence ofthemisagonistandtheotherisantagonist.
- Idiosyncrasy (PhaiTTiacogenetics) ~Abnormal reaction due to genetic ~(Acuteorsudden )e .g.Ephedrine <=:>Suddenincreaseblood
-When drug stopped ~ Withdrawal symptoms~ reverse the - Competitive e.g. Atropine with Acetylcholine. Non-competitive e.g
abnormality. E.g.hemolylicanemiainpatient withG6PDenzymedeficiency Pressurethendecrease {Gradually). 31Bacterialresistancetoantibiotics
normalphaiTTiacologicalaction.E.g.mOiphineandheroin
OfganophosphatewithAcetylcholine

Choline Esters
~-
. Cholinesterase enzyme breakdown ACh into
Aceticacid+Choline
- ·AChreleasecanbeblocked byBotullnumtoxin
• ACh act on Ml receptor in endothelium by indirect
action via (EORF) increase NO formation, cause VD
then Hypotension
- NotUsedCiinically, due lo
• Multiplicity of action {Non-selective) act on all
ACh receptors. Short duration due to rapid
inactivation bycholillesteraseenzyme
mmr!l!!ll (lsoplo'Carbach~)
-Totaltyresistanttocholinesteraseenzyme.
- Rarely used therapeutically except in the eye as a
m ioticagentdueto~longerhalf-life
- ~ rarely~ineye drops totreat glaucoma
~cause miosis ~ 1" outflow of aqueous
humour through canal of schlemm ~ "'
lntraocular pressure(IOP).
lll!!lEliD (UrotoneO)
-Totallyresistanttocholinesteraseenzyme
- Selectivetomuscarinicreceptors.
-Major actionon GIT andurinarybladder (UB)
- !.fnE Postoperative non-obstructive GIT disorder
andurinarytension andGastro-paresis
llii!!!lmlllDI!tProvocholin,.)
-Selective tomuscarinicreceptors
• !J.U!I. in bronchial challenge~est (or Methacholine
challenge test) to diagnose asthma (1' asthma
when inhaled)
- §k!J~ Cardiovascu tar effects,such as
bradycardiaandhypotension(M2)
Cholinomimetic Alkaloids
~{lsoptOSCarpine)
-Tertiaryamineatkaloid(CNSside effect)
- !.!Hll. intreatmentofglaucoma {drugof choice fOf
emergency lowering of lOP).
- It cause miosis and contracts to ciliary muscle, it
opensthetrabecularmeshwor1<pores and facilitate
out flow of aqueous humour into the canal of
schlemm, decrease iOP
ll!l!l!lmlll!ltEvoxac")
-It is an oral drug ll!!!J!. in dry eye and dry mouth
(xerostomia) associated with SjOgren's syndrome.
‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
ReH"ihlr \ntochnhnt•,tera'e
·• (Aricept<),
lill!!lllilmliltExelon")~ (Reminy~)
- Tacrinewasthefirsttobecomeavallabte,butil has
beenreplacedbyothersbecauseof ils hepatotoxicity
• ~ Delay the progression of Alzheimer's disease
- Adverseeffects: Gidistress
,, · {AtroPe~)
-Naturallytertiaryamine(pass),competitiveantagonist
Uses
-Sef~re eyeexamlnation{PaSsivemydriasis,cycloplegia)
- Antispasmodic (Relax the Gl tract)
-Urinarylncontinence{Relaxwall&sphinctercontraction)
-TreatbradycardiaandReduceAVheartblock.
- Preanestheticmedication{Anti-secretory, BronchOOilator
-AnUdotefor organophosphate polsoning
- Side effects: include dry mouth, blurred vision, "sandy
eyes ,"tachycardia,urinaryretention, and
constipation.
~ or llma (TransdennScopt)
-Naturally tertiary amine.
-lt differs fromatropineinthefollowing
-ltismorepotentinmydriasis,cycloplegia
- ttislesspotentinheartandbronchialmuscle
- ltisgreateractionontheCNS.
- 1tislongerdurationofaction
- Oneofthe mosteffective anti-motionsickness drugs.
-Topicalpatchprovideseffectsforupto3days.
~{lsopt~ Homatropine)
~(CiclopleiiooO)il!!lill!iiii!II Mydnacy ~)
-Atropinesubstitutes ~ formydriasisandcyclop/egfa
(before eye examinations)
- Homatropinemorepreferredinuveitisandiritis
ilil'.llmlll!ld1lili!lilll!litBuscopan")
~ (VisOOralgine*)
• Antispasmodic drugs, relief spasms in the gastro-
intestinal or genito-urinarytract.
•• • • or {Robinu~)
- Anti-secretorydrog used in anesthesia, preoperative
medication (reduce salivary, ~rachea, a~d. pharynge~l
secretions, as well asdecreas1ng theacldltyofgastric
secretion).
~(Gastrozepin")Dmm
-Selective M1receptor, ll!!!J!. in peptic u/cer{reduces
gastric acid secretion).
llE!ll!llll (Atroven!&) lil!milill!lill (Spinvae)
- Sronchodilators,~ for treatmentof bro nc hospasm
- Tiotropium (24hours;oncedaily), lpratropium (4hours;
uptofourtimesdaily)
l!.l3'Jll!!i'li (Ditropan") GlD!iii !Detrusito~
~(Enablex>)lllli!Eiil (Vesicar,.)
- Used to treat symptoms of overactive bladder (OAB),
Sueh asfrequentorurgenturination andincontinence
lllm!l!lm (Coginto~) llllml!!ll (Akineton")
- Used intreatment of Parkinson's disease
Muscarinic Receptors Types
- M, (Neural) (Gq) (Excitatooy Effect)
- CNS (? Improve cognition and memooy).
- Gastnc panetal cells in stomach (increase HCI)
- Mz(Cardiac)(Gi)(lnhibitooy Effect)·
-Atnaof the heart(Cardiacinhibition).
- MJ(GiandulariSmooth musde) (Gq) (Excitalooy Effect)
- Exocrineglands(increasesecretions).
-Smooth muscles (Contraction).
- Blood Vessels (Vasodilation via NO release)
-Circularmuscle intheeye(Contraction;Miosis)
· Ciliaoymusclein theeye(Contraclion)
Nicotinic Receptors Types
A) N, Receptors (Nicotinic Neural): Found in autonomic
ganglia, adrenalmedullaandCNS.
B) N• Receptors. (Nicotinic Muscle): Found in
neuromuscular JUnction (NMJ) (motor endplate) on
skeletal muscle.
Effect of Parasympathetic Stimulation
1) Eye: Circular muscle contraction (Miosis) & Ciliaoy
muscle contraction (Accommodation for near
vision)(M,)
2) Heart:Oecreasecardiac properties(Mz).
3) Lung: Bronchoconstriction & Stimulate bronchial
secretion(MJ).
4) Salivary Gland: Wateoy salivaoy secretion (MJ)
5) GJT: Contraction of GIT wall and 1' Motility (MJ)
RelaxationofGIT sphincters.
6) Bladder Contraction of unnaoy bladder wall (MJ)
Relaxationofurinarybladdersphincter
7) Blood Vessels: Vasodilatation via release of NO
8) Male Sex Organ: Erection (Vasodilatation; '!' NO)
Depnlanzing
.·, •• • · (Tubarinee), • · (Succinylcholine€!)
~ (Tracnurn"). li!!!!!I!!III!IINimbexO), ~ (Syncunn,.)
IIJI!Ill!lll!!i iMivacron")&limllllilllllliFiaxe<li~) - Mechanism of Action: ~ (initial stimulation)
- Atracurium,sl~ghthiStammereleaseandlsmetabohzed openingoftheNa+channel(fasciculations)
totoxicmetabolitecaii~Laudanosine '* seizures * Phasell (prolongedinhibition)Receptordesensitization
. Cisatracurium most commonly used muscle relaxant and (flaccid paralysis)
ithavefewersideeffectsthanAtracurium. - Uses: Endotracheal intubation&electro-convutsion
- Atracurium & Cisatracurium safe in renal and liver
- Side Effects.
impainnent
- Mivacurium,shortdurationofadion,itcausehistamine
t Prolonged apnea in patient with deficient in plasma
cholinesterase enzyme
release.Ciearancebyplasmacholinesteraseenzyme ¢
2:Bradycardia:overcomebyatropine
prolongedinpatientwithimpairedrenalfunction.
!Post-operativemusclepain:duetoinitialfasciculation
- Ga//amine causetachycardiabyparasympalholyticeffect
4: 1' 10P:duetocontradionofextra-ocu1armuscle
W~b;lf1T.%jWh;~~:~~o~~~ (Esmero~) §;Hyperkalemia in patients with bums , nerve damage or
neuromusculardisease.Canbetreatedby regularinsulin
~(N~rcuron"),~ (P~vulon") (enhance entry of K+and prevent n is efflux from the
- Rapacuronium 1sashortactinoammo-stero1d used in
tissues)
short surgical operation.
- Uses: Surgicalrelaxation,endotracheal intubationand
6: Malignant Hyperthermia in susceptible patients,
- exposure to Halothane "'* Rabid 1' in muscle
electro-convulsion therapy metabolism
- Drug Interactions: 1) Cholinesterase inhibitors "'*
Characterized by:
overcome the action of NMB. 2) Inhaled anesthetics -Veryhightemperatureandunexplainedtachycardia
(Halothane) "'* Additive effect. 3) Aminoqlycoside -Musclerigidityandmetabolicacidosis
ant"biotics(Gentamicin)'* Synergisticeffect -Treated by Cooling patient and Oantrolene (Direct
4) Calciumchannetblockers ¢ enhanceeffectofNMB. skeletal muscle relaxant)
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬

· or .,, (EpiPen<)
-It is a natural catecholamine Norepinephrine (NE) is
methylated to yield epinephrine in the adrenal medulla
whichisstoredinchromaffincells.
-It is metabolized by MAO and COMT.
- Neurona/Uptake : Uptake1 {Neuronal)~by
Cocaine, Amphetamine, Tricyclic Antidepressants (TC.As)
Uptake2 ( Extra-N euronal)~by: Cortisone
Up take3 (VesicleUptake):~by:Reserpine
- Pharmacological Action
- Loca!Effects:Vasoconstriction (VC)in nose
· !::!.!!.!:1 (~1): (+ve)inotropic,chronotropic&dromotropic
- Blood Vessels (BV): ~(0 1) .:> VC. ~
~!r!(lh) c) VD_Thecumulative
effect is an 1' in systolic blood pressure {~1)
andslight .J... indiastolicpressure(jh)
-!Jmg:Powerfulbronchodilatation(fh)
- §!!: Relaxgastro-intestinaland nii(HJrinarymuscles.
- fx!:ActiveMydriasis. • (Propinee)isan
epinephrinepro-drugusedinopen..angleglaucoma,
easilypassesfromcomeaandpenetrateintothe
anteriorchamberthanepinephrine
- Hyptrglycaemiceffect: 1) 1" glycogenolysis(~2)
2) ,.a,.. insulinrelease(a,2). 3)1" glucagonrelease(lh)
- Uses: 11 Bronchospasm (acute asthma). ~ Anaphylactic
shock: drug of choice (is a physiological antagonism of
histamine). ID_ Cardiac arrest. ~ Local infiltration
anesthetics. IDEpistaxis (Nosebleed)
Of
- lt isanatura!lycatecholamine
- Act on a-receptors more than ~receptors (Great VC)
• It is rapidly metabolized by MAO and COMT.
- ~:asa vasopressor in treatme n tvasodilatoryshock
- ~§iJ!jetfects: Bianching alongthesiteoftheinfused
~opotentvasoconstrictoreffects).
•• or ••- (lsuprel')
- ltisasyntheticcatecholamine
-Stimulatesboth~1 andjh receptors
-ltisrarelyusedtherapetJtica!lyduetonoo-selectivity
- ~: Heartattack and irregularheartbeat (hea rt block).
Acuteattack of bronchialasthma
iiil!£llllLii (DA)(Inlropin<)
· (Prelrin<)
· l t isavasoconstridor ~ 1"blood pressure.
-lnduces reffexbradycardia whengiven parentera!ly.
- ~: Hypotension (Vasopressor), Haemorrholds , Nasal
Decongestant and Mydriatic
iialtlifi (Catapres•)
-ltisanC;?agonist(centrallyandperipherally)
- MechanismQfaction
1) Stimulate presynapticC;?receptors: .J,..NE release
2)Stimulate centrai C;?receptors: .J,.. Sympatheticoutflow
J)Sti.mulatelmidazoline1receptor: Sympatho-inhibitoryaction.
- ~: 1) Hypertension. 2)ADHD. J)Withdrawal symptoms
4)MigraineProphylaxis. S)Psychiatricdlsorders. &)Hot
1 flashes (menopause). 7)Diagnosisof pheochromocytoma
- ~Etfects: Drymouth , drowsiness , diuiness andsedatioo
- Cionidinewithdrawal: Clonidinetherapyshouldbegradually
taperedoff. Sudden discontinuationcancausehypertension
due to a rebound in sympathetic outRow, treated by 01& ~
blockers.
- Mechanismfllaction
1) Methyldopa is converted into the false transmitter
{metabolite) called; alpha-methy1norepinephrine, in theCNS
by dopamine beta-hydroxylase {OBH) enzyme ~ the false
(Adderal~) • · •· • ·
-ltisapotentCNSstimulanl
- llishasamood-elevating{euphoria)effect.
- MechanismQ!action: lncreasereleaseofNE
- ~: 1 ) ADHD2)Narcolepsy3) {0ff-/abel}
Performance-enhilncing, depression and
obesity treatment.
I:~~~:~~~c~~~ =~~~~~;e~::zt!:: {Parenterally) I
· Amphelam~in~ed~erim,vall!:livelmsw!l!ilh,~/e;:~~~~~ffects
- Addictionandpsychologicaldependenceare rare
- II is the most prescribed medications in ADHD
-llisalsoeffectiveinthetreatmentof narcolepsy
- (Provigil')
-ltisa wakefulness-promotingagenl
- ~: sleepdisorders ;such as narcolepsy .
- Notcfinicaffyused. ltisfoundinfermentedfoods,
suchasagedcheese {ripecheese)
-Ukeamphetamines, tyramine 1" releaseofNE.
· \!§!!: 1) Hyperten~on in pheodlromocytoma
2.)Symptomati.cbenignprostatichyperpla_si~(BP.H).
3) Raynaud's phenomenon . 4) Impotence
- ~ Effects: Postural hypotension,
-~J:Ji;Wu;a_il(~i~~~~;'ion
-ll ls a oon-selective irrellersiblenon-competitive.
- OurationQ!action:3to4days.(Orally).
imml!illiPriscoli.,..) & ~ (Rogitin..)
- Non-selective retJersib/ecoll1M!titiiJe
(Minipress•)
·less reflex tachycardia
- ~: Treatment ofhypertenslon , symptoms ofBPH ,
Congestiveheartfailure, Pheochromocytoma&
Raynaud'sphenomenon .
- ~ Effects : First-doseorthostatichypotension
(initialsyncopeattack) toovercome;thefirstdosemust
be minimized and giving at bed time. Headache,
diuiness, drowsinessandnausea
••. • • (lndera~)
-llblocksboth~1 andjhreceptorswithequalaffinity.
" PharmacologicaiA.ruQ!l ..
- ~: (-ve) Inotropic & Chronotropic & slow SA and AV
nodal conduction . .J,.. cardiacworkandD-lconsuming
- .!.!mg: Bronchoconstridion
- m:~blockingagents ,.a,..I OPespeciallyinglaucoma
dueto .J,.. aqueoushumourformatioo.
· Metabolic effects
-Biock l>-f"eceptorsi n adiposetissues ~ .J,.. Lipolysis
-Biock!h-receptors i n liver~ .J,.. Giycogenolysis
- Biock l32- receptors inpancreas ~ .J,..G iucagon .
- N.B: Glucagon hormone used to combat hypoglycemia
effects, so; non-selective~blockersusedw~hcaution in
insulin-dependentdiabeticpatients
- Chronic use ~ 1" VlDL (verylowdensitylipoprotein)
and "'·H
. D.L(highdens. itylipo~rotein;..good cholesterol)
~ 1"nskforcoronaryarteryd1sease
1
-~: 1)Hypertension . 2)Angina . 3) M yocard i al
lnfarction. 4)Arrhythmias5)Hyperthyroidism
Reflex (tnhlbitsthepenpheralconversiOilofT.toT3).
I 5)Migr;Mneprophylaxis. 6)Anxietystatus.
- ~ftfects: Hypotension,Bronchospasm,Arrtlythmias .
Metabolic disturbances {fasting hypoglycemia). Cold
1 - =~TheM~=~ts:ra~:~~~duany.
.... (Cilfl/ard')
-Very long duration with low lipid solubility and used in
hypertension, angina, migraineprophylaxis.-
· Nadololwidely !:!§Jl!J in esophagealvarices to prevent
bleeding in peolgmj~~~~:~~sion
- ~ inchronic-~~~:~~~~
-ltisa n ~~ withCiassllandCiasslll
.•• (Belopli<:O)
- ~ intrealmentof chron/copen -angleglau coma
IDll!llili iBrevibklc')
- U/tra-short-acting {hatf-life: about10minutes) !:!§Jl!J to
contro/bloodpressure or heartrhythm duringsurgery
: " • • (COOCQIO)
-II is yJ£!1 in hyiJti@fli(~:~i~ :;lure

-lt isanatui"allycatecholamine
-ltisadivatec&jH!drenergicanddopaminergic receptors
- Q2g:~Effect
- Smalf dose 9 activate 0-dopaminergic receptors
- Moderatedose ~activate~adrenergicreceptors
- ~ ~activateo-adrenergicreceptors .
- Pharmacological Action
- Cardi acsti m ulatoryeffects{~1)
- Dilatesrenalbloodvessels: lncreasebloodflow(0 1)
-Vasoconslrictoreffects(atveryhighdoses): VC(c1)
- ~: Cardiogenicand septicshock , Hypotension and
severe heart failure
I
transmitteriscentralaz-agonist 9 .J,.. sympatheticout flow~
,.a,..N E release9 .J,.. reninrelease ~ .J,.. bloodpressure
2) 1tisacompetitiveinhibitorofdopa-decarl>oxylaseenzyme
~ which converts L-dopa into dopamine ~ Dopamine is a
precursor fornorepinephrineandsubsequentlyepinephrine
- ~ : Gestational hypertension and pre-eclampsia
(pregnancy-induced hypertension)
- ~Etfects: Posturalhypotension, Sedatio_ n, drowslness,
increase prolactin hormone
· (lopidine8)
- ~ in glaucomatherapy
: •,
"*CheesReaction** · Most highly selective ~, -blocker with NO-potentiating
- It is metabolized by MAO in the GIT and liver, but, if
effect. Usedi!i]&n{~l;!s~~7nglnalagent.
thepatientistakingMAO inhibitors, tyramineisnot
metabolized, aswellasNEisnotmetabolized ~ - ~; hypertension , angina, heartfailure, myocard ial
(OmnicOcas•)
powerful 1" in NE release from nerve ending~
seriousvasopressoreffects ~ Hypertensivecrisis
-SelectitJea1Areceptorblocker inthesmooth muscleof infarction, arrhi~@fflj'(~~~O:~raxis &anxiety
prostate {notacton a1sreceptor inthebloodvessels).
{treated by 01and~ blockers)
· MQ!!f!wl~ insymptoms ofB PH - ~ in hypertension , angina , myocardialinfarction ,
- ~effect Failureofejaculationorretrograde arrh mias
ejaculation.
Mixed-Acting · ·• • • (Seclra~)
-lt is ~ in hypertension & ven trlculararrhythmias .

1- ~: mydri!!!!!~:S~n::c=] ll!!l!B (Visken<)

Selective • {Ephedrinesutfatee)
- Orally sympathomimetic drug ~ -llis Jill!! inhyiJMISeleclol')
I Adrenergic Receptors Types-----r
- Mechanism Qf Action: Direct and indirect actions (mixed-action) -~~ -seleclivebloc:kerandactivatelh-feceplors .
- ~: Hypotensionassociatedwffhanaesthesiaand Nasal · ar(G,): ·Vascular smoolhmusc~(VC) .
congestion (duetonasaldecongestanteffect) - Radialmusclein theeye{Mydriasis)
- ~ Etfects: Pa lpitation , headache and insomnia . - a2{G):- Presynapticneurons (lnhibilion NTsrelease).
: (Oobutre~)

J
-Pancreas(inhibitionofinsulinrelease). . •..• (Trandatee)

j
-lt isa se/ectivep 1 receptoragonist ~ 1" HR&CO.
· Pr(G.):· Heart (1' heartproperties) - ~ in hypertension d pheochromocytoma and
,~g~~(Sudaled") ~
Major advantage of Dobutamine over other
- Kidney(1"Renin release) hypertensivecrisis and pregnancy-hypertension
sympathomimetic drugs ~ it increases CO and does not
- lt hasfewerCNSandCVSsideeffectsthanephedrine. -~ l(Gs): - Smoothmuscles {relaxatioo).
significantlyelevateoxygendemandsofthemyocardium.
- ~ : Acuteheartfailure {septiccardiogenicshock) - II used widely as a combination to relieve common cold symptoms -Skeletal Muscles (Tremors) associaled w:ranam,s:~ilatrencte)
- Adverse effects: hypertension, tachycardia , phlebitis, - ~: N~~~~g~o;;i~~~tion, sinus congestion & eustachian tube . - Liver (Giycogenolysis) - ~ inCHF: due toit .J,..Iipidperoxidation&oxidative l
nausea , headache andanginalpaln - ~1 (Gs)- Fate tissues {1" Lipolysis thermogenesis). injury to endothelial cells, ,.a,.. vaSC1Jiar wallthickening~

H1stam me
· Histamlne isformedbydecarboxylationc:A L.flistidine, a
reactioocatalyzedby hlstidinedecarboxylaseenzyme
- Histamineexertspowerfuleffectsonsmoothandcardiacmuscle,
oncertaineodothelialandnervecells,oothesecretory ce!lsof
thestomach,andoninflammatorycetls
"Histamine Receptors*'*
- H1(Gq); /QwQJn smooth muscles, endothelium and brain, Main
~Spasmogeniconsmoothmuscle,VDandskinitchTr;O
- H2(Gs); !sl!ms!..1a gastoc mucosa, cardiac muscles mast cells and
brain, Main effects· Increase HCI secretion & cardiac stimulation
- HJ(Gi); Oecreaseneurotransmitterrelease
- H,(Gij; Piaysaroleinchemotaxis.
"Pharmacological Action of Histamine**
- ~ : Powerfulstimulationofsensorynerveendings
c:) painanditching(H1).
-ill: DirectVD IH•) (via NO production). '!' HR; Due to 1)Direct
stimula!Of)' on the heart (Hz). 2) Reflex tachycardia (due to VO)
1ripleRnoonseotlewis"
- lnlraderma! histamineinjection;cause
1)Redspot;bydirectVDofsmallvessels. 2)Fiare; by
axon reflex. 3)Edemaformulation; by1'capillary
permeability
- !..Y.ng: Bronchoconstrictioo(H,).
- rui: Intestinalsmoothmusclecontractioo(H,)
- ~ : PowerfulstimutantofHCisecretion(H 2)
-HP.§!: Runnynose, Sneezing &Nasalcongestion
- Q!§;: 1'wakefulnessand preventsleep (H1)
"Antihistamines"*
-Penetrate
-Shortdurationoiacik>n(4t<>6hol•rS)
-Someof thesehave e.g.Anticholinergic,
Antiemetic, Antiserotooinandlocalanestheticeffects
- Diphenhydramine , Dimenhydrinate , Cyclizine , Meclizine,
Doxylamine and Promethazine arethemosteffective for
motionsicknessandvertigo.
- Doxylamine; strongsedation,usedininsomnia.
- Cyproheptadine alsoactsasa serotoninantagonist uSedotr-
labelasanappetitestimulant
Second Generation !Non-sedating Antihistamines!
E!lli!lli!IIZyrtecO).I!l!!!l!liriiC~ritin'),l'l!l!ll!li!i!l
(Semprex<).llmllil!l (Kestine') aoollimmlli!l (Z~ime)
-LesspenetrateCNS(morepolar)Qiessoroo sedation
-longduralionotaclion(12to24hoors).
-Moreselectivefor H1-receptors.
fOphthalmlc Antihistaminesl
E!!l!:l!!!DIZad~en').ml!!!imllastacaf!O)
~(TaJion")lmmlli!IIEmadine")
ml!l!lmiAz~as~)Bml!i!IIPatanotO)
used for allergic conjunctivitis .
- Azelastine and Oiopatadlne ; haveintranasalformulatiorls,
Ketotifen ; hasoralformulations.
- Azelastlne and Ketotlfen ; havemastcellstabilizi effects
‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Third Generation !Non-sedating Antihistamines)
~ (AJiear&),
~(Aerius•) IDmlli!I (Telfas~)
-Theyareactiveenantiomerocmetabolitederivativesof
second~eneration Q 1' effiCacy w~h fewer adverse
reactions
- Loogdurationofaction(24hours).
-Pureselectivefor H1-receptors.
"' Therapeutic Uses of Antihistamines "'
1)AIIergicReactions:AIIergicrhinitis (hayfever),
Urticaria,Aiopicdermatitis&(asthma; ineffectivealone)
2)MotionSicknessandVestibularDisturbance.
l)NauseaandVomitingofPregnancy(NVP):
- Mecllzine, Cyclizine and Ooxytamine arecombined
with vit.B, tocootrolc:JNVP
~p~:~~~~er:~~:''IOtic):
4) Especially Doxylamine and
" Toxicity "
-Systemic AcuteToxicity arecommon inyoungchildren;
hallucinations,excitement,ataxia,andcoovulsions
~ oruglnleraction "
- Firstgeneratiooantihistaminicinteract;withanxiolytic
hypnotic drugs and MAO inhibitors (1' anticholinergic)
-Secoodgeneration Terfenadine interactWith LMEis,
inhibilmetabolismofTerfenadine,leadto 1' coocn.of
Terfenadineintheblood¢ BiockK·chanllelsinthe
heart Q cardiac arrhythmia (QT interval prolongation)
HrleceotorAntaaonists
~ (Tagamete)~(Zantace),
ll&llill (Uk:freeO) llmllll!!m (Arltodine")
: ~=~=;;~a:::~ oo the dose given
_H:t:::::~::p~:s:=:so~~~~~e
meal stimulated acid secretion.
-H2receptorantagonistsinhibit60-l0%oftotal 24 _hours
acidsecretion
- Therapeutic!lm
1)PepticUicerDisease(PUD), 2)Zollinger-EIIison
Syndrome(ZES), l)GastroesophageaiReflux
Disease (GERD), 4) Non-ulcer Dyspepsia, 5) Acute
Stress Ulcers {IV).
- ~~ =
- C~~~~i ~ e~s~:~~:;n~~:~~~~~~rum
Gynecomastia, Galactorrheaandamef'IOO'flea.
- Cimetidine inhibitsseveralcytochrome P450 (is aLME
inhibitor),interferewiththemetabolismc:Jmanydrugs
HJ.receptor Antaaonists
-lsan .,ti-vertT~M!?J!'in(:~~~~~sordersor
relievevertigosymptomsassociatedwithMl!niere's
(meo-YEERS]disease
- Mechanism!2fAction
- Betahistineseems todilatelhe bloodvesselswithin
:~:~~u~:ra:i:t:~~~i::a:s~~=c~:n
_ _ _ _ _ _ _ _ ___j
Autacoids
Scrotomn
- Serotonin or 5-hydroxytryptamine (5-HT)isa
moooamineNTs, alocalhormoneinthegut
-ltisformedby decarboxy/ation of l-tryptophan
-lt ismetabolizedbyMAOto5-Hydroxyindoleaceticacid
(5-HIAA)(normallevel2-7mg/dayin u.rine), lncrease
5-HIAA level in patient w~h carcinoid tumors
iriphasicb!oodprnsurarnponyofumtonin"
- lnjectionofserotonininexperimentalanimal;cause:
1:"-'HR,COarKI BPduetocl'lemoreceptorresponse
2: 1' inBPdue toVC
3: "-' in BPduetoVDinskeletalmusclebloodvessels
5-~T,,,,'ag~ni.st, \~~~~/;anxiety agent
. - Is a selective
- 1!.Hsf to treatgeneralizadanxietydisorder
- ~effects : dizziness, headacheandnervousness
~ (lmigrane) fEmmmi (Zomigl!l)
~ (Maxalte) EEmDJim (Amergee)
IGimli!lilil iRelpax') ~ (Axerl")
(Frovafl)
• Triptans Family used in treatment of migraines and
c:lusterheadaches. Mechanism!2faction: Triptans
are sefectiveagonists for5-HTtaand5-HTtD:
1)1nhibit thereleaseofvasodilatingpeptides
21
~:=~:\:~~~t:·i:~~:i~cv'!::ls
- Contraindication:patientsatriskforcorooary artery
diseasedueto; coronaryarteryvasospasm.
' • • (Zelmac")
~ :! :: ~~~ e:~~~::::: ~~~~r:~~ ~:· Gl mOOiity
constipatiooiU!&~;:;s:;~the market
• II is a gastroprokinetic agent Q (enhance Gl motility),
llacts directly as S-HT.receptoragonist and
indirectly asa parasympathomimetic
~ ~~~~~~~:~~~~~~~a~:~~~~ ~~~~ai~~e~~RD).
, . • •: (Fiuxopridefl)
- llisagastroprokinaticagant. Used ingastritis,
GERD , functional dyspepsia and 185.
- !lnl!J. interaction: w~h LMEis Q QT interval prolong
Serotonin Receptor Antagonists
~1lliti (Sandomigran')(MosegQiil)
-ltisa 5-HTu.and 5-HT2<: receptorsantagonist.
-1!.Hsf forpreventionofmigraine (Prophyfaxis).
- Q!f-!.!!W.!!HS!. asappetitestimulant.
(Sufrexalfl)
-Is a 5-HT2antagonist on smooth muscle and platelet, it
j!M{@$$1~~f~~Mmf~~~
~ (Aioxi®) l!m&m (Anzemet®)
~ (Navoban")
- 5-HTs antagonists. ~ topreventnauseaand
vomiting causedbycancerchemotherapy,radiatioo
,r&Wt.i~;;:x:;iimim (catmactintl
- 5-HTsreceptorantagonist ~ inlBS-Diarrhea
Vasoactive Peptides
Ang1otensm
- Angiotensin isapeptidehormooe thatcauses potentVC.
-ll is apartoftherenln·angiotensinsystem (RAS)·
'Whe~blood .pressureis "-' , the renal ~loodHow.is "-' , the kidneys
feellschem~aandcoovertthepro-remnintoren~nandsecreteit
directly into the circulation
"Piasma ren in convert angiotensinogento angiotensinl
'Angiotensi n I (ANG I) is converted to angiotensin II (ANG II) by the
angiotensin-convertingenzyme (ACE)
'Angiotensinllactsbybindingangiotensinreceptorscause; Potent
di~tVC . 1'aldosterone , Na+andwaterretention,1'sympatheOC
activi1y (1'NErelease).
lnhibitionof theRenin-AngiotensinSystem
(Zaecari!')
- Mechanism !2f Action: The hypotensive activity of ACEis, due to;
-Biockstheconversionofangiotensin l toangiotensinll
-lnhiMsthedegradationolbradykinin(vasodilatorQVDviaNO).
-!lill: Hypertension, Heartfailure,aftermyocardialinfarction ,
chronickidneydiseaseanddlabeticnephropathy
- ~Effects : Hypotension afterinitialdose, Hyperkalemia, Acute
renalfailure and 0rypersistencecough; dueto1'1evelsof
bradykinin andotherinflammatorymediatoc.Canbetreatedby;
-lronsupplements(inhibitorofNOsynthase)
-NSAIDs(e.g.aspirinSOOmg/day)inhibitPGssynthesis
- Contraindication: ACE!sarecontraindicatedinpregnancy,¢ 1' risk
offetalmattormation(lung hypoplasiaandskeletaldeformities).
-ARBs are have no effect on bradyifriirilmetalbolism~
-ARBsmoreselectiveblockersofangiotensineffectthanACEinhibitors
-ARBs have a similar uses to those of ACE inhibitors
-ARBs have a similar adverse effects to ACE inhibitors, but less
-ARBshavea similarhazard toACEisofuse duringpregnancy
3 DirectReninlnhibitors
(Te~um,.)
-ltisadbybindingtoactivesiteof renin ¢ "-'plasmareninactivityQ
inhibitingconversionofangiotensinogen toangiotensin l
-ltisused inhypertension.Adverseeffects:Gi symptoms, Rashand
coogh; butlesslhanACEisorARBs
- Contraindicated (Cn): Pregnancy (sameasACEis).
Kinins (Brad~ kinin)
-Kininsare potent vasodilatorpeptldes. Kininson arteries Q
dilatation, but.in veins Q Contraction
-Bradykinin Q produce; four classic symptoms of inflammation;
1) Redness 2) Localheat l )Swelling 4) Pain
(Trasyfot<) '' (Ka!Mor")
-Actby inhibitsbradykininsynthesis (Kallikrein lnhibitors)
- Aprotinin !l.llS!. Ioreducebleedingduringcomplexsurgery
- Ecallantide ~ i nhereditaryangioedema (HAE ).
. •· (Firazyr<)
- lcatibant isabradykininB2receptorblocker.
- ~ ;TreatmentofacuteattacksofHAE
Eicosanoids
Proo,t.tgl.mdlll'• ( P< ,..., ! I hromhm:ant: ..,
( I X,) HHI I t:ukotncnt:" (I I')
- PGh (Prostacyclin) & PGEt; "-' plateletaggregation&VD
- PGE2; VD,uterinecontractions& 1' plateletaggregation
- PGD2; inflammatory response, bfoochoconstrictiol) & VD.
- PGF2a;VC,bronchoconstriction&uterinecontractlons
- TXAz; 1'plateletaggregation, VC&bronchoconstrictioo
- LTS.;chemotaxisandT-cellproliferation
- LTC,, LTD,, LTE.;VCandbronchoconstriction
lnhibitlonof EicosanoidSynthesis
- Corticosteroids palhwaysofeicosanoidsynthesis
- NSAIDs blockPGsandTXsformationbyinhibitingCOX
-5-LOXinhibitor(e.g. Zileuton)and selectiveantagonistsof
theCysLT1 receptocforleukotrienes(LTC4, LTD4and
LTE4) (Zafirlukast , Montelukast and Pranlukast), are
usedclinically inmildtomoderateasthma.
Prostaglandin Analogues
· • " '• (Cave~ec..)
-lsa PGE, analogue, used to maintainingapatent
ductusarteriosusinnewbornsandinimpotence
•• • • (C~otecO)(Misotac")
-lsa PGE1analogue, withoxytocicproperties
-ltisapprovedfor use inthe preventionofNSAID-
inducedgastrlculcers. C/I duringpregnancy
- Off-labe/uses: Laborinduction , abortion, missed
miscarriagaandpostpartumbleeding
-Cause;softeningofcervixanduterinecontradion
I I I (Cervidilfl)
I '
- lsa PGE2analogue, withoxytocicproperties
- ltadministeredvaginally{vaginalinsert)forlabor
induction ¢softeningofcervix&uterinecontraction
(Hemabate®)
-tsa PGF2aanalogue, withoxytocicproperties
- Used in postpartumhemorrhage in thepresenceof
uterineatooylhathas notresponded tousualtherapy
(oxytocin,uterinemassage,ergot alkaloids)
· "• (xalatan") : "• (Lu m~n')
- lsa prostacyclin (PGh), has2majoreffects: 1)direct
vasodilationof pulmooaryandsystemicarterialvascular
beds, 2) inhibitionofplateletaggregation
- Used intreatmentpulmonaryarterialhypertension
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Hypertension Antihypertensive Drugs
> Definition:- > LifestyfeModification (Non-pharmacologictreatments);

• Hypertension (HTN Of HT), isconsideredablbodpressure (BP) of140190mm - DASH eating plan 1) ~-blockers 2) ACE Inhibitors
Hgcirhigher -BPreducedby~14mmHg.
- Dietarysodium {salts) restriction:
-Theyareblock~adrenoceptorintheheart ..:> de<:tWsecardlaco utput ~ "'BP.
- mE!l and ~ area non~ective~locker.
- =.i=~~a~u~
·ACE inhibitors are first-line drugs for hypertensive patients with
[~~~~~~~~i~~~~~!~~i~~}~~~~~~~~~~~~~~~~~~~~~~c~~~~~~~:! -BPreducedby2-8mmHg
· Weight loss; Normal weight (BMI18.5-24.9 k~m2)
· IIJmm, !imiml), El!ll.
~ and lll!!llml!ll
bfockers.{AIIfJ·block.ersshouldbegraduallytaperedoff).
are seledve p,. ~.~. &oatientswithcoronaryarterydisease

o ~ : CO = StrokeVolume (SV) X HeartRate ( HR)
o Strok•VolumetSVl: isthevolumeofblood pumped from the left
ventricleoftheheartperbeat
o ~: isthespeedoftheheartbeatmeasuredbythe
numberofpoundingsoftheheartperuniloftime(typicallybeatsper
minute)
- /ncrease COorPVR, orbolh Q fncreaseBP
· Decrease CO or PVR, or both¢ Decrease BP.
=
-The hypotensiveactivity ofACEinhibitOfS, dueto;
- BP reduced by 5-20 mm Hg per 1(}-kg weight loss. - ~~~ and ~ are only/3-blockersmaybe usedin 1) Biock.s the conversion of anglotenslnl to angiotensinll
- Regularaerobicphysicalactivity· iveheartfailure(CHF). 2)1nhibitsthedegradatlonof bra<lykinin~ VDviaNOrelease
-BPreducedby2-9mmHg. - inducereleasesofnitricoxide andcauses VD. - Avoid otherdrugsthat1'K+Ievele.g.ARBs,AliskirenandK+sparing
- Moderate alcohol consumption • 1San ultra-short-acting, half-life about10minutes -ACEismaydevelop_d~persistencecough and angioedema ;dueto
-BPreducedby2-4mmHg. ·r.m:l!!!ml.ma.!!!111m. mmJ:II and ~ are partial agonists, 1' levels of bradykmm and substance P. Can be treated by 1) Iron
- Smoking cessation. _i.~! _!_!!ocker with some intrinslc sympathomimetic activity (ISA) supplements(aninhibitorofNOsynthase), 2)NSAIDs(e.g.aspirin)
- Reductionofenvironmentalstressors - !!lmlm and ~ are a non-selective ~-blocker and selectivea1· blocker. ·ACEisare contraindicated withpregnancy; triskoffetalmalformation

Re<eptorBiockers;~~-lmm!lil&lli&!!lil.
Diuretics - AnglotenslnU
- ARBs have a similar uses and precautions to ACE inhibitOfS, but less in cough

4) Direct Renin Inhibitors

Thiazide Diuretics Loop Diuretics (j Ceiling) · rJm!m is the first and only drug avallable
ppijM!Mt)l:iijf1i (Esidri~) • II is act ~y binding .to a~e s~e of ren!n ~ decreasing plasma renin activity ~ inhibiting
~ or ~ (Thaliton..)
li!IZmii!!!Z (lasix<) ~ (Examid..) convers~onofang10tenslnogentoang101ensinl.

- Thiazidediurelics, lowerbloodpressure /n/Uallyby/ncreas/ngsodium ~(Burinex<)~(Edeain") • Has a similar uses and precautions but Angioedema and cough; less common
Furosemide, Torsemide, Bumetanide are • Most common side effects: Diantlea. Gl svmotoms and rash. headache and dizziness
and water excretion
- MechanlsmgfAction: Decre.tsebloodpressure bylncrNslngsodlum and sulfonamide loop diuretics.
waterexcretionbyreducingreabsorptlonolsodlumandchlorideattheear1y · Ethacrynicacid isnotasutfonamidediuretics
· Mechanism gf Action: Decre<tse blood pressure by
5 a-blockers
partofthedistalconvolutedtubule inthenephrons. Bmill!J!g_ in decrease · ~~ and • areselectivecompetitivea1receptorsblockers ·
extracetl ular vol ume , decreasecard laco utput ~ decmsebloodpmsure Increasing sOOium and water excretioo by reducing
reabsorpliono!Na·, K•&Ctat the thickascendlng llmb of ·Acts by blocking 01-adrenoceptors on vascular smooth muscle~ VD ~ ! PVR ~ ! BP.
- Therapeutic~:
1)Mildandmoderatehypertension Henle'sloop{TAL)in lhe nephrons. Oecreaserenal · Used mainly in men with hypertension and benign prostatic hyperplasia (BPH)
2)Congestiveheartfailure(CHF) vasctJiarresistanceandlncmserenal bloodflowWI - Most common side effects is first-dose orthostatic hypotension (initial syncope
lncmselheproductlonofvasodUatorprostaglaodlns,so attackorfirstodosephenomenon)
3)Nephrollthlasis (ldiopathichypercalcluria) NSAIDscanreducetheefficac:yolloopdiuretics
4)Nephrogenicdiabetesinsipidus. · Theraoeutic~:
- §kt1Effects:
:> Classification of Hypertension Defined by Causes:- • Hypokalemia Hyponatremia & Hypomagnesaemia
1) Edema; caused by congestive heart failure, 6) Calcium Channel Blockers CCBs
hepatic cirrhosis, renal impairment, nephrotic
• Prlmary (Essentlal or ldiopathic) Hypertension·
o Themajorityofcasesabout90%(noidentifiablecauses).
- Hypercalcaemia and Hyperuricemia
- Hyperlipidemia and Hyperglycemia
syndrome, cerebral or pulmonaryedema
2)Hypertension ; ~;in hypertensionalone orin
-~~lttle·a m~~~ gr~ate;;~ni~
- Hypersensitivity f(l(vascularcalciumchannels thanforcalciumchannelsintheheart.
o Nospecificmedicatcauses combination. !_y, in emergeocy.
o Unknownetiology butmultiplefactorsmaycontributetothedevelopment - Metabolic alkalosis.
- Contraindications·
3)01iguria(<400mlurine/day); Useon/yhighdose : -a~!Bb~:~ ~~~~~sa~ ~~~~:~::o~~t~:~:.h effects on cardiac CC
• SecondaryHypertenslon tablet {500mg) orinjection {250mg) • §.i1!.! effects: Verapamil; First-degree atrioventricular block and const~tion
o Fewcasesabout10% - Digitalis; hypokalemia&hypercatcaemia1'toxicity.
4)0thernon-specificuses; Hyperkalemia Dihydropyridines; Dizziness, headache, fatigue and peripheral
o Mostofthesearecausedby ~ - Hepaticcirrhosisand renalfailure.
- §.k!.!.Effects
• Chronickidneydiseaseorrenovasculardisease. - Patientswithahistoryofsulfonamideallergy.
- Hypokalemia Hyponatremia &Hypomagnesaemia.
• Primaryaldosteronism&hypercortisolism - Gout and Oiabetesmellitus 7) Centrally Acting Sympathetic Inhibitors
• Pheochromocytomaandhyperthyroidism · !Jr!!R.Interactions: - ~-
- Lithium; dueto Wrenallithiumexcretion
·Mn mi/d~ and H yperu ricemia - ~ {Catapres•)isan a2agonist(centrallyandperiphera!ty)thatis used forthe
• DI'UQslhatmav illCfeaseBPsuchas:Corticosteroids - Hyperlipidemia and Hyperglycemia. treatmentofhypertension. ltdecreasesbloodpressureby;
- Oigitalis;dueto1'digitalistoxicity.
> Causes of Hypertension:- - Hypersensitivity. 1)Stlmulatepresynaptica2 receptors : "'PresynapticCa2·~ "'NErelease .
- NSAIDs; dueto "'diureticeffectoflhiazide
11ffM!P11 ;: ·Metabolic alkalosis 2) Stimulate central az receptors: "' Sympathetic vascmotor centers ..:>"'
-Salts
ll!!!Elmli!l (NatrilixO SR) - Contraindications:SameasThiazide Sympathetic outflow Q"'NErelease ..:>.J.; renin release
-Genetics. -ltisthefirst cia newc/ass of'antihypertensive/diuretics'. lthavea
- Alcohol - !Jr!!.g/nteractions: SameasThiazide+ 3)Stimulatel!(lmidazoline)receptor:Sympatho-inhibitoryaction
-Salt sensitiv~y uniquemechanismofaction; actbycombining dlureticeffectsw/rh - Cionidinetherapyshouldbegraduaffytaperedoff; Cionidinesuppressessympa!hetic
-Oral contraceptives Aminoglycoside,WarfarinandProbenecid.
-Obstructivesleepapnea{OSA). a direct vasodilatation effect
-NSAIDs outflow,butsuddendiscontinuationcancauserebound hypertension(life-threating
- lnsulinresistanceandhyperinsulinemia. -G/ycyrrhfzaglabra (liquorice ) hypertensivecrisis)duetoareboundinsympatheticoutflow
-Stressfulsituations, obesity, smoking -Decongestants Potassium (K•) Soaring Diuretics (Low Ceiling) - Methyldopa isana2agonistlhathasbothcentralandperipheraleffects
• ftdecreasesbloodpressureby;1 ) Methyklopaisconvertedintothe falsetransmitter
and other lifestyle -AntiQepressants ~ (Aidactonet) mmg (Eplorefixe)
-Sympathomimetics - /nhibits the effects of aldosterone, by competltiveantagonistat mineralocorticoidreceptors inthe distalconvol utedrenaltubule called; lilphrmethylnorepinephrine,intheCNS..:>thefalsetransmitteriscentralar
-Kidney problems
-Many industrial chemical ~ 1'Na·and water excretion,K•isretained, WH* agonist ~ ..J... sympathetic outflow c> "' NE release ..:> "' renin release
- Endocrine causes: 2) ltisa competitiveinhibitorofdopa-decarboxylase enzyme ~ whichconvertsL­
-Corticosteroids -Spironolactonehas othereffects e.g.: antiglucocorticoldic, antiandrogenic, progestogenic & estrogeniceffects
a Primary aldosteronism ·Ergotamine alkaloids - Sp i ro nolactone ~ Primary hyper_al~steronism, Edema (CHF, Cl rrh~sl s cr Nephrotic syndrome), Essential hypertension, dopaintodopamine.Dopamineisaprecurs(l(forNEandsubsequentlyepinephrine
o Pheochromocytoma -Cyclosporine(lmmunosuppressant Hypokalemia, and Antiandrogen (HirsutiSm, acne pn women) & androgemc alopecia) • Mainlyused formanagementofhypertensioninpregnancy(categoryB)
a Hyperthyroidism drug). - Eplerenon e ~ Congestiveheartfailurepost-myocardialinfarctionand Hypertension.
- §.k!.! Effects: Hyoerkalemia {risk of this complication is greaUy increased by; Renal disease, K· supplements or diet rich in K•, ~
Peri ~!~~!~~9u;:~;~~.e.'!t~;~~!~~!. ~~t~~~E
-Cocaine
o Cushiog'ssyndrome
Hypertension Risk Factors:-
- Caffeine. blockers, NSAIDs, ACEis, ARBs and Aliskiren) and Metabolic acidosis
· Endocrineabnormalities; Gynecomastia, lmpotence, and benignprostatichyperplasia {BPH isveryrare) allhave
s
beenreportedonlywith spironolactone Peri herally Actin S m athetic Inhibitors
• Riskfactorsthatcanbe controlledare· - ~( Midamo~)and ~ {~yrenium8)aredirectinhibitOfSofNa·_inftuxintheCCT (corticalcol lectingtubule)Q 1' 1oss usedinemergency,while usedinmoderatehypertension
o Highcholesterollevelandtobaccouse(smoking). of Na· and water with "' K• and H• secrebon. !lH!l as adjunctive treatment with thiazide diuretics or loop diuretics in congestive
a Dia~tes _ mellit~s . ove~eight a~ obesity heart failure or hypertension
10) Vasodilators
o Physlcalmactivltyandhlghsaltmtake - ~ isa directvasodi/alor (arteriolesbutnotveins) . Uses;Severe
o Coarctationoftheaortaandsleepapnea
•Riskfactorsbeyondourcontrolare - ~ is asulfonamidederivatives , isaprototypicalof CarbonicAnhydraseinhibitordiuretics , ~ in glaucomaand -~~i~~~~Js~o~~~~ 9A1~:t'~~~e~n~i~~!~~~%;_egnancy
o AQeandfamilvhistorvofheartdisease acutemountainsickness (Aititudesickness) -rmml:Im isanagonistofperipheraldopamine01receptors that is used in emergency
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Angina Antianginal Drugs
>Background:·
• An.9.i.D! [an.JIE-nuh or AN-juh-nuh], thetermderivesfromthelatin angere "tostrangle"and pectus ' chest', andcan thereforebetranslated
as"astranglingfeelinginthechest",commonlyk"nownas angina. ~ (NiromA~k*)
• Definition; Chest pain caused by transient myocardial ischemia due to an imbalance between myocardial oxygen supply and oxygen demand - Mechanism!2[Action
• Angina is not a disease. It is a symptom of an underlying heart problem and is usually a symptom of coronary heart disease (CHD) - Normally,
- Endogenous nitric oxide (NO) is primarily produced by vascular endothelial cells, which cause relaxation of vascular smooth muscle
>Angina Symptoms:· - NO " act by stimulation of guanylate cyclase, lead to increase cyclic guanosine monophosphate (cGM P), which subsequently cause vascular
• Anginapain;Sudden, severe, prickingchestpainradiatingtotheneck, jaw, backandarms smoothmusclerelaxationthroughseveralpossiblemechanisms; decreaseCa2+influxandK+channelsactivation,{hyperpolarization)
• Other symptoms;Nausea,fatigue, shortnessofbreath, sweating&dizziness - Organic Nitrates ;
• N.B; theseverity, durationandtypeofanginacanvary -Organicnitratesaredrugsthatnotdirect/yreleaseorsynthesisofendogenousNO withintissues
>Angina Risk Factors:· - Nitrategroup (N02)inorganicnitrate interact with enzymes (nitricoxidesynthase) and intracellutarsulfhydrylgroup (R-SH)(SHgroup) thatreduce
• Coronaryheartdisease-Familyhistoryofheartdisease - Unhealthycholesterollevels-Unhealthydiet (highfatandhighsalt) the nitrategroup (NO,.) tonitricoxide {NO)
• Smoking- Diabetes -Inactivity- High blood pressure- Overweight or obesity- Stressful lifestyle- Age (Men> 45 years- Women> 55 years) -DepletionofSHgroup '* leadto nitratetolerance
- Pharmacological Action;

· ·il!li.! l i·"'l l6••··~~~¥~;*!lll·TIIIl1 ·il l!.l!l i·"'l l6• • •

>Anginarypes.·-~~:Jm~n~lil!l·i.!I.IUII!'I6-•IIIII!~~~·nm~mmnllil
!I I -Powerfulvenodilator and increase venouscapacitance " decreaseventricularpreload
• Reduction in preload and after/oad lead to " Decrease myocardial oxygen demand
Weakarteriodilator " decreaseafterload (minimal effect)
Decrease cardiac work (decrease CO)
-CiassicaiAngina -CrescendoAngina - VasospasticAngina -Effectsoncoronarybloodflow; Organicnitratescanrelax vasospastic coronaryarteries Theyhavelittle ornoetfecton totalcoronarybloodHow
-TypicaiAngina - Pre-infarctionAngina - Prinzmetal'sAngina - ~Effects ,
- ExertionalorEffortAngina - AcuteCoronarySyndrome -Anginalnversa A) VasodilationRelatedSideEffects ••
Narrowing of coronary arteries due to 1)0rthostatichypotensioo (dizzinessorsyncope) 2) Throbbingheadache(Cerebralvasodilation) 3)Refluxtachycardia 4) Facialflushing
Narrowingofcoronaryarteries atherosclerosis, transientformationofablood Resultsfromcoronaryvasospasm, which B) Nitrate Tolerance ••
due to atherosclerosis clotwithinacoronaryartery, result, totalornear- temporarilyreducescoronarybloodflow -Continuousorfrequent exposuretoorganic nitratesmayleadtothedevelopmentofcompletetolerance(tachyphylaxis)
totalblockage. -Tolerance does not occur equally w~h all nitric oxide donors. The mechanisms by which tolerance develops are not fully understood
-NitrateToleranceHypothesis; 1) 0epletionofSHgroup. 2)Excessivegenerationoffreeradicals. 3)Dysfunctionofendothelial nitricoxidesynthase
4)Decreasesensitivityofguanylatecyclase 5) Activationofrenin-angiotensina1dosteroneaxis.
<r AvoidNitrateTolerance;
1: Nitrateholiday ("nitratefreeperiod" or NFP)ofat1east10hoursandpreferablyupto14hoursisrecommendedtoavoidtolerance;
2: Sulfhydryl group donors like N-acetylcysteine (NAC) and L·methionine have been shown to potentially reduce·nitrate tolerance, but they may potentiate
the effects of nitrates 3: Oral vitamin C, vitamin E (antioxidants) and folic acid may be effective in ameliorating nitrate tolerance
4: Carvedilol (antioxidantproperties)and Nebivolol (antioxidantpropertiesandNO-mediatedvasOOilatoryeffects) mayreduce nitratetolerance
Mostccmmontype Common Rare (2%ofanginacases) C) MondaySyndrome or MondayMorningSickness ••
-Physical exertion - Workers in nitroglycerin manufacturing, who are experiencing to regular nitroglycerin exposure in the workplace, leading to the development of tolerance for the
-At rest between midnight (12:00)&moming (8:00)
Occurs -EmotionsandHeavymeals - Atrestorminimalexertion vasodilatingeffects. Overtheweekend, thewOfkerslosethetoleranceand,whentheyarere-exposedonMonday,thedrasticvasodilationproducesafast heart
-Coldweatherandstresscancausespasm
-Exposuretocoldweather rate,dizziness, andaheadache, called"Mondaymomingheadache·
Attack -Lasts a short time (5min or less).- More severe and lasts longer, as long as 30 min · lasts from 5-30 minutes - Q!J!Jllnteraction; Sildenafii, Tadalafil and Vardenafil increasethebloodpressureloweringeffectsofnitratesandmaycauseexcessiveblood pressure reduction
-Oecreasesatrest - Notrelievedbyrestornitroglycerin
Relief - Relieved by nitroglycerin.
-Relievedbynitroglycerin. -Treatedasanemergency
2 ~-Blockers
> Angina Treatment Goals:- · Aithoughtheyare not vasodilators (withtheexceptionof • • and ~ , ~blockingdrugsareextremelyuseful inthemanagementofeffortangina
• Themaingoa/s oftreatmentinanginapectorisareto relievethesymptoms, slowtheprogressionofdisease, and reducethepossibility ·The beneficia/effects of~blocki ngagentsarerelatedtotheir hemodynamiceffects;
- Decreased heart rate, blood pressure and contractility c> Decrease myocardial oxygen requirements at rest and during exercise
offutureevents, especially myocardialinfarction (MI)andprematuredeath.
o Increase 02Supply; Vasodilators (Nitrates and CCBs)
o Decrease 02Demand; ~adrenergic Receptor Antagonists
r==---- - Lowerheartrate isalsoassociatedwithanincrease in diastolicperfusiontime, may¢ /ncreasecoronaryperfusion
-Agents with intrinsic sympathomimetic activity (ISA) such as mm should be avoided in patients with angina and those who have had a Ml
o lifestylemodification
o Treatcoronaryarterydisease; 3} Calcium Channel Blockers (CCBs}
• Oecreasebadcholesterollevei(LDL)e.g.statins - AI/calciumchannelblockers are arteriolarvasodilators thatcausea decrease insmoothmuscletone andvascularresistance
• Surgical procedurese.g.angioplasty -Theseagentsprimarilyaffecttheresistanceofperipheralandcoronaryarteriolarsmoothmuscle
- lnthetreatmentofeffort-inducedangina, calciumchannelblockersreducemyocardialoxygenconsumption by.J...vascularresistance c> .J..afterload
-Theirefficacyinvasospasticangina is duetorelaxationofthecoronaryarteries
> Lifestyle Modification:·
~ -i~~iz~a:~~:~~ z::~:~~-~cw~:z~sS!!ffi:i:~~~~~~~~e~::~ts~~~= d~~~:::.c!~~~o~:e~i~~~~;r!~:~~f::~~~:~se
0
• Nosmoking and noenvironmentalexposuretosmoke
• Weightreduction; maintenancetoabodymassindexof18.5-24.9kglm2 - Pharmacologic~ 1) Decrease coronary vascular resistance and increase coronary blood flow (1' oxygen supply)
• Physical activity; 30-60 minutes every day (minimum of 5 days/week), increase physical activity is a great way to reduce stress, improve sleep, 2) (-ve) inotropic effect, to varying degrees; Verapamil much greater than Diltiazem and Amlodipine (decrease oxygen demand)
loseweight,and improveoverallsenseofwellbeing 3) Decrease heart rate (Verapamil and Diltiazem only) Q decrease oxygen demand
• Diet; eat a healthy diet with limrted amounts of saturated fat, lots of whole grains, and many fruits and vegetables - Verapamil and Oiltiazem should be avoide~ in patients with heart failure or with atrioventricular block due to their -ve inotropic and -ve dromotropic effects.
• Chol~sterollevel and blood pressure; maintenance LDL cholesterol less than 100 mg/dl, ~nd BP less than 140/90 mm Hg
• Oiabetes;maintenanceaglycosylatedhemoglobin
(A1c)of7o/(1""9%andavoid rosiglitazone inthetreatment
4} Newer Antianginal Drugs
- ~ (Ranexat) isa newerantianginaldrug, classifiedasNa•channelblocker.lthasantiang inalaswellasantiarrtlythmicproperties
• Alcohol ;alcohol consumptionshouldbelimited
- ~ (Vastarett MR)isa firstcytoprotectiveanti-ischemicagent. lthas no -ve inotropic orvasodilatorproperties
• Avoid angina triggers; Physical exertion, emotional stress, extreme cold or heat, heavy meals, alcohol consumption and cigarette smoking - ~ (Randiitil) isa neworganicnitratewithvasodi/atorproperties.lthas dua/properties ofan itrate andpotassiumchannelactivators

> Myocardia/ Infarction Symptoms: The onset of symptoms in Ml is usually gradual , over several minutes (30-60 min.), and rarely instantaneous. Intense chest pain that often radiates up to the neck, shoulder, and jaw and down lo the ulnar aspect of the left arm

Myocardial > Myocardia/Infarction Diagnosis: 1) Electrocardiogram (ECG); ST·segment elevation {STE) or Non-ST-segment elevation (NSTE). The EGG by itself is often insufficient to diagnose. 2) Cardiac Biomarkers {Blood Tests); chemicals that released from the heart
are called cardiac markers and includes; creatine phosphokinase {CPK), myocardial creatine kinase (CK-MB), troponins, myoglobin and lactate dehydrogenase (LDH). Troponins (T & I) are considered to be the best. 3) Non-specific Diagnosis (e.g. Echo)
> Medications: All patients should receive anti -Ischemic and analgesic medications early in care; "MONA' i!!M§. ~-blocker; Morphine (1-5 mg IV every 5-30 min.) + Oxygen (<90%) + Nitroglycerin (sublingual 0.3-0.4 mg every 5 min X3 ) + Aspirin
(non-enteric-coated 162·325 mg) + P·blocker. Oral ACEis should be used in all patients wrth left ventricular ejection fraction (LVEF) s 40% and in those with hypertension, diabetes mellitus, or stable chronic kidney disease, without contraindications. Stalin therapy

Infarction e.g. Atorvastatin 40-80 mg/day, should be initiated. Dual Antiplatelet Therapy (DAPT); · · • 162-325 mg once, followed by 81 -162 mg/day, PLUS; a P2Y12 inhibitor for 12 months; one of: such as • • • (Piavix®); 300-600 mg, followed by 75 mgfda y
> Coronary Artery Revascularizatlon: Coronary Artery Bypass Grafting (CABG) [place a new blood vessels aroond existing blockages], Percutaneous coronary intervention (PC I), [a very thin, long catheter, is inserted into an artery in either the groin or arm and is
moved to the site of the blockage with help from an X-ray.] Coronary Artery Stents [is a tube-shaped device placed in the coronary arteries that supply blood to the heart, to keep the arteries open in the treatment of coronary heart disease]
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Heart Failure (HF)
}> Background:·
• H ~a rt failure (HF) is a complex clinical syrldrome that can result from any structural or functional cardiac disorder that impairs the ability of
theventricletofillw~horejectblood
~ Theheartisunabletopumpenoughbloodwitheachbeat
• Congestive Heart Failure {CHF); is often used as one of the common symptoms is swelling or water retention
• ChronicHeartFailure;isa !ongtenncondition, usuallykeptstablebythetreatmentofsymptoms
• Acute Decompensated Heart Failure (ADHF); is a worsening of chronic heart failure symptoms which can result in acute respiratory distress
• Ejection fraction (EF): is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by
echocardiogram;
• Normal EF; 55-70% (means; 55-70% of the total amount of blood in the left ventricle is pushed out wtth each heartbeat)
• A measurement under 40% may be evidence of heart failure
• Reduced ejection fraction (HFrEF); alsoreferredtoassystolic heart faiture. The heartmuscledoes not contract effectivelyand less
oxygen-richbloodispumpedouttothebody (heart fai lurewithejectionfractionunder 40%).
• Preservedejectionfraction (HFpEF); alsoreferredtoasdiastolic heartfaiture. Theheartmusclecontractsoormallybuttheventricles do
notrelaxastheyshouldduringventricularfilling(heart failurewithnormalejectionfraction)
Heart Failure Medications
- First-line therapy for people with CHF due to reduced systolic function (HFtEF) should include ACE inhibitors or ARBs w~h P-blockers.
- /n acutedecompensatedheartfailure (ADHF), thepatient need tohospitalization tore-establishadequateperfusionandoxygende!iverytoendorgans
- The majordrugc/asses used in ADHF include diuretics (reducingthefluidlevel), inotropes (improveheartcontraction),and vasodilators (decreaseheartload)
1) Angiotensin-Converting Enzyme (ACE) Inhibitors
- ACEinhibitors shou/dbeprescribed toallpatientswithHFt€F, unlessthereisacontrair.dication
- ACE inhibitors benefits, decrease mortality {25%-50% relative risk reduction compared with placebo), decrease hospitalizations (30%) and improve symptoms
- ACEinhibitors mechanism; decrease vascular resistance (afterload)and venoustone (preload), resu/ting in increasedcardiacoutput
- ACE inhibitor should be initiated at low doses (start low and double the dose every 14 weeks to target dose)
- Monitoring, renalfunctionandserumK·shouldbeassessedwithin1-2weeksofinitiationoftherapy
- Avoiduse inpatientswhohaveangioedemaorthosewhoarepregnantorplantobecomepregnant
- Side effects; - Angioedema {less than 1%): may switch to ARBs - Cough (20%): may sw~ch to ARBs (less than 1%)

)- HeartFailureRiskFactors:· 2) Angiotensin II Receptor Blockers (ARBs)

·HighBiood Pressure{Hypertension) -Coronary Artery Disease -Past HeartAttack(Myocardiallnfarction) ·ARBs are recommended in patients with HFrEF with current or prior symptoms who are unable to take an ACE inhibitor
·AbnormaiHeartValves -Heart Muscle Oisease - CongenitaiHeartDefects -Diabetes · ARBsaresimilartoACEinhibitorwhicharediscussedpreviously
· LungDisease(Sieep Apnea=inability tobreatheproperlyduringsleepatnight) -Obesity

3) Angiotensin-Receptor Neprilysin Inhibitors (ARNis) Mffiffiij$$ 1Entresto<1

)- Heart Failure Symptoms:- • ARNis are a new drug combination of a nepnlysi n inhibitor and an ARB. F1rstapproved by FDA in July 7th, 2015
• Shortness of Breath (Dyspnea); breathlessness during activrty (most commonly), at rest, or while sleeping, which may come on suddenly. -Entrestoflanoralfixed-dosecombinationof the neprilysininhibitor Sacubitril andthe angiotensinreceptorb/ocker (ARB) Valsartan
Due to; the blood backs up in the pulmonary veins, return blood from the lungs to the heart, because the heart can't keep up with the supply - Used inconjunctionwnhotherheartfailuretherapies, inp/aceofanACE inhibitororotherARBs
Thiscausesfluidtoleak intothelungs
• PersistentCoughing or Wheezing;coughingthatproduceswhiteorpinkblood-tingedmucus. Dueto;Fiuidbuildsupinthelungs
• Edema (build-up of excess fl uid in body tissues); swelling in the feet, ankles, legs or abdomen or weight gain (pitting edema). Due to;
. 4) ~-Blockers .
- ThreeP·blockersha~ebeenshowntobeeffective in redu ci ngtheris kofdeathinpatientswithchronicH_F~F :_~. ~. and ~
t~e blood flow out of the _heart slows, ~lood returning to the heart through the veins backs up, causing fluid to build up in the tissues. The
kldneysarelessabletodlsposeofsodlumandwater, alsocausingfluidretentioninthetissues Emm (Longactmg). P·blockers shou/dbe prescribed toallpatientswithHFrEF unfess theyhaveacontralndlcallon orarelntolerantofthesedrugs
• Tiredness or Fatigue;feelingtiredallthetimeanddifficultywitheverydayactivtties, suchasshopping , climbingstairs, carryinggroceriesor
walking. Dueto; theheartcan'tpumpenoughbloodtomeettheneedsofbodytissues
• Lack of Appetite and Nausea. Due to; the digestive system receives less blood, causing problems with digestion 5) Diuretic Agents
• Confusion or lmpairedThinking. Dueto; changing levelsofcertainsubstancesintheblood, suchassodium , cancauseconfusion ·Diuretics are recommended in patients with HFrEF who have evidence of fluid retention unless contraindicated, to improve symptoms (relieve pulmonary
• lncreaseheartrate (palpitation). Due to; lossinpumpingcapacity,theheartbeatsfaster congestion and peripheraledema). Diuretics shou/dbe prescribedtoallpatientswithfluidretention
• Loop diuretics are preferred diuretic agents for use in most patients with HF. Thiazide diuretics may be considered in hypertensive patients with HF and mild
)- Pathophysiology (Compensatory Mechanisms otHeart Failure):· fluid retention . Diuretics should be combined with an ACE inhibitor,P-blocker and a~dosterone antagonist
}- TypesofHeartFailure:-
• Several natural compensatory mechanisms in heart failure, in an effort to ·~ toStrvcture;
counteracttheeffectoffallingcardiacoutputonperfusiontovitalorgans. These
mechanisms include:
- Left-sided (LeftVentricle) Failure; 6) Aldosterone Antagonists
-Lesspumpingbyliftventricle · Aldosterone antagonists are recommended in patients with; Patients with NYHA class II-IV HF and who have LVEF of 35% or tess. Patients with HFrEF
/Ca•d;acoutput~ -Lessaorticbloodflowtothebody&brain. after myocardial infarction. Aldosterone antagonist should be added toACE inhibitor (or ARB) and ~blocker therapy
-Leftfailureoftenleadstorightfailure - Monitoring K• levels and renal function should be rechecked w~hin 2 to 3 daysand again at 7 days after initiation of an aldosterone receptor antagonist
- Right-sided (RightVentricle) Failure;
I CamUd Tus r;,;ng I Renal Tod flow · Lesspumpingbyrightventricle
-Lesspulmonarybloodflowtothelungs 7) Vasodilators
•Mixedpresentations(leftandright) A) Hydralazine+ Isosorbide Dinitrate (only for CHF)
t Sympathet ic t Renin • The combination of ~ and (BiOi ~) are recommended in addition to ACE inhibitors + ~-blockers to reduce morbidity and
discharge relrse -~.!QFunction;
mortality for patients self-described as African Americans with HFrEF. And may be useful in patients with current or prior symptoms of HFrEF who are
- SystolicFailure: Theventricles (usuallyleft
orbothleftandright)losesitsabilityto unable to tolerate an ACEI or an ARB. 8 ) Na• Nitroorusside or IV Nitroelvcerin ( onlv for ADHF) C) Nesiritide (onlv for ADHF)
t Force t Angiotensin II contractnormally. Theheartcan1pumpwith
t Rate enoughforcetopushenoughbloodinto
circulation(thin, weak heartmuscle)
8 Inotropic A ents
A ) Inotrooic Agents· ~ (Lanoxine) I 1 • (Unidigi~) • . 1. [Uabani~)
· DiastolicFailure: {alsocalled diastolic
- Effectsontheheart 1) +veinotropic effect (1'force of contraction)bydirecteffecton heart
+Aldost erone dysfunction):Theventricleslosesitsability
2) -ve chronotropiceffect( ...V h eartrate)bydirecteffectandvagaleffect(u nclearm~hanism).
t torelaxnormally(becausethemusclehas
become thick, stiff). The heart can1
3)-vedromotropiceffect ("-conductionvelocityofelectricalimpulsesthroughtheAVnode).
- Mechanism Qf action: 1) Digitalis inhibits Na•fK• ATPase enzyme lead to, inhibits Na•/K•
Na• and:t:raretention properly fill with blood during the resting
periodbetweeneachbeat exchange,causesq increaseintracellularNa• q accumulation of intracellularcalcium
viathe Na•-Ca2• exchangesystem. 2) 1ntheheart, increasedlntracellularcalciumcauses
more calcium to be released by The sarcoplasmic reticulum , which 1' contractility
> Goals of therapy:· )- Lifesty/eModification:- (+veinotropiceffect). 3) Digitalis also increase vagalefferentactivity totheheart Exhmelyt.ow &tremetyt.ow Extnmelylow
1) Modify or control risk factors (e.g., HTN, obes~y . diabetes) 1) 0uittingSmoking
(parasympathomimetic action) Q "- heart rate (-ve chroootropic effect) and -t- conduction velocity through the AV node (·ve dromotropic effect), making it
2) Managestructuralheartdisease 2) MonitoringWeightChanges:sudden 1'inweight1'2-3poundsmay
usefulforatrialfibrillation. -Digoxintherapy is fndicated inpatientswithsevereHFrEFafterinitiationofACEinhibitor. P·blockeranddiuretictherapy
indicate fluid accumulation.
3)Reducemorbidityandmortality . !lQ§!: Therapy with digoxin (digitalization) is commonly initiated and maintained at a dose of 0.125 to 0.25 mg daily. Doses of digoxin that achieve a plasma
3) DietarvChanges;Sodium(Salt) Restriction("- 1,500mgaday). Avoid
concentration of drug in the range of 0.5 to 0.9 ng/ml. Toxicity cardiac arrhythmia, anorexia, nausea, vomiting and visual disturbance called Chromatopsia
4)PreventorminimizeNa•andwaterretention processedmeats(hotdogsandsausage)
4) ~ startwith5-15minutesofeasyexercisewithfrequentbreaks e t \l i ff:tlmljiblorvision_ defiCiency in which there is a predominance of yellow in vision). Toxicity 1'1' by; hypokalemia, hypomagnesaemia or hypercalcemia
5)EiiminateorminimizeHFsymptoms
Althoughthegoalistobuildupto30-45minutesofwalking, Oflow-impact
aerobicexerciseslhreetofivetimeseveryweek a; R~-Adrener~i~ ~::~~~s,::~;~: ~~~~:®J{iii~~~~~;~~ra:j~M&TnWtW~~~~~::;:· q •ve inotropic
S) ManagingStress 6) FiuidRegulation; (...V1.5-2Ldaily) C) Phosohodiesterase III Inhibitors (onlv for ADHF) ; ~ & ~: ·1' cAMP in the Heart Q 1'Ca 2• influx Q +ve inotrooic effect
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Arrhythmias Antiarrhythmic Drugs
). Background:-
• Arrhtfhmias (uh-RITH-me-ohs] /sdefinedas; » GoalsofAntiarrhythmicDrogs:- •
- Lossofcardiac rtlythm Of aboormalheart rhythm. • -Theultimategoal ofantiarrhythmK: drug therapyis torestorenonnalrhythm and conductionoftheheart
• There areS mainclassesintheSinghVaughanWilliamsclassification:
• Cardiac arrhythmia, also known as cardiac dysrhythmia or i"egular heartbeat, - Class I; agents interfere with the sodium {Na') channel - Class II; agents are anti-sympathetic nervous system agents.
is a groupofcooditionsinwhichtheheartbeatisirregular, toofast or tooslow
- Ciasslll;agents affectpotassium(K•)efflux - CiassiV;agentsaffectcalciumchannelsandtheAVnode
oA fast heart rate(inadulls, 1' 100beatsper minute)iscalled tachycardia
oA slow heart rate(inadults, "' 60beatsper minute)isca11ed bradycardia.
• Many arrhythmias have no symptoms. When symptoms are present these may
1) Class I (Sodium Channel Blockers) .
includepalpitationsorfeelinga pausebetween heartbeats

);> EfectricaiConductionSystemoftheHearl:-
Al Class lA
~ (Quinacard®) ~ (Pronestyi') ' ••-• (Norpace*)
- Mechanism 2f Action:.- By blocking sodium channels, ~re~ent~ s~~um influx: thus slowing the rapid upst~ke during phase 0.
_f\
' ·'\ j \
Structure: f \

n\
• !':~~~;=~~~~:~bers of the heart (2 atria and 2 Yenlrides) contract in a very specific - Decreases theslope ofphase 4 spontaneousdepolanzalion,lnhlbllspotasslumchannels andblockscalclumchanne!s. \
-BecauseoftheseactiOfls,it slowsconductionvelocityandincreasesrefractoriness(profongsQRSduration)
• Theelectricalimpulse thatsignalshearttocontractinasynchronizedmaooer begins inthe · Therapeutic!l§H; Atrlal fibri11atlonlflutter andventriculartachycardia.
sinoatrialnode (SAnode) - ~Effects: Quinidine; common side effects; NVOand Cinchonism or ~ (blurred vision, tinnitus, headache, disorientation, and psychosis)
• ThesignalleaveslheSAnodeandtrawtlsthrooghthe2upperchambers(atria) Procainamide; common side effects; hypotension {IV). Chronic use (rare) q lupus-like syndrome (myalgias, arthralgias, arthritis, and pulmonary).
• :u:::::e::.:~=f~=node; atrioventricularnode (AVnode)and final/y, Disopyramide; common side effects; anticholinergic effects (dl)l mooth, urinal)l retention, blurred vision, and constipation)

B) Class IB
Electrochemical Mechanism (Cardiac Action Potential); mmli!Z (lidoPen") ~ (Mexiti~) \
Theaction potentialhasSphases (numbered0-4); - Mechanism of~: In addition to sodium channel blockade, lidocaine and mexileUne shorten phase 3 repolarization \
- Phase 4 (Resting Membrane Potential; RMP); Is the membrane --- ancl decrease the durationoftheactionpotential. \
potentialwhen thecellisnotbeingstimulated. The membrane is · Therapeutic.if.H!; Lidocaine isthe agentofchoice for terminat/on of ventriculartachycardla and prevent/on of ventricular \ ..
mostpermeabletoK·and relativetyimpermeabletootherions fibrlllation afteracutemyocardiallnfarction . Mexiletine isindicatedforthe treatment of ventriculartachycardla
- Phase 0 (Rapid Depolarization); Opening of the fast Na·channels - Side Effects: Lidocaine common side effects; CNS effects; nystagmus (early fldicator of toxicity), drowsiness, slurred speech, paresthesia, agitation, confusion

Jl\_
i
causinga rapid increaseinthemembraneconductancetoNa· - -and convulsions. Mexiletine common side effects; nausea, vomiting, and dyspepsia. ' •
- Phase 1 {Partial Repolarization); Inactivation of the fast Na•
channels. Movement of Cl- ions across the cell membrane as a
C) ClassIC
resultofthechangein membrane potential, andK•efflux
- Phase 2 {Plateau); A balance between inward movement of Ca2•
li!l!!!li!ll!l (Tambocor<) lmEiiJ (R~hmo~) !
- Mechanism 2[~: Suppresses ph~se 0 upstroke in Purkinje and myocardial fibers. This causes marked slowing /
through L-type calcium channels and outward movement of K+
throughthe s/owde/ayed Kchannel ofconduction in allcardiactissue,Witha minor effect onthe durationoftheactlonpotential andrefractoriness. 1
- Phase 3 {Rapid Repotarization); The L-type Ca2' channels close, - Therapeutic!lu§; Atrlalflbrlllatlonfflutterconverslonand maintenance, Ventrlculartachycardiaand I
while the slow delayed K+ channels remain open as more Wolff-Parklnson·WhlteSyndrome
potassiumleakchannelsopen -§.isl! Effects: Flecainide; common side effects; blurred vision, dizziness, and nausea. Propafenone; has a similar side effect, but~ may also cause bronchospasm
duetoits~blodc.ingeffects,~shouldbe.avoided in patientswithasthma

Electrocardiogram (ECG)

~:v:==~~:!e:=:~ 2) Class II (~-blockers)

nodetowardslheAVnode, andspreadsfrom ~ £m::DI r..m:m : ... .
- These drugs diminish phase 4 depolarization and, thus, depress automaticity, prolong AV conduction, and decrease heart rate and contracti lity
:~:~~~~~ftatrlJm. This turns into
- Class II agents are useful in treating tachyarrhythmias caused by increased sympathetic activity. !lHs!. fQ[ atrial flutter and fibrillation and for AV nodal reentrant
QRScomplex;TheQRScomplexreflectslhe tachycardia .inaddition,~ers preventlife-threateningventriculararrhythmlasfollowingamyocardlafinfarction
rapiddepolarizationoftherightandleft - Esmolol is a short acting IHMocker used primarily as an antiarrhythmic drug for intraoperative and other acute arrhythmias
wntricles. They haw a large mliSCie mass - Sotalol is a nonselectiveli-bfockerlhatproionQsthe actionpotential q classlll action
compared to the atria, so the QRS complex
usuaDyhasmuchlargeramplittxlethanlheP-

ST segment; TheST segment connects the 3) Class Ill (Potassium -Channel Blockers)
ORScomplexand the Twave.TheSTsegment
represenlsthe pefiodwhen lhewnlriclesare
depolarized.
-Theseagents prolongthe durationoftheaction potential withoutalteringphaseOofdepolarization orthe resting ~;:"'
membrane potential (prolong the effective refractory period, inc;c£i£ffjt(~~~darone•)
T wave; The T wave represents the
repolarization(~recovery)of theventricles - Mechanism Q[ Action: It has complex effects, showing class I, II, Ill, and IV actions, as well as a-blocking activity.lts dominant
effect is profo ngation oft~e action potential duration and !he refractory period by blocking K• channels
- Pharmacokinetics; ~ contains iodine and is related structurally to thyroxine. Onset of action· may occur in 2 to 3 days, but more commonly takes 1 to 3 weeks, even with loading doses. Elimination hatf-life; is a complex, with a rapid component of 3-10 days (50% of the drug) and a slower component of
several weeks. After discontinuation of the drug effect are maintained for 1·3 mooths. Measurable tissue levels may observed up to 1 year after discontinuation. Metabolism; amiodarone is metabolized to des-eth)1-amiodarooe (OEA) by the cytochrome P450 enzyme group CYP3A and CYP2C8. Dose shoold be reduced

~~~fo~~~~~~u~;:a~:~~i~~~=~:~·di;J:;:::.ti~e~~~~r~:;p:;'!s~~~~ aL~e~1~:~~~~~~~-af.;;;$.ji(~:~~~~:~~~aaa~00~}~;n~~~:O~~fu~:r~~~:~;a~i~:s~:~~=:~~::~~~~~~::r:;ii~i~~~:~~i~~;~;:~~::~c t~!~~~:1i1~~:~s; AIT), neurologic toxicity, Gl upset,

•Elm is a non-selective competitive ~-adrenergic receptor blocker that also exhibits Class Ill antiarrhythmic properties. !lHs!. for atrial fibrillation, atrial flutter, or ventricular arrhythmias

4) .Ciass ~ cium Channel Blockers) 5) Miscellaneous Antiarrhythmic Agents

..•. (lsoptin"J :Iil!illimiii (AIIiazem') lll!!m A) (Lanoxin<)
- Verapamil shows greater action on the heart than on vascular smooth muscle, and Diltiazem is intermediate in ~s actions. - Digoxin inhibits the Na•/K•-ATPase pump, profonging the ~refractoryperiod and diminishing conduction velocity inthe AV node
- ~; Supraventricular tachycardia is the major arrhythmia indicationfoc Verapamil. Verapamil can also reduce the ventricular rate in atrial fibrillation -Digoxinis usedtocontrol atrlalfibril1ationand flutter. !:isl!!:Serum digoxinconcentrationsof1-2ng/mlaredesirablefocatrialfibrillationorflutter, wtlereas
and flutter. Diltiazem appears to be similar in efficacy to Verapamil in the management of supraventricular arrhythmias, including rate control in lowerconcentrationsof0.5 to0.8ng/ml aretargetedfor systolicheartfailure
atrial fibrillation B) IV ~ is lhe !l!!t9.2fcholce foracute supraventricular tachycardia . C) IV ·• · - usedfor digitalis·induced arrhythmias.
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Blood Coagulation
• fnnorma/situation thereisa deficatebalanc~ that preventsthrombosis and hemorrhage
• Disordersofcoagulatlon can/eadto an increasedriskofbleeding (hemorrhage) orobstructiveclotting (thrombosis)
• Inside lhe vascular system the blood must be remain fluid but when exposed to non-endothelial surface outside the vascular system, i!
~asincaseofvascularinjury. Whenintravascularthrombioccur, asystemof~isactivatedtorestore fluidity
- MalnStepsofCJot Formatlon:-
1: Vasoconstriction {VC); todecreaseblo00flowininjuredarea
2: Piateletadheres tomacromoleculesin thesubendotheliatregionsof theinjuredbloodvessels
3: Releaseofintracellulargranules containingchemicalmediators.
4: Piateletsaggregate toformthe primaryhemostaticplug
S: Activationofplasmacoagulationfactors,leadingtogenerationofthrombin which catalysis theconversionof fibrinogen to fibrln
3) Direct Factor Xa Inhibitors
A) ParenteraiDirectFactorXalnhibitors· • '·'· (ArixtraO)
-It is a pentasaccharide anticoagulant that is synthetically derived, is a chemically related to low molecular weight heparins (LMWHs).
· Therapeutic~ Treatment or prophylaxis of venous thromboembolism (DVT & PE).
B) Oral Direct Factor Xa lnhibitors·lill!lm!llli!ll (Xarello") li'!llEEim (EI~uis•)
• Rivaroxaban is the first oral factor Xa inhibitor. • ~ . Prevention of stroke In non-va~ vular atrial fibrillation. Prophylaxis of DVT and PE in knee or hlp surgery.
4) Vitamin K Anta onist (Coumarin Anticoagulants)
(Coumadinf' -Marevanfl)
• Pharmacokinetics· rapidly absortled after oral administration. Oral bioavailability = 100%. Warfarin readily crosses the placental barrier. Over 99% of racemic warfarin
is bound to plasma albumin. It is metabolized by the CYP450 system. Elimination Half-life; Mean half-life is approximately 40 hours
• Mechanism P1 Action: - Warfarin inhibits vitamin K epoxlde reductase enzyme, resulting in depletion of the reduced form of vitamin K
Treatment initiated · Vitamin K is a cofactorfor the carboxylation of glutamate residues on theN-terminal regions of v~amin K-dependent proteins, this li m~s the
with UFH or LMWH tor gamma-carboxylation and subsequent activation of the v~am in K-dependent coagulant proteins
the first s-7 days, with - The synthesis of vitamin K-dependent coagulation factors 11. Y.!l. JX, and X.and anticoagulant proteins C and Sis inhibited
anoverlapwith -Depression cl vitaminK-dependentcoagulationfactors (factorsii ,VII, andX)resultsin decreasedprothrombinlevels anda decrease in the
Warfarin amountof thrombin generatedandboundto fibrin
· Therapeutic~; DVT, PEand thromboembolic complications. The ~ must beind ividualizedforeach pa tient according tothepatient'si NR
- §kt!~ 1) Hemorrhage; bleeding may be treated by vitamin K (warfarin antidote). 2) Warfarin Necrosis; Rare complications of warfarin therapy, more common

Anticoagulant Drugs in obese women. 3) Osteoporosis; due to reduced intake cA vitamin K, which is necessary for bone. 4) Purple Toe Syndrome
· ~Interaction· Metronidazole, Fluconazole and Trlmethoprim-Sulfamethoxazole also stereo selectively inhibit metabolism of S-warfarin .
Amiodarone, Disulfiram and Cimetidine inhibit metabolism of both enantiomorphs of warfarin. Aspirin augment warfarin's effects by its effect on platelet function
Hepaticdisease and hyperthyroidism augment warfarin'seffectsbyincreasingthe turnoverrate ofclottingfactors. Third-generationcephalosporins kil/ the bacteria
- AnticoagulantsCiassiflcation (Mechanism)
in the intestinal tract that produce v~amin K. Barbiturates and Rifampin cause a m<.ll'ked decrease of the anticoagulant effect by induction of the hepatic enzymes that
1) 1ndirectThrombinlnhibitors(Heparins) 3) DirectFactor Xalnhibitors transform racemic warfarin. Cholestyramine binds warfarin in the intestine and reduces its absorption and bioavailability. Diuretics; Chlorthalidorie and
2) DirectThrombin lnhibitors (DTis) 4) Vitamin K Antagonist (Coumarin Anticoagulants) Spironolactone (clotting factor concentration). Vitamin K; increased synthesis of clotting factors. Hereditary resistance; mutation of vitamin K reactivation cycle
molecules. Hvoothvroidism: decreasedtumoverrate ofclottinafadors
1) Heparins {Indirect Thrombin Inhibitors)
- Heparln isan injectablerapidlyactinganticoagulant thatisoften usedacutely to interfere withlhe formation of thrombi
A) Unfractionated Heparin (UFH); . •·•
B) Low Molecular Weight Heparins (lMWHs);
· Antlcoagulanteffectwith unfractionatedheparinoccurswithin
minutesof iVadministrationor1to2hoursafterSCinjection.
(lnnohep&)
Fibrinolytic Drugs Antiplatelet Drugs
- Activatedpartialthromboplastintime (aPTI)isthestandardtest
usedtomonitortheextentofanticoagulationwithheparin - Severaltargetsforplatelet inhibitorydrugshavebeen identified
Fibrinolyticdrugs (Thrombolyticdrug)rapidlylysethrombi(disso!ve blood clots)
·The maximum anti-factor Xa activity of the LMWHs occurs 1) /nhibltProstaglandlnSynthesls (Asplrin)
by catalyzing the formation of plasmin (serine protease) from its precursor 2) /nh/bitADP-InducedPiatele!Aggntgatlon (Ciopldogret,Prasugrei &Ticlopidne)
4hoursaftersubcutaneousinjection plasminogen
- Not necessary to monitor coagulation values with LMWHs 3) 8/ockGtycoproteinllhllllaReceptors (Abclxlmab, Tlroflban and Eptifibatide)
4) Protease-Activated Receptor-1(PAR·1)Antlgon/sts (Vorapaxar and Aiopaxar)
because theplasmalevelsandpharmacokineticsarelnOfe
S) OtherAntiplateletDrugs (Dipyridamole and CIIostazoQ
predictable, but inrenallyimpaired,pregnantandobesepatien\s
monitoringoffactorXalevelsisrecommendedwith l MWHs
- MechanismP.[Action:
Load:=by Onceorlwicedaily
(Fixed dose) • II combines !i
the vatorlii!J~:):Jas!Eimin3J(~~~:s~zyme
w~h p~ro-amc)ti!!!!l oge complex. This
- UFH; Heparinmolecules bind to antithrombiniii (AT-111)
(Unfixed dose) enzymatic complex catalyzes the conversion of inactive plasminogen to Thromboxane A2 Inhibitor
1.5hours active plasmin
conformationalchange occurs ~ activation of AT·III ~ f.J!T:llmi (Aspocid")
inhibition cl thrombin about1000-fold andfactorXa Cheep - ~ a cuteMI, DVT and PE - Aspirin inhibits the synthesisof thromboxaoek. by irreversible acetylationof
- lMWHs; One molecules bind to with AT-Ill ~ Activated partial ttvomboplastin -lthas highantigenicitv, so patients with anti-streptococcalantibodies can cyclooxygenase(COX)enzyme, inhibitplateletfunctionwithin60min
inactivatefactorXa tme(aPTT) develop fever, allergicreactions and therapeutic reslstance. - Aspirin is ~ inthe prophylact/c treatmentoftrans ien t cerebralischem i a
-A unique pentasaccharidesequence Tlwombi'l,IXaandxa and thromboembollcstroke,andreducethe lncidenceofrecurrent MI.
and lMWHsperrnitstheirbindingtoantithrombin (~) The recommended dose; ranges from 75-325 mg/d
- Therapeutic !l!!§; . Heparin and the LMWHs !lmJ!. the expansion of thrombi by preventing fibrin formation (Angikinas..) - ~effects ; Gl distulbances, t bleeding time alld may cause bronchospasm
. These agents are used for, acute venous thromboembolism (DVT or PE). Prophylaxis of postoperative venous thrombosis in patients -lt alsoca/ledurokinase-typeplasminogenactivator (uPA), itis produced in susceptible patients.
undergoing surgery and those with acute MI. Drug of choice for using in pregnant women (do not cross the placenta) naturally in thebodybythe kidneys.
• §is!! Effects: 1) Bleeding; Major adverse effect of heparin Monitoring is required to minimize bleeding -Therapeuticurokinase isisolated from culturesof human kidneycells and
fxcessivebleeding may bemanaged by discontinuing thedrug or by treating with protaminesulfate has low antigenicity P2Y12 Receptor Inhibitors
2) HypersensitlvltyReaction; Suchas;chills,fever,urticaria,andanaphylacticshock, dueto;heparinis ofanimalorigin · !l!!§; PE, DVT, acuteMI,coronaryarterythromboslsand arterialthrombosis mBI%li 1PiavixO) IIilm!mlliii (Ticlid")
3) Thrombocytopenla; Heparin-ind ucedthrombocytopenia (HIT)is a seriouscondition that occursin 1-4% ofindividualstreated withU FH for lil!l!l!lllmi iEffient<) llil!mlilllZ IBrilinla<)
aminimumof7days. HIT iscaused bythe formation of abnormalantibodies thatactivate platelets. lncases of HIT.heparin canbereplacedby - Mechanism!!!. Action: Acts by inhibit the binding of ADP to its receptors
anotheranticoagulant, suchas Aigatroban . 4) 0ther5ideEffects; Osteoporosis, Hairloss and alopecia (Eminaset) {P2Y12 receptor) onplatelets ~ /nhlblttheactivationof GPIIbllllareceptors
- ltisa/soknownasanisoylatedplasminogenstreptokinaseactivatorcomplex requiredforplateletstobindto fibrinogenandtoeachother
(APSAC ). ~; acuteMI. .- Ciopidogrel isa prodrug thatrequiresactivat/on via the cytochromeP450
2) Direct Thrombin Inhibitors {OTis). enzyme isclorm CYP2C19. Drugs that impairCYP2C19functioo, stx::h as
A) Parenteral Direct Thrombin Inhibitors Omeprazole,should be usedwithcaution.
• • (Angioma~) • • (Refludan') • • (l privas~) - Therapeutic~; NonST-e levationacutemyocard i alinfarction ; NSTEMI

-Theyareparenteraldirectthrombininhibitorthat areanaloguesof Hirudin. Likeheparin; admlnlsteredparenterally &is monitored bythe aPTI (Unstableangina) &ST-elevationmyocardlal lnfarction (STEMI) including
. Therapeutic !l!!§; . Bivalirudin percutaneous coronary intervention (PCI). Leplrudin thrombosis related to heparin-induced thoseundergoingPCI . Stroke and perlpheralarterlaldlsease .
· Plasminogen can also be activated elldogenously by tissue plasminogen
thrombocytopenia (HIT). Desirudin prophylaxis of deep vein thrombosis. which may lead to pulmonary embolism, in activators (t·PAs). Human t-PA is manufactured as Alteplase (by recombinant - ~effects; theseagents cancauseprolo nged bleeding (noantidote).

·IS :::~l:::,h::.:~:~!~~t~~~:~~,Uke t;heott10rs. t;teeding is the major side effect DNA technology), Reteplase (by recombinant DNA technology) and
Tenecteplase is aoother recombinant tPAwith a longer half-life and greater
- Ticlopidine; has moreadverseeffects.

billdingaffinityforfibrin.
• Therapeutic~ - Prophylaxis or treatment of thrombosis in patients with heparin-Induced thrombocytopenia{HIT)
- ~.
Gl coprotein lib/lila Inhibitors
- During p ercutaneou s coronary i nterventi ons (PCI)in patientswhohaveHIT or areatriskfordevelopingit. - ~effects; bleeding. ·• .• (ReoProO) m i J m (tnlegrilin") iDJm (Aggraslat<)
- Aiteplase; TreatmentofacuteMJ, massive PE andacutelschemlcstroke.
B) Oral Direct Thrombin Inhibitors -These agents should be used in combinatioo with anticoagulant therapy &
- Reteplase; TreatmentofacuteMI (off-labelused in DVT and massivePE)
(Pradax..) aspmn.
- Therapeutic~; Preventionofstrokelnnon -val vularatrlalfibrillatl on and DVT and PEinh l por k neereplacementsu rge ry.
- Tenecteplase; TreatmentofacuteMI - ~ ; theseagentsare giveniV , alongwithheparin and aspirin , asan
- Dabigatranantldote; (Praxbind®)is a monoclonalantibodyandthe firstreversalagentforthe Dabigatran. - 5/deeffects; bleeding. adjuncttoPCi forthepreventionofcardiaclschemiccomplications.
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Hyperlipidemia Antihyperlipidemic Agents
l»Overview:-
• Plasinalipids aretransportedincomplexescaffedlipoproteins 1 HMG-CoA Reductase Inhibitors Statins)
• lipoprotein; isabiochemicalassembly thatcontains bothproteins and lipids · • . . • (U~tor<) lil!i!ll!m!lil (Lesco!O XLI I!!:.m!!lllil (lipdip") ." " • · (Uposta~)
• Metabolicdisorders thatinvolveelevationsinanylipoproteinspeciesaretermed hyperlipoproteinemiasor hyperlipidemias lill!!l!l!m!lli iCrestorOI Illilrl!ml!lii iZocor') ~ (liposta~)
• Hyperlipldemia or Hyperlipoproteinemia; invotves abnormallyelevatedlevels of anyoraJ/Iipidsand/orlipoproteinsintheblood - Mechanism Q[ ~; the active forms of the statins are structural analogues of the HMG.CoA Intermediate that is formed by HMG-CoA reductase in the
• Thetwomajorclinica1syndromeofhyper1ipldemiasare acutepancreatitis and atherosclerosis. synthesisofMevalonate. Theseanalogues{statins)causepartialinhibitionoftheenzyme. Resuft/n;
• Atherosclerosis is correlated w~h elevated levels of low-density lifK>protein cholesterol (LDL-C; bad cholesterol) and triglycerides and low 1) 1nhibitiondenovosynthesisofcholestero1 Q depleteintracellularsupplyofcholesterol
levelsof high-densitylipoproteincholesteroi (HOL-C;goodcholesterol) 2) 1ncreasenumberoflOlreceptors,duetodepletionofintracellularcholesteroi Q PromotesuptakeoflOlfromblood
• During fasting (12-hour fast; no food or drink, except water), total plasma lipids concentration range from 360.820 mg/dl 3) Modestdecreasesinplasmatriglycerides and smaf/increasesinHDl alsooccur
>Cholesterol Biosynthesis; · Therapeutic~; Statlns are usefu laloneorwith resins,niacinor ezetimibeinredu el ng leve l s of LDL
• HMG-CoA {3-hydroxy-3-methylglutaryt-coenzyme A) reductase enzyme is the key enzyme for cholesterol synthesis Use in children is restricted to selected patients with familial hypercholesterolemia or familial combined hyperlipidemia.
> Plasma Cholesterol Levels:- - ~ Reduce LOL-C by 24-60%, reduce TGs by 10-29%, raise HOL-C by 6-12%, , reduce CHO mortality, reduce coronary procedures and reduce stroke by 17%.
- ~~;
i > Atherosclerosis Lifestyle Modification:· • Hepatlc; f/evatedliverenzymes up to3timesnorrnal insomepatients. Monitoringisusually needed)
• Diet high in vegetables, fruits and whole • Muscle; the most common statin side effect is muscle pain {10-15%). Very rarely, statins can cause life-threatening muscle damage called rhabdomyolysis
grams. [rab-doe-mi..QL.Jh·sis]; severe muscle pain, liver damage, kidney failure and death. The risk of stalin-induced rhabdomyolysis increases with older age, use
• Dairyproductsshouldbelow-fat of interacting medications such as fiDrates and hypothyroidism. Monitoring; check creatine kinase {CK) at baseline arK! then only if muscle symptoms
occur; no regular monitoring. Coenzyme Q10 (is a cofactor for m~ochondrial energy production) levels are decreased in stalin use, Co010 supplements
• Fish, legumesandpoultry are sometimes used to treat stalin-associated myopathy. Dose; 100-240 mg./daily foc up to 2.5 years.
• Vegetable oils arK! nuts · Digestive; Somepeople takingastatinmaydevelop nausea, gas, d!arrhea or constlpation aftertakingastatin.
• Umitationofsugarandredmeats - Neurological; Mttf.lnllysls reported cognitive impairment (memory loss) from stalin use for several years.
• Reduceintakeofsaturatedandtrans-fal · M2!fCommonQcygfnteractions·
· Fibrates: fncreaseriskofmyopathy {Gemfibrozil greaterthan Fenofibrate).
• Nomorethan2,400mgofsodium/day.
'i T • OASHdietarypattem
- Niacin: Oosesgreaterthan1glday increasetheriskofmyopathyandrhabdomyolysls.
• Amlodarone, Verapamll arK! Dlltlazem a/so causes an increased risk of myopathy with Lovastatin and Simvastatin
• Regular aerobic physical - Inhibitors of CYP3M such as Macrolides, Cyclosporine, Ketoconazole, increase plasma levels of Lovastatin , Simvastatin, and AtOfVastatin
- Inducers of CYP3A4 such as Phenytoin , Griseofulvin, Barbiturates , Rifampln, reduce plasma levels of Lovastatin , S ~mvastatin , and Atorvastatin
--~------------

2 Bile Acid Sequestrants Resins) 3) Niacin 4) Fibric Acid Derivatives 5) Cholesterol Absorption
• ' (Questran') ~
- Theyare anion-exchangeresins thatbindnegativelychargedbileacids
(Nicotinic Acid or Vitamin 83) (Fibrates Inhibitors
and bilesaltsinthesmallintestine {Niaspane) (Lipanthy~) • • (LopidO) • • · {EzetroJt)
- Bileacidsequestrantsare inso/ub/einwater arKihavelargeMwl - Mechanismfl!Action; - Mechan/sm2fAf11!m; - MechanlsmQ!Action;
- After oral administration, they are not absorbed and not metabolically -At1gmdose; - Peroxisome Proliferator-Activated Receptors (PPARs) are -ltisaselective inhibitor of intestinalabsorption ofcholesterol arKI
altered by the intestine. - Niacin stronglyinhibitslipolysis inadiposetissue, thereby membersofthenuclear receptorsupergenefamilythat regu/ates phytosterols (ptantsterols), leadingtoa decrease inlhe delivery of
· Mechanismg[Action; reduc/ng productionof freefattyacids. /ipidmetabo/ism. Uponbindingtotheif-naluralligands{fattyacids intestinal cholesterol tothe liver
- Bileacidsequestrants areanion-exchange resinsthat bindnegative/y -The liver normally uses circulating free fatty acids as a major oreicosanoids) PPARsareactivated · Reduction of hepaticcholesterol stores, leadingtoanincrease in
charged with bileacids inthesmallintestine, resinlbileacidcomplexis precursorfortriglyceridesynthesis - Fibrates functionprimarilyas ligands forthenucleartranscription clearance ofcholesterot fromtheblood
excreted in the feces Q /oweringbileacid concentrationQ This - Reduced livertriglyceride levels; receptor (PPAR-a) Q activate PPAR-a Q decreased -ltis effectiveeven inthe absenceofdietary cholesterol because k
causeshepatocytesto increaseconversion of cholesterol to bile - Oecrease hepatic VlDL production triglycerideconcentrations byincreasing theexpressionof inhibitsreabsorption of cholesterolexcreted in thebile.
acids - ReducesLDL·C plasmaCOflcefltrations lipoprotein lipase and decreasing Apo-CII concentration -~
-Consequenlly, - Therapeutic.!ln!: Niacin otten used in combination witha Resin or {Fenofibrate is more effective than Gemfibrozil in lowering · Lowers lOL-Cby H~·20%.
-Decreaseintracellutarcholesterolconcentratlons Statins , it isnoonalizesLOLinmost patients with triglyceride levels) ·May raise HOL-Cby1-5%
- lncreasehepaticuptakeofLDL·C familial hypercholesterolemia andotherformsof - Fibrates also increasethelevelof HDL.C by increasing the - Lowers TGbyS..10%
hypercholesterolemia. expressionof Apo·A - Therapeutic~;
-Decrease in plasmaLDL-t
- ~ ReduceLOL-C by 15-26%, RaiseHOL-C by3-6%, May increase . ~ Lowers LDL-C by 15-26%, Lowers TG by 20-50%. - Ezetimibe is synergistic with Statins, so itisoften used asan;
TG concentrations, Reduce major coronary events, Reduce Raises HDL·C by 15-26%, Reduces major coronary events ·Severe hypertriglyceridemia · Adjunctto statintherapy
CHOmortality Lowers lipoprotein{A) - Hypertrlglyceridemlainwhlch VLDLpredominate · Statln·intolerantpatients
- Therapeutic~ ; Resins arealso used in combination withothe r drugs · Oysbetalipoprotelnemia (Type lllhyperlipidemia) · !Jn!!l.lnteractlon; there are nosignificant interactionsw~h Warfarin or
- ~effects ,
to achieve further hypocholestero!emic effect in .. Hypertriglycerldemia that results from treatment with viral Digoxin .
1) NiacinFiush {FaciaiFiushing); Themostcommonsideeffectsof
patients with primary hypercholesterolemia and protease _Inhibitors
niacinarean /ntensecutaneousflush and pruritus, dueto
treating type iiAandtype iiBhyperlipidemias
- Cholestyramine canalsorelleve prurltuscausedby
prostaglandinmediatedvasodilationeffect.
- Fiushingusually fasts for about 15 to 30minutes
-~ 6) Omega-3 FaHy Acids
- Lower lOL-Cby5-20%{with normai TGs)
accumulation of bile acids in patients with biliary
-Fiushing canbe minimizedby; .. May raise LDL·C by 45% {with very high TGs) • The three types of omega·~;:: ~:i~~~~v~li~:. ~~
·n ~ii:j
~mii:
'":fuph~
ysilo/og
\iiiy:~
a re
stasis. 1)Taking Aspirin 325mgor lbuprofen 200mg30-00minutes
- Secause the resinsbinddigitalisgtycosides, they - Lower TGby30·55% · , arK!
beforeniacin. 2)Useofanextendedreleaseformofthedrug {bothcornmonly foundin
maybeusefulindigitalistoxicity. - Ralse HDL-Cby16-22%
3) Gradualdosagetitration{over2to3months) marine oils).
- Colesevelam isalso indicated fortype2diabetes - Reduce progressionofcoronarytesions.
4) Administeringthedoseduringorwilhin30min. aftermeals -Min: treathypertrlglyceridemia as an adjunct todiet ina dultsw~hTG
duetoitsglucose-loweringeffects co n ce n trati o n of ~ 500 mgldl
5)TakingNiacinatbedtimewithfoodarKiavoiding, spicyfoods
- ~Effects , - Mild Gl disturbances; Mild Gl disturbances are the most common. · N.B;
ai'Kihotshowersaroundthetimeofadministration
· Gl disturbances; such as; Constipation, nausea arK! flatulence, · Gallstones; Galistones mayoccur, 1' biliarycholesterolexcretion - Omega-6 fatty acids; areessentialfattyacids {polyunsaturated fat).
2) UpperGIDistress; Nausea and dyspepsla {indigestion)
Colesevelam has fewerGisideeffects - Myositis; Muscle inflammation and paincanoccur. - Omega-9 fattyacids; aremonounsaturatedfats
3) Hepatlc; reversibfeelevations in liverenzymes.
- Malabsorptionoffat-soluble vitamlns (A,O, E arKIK) mayoccur, · Myopathy and rhabdomyolysis havebeenreportedin - Omega-3-6-9fatty acids playspecificroles inoverall health;
4) Metabolic; Hyperuricemia; dueto niacininhibitstubularsecretion
Colesevelam has no or fewer effeds. patlentstaking Gemfibrozil and Statins together. -Prevent,coronaryheartdisease, strokeanddiabetes
of uric acid, more common in men. Allopurinol may give if needed
- Usually not used with pregnant women due to v~amin deficiencies · Gemfibrozil is contraindicated with Simvastatin - Promote; healthynerveactivityai'Kicelldevelopment
thatmayaffedthefetus - Contraindications; Liverdisease, severegout ai'Ki pepticulcer. · Fenofibrate isthefibrateof choicefor usein - Malntain ahealthyimmunesystem
- !Jn!!l. Interactions; in general, additional medication {except Niacin) - ~ CategoryCbytheFOA,ithasbeenassociatedwithbirth combinationwitha Statins - ~effects ;
shouldbe givenatleast 1to2hoursbeforeor4to6hoursafter, defects in laboratory animals - Hepatic; flevatedliverenzymes mayoccur insomepatients - GI {abdominalpain, nauseaanddiarrhea) and fishyaftertaste
the bile acid-bindingresins - ~Women ; Niacinisexcretedinhumanmilk,maycauseserious - Contraind/cat/ons: Severerenalorhepaticdiseaseand patients with - Riskofbleeding especiallyinpatientswhoaretakinganticoagulant
- Contraindications;in patientswlthhypertrlglyceridemia (<!:400mg/dl ) adversereactionsininfants pre-existing gallbladder disease orantiplateletdrugs{dueto itinhibitplateletaggregation)
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
CNS Brain Subdivision and Functions Sedative-Hypnotic Drugs
** Forebrain ** ** Mi~brain ** .1) Benzodiazeplnes (BDZs)
- Cerebral ' Cortex; essential for memory, - Auditory and visual processing Lon -acting (>24hrs. half-life)
attention, awareness, thought, language and
(Tranxene®) 1111. (Doral8) ( Fris i u ~)

c.. consciousness.
- ~::!m~; control of voluntary motor
** Hindbrain **
- Cerebellum; voluntary movements such as posture, balance, coordination and (At:~:~)med~~te~acting(~;~;~~~~:~
· hmalf-ilife1:m
l DB

ro - limbic~; supports avarietyof

functions; emotion and olfaction
speech
- f2.n!; re/aymessages fromtheforebraintothecerebellum. Regu/ationofrespiration
and sleep and ithasarolein dreaming
- Medulla~;importantin heartrate and bloodpressurecontro/.lt's
(Xana~)
Short-acting (<12hrs.half-life)
(Dormicum®) t . (Comedormi~) (Halcion®)

~
- Thalamus; essentialfor sensoryprocessing
- Hypothalamus; contro/s bodytemperature
- Pharmacokinetics: BDZs are lipophilic, rapidly and completely absorbed. Distribution; throughout the body (brain, placenta and mothe(s milk)
responsibleformultiple autonomlc - Mechanism g[ Action: 1) BDZs potentiate the action of GABA by binding to BDZs sttes (BZ1or 822) on GABAA receptors ¢ increasing their affinity for GABA.
2)This results inan increasedopening of CI· channels andenhancedhyperpolarization ¢ sedativeeffect
- Pharmacological Action: All BDZs exhibit ~ therapeutic properties;
!) Anxlolytic (also known as minor tranquilizers), f ) Hypnotic, ~) Amnesic Actions (memory loss), ~) Anticonvulsant and ~) Muscle Relaxant

""C Central Neurotransmitters

- Therapeutic~ : l) AnxietyDisorders ; selectiveserotoninreuptakeinhibitors(SSRis) , arenowconsideredtobedrugsof firstchoice inanxietydisorders
.f)SieepDisorders; ' Non-pharmacologictherapies are useful and safer forsleepdisorders(shouldbe usedfora limitedperiod), cancause

c adose-dependentchangeinsleeppatterns (Zolpidem,Zaleplon and Eszoplclone arelesslikelychangesleeppattems)

~) Adjuncts to Anesthesia; Diazepam, Lorazepam & Midazolam are used IV in anesthesia , to facilitate amnesia.
~) Seizures ; IV Cionazepam (slronger), Lorazepam (/onger)and Diazepam (faster)are first-linechoices
~) Alcohol Withdrawal Syndrome; Chlordiazepoxide {most commonly), reduce the risk of withdrawal-related seizures.
Synaptic Potentials
~ -Synapticpotentialreferstothe difference in voltagebetween the inside and outside ofapostsynapticneuron.ttiscomesin threeforms;
A) ExcitatoryPost-SynapticPotentials (EPSPs);The EPSPs(depolarize)aregeneratedbythefoltowing
1) Stimulation of an exc~atory neuron causes the release of excitatory neurotransmitter molecules, such as glutamate or acetylcholine, which
- ~Effects: !)
§)Muscle Spasms ; Diazepam is useful in the treatment of skeletal muscle spasms
Next day drowsiness and confusion (most common side effects); Most common w~h long-acting as Diazepam & Flurazepam
f ) Next day sedation, ataxia and impair driving ; Most common in elderly. ~) Hypotension & Respiratory Depression
~) Rebound Insomnia; occur when t discontinued abruptly, most common after the use of short acting agents (most common with; Triazolam)
bindtoreceptorsonthepostsynapticcellmembrane. Thiscausesatransientincreaseinthepermeabilityofsodium(Na•)ions
2)TheinfluxofNa•causesaweakdepolarization,orEPSP,thatmovesthepostsynapticpotentialtowarditsfiringthresho1d ~) Tolerance, Dependence and Abuse; Triazolam (short acting agent) often shows a rapid development of tolerance and withdrawal symptoms

Q) 3) Stimulation of exc~atory neurons increases, more exc~atory neurotransmitter is released

B) lnhibitoryPostsynapticPotentials (JPSPs); TheiPSPs(hyperpolarize)aregeneratedbythefollowing
1) Stimulation of inhibitory neurons releases inhibitory neurotransmitter molecules, such as y-aminobutyric acid (GABA) or glycine, which bind
- BDZs reversal~ [floo-MAZ-eh-nill] rapidly reverses the effects of BDZs by competitive inhibition at the BDZs binding site on the GABA...
receptor. IV administration only. Onset is rapid (within one to two min.), but the duration is short, w~h a half-life of about1 hour

-c toreceptorsonthepostsynapticcellmembrane. Thiscausesatransientincreaseinthepermeabilityofspecificions,suchasK•andCI·
2)TheinfluxofCI· andefftuxofK•causeaweakhyperpolarization,oriPSP, thatmovesthepostsynapticpotentiai<Mayfrom itsfiringthreshold
C) CombinedeffectsoftheEPSPandiPSP;
-MostneuronsintheCNSreceivebothEPSPandiPSPinput
-Severaldifferenttypesofneurotransmittersmayactonthesameneuron,buteachbindstoitsownspecificreceptor. Theoverallactionisthe
summationoftheindividualactionsofthevariousneurotransmittersontheneuron
~J;:;;~;:!·~~~;J (Luminal*)
(Secona~) (Amyta~) -- (Fiorice~)

:::l Gamma (y)-Aminobutyric Acid (GABA)

Ultra-short-acting; (Pentothal"®)
- ~ theyhavebeen largelyrep/aced bythe benzodiazepines , because; !) !:iightherapeuticindex. f)Moreselective. ~)Mildphysicaldependenceandtolerance
!) ).ittle cardiovascular and respiratory depression . ~) Not significantly enzyme inducer. §) ~vailable of specific antidote (Fiumazenil)

<.9
- GABA isthe f1W9.!inhibitoryneurotransmitters (NTs)lnlhe CNS,Includinglhespinalcord - Pharmacokinetics: Completely absorbed. Distribution; to all tissues and fluids (brain, placenta and mothe(s milk). Alkalinization of urine 1' elimination
- GABA receptors are divided into two main types: GABAA and GABAs - Mechanism g[ Action: Barbiturates enhances GABAergic transmission by binding to the site of barbiturates on the GABA... receptors ¢ prolonging the
- GABA...receptors are ionotropicreceptors (/igandgatedionchanne/) thatare selectively permeableto CI-. These receptors are selectively
durationoftheCI·channelopenings ¢ sedative-hypnoticaction. Barbituralescanblockexcitatoryglutamatereceptors
inhibited by ~ whichcausegeneralizedconvulsions
- Pharmacological Action: !) CNS Depression , .V CVS Depression , ~ Respiratory Depression , ~) liver Microsomal Enzyme Inducers
• G~B ~~i~~:~?~~:~en~:~~~~:~~~;~;~t:::;~!:~!:~; ~~~~!~J~~e-e:~~is~~ ~~;)~ellular location, either inhibit
8
2
Ca • channels - Therapeutic~: 1) Anesthesia (Thiopental). f) Sedative-hypnotic (rarely or not used), Butalbltal is commonly used in combination with analgesics as a
sedative to assist in the management of tension-headache or migraine headache.~) Seizures; Phenobarbital has specific anticonwlsant activity

ro Glycine
-Both GABA and Glycine are inhibitory neurotransmitters
- lntemeuronsthatrelease glycine are spinalcord and brainstem
Glutamate and Aspartate
- Giutamate and Aspartate arethe !!1!iQr.excitatoryneurotransmitter in
- ~Effects : !) Drowsiness, confusion and Impaired concentration (most common). 2.) CNS and CVS depressant effects . ~ Tolerance and dependence

3 Non-Benzodlaze ines (Z-drugsornewerhypnotics)

E
the brain, acts on many subtypes of receptors such as: N-methyi-D-
0
- ~~~~~~e~:~b~o~e(~Z:~~~!~;~ s:~:t~:=.le to Ct-. aspartate (NMDA) (S:tilnox®) •• (Siesta®) •• • (Lunesta®) •• • (Hypnor«')
- Pharmacokinetics: Zaleplon isshortdurat!onofaction(3hours)- Zolpidem and Zopiclone areintermediateacting(Shours}- Eszopiclone islongacting(7hours)
- Mechanism Q!Action; are agonists at the GABAAa1 subunit, by selectively binds to the BDZs binding site subtype BZ1
- ~Mr!lBDZs ; 1) More selective as hypnotics agent. 2.) Lower risk of tolerance and withdrawal. ~) No significant~ alter the various sleep stages
Acetylcholine ~) No anticonvulsant or muscle-relaxing properties. _S.) No respiratorydepressanteffect
5.-- - Acetylcholine was the first compound to be identified phannacologically as a transmitter in the CNS
-Ata fewsites,acetylcholinecausesslow inhibilion oftheneuronbyactivatillgthe M2receptor
- ~Effects ; Nightmares, agitation, anterog rade amnesia, headache and daytime drowsiness

ro -A far more widespread muscarinic action in response to acetylcholine is a slow excitation that in is mediated by M1 receptors
-Cholinergicpathwaysappearto playanimportantrole in cognitivefunctions, especia/ly memory 4) Serotonin Ag.onists 5) Melatonin Agonists

..c:
- Pathways are; 1) Substantia nigra to the neostriatum
3) Hypothalamustopituitarygland
'" (Rozeremf})
(Buspa~)
Dopamine -ltis first ina newclass ofsleepagentsthatselective agonist at the MT1and
MT2 subtypes of melatonin receptors in the suprachiasmatic nucleus
2) Ventral tegmental to limbic structures, particularly; limbic cortex -lt isa selective5-HT1A agonist,whichisan antianxietyagent
-ll isprimarily used totreat generallzedanxietydlsorder (GAD) (SCN)

(}_ - Dopamine general/y exertsa slowinhibitoryaction onCNSneurons(D2)

- Parkinson'sdisease;causedbya foss ofdopamine-secretingneuronsinanafeaofthe substantianigra
- Schizophrenia involves alteredlevels of dopamineactivity
- Contraindication: should not be used with patient taking MAOis may cause
serotonin syndrome
- Ramelteon used for longtermfor chronicinsomnia, particularly in patients
withdifficulty in sleepinitiation

Serotonin Norepinephrine Neuropeptides 6) Others

11
-Most serotonin pathways originate from
neuronsinthe raphe
- ~Effects ; S-HT1 receptor
- l!!l1i.QiJQaEffects; S-HT1A receptors
-Mostnoradrenergicneuronsarelocatedinthe - Opioid peptides; e.g., Enkephalins, - ~ isa non-barbituratesedative-hypnotic
locuscoeruleus (LC) EndorphinsandDynorphins - ~ isaselective , dualorexinreceptorantagonist(OX 1 andOX2) .
- ~Effects ; a2 receptors -Non-opioidpeptides;e.g., Neurotensin, - OTCFirstgenerationantihistamines wtth sedatingproperties, suchas • nd reeffective
- ~Effects ; a 1 or preceptors and SubstanceP - mifm isan older tricyclic antidepressant. II was recently approved at low doses for the management of insomnia
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Depression Antidepressant Drugs CNS
Major Oepr~sive Disorder (MOD) Bipolar Depression
(Unipolar or Clinical DepressiOn) (Manic Depression or Mania) 1) Tricyclic Antidepressants (TCAs)
-Sadforalongperiodoftime (2weeksor longer) <:r Unipolar - Mood swings from extremes of high energy with an "up" mood to low
(Tryptizot®) W=~=afranii®) ~ (Surmontit®)
-u
-Hatehim-selfandhopelessness (despair) "depressive" periods <r Bipolar
- (Tofranil®) •• -· (Silenortl)
-Extremelyelevatedmood (Mania)
-Lossofappetite(weightloss) or overeating (weightgain)
- (Norpramine) :£Gttfi%M (~ae:elor®) • • •
1
-Duringmaniaanindividualfeelsoractsabnormallyhappy, energetic
- lnsomnia or hypersomnia - (Vivactil®)
orirritable (abnormallyelevatedenergylevels)
- Reductioninlibido (reducedsexdrive) TetracyclicAntidepressant

-Theneedforsleep isusuallyreduced
-Fatigue(lossofenergy) -Duringperiodsofdepressiontheremaybecrying, pooreyecontact
-Thoughtsofsuicide(thoughts ofdeath) with others, andanegativeoutlookonlife
::::r
· (ludiomil®) • (Amokisan®)
- Pharmacokinetics: rapidly absorbed and bind strongly to plasma albumin, long half·lives, dosed once daily, narrow therapeutic index, widely distributed
- Mechanism Q[ Action: - TCAs inhibits neuronal reuptake of NE and 5-HT into presynaptic nerve terminal ¢ 1' concentration of monoamine in synaptic cleft
- TCAs also blockserotonergic, a-adrenergic, histaminic, andmuscarinicreceptors

-Monoamine Hypothesis;
Pathophysiology of MOD - Pharmacological Action: - TCAs elevate mood, improve mental alertness and increase physical activity
-Theonset ofthe moodelevation is slow, requiring 2weeks or longer Q)
.......
- Therapeutic~: Management of moderate to severe depression, panic disorder, neuropathic pain , Doxepin; low doses used to treat insomnia, Clomipramine
-Deficiencyinlheamountorfunctionofcorticalandlimbicserotonin(S-HT), norepinephrine (NE), anddopamine (DA)
usedtodelayejaculationin prematureejaculation(rareandoff-labeluse), lmipramine usedtocontrolbed·wetting(rareandoff-labeluse)
-Neurotrophic Hypothesis; - ~Effects :- Muscarinic Receptors Blocking Effects (Atropine like action); Blurred vision, dry mouth, urinary retention, constipation & aggravation of glaucoma
-Brain-derived neurotrophicfactor(BDNF) (nerve growth factor) one of the major neurotrophic factors, plays animpol1antro/ein - a-adrenergicReceptorsBiockingEffects; Orthostatic hypotension, dizzinessandreflextachycardia

3
neuroprotection, neurogenesisandsynapticconnection - Histaminic(H ,) ReceptorsBiockingEffects; Sedation, especiallyduringthefirstseveralweeksoftreatment
- Decreasinglevelsof BDNF inspecificareasofthebrain, suchasthe hippocampus , /eadstodepression and suicide - SerotonergicReceptorsBiockingEffects;Weightgainandsexualdysfunction (delayejaculation).
- /ncreasemonoamineslevel ¢ increaseBDNFsynthesis ¢ Antidepressanteffects - QuinidineLikeEffects (SodiumChanneiBiockers); life-threateningarrhythmias inanoverdose
- Contraindications: Benign Prostatic Hyperplasia (BPH), urinary tension and glaucoma (atropine like effect), Epilepsy (due to; lower seizure threshold)
- ~ Sodiumbicarbonate usedforpatientswilhsevere or life-threateningtoxicitytoresolv ingthemetabolicacidosisandcardiovascularcomplications

Lithium Therapy 2) Selective Serotonin Reu take Inhibitors (SSRis Q)

· (Prozac®) · (Lustralt) " . • : · (Seroxa!Cl) · (Faverin«') ~ (Cipram®) ·''· (Cipralex®)
- Pharmacokinetics: Fluoxetine having a much longer,half-life, due to it active metabolite Norfluoxetine, The elimination half·life of Norfluoxetine is about thr,ee

G)
times longer than fluoxetine. Fluoxetine has to be discontinued 4 weeks or longer before an MAO! can be administered to decrease the risk

mood'll]diU!jsor~de~rs(~bip~ola~rd~iso~rd~
er o~p~:~\:~
-It is a mood-stabilizing medication used for
- Pharmacokinetics: Absorption ; Complete absorption within 6-8 hours. Therapeutic index ; extremely low. Metabolism; Not metabolized
Excretion ; Morethan95%urinary. Dose ;O.SmEqlkg/d individeddoses (600-900mglday)
- Mechanism gf Action: lithium inhibits inositol monophosphatase enzyme (IMPase) (plays an important role in phosphatidylinositol
bisphosphate PIP2recyc/ing). This leads to lower levelsof inositoltriphosphate (IP3), and diacylglycerol (DAG),
which are important second messengers for many cells (Ca2• mediated)
- ~Effects
of serotoninsyndrome. Fiuoxetine 90mg extendedformulation canbetaken onceweekly
- Fluoxetine and Paroxetine are potent inhibitors of the CYP206. - Fluvoxamine is an inhibitor of CYP3M
- MechanismQ[Action; SSRisb/ock the reuptakeofserotonin , leadingto increasedconcentrations ofthe neurotransmitter inthe synapticcleft, blockade of
serotoninreuptakefeads toan increase in serotoninoverall andmay influence all subtypes of serotoninreceptors.
- Theraoeutic ~ :Dep ression , Generalized Anxiety Disorder (GAD), Obsessive Compulsive Disorder, Eating Disorders (Bulimia Nervosa); only, Fluoxetine
StrokeRecovery, PrematureEjaculation (include; Dapoxetine)
c:
-·
- ~Effects : Gl side effects (nausea, vomiting and diarrhea), headache, anxiety, agitation, fatigue, sexual dysfunction, changes in weight and sleep disturbances
- SexuaiDysfunction ;Whichmayincludeloss oflibidoanddelayedejaculation. TreatmentofSSRI·inducedsexualdysfunction;
1)Adding Bupropion ,or2)Loweringthedoseof theSSRI , or 3)Addinganagentsuchas Sildenafil or Cyproheptadine,or 4)Changingtoadrugless

c..
• Neuromuscular, Tremor, most common. lithium-induced tremor can be treated with Propranolol (or Atenolol) or reduce dose
• CNS; Confusion and Agitation ; treate-d by reducedose likelytocausethisproblem
-GIT; Nausea, Vomiting and Diarrhea ; treated by reducedose or useextended-release formulation - Citalopram 40mg increase the risk of QTintervalprolongation
- Serotonin~: 1) Neuromuscular hyperactivity ; Muscle rigidity, tremors and incoordination. 2) Aitered mental status; Agitation , confusion and hypomania
• Hypothyroidism ; treated by discontinueU• or givelevothyroxine
• l(jdney, Polydipsia and Polyuria ; dueto lossofresponsivenesstoantidiuretichormone (nephrogenicdiabetesinsipidus). Treated 3) Autonomicinstability; Hyperthermiaanddiaphoresis
by, reduce dose or use of Amiloride or single bedtime low dose ofThiazide or NSAIDs (block Li' uptake by kidney tubules)
Nephrotoxicity mayoccurduring fong-termlithiumtherapy
- Pregnancy, Teratogenicity ; Avoid during firsttrimester, ifpossible
- !'m!glnteractions
3) Serotonin/Nore ine hrine Reu take Inhibitors (SNRis)
(Effexor®) t· (Pristiq®)
CD
- Thiazides ; Duetoli•and Na•ions simi/arity,Thiazide increasing the reabsorption of Li•. Renalclearance of Li• isreduced about
- Desvenlafaxine is the active metaboHte of Venlafaxine , ~effects ; similar to that of the SSRis, they are can cause increases in blood pressure, which are usually

~
25%and doseneedtobe reduced bya similaramount mild andnotclinicallysigniftcant un/ess the patient already has hypertension thatis notwe/lcontrolled
- NSAIDs; Due to block synthesis of vasodilator prostaglandins in the kidney ¢ -1- renal clearance of U• ¢ 1' u• plasma cone
t 1 • • (Cymbalta®)
- Aminophylline!Theophylline ;1' U• excretion ¢ .J...Li•plasmaconcentration
- ACEis; Due block AG·tl ¢ -1- aldosterone ¢ -1- Na• excretion ¢ Due to u• and Na• ions similarity ¢ -1- Li• excretion - Duloxetine indicated for. 1) Major Depressive Disorder 2} Generalized Anxiety Disorder 3) Diabetic Peripheral Neuropathy
4) Fibromyalgia 5) ChronicMusculoskeleta1Paincausedbychroniclowerbackpainorosteoarthritispain
- Notes; duringlithiumtherapy,perform renalfunctiontests, thyroidfunctiontests, anda urinalysisevery6-12months
(Fetzima®)
- II is a newly approved SNRI , indicated for the major depressive disorder and management of fibromyalgia ::J
5) Atypical Antidepressants 0..
: (Wellbutrin€1)
o II I

- ltisa weaknorepinephrine-dopaminereuptakeinhibitor (NDRI), indicatedfor Majordepressivedisorderandseasonalaffectivedisorder.

4) Norepinephrine Reu take Inhibitors (NRis)
~
· .,,. · (Edronaxfl)
Smokingcessation , Sexualdysfunction(drugofchoiceforthetreatmentofSSRI-inducedsexualdysfunction)
-II is primarily metabolized by the CYP3A4 isozyme, indicated for depression, side effects ; insomnia, nausea, sweating, dry mouth & constipation
· (Remeron€1)
-It has a complex pharmacology; 1) Block presynaptic 0 2 receptors ¢ enhances the release norepinephrine and serotonin. 2) Block S.HT2
andS-HT,receptors. 3) PotentH, antagonist, used primari/y inthetreatmentofdepression
6) Monoamine Oxidase Inhibitors (MAOis Q)
·•••- (Tritlico®) · -••1 · (Serzone®)
-TheyareaS.HT2serotoninreceptorantagonistsandserotoninreuptakeinhibitors.
' ••• (Viibryd®)
:~:~:~~~~:c~~~~~~h~:o~sA!~:J~~~~~~\~1,\Wmw;~A~=rm INardi~l mm!lllDI IMarplan&l m.H ! l ·:;.m·
- · " orug-Foodlnteraction (Cheese Reaction) *'•
IPamal..l
""C
• is a naturally monoamine found in foods , such as aged (or rip) cheeses, meats, chicken liver, pickled or smoked fish and red wines. Tyramine acts

12
· (Brintellix®) as a catecholamine releasing agent and normally inactivated by MAO in the gut Patients taking MAOI are unable to degrade tyramine obtained from the diet
-llisserotoninreuptakeinhibitor, S-HT1Aagonist, S-HT,a partia/agonist and 5·HT1o, S-HT,, 5-HT7antagonisl ¢ release of large amounts of catecholamines from nerve terminals ¢ hypertensive crisis (Phentolamine & Prazosin are used in treatment)

-Obsessive-Compulsive Disorder (OCD); OCD is a mental disorder where people~ the need to check things repeatedly, ~ certain routines repeatedly or havecertain ~ repeatedly. SSRis; are considered first-line agents; Escitalopram, Fluoxetine , Fluvoxamine , Paroxetine &Sertraline
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
- Pharmacotoqlca/Action:
1) Antipsychotic Effects; A) Positive Symptoms; AH antipsychotic drugs can reduce Positive Symptoms
Attention Deficit Hyperactivity Disorder (ADHD) B) NegatlveSymptoms; Notresponsivetothe first-generationagents,butm.tnysecond-generationagents
C) CognitiveSymptoms; Notresponsive toa/lantipsychoticdrugs.
2) AntiemetlcEffects;Afost ofthe antipsychoticdrugs (except Aripiprazole)have antiemeticeffects, blockingD2 in CTZ
· Attention Deficit Hyperactivity Disorder (ADHD); is a neurodeve/opmental {impair of the development of the brain) psychiatric disorder 3) Anticholinergic Effects; Some of the antipsychotics (particularly; Thioridazine, Chlorpromazine, Clozapine and Olanzapine)
• ADHD is a disorder that manifests in childhood with symptoms of hyperactivity, impulsivity and/or inattention 4) Extrapyramidal Symptoms (EPS); are drug-induced movement disorders. II can occur with both acute and chronic treatment. Blocking of dopamine
• 3 types of ADHD; 1) Predominantly inattentive. 2) Predominantly"hyperactive/impulsive.3) Combined hyperactive-impulsive and inattentive receptors in the nigrostriatal pathway may cause unwanted movement symptoms
- Condltions of EPS;
Stimulants <Psychostimulants>
- Stimulants arethe first-/inetherapy andprobablythe mosteffective inADHD because stimulantshavea rapldonsetofaction and longrecord
· Dystonia isasustainedmuscleoontractionsorabnonnalpostures
ofsafety and etflcacy. Mostcornmonly prescribed stlmulants for AOHD arephenethylamines: ~ (Adderal l«'), ~
• Muscular spasms of, neck, jaw, back, extremities, eyes (oculogyric crisis), throat ~aryngospasm) and tongue
(Ritatine). ~ (Focalin®), ~ (D exedrinee), i•Mjit.fl tillffitf:1ititJiillil' (Desoxyne) & ~
- Highestrisk in youngmen
(Vyvanse®)
-Thisisalso treatedwftll anticholinergic
Non-Stimulants
!!)Akathisia
· m:mm:mmm is a norepinephrine reuptake inhibitor approved for the treatment of ADHD · Akathisia; A feeling of internal motor restlessness that can present as tension, nervousness, or anxiety (inability to stay still or calm)
· mi!m is a centrally acting 02-adrenergic agonist used as antihypertensive agent. approved for the treatment of ADHD · Treatments ; reducing the antipsychotic dose or switching to an agent with a lower incidence of Akathisiaare the best options. ~-blockers (lipophilic)
-m m like Cionidine, isa centrallyacting a2-adrenerglcagonist,usedinthetreatmentofADHDandhypertension suchas Propranoiol and Nadolol areeffectiveandaretheagentsofchoice. ltpoorlyrespondstoanticholinergic
g Pseudoparkinsonism (Parkinson-like Symptoms)
-Parllinson.Jikesymptomssuchas;bradykinesia, rigidity, tremororakinesia
-Greaterriskintheelderly

Schizophrenia ·ltis usual/y responsive to anticholinergic agentssuchas Diphenhydramlne, Trihexyphenidyi &Benztropine

ID TardiveOyskinesia
·Characterized by; abnonnal involuntary movementsthatoccurw~h~antipsychotictherapy
-ltusua//yinvo/vestheorofacialmusclesandisofteninsidious
· Schizophrenia; is a thought disorder, the hallmark symptom is psychosis "loss of contact with reality", such as auditory hallucinations ·If treated early, it can be reversible, continued drug exposure, particularly at high doses , ~ is often irreversible
(voices)and delusions (fixedfalsebeliefs). Usually, symptomsaredividedintotwocategories; positive & negative · Symptoms may decrease with lowering the dose of antipsychotic or switching to an agent that is associated with less tardive dyskinesia (Ciozapine has not
- Positive~ (generallyresoondwelltomedications); Hallucinations , delusions , thoughtdisorders and movementdisorders beenassociated withtardivedyskinesia). Anticholinergicagentsshou/dnotbegiventotreattardivedyskinesiaand mayactually worsen thesymptoms
- ~~ (Oftenlimitedresoondtomedications); flataffect (diminishedemotionalexpress;on)and red u cedability top lan Of" carry 5) AntiadrenergicEffects; b/ockade of a-adrenergicreceptors cause orthostatichypotenslon and llght-headedness.
outactivities (decreasedtalking,/ackofpersonal hygiene,/ossofinterestineverydayactiv~iesandsocialwithdrawal) 6) Antihistamine Effects; Sedation occurs with drugs that are potent antagonists of the H1receptor (Chlorpromazine, Olanzapine , Quetlapine & Ciozapine)
- N. B: ~~ (Notresoondtomedications) : Poor "executivefunctioning " (theabilitytounderstandinfonnation) , trouble focusing 7)NeurolepticMalignantSyndrome(NMS);
or payingattention and problems with 'workingmemory' - This isanother serlouscompllcation afterEPS
· Pathophysiolooy: excessive mesolimbic dopaminergic activity, or hypo-function of NMDA receptors, or hyper-function of certain lypes of • It occurs with aH agents but more common with high-potency drugs
serotoninreceotors - Symptoms; agitation, oonfusion, oonsciousnessdisturbance,fever, tachycardia,lllstablebloodpressureandsweating
- lts mortaiityrate ishigh (shouldbetakenserious/y)
- Treatments ;
-Discontinuethedrugandgivesupportivetherapy,including fluids and cooling

Antipsychotic Drugs S) EndocrineEffects;

- Bromocriptine (dopamineagonist) and Dantrolene (directskeletalmusclerelaxant)maybehe!pful

- Dopamineinhibitsprolactinhonnone frompituitary
- Dopamineantagonists can increaseprolactin concentrations, cancause hyperprolactinemia;
- lnfemale; Menstrualdisturbance (amenorrhea)& galactorrhea
First-Generation Antipsychotics; FGAs (Typical) - lnmale; Gynecomastia and impotence (erectiledysfunction)
1!m:~
- Therapeutic!l!!§:
(F;~:~::~:!~~~7u.rH~JLt!it!t:~~~~~:::~ •~==~~~~:n~~) A) Psychlatrlclndications;
-Schlzophrenia; isthe primaryindication foranlipsychoticagents.
Highl'2lmu
- Psychoticblpoiardlsorder (BP·I), psychotlcdepresslon and treatment-reslstantdepresslon
Phenothlazines: mmH~~~~=;~~;;ab;n~:::;J W=@tMM~
1
-Schlzoaffectlvedisorders; characteristicsofboth schizophrenia and affectivedisorders (depression, bipolardisOfder&anxiety disorder)
- Tourette'ssyndrome cind disWrlJedbehavlor in patientswith Aizheimer'sdlsease
Butvrophenones: ~ (Haldolt) ~ B) Non-psychlatriclndications;
Others: · !mlm (loxitan,.) ~ (Ciopixo~) lil!l!lmlliEmi (Fiuanxo~) llii&!I IO~P') - Preventionofnauseaandvomlting; most ofoldertypicalantipsychoticdrugs (except Thioridazine) havea strongantiemeticeffect
- Neuroleptanalgesialnmedlcalprocedure; Droperidoi (Butyrophenone, typicalantipsychotic) is used in combination wrth Fentanyl (opioid)
Second-Generation Antipsychotics; SGAs (Atypical) in neuroleptanalgesia
- Second-generationagentsare genera/ly usedas firsr·linetherapy forschizophrenia to minimize therisk ofEPS assocfated withthefirst-
generationagents A) SerlousSideEffects;
1!m!EB (Ciozan~l lilll!ll!!!.!il iAbilityo) liJEm (Zyprexa') 1) ExtrapyramidaiSideEffects (EPSE) 2) Neuroleptic MalignantSyndrome (NMS)
~ (lnvega*) ~ (Seroquert) ~ (Ris~rdaP) B) Genera/SideEffects;
ll!!ll'l!!ll!m llatuda') llll!lmm iFanap~) lilml!lill (Zeldox<) 1) Sedation and drowsiness; Due to antihistaminic effects, particularly with Chlorpromazine, Oianzapine, Quetiaplne & Clozaplne
2) Antimuscarinic Side Effects ; Particularly; Thioridazine, Chlorpromazine, Clozapine and Olanzapine .
li'miE!D ISaphns') ~ (Serdolect') ll!lllllml!II IDogmati~)
· Haloperidol is the most widely used typical antipsychotic. Aripiprazole is the most widely prescribed antipsychotic agent 3)0rthostaticHypotensionandlight-headedness ; Duetoblocka-adrenergicreceptors
- Pharmacokinetics: Depotforms (/ong-actingforms) of Haloperidoi , Fiuphenazine, Zuclopenthixoi, Risperidone, Paliperidone, Oianzapine 4) Hyperprolactinemia; -lnfemafe;(amenorrhea)and galactorrhea
and Aripiprazole · lnmale; Gynecomastia and impotence (erectiledysfunction)
· Mechanism g[ action: 1) Dopamine Antagonists ; A!.!. of the first-generation and .ffiW of the second-generation antipsychotic drugs block D2 5) Sexual Dysfunction; erectile problems occur in 23-54% of men. Loss of libido may occur in men and women
dopamine receptors in the brain and the periphery. 2) Serotonin Antagonists; MQ!t ofthe second-generation 6) WeightGain ; Duetohistamine or serotoninreceptors
agents appeartoexertpartoftheir uniqueaction throughinhibition of 5-HTreceptors, particular/y5-HT2Areceptors C ) SpecificS/deEffects for !mlg!~ ;
• Differences In Second-Generation (Most Common Agents); - Low-potencyagents (Thioridazine and Chlorpromazine)cancause pigmentarydeposits onthe retina andcornealopacity
· Clozapine; Strong 5-HT2A antagonist, weak D2 antagonist (Antipsychoticmechanism), it also acts as an -Many ofthe typicalagents (Thioridazine, Pimozide , and /V Haloperidol )cancauseseriousQTintervalpro/ongation
antagonist ata, M, H1andother D&5-HT receptors D ) Spec/flcS/deEffects for ~Antipsvchotics ;
- Aripiprazole; D2 &5-HT,Apartia/agonist and 5-HT2Aantagonist - Ciozapine SeriousSfdeEffects:Agranulocytosis ; Reduction in whitebloodcellcount,and it increases lherisk ofserious or fatalinfections
- Risperidone & Oianzapine;S..HT2A antagonist>D2antagonist lt isoccurs about1·2%andis highest duringthe first4-6monthsoftherapy
- Quetiapine ; D2antagonist>5-HT2A antagonist - Ziprasidone cancause seriousQTintervalpro/ongation
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Neurcdegenerative Diseases CNS
2) Dopamine Receptor Agonlsts
Parkinson's Disease (PD) ErgotDerivatives; ~ (ParlodeiC)

- Neurodegeneratlon;isthe umbrellatennforthe progressiveloss ofstructure or function ofneurons, includingdeathofneurons

· Parkinson'sDisease (PO); isa neurodegenerativedisease ofthe CNS mainlyaffectingthe motorsystem
- Parkinsonism (Parkinsonian); is a term used for a motor symptoms
· Bromocriptine isan ergot (ergoJine) derivative,is a dopamineagonlst thatisusedinthe treatment ofPartdnson'sdisease,Hyperprolactlnaemla,Neuroleptlc
Malignant Syndrome (NMS) and Type 2 Diabetes
· ~Effects; Hallucinations, confusion , delirium, nausea and orthostatic hypotension are more common than Carbidopa/levodopa, and Dyskinesia is less
prominent. Potent/al to cause pulmonary and retroperitoneal fibrosis. Used with caution in patients with myocardial infarction or peripheral vascular disease
Non-ergotDerivatives; ~ (l\jlokyn&) ~ (M<apex<) lll!l!lllm!l!Z IRequipO) ~ (Neupro")
-Theyare non-ergot dopamineagonists thatareapprovedfor thetreatmentofParkinson'sdisease, Pramipexole hashighafflnityforthe D3 receptor
-u
:::r
· Pharmacokinetics; - Pramipexole and Ropinirole areavai/ab/eorally in extended-re/ease formulations
» Signs {orSymptoms):·

...,
· Apomorphine is availableinjedable formulatioo
• Cardinal§!gni;
1) Tremor; RESTTREMOR
2) AkinesiaiHypokinesia (Bradykinesia); Akinesia; without motion, Hypokinesia (Bradykinesia); slow (decrease) motion
· Rotigotine is ava/lablelntransdermal formulation (once-daily). ,
• Indications· · Apomorphine is used for acute management of the hypomobility "off" phenomenon in advanced Partdnson's disease
· Pramipexole, Ropinirole and Rotigotine used for Parkinson's disease and ResUess Legs Syndrome (RLS).
Q)
3) Rigldity;Musclestiffness to movement - ~~
4) Posture {Gait) lnstability; lmpairedbalance · Hallucinations, confusion, delirium, nausea &orthostatic hypotension are more common than Carbidopal\..evodopa, and Dyskinesia is less prominent.
- Unlike the ergotderivatives,theseagentsdo notexacerbateperipheralvasculardisordersorcausefibrosis.

3
• ~~; 1) CognitiveOysfunction. 2) Autonomlc Oysfunction. 3) SpeechDisturbances. 4) Micrographia (Handwriting).
5) Mask&dfacies (Hypomimia)

3) Monoa=~~~P~~~=!~lB) Inhibitors
> Pathophysiology:-
1) Loss of dopaminergicneurons inthesubstantianigra
2) Presence of Lewy bodies and Lewy neurites.
· Monoamine Oxidase-B (MAO-B); metabolizes Dopamine selectively.
· Selegiline, also called Deprenyl, selectively inhibits MAO-B al low to moderate doses, at high doses (greater than 10 m{fday) it loses its selectivity
· Rasagiline, an fmversible and selective inhibitor of MAO-B at all doses, has five times the potency of Selegiline
· Selegiline; tablets, orally dissolving tablets and patches. The patches (Emsa~) are FDA approved only for depression. Rasagiline; once daHy tablets.
Q)
Antiparkinscnian Drugs · Common~~ Nausea, hallucinationsand ortllostat!c hypotension (insomnia onlywilt! Selegiline).

1) Levodopa (L·dopa)
4) Catechoi-0-Methyltransferase (COMT) Inhibitors
IE!Illi!I ITasmarO) ~ (Comtan&)
· Normally, the methylation of Levodopa by catechoi..Q.methyltransferase (COMT) to 3-0..methyldopa (J.OMD) is a minor pathway for levodopa metabolism
G)
!l!jl'M@!i1ftJI@i1fj@1ii (Sinemete)(Parcopa*)
• Dopamine can't be given in the treatment of PO as tt doesn't penetrate the BBB. Dopa is the amino acid precursor of Dopamine
When peripheral dopa-decarboxylase is inhibited by Carbidopa ~ a compensatory mechanism of Levodopa metabolism is activated through COMT c::>
increases plasma levels of 3-0MD. Elevated levels of J.OMD c::. associated wllh a poor therapeutic response to levodopa (It is competes wHh levodopa for
c
-·
- Levodopa (L-dopa)isthe levorotatoryst&reoisomer of dopa. Levodopa is metabolized to Dopamine bythedopa-decarboxylaseenzyme activetransportintotheCNS)
· Morethan 95%of levodopa is metabolizedoutside the brain by peripheraidopa-decarboxylase · Tolcapone and Entacapone are selective/yalldreverslb/yinhibitCOMT. Tolcapone is severe/ywldelyrestrlctedbecause of hepatotoxicity.

c..
· Only about1·3%of levodopa enters the brain. •
· Levodopa is combined with peripheral dopa-decarboxylase inhibitors (DCCI); Carbidopa (KAR·bi-DOE-pa] and Benserazide (ben-SER-a-zidej
(doesn't cross BBB)c::> Preventssome ofthe peripheralconversion of levodopa to Dopamine c::> increasebrainlevel of levodopa
· Pharmacokinetics - Anticho6nergicAgents; ~(Cogentin&)~-+ji~P?..~~~ (Akineton")
- Blockage of cholinergic transmission in the brain, helps to correctthe imbalance in the DopaminelAcetylcholine ratio;

CD
-Absorptlon dependson gastricemptyingrate & pHofgastriccontents
-Food de/ays theabsorptionof levodopa. • Benztroplne, Trihexyphenldyl and Biperiden are more common antimuscarinic agents used In Parkinson's disease.
·Amino acids from ingested food (high-protein diets) can compete w~h Levodopa for absorption and for transport to the brain - ~ is an antiviral agent, was bychance foond to have Antiparkinsonismproperties, current evidence supports actJon at NMDAreceptors. lthas
symptomatic benefits andmayreducedyskinesiacausedby levodopa or dopamineagonists
-~ - ~~ Dizziness , insomnia , anxiety , llvedo reticularis {skinconsistsofamottledreticulaledvascular pattem), nausea and nightmares .
-Greatesteffectonbradykinesiaandrigidity

~
-Lesseffectontremor(confro//edby Propranolol)& posturalinstablllty.
-/mprovementindisabilityandpossiblymortality

Alzheimer's Disease (AD)

- ~Effects ·
A) AcuteSideEffects (Levodopa!Carbldopa);
1) GIT Effects; Nausea and vomiting, due to stimulation of chemoreceptor trigger zone (CTZ)
2) CVSEffects; Orthostatichypotensionand cardiacarrhythmias ::l
3) CNSEffects; Depression, insomnia, confusion , agitation and hallucinatlons
B) Long-termS/deEffects (Levodopa!Carbidopa)";
1) ResponseFiuctuations;
a) Wearing-offphenomenon or end-of-doseakinesia (relatedtothetimingofdoses);
· Alzheimer's disease; is a slow progressive neurodegenerative disease that destroys memory and other important mental functions
· Pathophysiology Cholinergic H voothesi s; Acetylcholine needed to pass signals along from cell to cell. A myloi d Hvoothesis; ~-amyloid or amyloid
beta (A~) protein is a sequencing of its amino acid chain and the cloning of the gene encoding its precursor protein (Amyloid Beta Precursor; APP). Amyloid
c..
protein is formed by enzymatic cleavage of Amyloid Beta Precursor (APP). Over aggregation of ~-amyloid , can blocks the normal transport of electrical

- Characterizedby; Return ofPartinsonsymptomsbefore lhe nextdose
·Treatments; adding a dopamine agonist or MAO·B inhibitor, or COMT inhibitor or increasing the frequency/dose of levodopa
b) On-offphenomenon (unre/ated tothetimlngofdoses);
-Characterizedby;·Qft:;Off-periodsofmarkedaklnesia.
· Qn; On-periods of improved mobility
-Treatments;adding Entacapone, Rasagiline, Pramipexole, Ropinlrole, Apomorphine, & Selegiline or redistributingdietary
protein.
2) Dyskinesia;lsa drug·inducedinvoluntarymovements inciuding choreaanddystonla
- Treatments; decrease levodopa dose or adding Amantadine (asan ant/dysklneticdrug)
• N.B; A drug holiday (discontinuance of the drug for 3-21 days) may temporarily improve responsiveness to levodopa but is usually little help
~
messages between the neurons and may cause cell death. Tau Hvoothesi s; Excessive or abnormal phosphorylation of tau protein results in the
transformation ofnormaladulttau into PHF-tau (paired helical filament)and NFTs {neurofibrillarytangles) 9 interacts with tubulin (tubulinresponsiblefor stabi/ize
microtubule assembly) c::. disintegration of microtubules in brain cells c::. cell death.
- Medlcatlons are used totreatthecognitiveproblems ofAD; Q)
I> Cholinesterase Inhibitors
·The inhibition of acetylcholinesterase (AChE) within the CNS will improve cholinergic transmission; iE!ilim was the first to become available, but fi has been ""C
- ~,{clJ@j@,;~~~$Jll£fj@(~Q~~~cir~~ersibfeAChE inhibitors approved for the treatment ofmi..!il to moderate Alzheimer's disease (Only Donepezil
isapprovedfortreatmentofadvancedAizheimer'sdisease. Rivastigmine isavailablein tablets;and Transdermalpatches.

14
· !J.!:.!!!l.lnteractions
-lf levodopa usedaione; 2) N-Methyl-D-Aspartate Antagonists
• Pyridoxine (VItamin Bs); enhances activity of dopa-decarboxylase eruyme c::. enhance metabolism of Levodopa - ~ is an NMDA receptor antagonist first used as an anti-influenza agent, ~ indicated for moderate to severe Alzheimer's disease and in dementia with
. MAO-A Inhibitors or within 2 weeks of their discontinuance c::. can lead to hypertensive crises Lewybodies
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
~(CerebYJ<"IGillll!!lii (PeganoneOI
- Fosphenytoin isa prodnJfl thatisr~pld/yconvertedto Phenytoin withinminutes.

Epilepsy • Adnnr.ges over phtny10irt: 1) .. dosing and more safely IV dosing 2) Phlebitis is minimized.
3) lnfusionrate3timesfaster(150mglmin). 4) C.ndellvtrinnonnalsallneor5%dextrose.
• Ethotoin is a hydantoin •ntlcon'ffllsant, commonly used in pltienta who are hypttHnJJtfvt to Phenytoin, but less effectjye

-Epilepsy;isa ehronleneurolog/clld/sorder affectspeopleofallagescharacterizedbyanenduringpredlsposltion to generate epileptlc ~Wegrel..l

selzures.' Epilepticseizures; isa brlefeplsode of llgns or symptome due todisturbances of electricalactivity inthe bfain - It is a major most popuf., first-line •ntlepileptlc drug forfoealseb:ures and generatizld tonic-donie ..aum.
-Ciass/ffcatlonofSe/zures; • ltis nofeffectlye focabsenceseizuresocmyoclonicseiz.ures. ~netics; · cnamaz.epine is an lnducer ofCYP1A2, CYP2C&CYP3A.

A) Focal-Onset Seizures; - ~Effects: • ~tldfttrtcfl; ~, ltaxia. m-owsiness and mildGiupsets . Hyponatremia dueto ananli<liurelichonnone {AD H)-ikeeffecl
· - f l d o - (lltnNfok>QiclkltllrlcUI; Ajllastic.....,;.,, lhrombocytopenia and letlkopenia
o ~ffect~~eglono/lhe brain • kfotyncrt~~caldtetFtcc~;i;m:SJii=~~#!m.fiWMijfj-!@!fittC (Afloo.ne)
• Preserved consciousness
- Se/zuresCategorles; Motorselzures (changeinmuscleadivity), Sensoryselzures (changes inany oneofthesenses), • Oxcarbatepine (OXC) is a prodrog, useful in the same seizure types that treated by Carbamazeplne, but it may have an improved toxicity profile, with less
Autonomicseizures{changesinautomaticfunctioos) andPsychicseizures (changes in think orfeel) potency. Oxcarbaz:epine isCYP3M&CYP3A5inducers, (/esspotentthan carbamazepine).

l)~y~n~rea, thenquick/yinvolveother areasofthebrain - ~~ • Hyponltrtmla more common than with Carbamazepine, Hematotogic side effects and Hypersensitivity less common than Carbamazepine.
- Esficarbaz.eplne (ESL) Acetate isa prodrug that isconvertedtotheactive metabolite Eslicarbazepine (S·Ilcarbazepine). s-licarbazepine istheactivemetabol/te
• somealteratlonorlmpalnnentofconsciousness.
of Oxcarbazepine.The poss/bleadvantage of Eslicarbazepine is fnearpharrmtcoklneUcsanddose is ~
-Typica/ly/ast30sec. to2mln., butmayfeel tiredfocseveralhoursafterattack
- AA aura ~mayoccuratthebeginningofaseizure,itmayconsistofa strangesmell , taste,sound orvisual
disturbance, anunexplainedfeeling offearoranxiety
otherail~~~i:!w,ke"
3) Secondarl!v Ceneral~ad ~ . Lamotrigine (lTG); Major mechanism is blocking voltage-gated sodium channels, ~ has been found to inhibit glutamate release and Inhibits voltage-gated
· Oftenbegln wlthan aura ~c:) th&nintoageneralizedtonic-clonlcconvulslon (seefonic-clonicconvu/sion). Ca2•chann~s . ~; partlal , gtntrallztd, abltnce, myoclonlcselzwn , lennox-Gastautsyndrome a ndblpolardlsorder
- N.B; the focalseizuresclassiflcation is notrecommended
B) G eneralized-Onset Seizures;
- ~~ R/skof skinrash (steve;;;;ms;;~;;;~"!~l!W¥:f&r~~:~·tffimri7=:';ing reaction
1) Ceneral~ad Tonlc-sJ2!l!s Seizure~; - Zonisamide (ZNS) is a sulfonamide anUconvulsant Used as lldjunctive therapy in pati&nts with focll aelzum
' The oldterrn is grand mal (grahn-mahl] selzures (from fhe f rench"greatiHnessj. - lacosamide is an amino acid derivative. Used as monothfnpy or as acfunctive thflflpy foc partlal'1)nset stlzures
• Typica/fylast1-3mlnutes · Rufinamide isatriazole derivalive, withanticonvufsantactivity. Usedas adjunctive inLennox-Gutaut syndrome.
- A tonic-clonlcseizure comprlses~lM!Jlphases ;
• Tonic phase (comes firstandshorl); Quick loss of consciousness c) falls to the floor c) suddenly muscles tension
(stiffness); body flexion and extremities pulled towards the body (may cry out due to air is fotr;ed from the lungs and may
tumblueinface).
' Cionlcphase; Thearmsandusually thelegsbegin to jerkrapidly and rtJyttvnically (rhythmlc}erldng)c:) after a few
2
) ~!~~~~1~~ib'!i(l~2~nts
minutes, the jerkingslows and stops · Phenobarbital potentilte the action of GABA, usu1Ryused in status ephptlcus (emerg&ncy), when other agent& fall ~

2) A~~c::~~~etltmal (PET-ee-mahl] seizures (fromlhe French ,ittle illness")
' Typical/y begin during chlldhoodand maypersistinto adulthood {morecommon inchildren).
' Shortperlod ofimpalredconsciousness.
• Typica//ylast10-30seconds
• Attack. Generally, short period ot impaired consciousness (may be the only clinical symptom).
3) ~Selzuret;
·Myoclonic (MY-o-KLON·Ik] selz.urea are a brief of sporadic (isolated) shock·like jerking of a muscle or group of muscles
• PaUentusua/ly awakeandabfetothlnkc/early.
• Jerkingmovementsoccursfntheupperorlowerextremities,or mayoccurinentirebody
4) AtonlcSelzuras;
• Atonic (a·TON·Ik] seiz.ures (means "without tone", muscle "tooe" is the musde'si'Omlal tension)
' Characterizedbya briefloss of muscletone and falls to the ground (a/soknownas dropattacks).
S) TonlcSelzures;
• Only tonlcphase of a tonic-clonicseizure; suddenstfffeningmovements.
6) Cionlc5elzur01:
~/y clonlc phase of a tonic-clonic seizure; rhythmicjerkingmusc/e movemen ts.
C) Status Epil epticus (S E);
• status Eplleptlc u s (SE) ~is anyseizure that l asts morethan S: m inutes oc morethanoneseizurewithin a ~
minutes perlod without the personretvrninglonormalbetwetmthem
· BDZs potentl•tetheaetlonofGABA, mostcommon/yuseddru~!~~=~tfibru:tLlJ\Iooger) and ~faster)
filprwtn CVPA!l ~ (Depakenee) f$M®¥Mi (Depakinee) fH'tUtlMUM (Depakotee)
- Valproates are very effective against all types of s&lzures. llechatWsm of action; blockade a GABA transaminase (enzyme breakdown of GABA) and blockade
of sodk.lm channets and action at T-typecalclum channels. llostcommonsideetrects; Nausea, vomiting and drowsiness: f!M~; Fatal hepatotoxicity
(liver enzyme monitoring within the first 6 months), Severe birth defects (Spina blfida and lower intelligence quotient; 10). fatal pancreatitis and suicidal ideation).
OtbsrGABA Ephagclog Aunt! ID!m!I (Sabrilt) ~ (Gabitrilt)
• Vigabatrin (VGB) is an Irreversible Inhibitor of GABA aminotransferase (GABA-n, the enzyme responsible for the degradation of GABA.
• fndie<~Uons; Partlllltlzuruand inflntlltspums, BM_~; vision loss
- liagabine (TGB) is a derivative of the GABA reuptake inhibitor Nipecotic acid, act as a reversible inhlbllion of the GABA transporter-1 (GAT-1 ) Q inhibitGABA
reuptake c) incrNse level of GABA. IIHll£!1im!; adjunctlw trNtment for partial seizures
3) GABA Analogs i i i ! I(Neuronti,.IIIIJI(lyrica'l
- ~Rfmt2!!; dec:re~seCa2•entry , bybindlngandinhibltingthea~ (alpha·2«11a) subunitof the voltage-dependentCaZ•channels.
- ~; Mfunctlvt frNtment foc focal'1)nltt Mizum, lllbttic periphtrll neuropathy. postherpetlc neur~lgla , ftbromyalgia and neuropithlc pain
associatedwitltsplnalcordlnjury.

Antiepileptic Drugs (AEDs)

·PharmacqklnoU~s; Noit~~~~~~~~~~~~~~~~o;faction; 1)b/ockvo1 age-gatodsodlum
>General Mechanism of Action of Antleplleptic Drugs:- channels, 2) block receptors (o-amino-J..hydroxy-5-methyl-4-
1) Blocking voltage-gated channels (Na• or Ca 2• ). 2) Enhancing inhibitory y-aminobutyric acid (GABA). 3) Interfering with excitatory isoxazolepropionicacidreceptorisasubtypeofglutamate
glutaAlatetransmission. N.S.; Antlepllepticdrugssuppressseizures but donot •cure·or •prevenrepllepsy. - ~; P1rtlaland

- ~; b/ockfngT-typeCal+channelsreceptors . Gastricdistress, nauseaandvomiting

1) Sodium Channel Blockers
· Mechanismg[action; blocksvoltage-gatedsodiumchannels c:) prolongtheinactivationstateofsodiumchannels. ; By bindsse/ectivelyto the synaptic
I on vesicularfunction
Hydantolns
tonk-donie
lilil:!il'ilimi !Dilantin'I(EpantJ!ilOI protein2Aiigandandanafogof levetiracetam.
· PharmacokinetJcs; ' Phenytoin is an /nducer ofthe CYP3A4 anciCYP2C19fami ies
; is a un.lqueanllconvufsant (novel mechanism), approved in 201 1; Potassium channel opener, for partlal-onltt seizures.
· /ndications; Foeal (or partlal), generallzedtonlc-clonlcaelzuresandstatusepHeptlcus
(Oi3001iito]: ln!tJg~Jmj; With Clobazam and Valproate in the adjunctive therlpy of refractory generalized tonic-clonic seizures i"l patients with
· ~Effects: · Oose-rt/tted lidt tfrtctl; Nystagmus, Diplopia, ataxia & drowsiness.
MWn~myoclonlctpltepsy oflnfancy (SMEI , Orav-tt'ssyndrome).
• NotHios•rtllted side t frtctJ (chronic); Gingival hyperplasia (gums overgrowth), hirsutism (is a male-pattern hair growth in
~Dia~); is a Cillbonlcanhydnseinhibitor. Effectlvefor al types of seizures but is severely/imitedby the rapid development of tolerance.
women), acne, rash, hepatotoxictty and coarsening of facialfeatures (changeinnormalfacialfeatures)
• Chronic Ult may associated with decmse bone mineral density (vl amin D metabolism abnormality) and megaloblastic anemia
· IV/nfus/ons/dttfrtcts; phlebitis and hypotension (wihrapidinfusion)
- ~ categoryD 'Em[~~; cleftllp oc palate, congenitalheartdisease , slowlngofgrowthanclmentaldeflclency. • .-~:~bn~tiN:~~~·i M~~M1b:~k~!>W&rm:~a#r:~nr.;~;,~:rrw,~oila nti~).
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
llpioid Analgesics and Antagonists
- Oplolds; are natural, semisynthetic, or syntheticcompounds that producemorphine-Jikeeffects. Allopioidsactbybindingto specifiC opioid ~(Di~udid') . lil:!milm(Opana<)
receptors to produceeffects lhatmirtlictheactionof endogenous opioid peptideneurotransmitler (Endorphins, Dynorphins and
-lsa phenanthrene seml-synthetic Morphine derivative, is hydrophiliclille, ·Is a phenanthrene semi-synthetic Morphine derivative, is more lipid
' Enkephalins)
morewatersolublethan Morphine. soluble than Morphine -o rapidonsetofactlon when giveninoralroute.
- Theterm ' opioid" originatedinthe1950s. ltcornbines'opium" +'-oid" Oplold Detoxllcatlon - Oral formulations is approximately 8-10 times more potent than Morphine.
meaning ' opiat&-like"("opiates"beingmorphineandsimilardrugs) 1) Methadone Maintenance Treatment (MMD
- Op/oidReceptors: are agroup ofinhibitoryGprotein-coupledreceptors; - Is extensively metabolized in the liver to morphine-3-glucuronlde {M3G) lll!l!ll!l!m!Doloph;nee)
- Long-tenn useof llethadone asa substihlte !othe oplold onwhich (>95%), whichhasnoanalgesicactivity,canproduceexcitatoryneurotoxic
i$!ilj.i!IM)i!ij, 1113 the patient was dependent. -lsa synthetic opioids, structurallyunre/ated to Morphine
'Supraspinal anagesia... ' Spi\alanagesia·· 2) Buprenorphine Maintenance Treatment (BMn -ltis verylipophllic,leading toaccumu/atlon in the fattissues,(/onghalf-life;
2S.52hours)
., (Mu) lhp~t, :=~~~ence··· :~~orydepression••• - Buprenorphine tobea safer over Methadone in opiatareplacement
therapy, due to ~s partial agonist and cause mild withdrawal
llmll!il -It is not only a potent ~ · receptor agonist .1M it can also block NMDA
-lsa phenanthrene seml-synthetic Morphine derivative, byadding twoacetyl
'OecreaseGi motility.. ' Sedation.. symptoms and little sedation, respiratory depression or receptors andnorepinephrine andserotoninreuptake/nhibitor.
groups to Morphine, 2-4timesmorepotent than Morphine, faster in onset

.
hypotenslon&venathighdoses - ~; - Paln ( neuropathlcpalnis includeddueto non-opioidmechanisms)
5 (Delta) 61 , 62 :~:;:;~~==·· : =~:~~:;~;~. l ) Levacetylmethadol or levo-a-acetylmethadoi (LAAM) -Rapidly hydrolyzed into 6-monoacetylmorphine (6-MAM) and Morphine.
- Control withdrawal symptoms of oplold dependency (Methadone
- L.AAM isa long-acting (lflrice-weeklydosir.g), second-/ine. - Withdrawal syndrome may ~ in within 6-24 hours of discontinuation.
(Kappa)
.'=~~~~=~ns :~=·anagesia• 4) OpioidAntagonist
MaintenanceTreatment; MMT)
' SedaOOn.. 'DecreaseGimotility' - Naltrexone (month/y)is usedforrelapu pmentlon :wnmG®tti@!@N {Demerol')
- Splnalanalgesla;anages~Wlspina!cord anddorsalroolgar.gia-substantiagelatinosa S) az-adrenergicAgonist
- Suprasplnalanalgesla; anagesiainperiaqueductaVpefiventricu\argraymatter in brain
· Is _a syntheti~ opioid, stru~urally unrelated to Morphi_ne, b!.!! related to Atropine, it is very lipophilic &has anticholinergic effects, Increased incidence of delirium
- Cionldine &Lofexidine areusedto controJ sympathetlcsymptoms - It !s metabol1zed to an ac_t1ve metabolit~ Norme~ridine (neurotoxic and serotonergic effects), serotonin syndrome may reported {in patients receiving SSRis).
• IllS the preferred opioid 1n some countnes used 1n labour and delivery. Due to anticholinergic effects, it is preferred in pain with biliary spasm or renal colic
Strong Agonists
llmli!DI (DuragesK:<)
· (MSContine) - Is one of the most widely synthetic oplolds used, approximately 80-100 times more potent than Morphine and approximately 40-50 times more potent than
-lsa phenanthrene (chemicalc/ass) strongiJreceptoragonist. Heroin, ~ is high/ylipophilic andhasa rapidonset and shortduration of actlon
- Pharmacokinetics: - Common Routes and Formulations; - IV injection {adjunct to an anaesthetic (analgesic and sedative effects) and analgesia fOf moderate and severe pain
• Absorption; extensive first-pass metabolism, so the oral dose need to be ~uch higher than the parenteral dose (Bioavailability. 30%) ·_Transdenna/patch (duration; 72hours, usedforchronlcpain). - Transmucosa/ (usedinbreakthroughpain)
· Administration: Morphine can be taken orally, parenterally (IV, SC, IM and 1ntrathecally), rectally or intranasally -ltappears tobe safe to useinrenalfal1ure. Aifentan ii, Sufentanil and Remifentani1 are synthetic oploid, Fentanylstructura/ana/ogues
• Distribution: Morphine rapidly enters all body tissues, including placenta. Only a small amount of Morphine crosses the BBB, because
Morphine isthe /eastlipophi1ic ofthe commonoploids
• Metabolism; Morphine is conjugated with glucuronic acid in the liver to two main metabolites (excreted in urine, small amount in bile);
1) Morphine-S-glucuronide (M6G) (aboul10%) is a very potent analgesic {4to 61imes more than Morphine)
Mild to Moderate Agonists
2) Morphine-3-glucuronide (M3G) does not have analgesicactivity, butisbelievedlocausethe neuroexcitatoryeffects
- MechanlsmR[Action m:m
• Or 3-Methyi-Morphine is a natural opioid alkaloid (about 2% of opium) and
llmma (lortab') l!l:imm !Oxycontin<)
- Morphine and otheropiolds stimulates specific oploldreceptors
is a weakopfoidagonist. ll is converted to Morphine by the CYP206 -Ate seml-synthetlc Codeine derivative
• Stimulation of opioid receptors in the CNS decreases release of substance-P (which responsible for pain transmission i~ spin~l cord)
- AI/opioidreceptorsarecoup/edtoinhibitoryG-proteinthat/eadsto K•channelsactivationand Ca 2•channelsinhibltion th1s leads to enzymei n theli ver.ltis typical/y used lo treat mJM to ~paln ,and - Hydrocodone isstrongerthan Codeine (about 50%), while Oxycodone is
hyperpolarizationofnervecell. lnhibition of nervecell leadsto decreaserelease ofexcitatoryneurotransmitters commonly used in combination with Paracetamol (Tylenol' No.3) or strongerthan Hydrocodone (aboutSO%)
· Pharmacological Action Aspirin (Co-wdap ri~).l texh ibits good antituss/veactlv/ty a\ dosesthat - Are used to treat !!JSHl!W! to W!!1 pain, and sometimes used in
-~ do not cause analgesia combinationwithNSAIDs. Extendedre/easeformulationsareavailable.
1) Analgesia (reliefpainwithoutlossofconsciousness)Qt, ralslng the painthreshold and altering the brain'sperception of pain.
2) Euphoria; · Morphine produces a powerlul·pleasant sensation (sense of contentment and well-bein~ )
- Dysphoria , a n unp/easantstate characterizedby restlessness & malaise , ~ occur (notmpain ).
3) Sedation; - Drowsiness are common effects of opioids. Morphine disrupts normal ~apid eye m~~ement (REM) & non-RE.Msleep patterns
4) Respiratory0epression ; AIIopioids canproduce s/gniflcantrespiratoryd~presslon by fnhfbltingresplrato~centres lnthe_bralnstem
{reducesensitivity ofthe brainstem to carbond1oxide). Respiratorydepression 1Sthe mostcommon cause
of death in acuteopioidoverdoses
S) CoughSuppression;both Morphine and C~eine have antitussiveproperties (Codeine has /esseranalgesicacti~o/)
6) Emesls; Opioidanalgesics can activate bramstem ~IDinw:I2Dl~ to producenausea and vomtllng
7) Miosis; Opioids stimulate 11 & "receptors at Edinger-Westphal nucleus of oculomotor nerve to constrict the pupil causing miosis
whichiscalled "' ~PMR!! (fffl . This is importa_ntdlagnostically fOf physicians or policemen
- ~ ·With largedoses, hypotension and bradycardia ( Meperidine lsanexce,:ticncancause tachycardia)
- Hypotension; due to vasodilatation dueto t ) release of histamine & 2) depression of vasomotorcenter{VMC)
- N.B.; Becauseofrespiratorydepresslon &carbondioxiderelention, cerebralvesselsdilate &incteasecerebrosplnalfluldpressure
• §!l: 1) Decrease Gl motility (peristalsis) _. constipation. V Increase Gl tone (contraction of circular smooth muscle). ;u Biliary colic
• ~ 1) Decrease renal function (enhance renal tubular sodium reabsorption and increase antidiuretic hormone {ADH) release)
V lncreaseureteral and bladdertone. ;D increasesphlnctertone (urinaryrelention)
- ~: Opioidsmay prolonglabor • •• (Contramal')
- ~: 1) Stimulaterelease of antidiuretichormone (ADH), prolactin, and somatotropin (growth hormone; GH) - •• (Nucynta$)
- ls a1.1receptoragonist and norepinephrine/serotoninreuptakeinhibitor -lsa modest~receptoragonist. ~norepinephrinereuptake
2) 1nhfbltrelease of luteinizinghormone (LH). - ll is used formoderatetomoderately~everepaln inhibitor ( NRI ), a nd~effects onserotoni nreuptake
3) Pruritus; Flushing andskinwa rming w~h itching due to centraleffects and peripheral histamine release - Tox/city oi Tramadol areassociatedwi!hseizures
- Therapeutic!lll!: ' CIInlcaiY..nQf~ ( Morphine and otheropioids ) ~ ·
-' It is used for moderate to severe pain , it is also indicated for diabetic
- Risk of serotonin syndrome, are increased especially if selective serotonin neuropathypain (NRI)
t ) Analgesia (refiefpainwithoutlossofconsclousness); reuptakeinhibitor (SSRI) antidepressants are co-administration with Tramadol
2) Acute Pulmonary Edema; IV Morphine may use in dyspnea from pulmonary edema associated with left ventricular heart failure, - Riskfor seizures andforthe deve/opmentof serotoninsyndrome
dueto reducedanxiety (perceptionofshortnessofbfeath)and reducedcardiacpreload {reducedvenoustone)and reducedafterload
{decreasedperipheralresistance). lfrespiratorydepression isa prob/em, Furosemide maybe prefeffed. Other Opioids Not Used as Analgesics
3) CoughSuppresslon; Syntheticcompounds (Dextromethorphan) havebeendevelopedthatarenotanalgesicandnot addictive
4) Diarrhea; Syntheticcompounds (Diphenoxylate and loperamide) morese/ectivegastrointestinaleffects &few or noCNSeffects
S) PreanestheticMedication; because oftheir sedative, anxiolytic and analgesicproperties
- ~fffects: t ) Tolerance; usuallydoes notdevelop tothe pupil-constricting and constipati ngeffects. 2) Dependence
3) AcuteSideEffects; Respiratorydepression, nausea, vomiting, attergicreactions, bronchoconstriction and constipation
- Contraind/cations: 1) Combinationoffu/lagonists wilh weakpartialagonlsts (risk of dlminishlnganalgesia), 2) Headlnjuries (elevated Opioid Antagonists
intracranialpressure), 3) P regnancy ( Fetus maybecome physicallydependent). 4) 1 mpaired Pulmonary~unction (respiratorydepressant

II-Ora/lyactive!!!!g~~~:=~ /ong!f!!! ~~e~::r)toxicity

effects), 5) liver Failure and Kidney Failure (Morphine), 6) Endocrine Disease (Adrena~ insufficiency (Addison's diseas~) and
hypothyroidism mayhavepro/onged and exaggeratedresponses to opioids, 7) BenlgnProstatlcHyperplasla (BPH)(urinaryretent10n) of action II- On/yiV,
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Anesthetics
- Anesthetic ~or Anaesthetic) is a drug that causes anesthesia. Anesthesia (or Anaesthesia) is an induced, temporary (reversible) state with
one or more dthe folfowingeffects; 1) Analgesia" (re/ief or prevention of pain). 2) Paralysis" (muscle relaxation). 3) Amnesla" (loss of
memory). 4) Inhibition of autonorric refteJ:es•. 5) Unconsciousness"
- No sing/eanestheticagent currenUyavailablewhen usedalone can achieve aii Soflhese desiredeffects.
- PreanestheticMedlcatlons;isa drugs thatis givenbeforeanesthetic to produceoptimal anesthesia
- ~g!Anesthesia~gJAnestheslal: Thesestages weredefined forthe o riginalanesthetic Ether,
Inhalation Anesthetics
1) Stagel (lnduction); isthe period betweenthe inifialadministration ofthe induction agents and loss of consciousness; · Min!ml!mA!mllr~~ :
• Patientconscious. • Analgesia - MAC; is the minimum concentration of inhaled anestheUc in the lung needed fo produces anesthesia in 50% of patients. ,
2) Stageii (Oelirium'Extitement); isthe perlodfollowing fossofconsciousness and excited & detiriousactivity,duringthisstage; - MAC used to measures the potency of inhaled anesthetics, MAC is smal/ for potentanesthetics such as Halothane "**- ~
·
* Irregular respiration • Irregular heart rate. • Uncontrolled movements. • Vomiting andlarge for lesspotentagents suchas Nitrousoxide. llcllunDe .1s
3) Stageiii (Surgica1Anaesthesia);isthe ldeal stageforsurgery,duringthisstage; - Factorsthat can increase MAC; hyperthermia, drugsthat increaseCNScatecholamines,andchronicethanolabuse. s.raa...
* Patient is unconscious. * Regularrespiration. * Novomiting * Nopain reflexes , - Factors that can ~ecre . ase MAC; .increased-. a~e, hypotherm.ia, p.regnancy, sepsis •. acute intoxication, co.ncurre.ntiV anesthetics ,..._ · ~,
• Normal Blood pressure • Normal pupil size • Slow eye movements and a:z-adrenerglcreceptoragon1sts (Cionid1ne). ._
•l Stage IV (Medullary paralysis or overdose); is the stage where too much medication has been given and the patient has severe - !i.21!!:, - FJ F1Ratio; ratiO of alveolar agent to Inhaled agent, 1s an Important determmant of the speed of mduct1on. em. ~
brain stem or medullarydepresslon -FNF1 fastestfortheleastsolu~teagents(Nitrous .oxide) . . . . 0 1 100
.MAC ,
- Bioodlgn~~ (f&); lheratiOoftheconcentrallonofanesthellclflthebloodlotheconcentrationofanestheti C

* Respiratory depression.
·-
*Hypotension • veryweak pulse * Death mayoccur
inlhegasthatisincontactwiththatbloodwhenthepartialpressure inbothisequal
-.J..Biood gasPC Q rapidonset ofinduction&recovery(Nitrousoxide)
-1'Biood gasPC Q slowonsetofinductionandrecovery {Halothane).

Preanesthetic Medications lll!!l\l!l:l!lm ·(N,O)

-lsan oxideofnitrogen, commonly knownas laughinggas, non-irritatingpotentanalgesicbut a weakgeneralanesthetic.
- ~ in surgery and dentistry for ~s anaesthetic and analgesi ceffects.
·IS poorlysoluble in blood and othertiss ues , al lowi ng~to move very rapidly in{lnduction) and .QY! {recovety)ofthe body.
1) Anxiolytics (Sedatives)/Hypnotics - ~does
illoodl&n~>~<tmoncoelfioM
not depress respiration and does not produce muscle relaxation, little or no effect on CVS or cerebral blood flow, last hepatotoxic effect.
- Benzodiazepines (still commonly used); Midazolam (short-acting), Lorazepam (Yitermediate) and Diazepam (long-acting) are commonly used
- Advantages; * Deaeaseanxiety. * lnducepostoperativesleepandrelaxation. · Providingamnesia. · Reduceamountofallesthelics.
- Disadvantages; Depressant effect{cardiacand/or respiratory), Barbiturates; moredepressant llEllllll!lli!I (FiuolhaneO)
- Hot adequateanalgesi a and not sufficientmusclerelaxation , metabolized to!ii!Y!-~~ Uses;inductiOtJ and maintenance of general anesthesi a
2) Tranquilizers (Neuroleptics) - Pharmacological Action: Heart depress heart contractility and Induces vasodilation. Y!!!g. Non-irritate, dilates the bronchioles, decrease salivation and
- Common neuroleptics used are Chlorpromazine (CPZ) & Promethazine
bronchialsecretions. Halothane and Sevoflurane agentsofcho/ce in patientswithairwayproblems (nothave pungentodour to
- Advantages; • Decrease postoperative nausea and vomiting. • Decrease postoperative muscular pain caused by neuromuscular blockers
stimulate respiratory reflexes). ~ • Hepatotoxicity (Halothane Hepatitis)* following repeated administration of Halothane
- Disadvantages; Orthostatic hypotension. N.S.; Neuroleptics commonly used as a preanesthetic in veterinary surgery · ~~ · : lsa rarelife-threatening geneticdisorder ofskeletalmuscle,thatusuallyoccursin susceptiblepatients , exposureto halogenaled
3) Analgesics (Opioids/Non-Opiolds) hydrocarbon anesthetics (e.g. Halothane) and depolarizing neuromuscular blocker su«inylcholine {rapid 1' muscle metabolism). Characterized by: 1) Very high
- Opioid Analgesics; Morphine, Meperidine (or Pethidine) and Fentanyl are commonly used temperature and unexplained tachycardia. 2) Muscle rigidity and intensive pain {increase muscle contraction and abnormal increase of Ca2• from sarcoplasmic reticulum)
- Advantages; * Providesufficientanalgesiaduring procedure&postoperatively. *Reduceamountofanesthetics 3) Metabolicacidosis {thebodyproducesexcessivequantitiesofacidor kidneysarenotremovingenoughacidfrom thebody)
- Disadvantages; Depressanteffect(respiratory),nausea/vomitingandpostoperativeconstipation - Treatment by: Cooling patient and ~ (Directskeletalmusclerelaxant) Q Prevent release ofCa2• fromsarcoplasmic retk:u!um
- N.S.; Droperidol {neuroleptic)is used in comblnation with Fentanyl (opioid}in neuroleptanalgesia.
- Non-opioids Analgesics (NSAIDs and Paracetamol) can be used (commonly used postoperative) -d'!t·'''-i•'"·¥·4·
·Cd::witss'«llatilagas
tmt!1 1·6's ·
-Cd::witssWllatilelqtid
mil!IEmJ (Forane&)
4) Neuromuscular Blockers (NMBs) -lsa structural lsomer of Enflurane (Ethrane'l), Enflurane no longer use dueto
-lowbbJdlgaspartitioncoefflcient :: 0.47 -Hghl*xxllgaspartitioncoeflicient=2.4 depression of myocardial contractility, higher metabolism (high toxic
- Neuromuscular blockers; include Cisatracurium, Pancuronium, Rocuronium, Succinylcholine, and Vecuronium <r RapidonsetdactOOand rect:llf!IIY. cr SJowonsetofactOOandrecoYerf. metabolites, potential/y nephrotoxic)and lowerseizures threshold
- Advantages; * Provideskeletalmusclerelaxation. • Abolishreflexestofacilitatetrachealintubatioo · Wealtanestheb:{MAC=105'1t) -PotentMeSthetic(MAC =0.74'1t) -II has a pungent odour and cardiac arrhythmias Of dose-dependent
- Disadvantages; Histamine release (bronchospasm and hypotension), bradycardia and postoperative muscular pain (inhaled anesthetics
enhanceeffectNMBs.) ~=~~~:::CVs. ~:ea:ni:t~a~actimy hypotension mayoccur (Desflurane & Sevoflurane; less arrhythmogenic).
·littleOtnohepatotoxiceffect - Hepatotoxiceffect
5) Anticholinergics - Local anesthetlcs are used rrmifl!xin · Goodchoiceinpatientswithli\181'irj.wy. -GoodchoiceinpatientsM!haiwayproblems I· · (Suprnne")
- Anticholinergics; Atropine, Hyoscine {Scopolamine) & Glycopymmium {Giycopyrrolate). combination with Epinephrine -lliS Ymrapidonset and recoverydueto fowbloodsolubility
- Advantages; * Reducesalivary, broochial andGITsecretions. · Protectlheheartfrombradycardia. {vasoconstn'ctOI), to ; ~ (Sevorane") · Like lsoflurane, ~has a pungent odour
- N.B.; GlyC:opyrrolate little across to BBB (little CNS effeds), in contrast to Atropine & Hyoscine 1) Reducebleeding -It has low pungency, Metabolism of Sevoflurane may generate toxic • N.B.; lsoflurane, Desflurane and Sevoflurane are a trigger ci malignant
2) 1ncreasesdurationalldqualityof metabolites thatare potentiaflv nephrotoxic hyperthermia
6) Others (if needed)
· Antacids; H2blockers (Famotidine & Ranitidine)to reducegastricacidity anesthesia{decreaseabsorption)
- Antiemetics; 5-HT3blockers;(such as, Ondansetron);to prevent nausea and vomiting. 3) Decrease amount of drug from
reaching systemic circulation
- Antihistamines; Oipheohydramine toprevent allergic reactions

local Anesthetics (lAs)

Intravenous Anesthetics Esters aremetabolizedin plasma
isthe firstlocatanesthetic used, largeiyrestricted to topicalanesthesla, dueto intense vasoconstriction canserveto reduce bleeding
used mainly for oral ulcers. May cause Methemoglobinemia {most common in children under 2 years)
frequently.~ mainly used topicaf/y in ophthalmology (topicallocalanesthetic fOftheeyes).
(Am ida I,.) is rapidlymetabolized and placental transfer is limited, so, ijis used as obstetricanesthesia, for epiduralanesthesia
- Not has analgesiceffects. lthas little or noeffect onthe heart Amides aremetabolizedinthe liver
and circulation, it is used especially in patients with
cardiovascular dysfunction ••. • · . used systemlc asan a.ntiarrhythmic.~rug and locally as localan.esthetic (eplduralanesthesia and o.phthalmology)
- · • - . ;,; used fOf epi<llral anesthesia, but ~has markedlycard i otoxi c
- ~~ decreaseplasmacortisol & aldosterone
- ··· . . · lesscardiotox.ic. ltiSalsoa popularchoice for nerveblock anaesthesia and epiduralanesthesia
· (Kelalar") I· · (PrecedexO) - ' . ·· lslhe bestchoice of localanestheticm modem dentistJy.
-ls a dissociativeanesthetic (trance-likestate); analgesia-amnesiastate in LocaiAnestheticsSystemicToxicity
which the patient's eyes remain open, but is dissociated from the - a2agonist, ha~
ss~
ed~
ati~
ve,~
an~
alg~
esi~
c, s~y~. ~:v~~;c & anxiolytic - ~~ · Lowtoidcity, Circumoral andlortonguenumbness , dizzinessandvisualandauditorydisturbances
environment, is immobile and does not respond to pain - High toxicity; Convulsions, unconsciousness, ccma, respiratory depression , arres~ CVdepression&collapse
- Droperidol (anlipsychotic) +Fentanyl {opioid); provide amnesia & - Cardiotoxicity, Chest pain, palpitations, diaphoresis, hypotension and syncope. Hematologic !!l!i£l1y, Methemoglobinemia {cyanosis), frequently with Benzocaine
- It is beneficial in patients with hypovolemic or cardiogenic shock and analgesia; usedas neuroleptanalgesia&neuroleptanesthesia
asthmatic - ~~ rash , urticaria&anaphy1axis (veryrare) , amino-esterssuchas Procaine isaderivativeoftheallergen para-aminobenzoic-acid (PABA )
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
CNS Stimulants Drugs of Abuse
• CNS Stimulants; are a groups of drugs that alters activity within the CNS. Classifications; According to, Effects; - Abused!2!.!!.g§_; excessivemisuseof drugs fornon-therapeuticeffectsonthemindor body
A) Psychomotor Stimulants; temporary improvements in either mental or physical functions or both, such as Caffeine and Nicotine - Common Abused ~; Alcohol, Alkyl nitrites (Poppers), Amphetamine, Anabolic Steroids, Ayahuasca (DMT containing plants), Barbiturates,
B) PsychotomlmetlcDrugs (Halluclnogens);produce hallucinations byalteringthe perceptionofthe surroundingenvironment, suchas(LSD) Benzodiazepines, Cannabis/Marijuana/Hashish, Cocaine , Dextromethorphan, Dimethyltryptamine (DMT), Gamma-hydroxybutyric acid (GHB), Heroin,
C) Convulsants & RespiratoryStimulants; noc/inlca/application andoftenused in poisons, intensivecare andfor research ,suchas Picrotoxin. Ketamine, Khat (Catha edulis), Kratom (Mitragyna speciosa), lysergic Acid Diethylamide (LSD), MDMA (Ecstasy/Molly), Mescaline, Methamphetamine,
Phencyclidine (PCP), Psilocybin, Rohypnoi'(Fiunitrazepam), Salvia (Sa/viadivinorum), Scorpions/lizards, SyntheticCannabinoids, SyntheticCathinones,
Tobacco and Voodoo
A Ps chomotor Stimulants
I) Methylxanthines; . I
- Mechanism Q[ Action; · Inhibits phosphodiesterase enzyme 9 increase cyclic adenosine monophosphate {cAMP); ~mmlllla -ltisa llSl!WMpsychedelicdrug, structural
• Jn ~ ~ Wcontraction (bronchodilatation}. * ln cardiacmuscle '* 1'contraction ( 1'heartrate) - It is commonly associated with dance parties analog of Serotonin & Melatonin
-8/ockadenosinereceptors; • tn l:l!m '* 1'heartrate. • tn .!1..@in '* Stimulanteffect anddancemusic "clubdrugs" - Alone is not active orally, because it is rapidly
Pharmacological Action: - Mechanism ; Similar to the Amphetamines. metabolized by MAO enzyme, So, is combined
-ill: - 100-200 mg of Caffeine; W Fatigue & 1' Mental alertness (cerebral corlex stimulation). - Action: Feelings of we!l-being and euphoria, with a MAOI such as Harmaline
- ~: <500-600mg/day of Caffeine ; +veinotropiceffect ( 1' forceofcontraction). +vechronotropiceffect ( 1' hearlrate). - Action: Intense visual & auditory hallucinations
increasephysical andemotionalenergy, increase
- ~: Mi/ddiureticeffects ; particular/y, Theophylline ; /nhibition of Na• reabsorption and increaserenalbloodflow Changes in bodyperception &time
sociabilityandha!lucination.
-l:!!!!9.: Methylxanthinesrelaxbronchialsmoothmuscle; particu/ar/y, Theophylline; Bronchodilation - Dependence; notphysicallyaddictive
- Dependence; notphysicallyaddictive
- Qf[: Methylxanthinesstimulategastricacidsecretion; particu/ar/y, Caffeine; fxcessivecoffeeintake may leadtogastricirritation
- Therapeutic~
• Bronchial asthma and chro~lc obstructive p~lmonary disease (COPD); Theophylline (largely replaced by ~ther agents) I •HfimrtjijlimttMftil
• Simple headache; Caffeine m combination w1th NSAIDs or Paracetamol . • Migraine headache; Caffeine m combination with Ergotamine -It is an intermediate-acting benzodiazepine, - The primary use is as a cough suppressant
- ~~: whichisa powerlu/ sedative (antitussive)
• Moderate doses of Caffeine ; Insomnia, anxiety and agitation. • High {Toxic) doses of Caffeine; Emesis and convulsions
• Lethaldose of Caffeine (10g, 100cupsofcoffee); Cardiacarrhythmlas. Theophylllne hasa narrowtherapeuticindex - Rohypnol* is also called "Date rape drufl , i.e -At high doses {> 200 mg) acts as an NMDA
Drog Facilitated Sexual Assault (DFSA) - Poppers areprimari/y used to enhanceasexual
- !kJ!glnteractions : Theophylline interacts w~ha widevariety of drugs receptorantagonist cause hallucination alld
activity, and to facilitate anal sex in
Rohypnol* isa drugofabuse at bars, nightclubs mild dissociate effect
2) Nicotine {Nicorette-Z) homosexual by relaxing the internal and
- lm!:Imm is notcurrentlyusedtherapeutically, except in smokingcessationtherapy e.g., Nicoretteeproducts and parties to commitsexualassaultsbyadding ->1000mg; Fu/ldissociativeeffect {/ikenedtoa
externa/analsphinctermuscles
- Mechanism Qf Action; Nicotine act on nicotinic receptors (deeending on the dose); - Low doses ; Stimulate autonomic ganglia it to Aicohol orjuice highdoseof Ketamine)
- High doses ; Prolonged stimulation with dose increased '* (desensitization)'* block autonomic ganglia by depolarization.
-lnCNS; Stimu/atenicotinicreceptors '* CNSstimulanteffects (complexpathway). ·
- Pharmacological Action; i·ffiiiffli4iM¥ l!li11lllll:mli 13fJf.JuiJ di£.B,EiJUU&&fii '
-Are syntheticagents ofthe malesex hormone - ltis amonoaminealkaloid foundinCathaedu/is -It is a plant found In Southeast Asia in the
- ~: - Cigarette smoking or low doses of Nicotine; euphoria (little), arousal, relaxation, improves attention , learning, problem solving and
appetitesuppressant. Highdoses of Nicotine; centralrespiratoryparalysis and severehypotension (medul/aryparalysis) Testosterone (khat)in EastAfrica andthe ArabianPeninsula Thailand, lndochina and Malaysia.
- ~:- Nicotinicreceptor onboth sympathetic and parasympatheticganglia; -Are used illegally to increase muscle mass, -It has been found to stimulate release of
- Withdrawal syndromes are developed rapidly after discontinuation; irritability, anxiety, restlessness, headaches and insomnia decreasefat and enhanceathleticperfonnance Dopamine and lnhibitreuptake of Epinephrine,
and body appearance Norepinephrine and Serotonin .
3) Varenicline (Chanti~) (Champix*)
-lsan oraldrug !lHSf. toquitsmoking(treatnlcotineadd/ction), actas a partialagonist inthe nicotinicreceptors (especiallyCNS) -Are usuallyinjectedintothemuscle, but some - Syntheticform, commonlyknownas"bathsalts"
- ~ ; Days 1 to 3 '* 0.5 mg orally once a day, Days 4 to 7 '* 0.5 mg orally twice a day, Days 8 to end of treatment '* 1 mg orally twice a day; areavai/ab/e in tablet or cream or gel are strong andmoredangerous
- "' Patientsshouldbetreatedw~h Varenlcllne for12weeks
-Most common adverse effects " Nausea, vomiting, headache, constipation, sleep disturbance and unusual dreams
4) Cocaine ·ltisa c/earcolor1esshydroxylatedhydrocarboo thatis the product of fermentation of fruits, grains; orvegetables
-lsa wlde/yavallable illegaldrug and h/ghly addictivedrug . Mechanism: lt /nhibitsreuptake ofSerotonin, Norepinephrine and Dopamine (Serotonin · ammmJ isthe mostcommonlyabused substance in modern society ;=.:.c=:__::.__ _ _ _ _ _ _ _--j
Norepinephrine Dopamine Reuptake Inhibitor, SNDRn. It also blocks sodium channels (local anesthetic)
- Pharmacological Action Pharmacokinetics
-m : Feeling of well-being and euphoria .lncrease attention sexual excitement, promotes talkativeness, enhance mental alertness and learning - Absorption; Rapidly from GIT (food in the stomach delays absorption)
- At higherdoses or chronicuse; restlessness, sleeplessness, /oss of libido, nervousness, hallucinations and delusion.
- Distribution; Throughoutthebody (brain, placentaandmothe(smilk)
- ~:lncreaseheartrate and bloodpressure, increasebodytemperature , dl/atedpuplls ( mydriasis)& increaselightsensitivity .
5) Amphetamines - Metabolism; Primary in the liver, and mainly by a pathway involving successive
-Is a potentCNS stimulant, medically used in'the treatment of attention deficit hyperactivity disorder (ADHD}, narcolepsy and obesity oxidations, first to acetaldehyde (Alcohol dehydrogenasepathway)
- Abused asa performance and cognltiveenhancer and recreational/y asan aphrodislac and euphoriant andthen to aceticacid (Acetaldehyde dehydrogenasepathway)
- Mechanism Qf Action: are sympathomimetic amines with CNS stimulant activity, act in CNS and peripheral nervous system as indirect increase
release and decreasereuptake of monoamines (Serotonin, Norepinephrine andDopamine) - li.J!l!IIB isadrugthat b/ocksoxidation of Acetaldehyde to Aceticacid by
- Pharmacological Action: - m: Feeling of wakefulness and euphoria, increase alertness and decrease fatigue, slight analgesic effect and inhibitingaldehydedehydrogenase.Jthasbeen usedto
anorexlgeniceffect (/ossofappetite) deterdrinkingbypatients withalcoholdependence
- ~: /ncreaseheartrate and bloodpressure, urinaryretention and nausea , vomiting , diarrhea or constipation .
- ~Effects: "" CVS side effects; Tachycardia & increase blood pressure . .rCNS side effects; Insomnia, anxiety, hallucination and tremor
~ --¢ Acetaldehyde accumulates and causes an
unp/easantreaction of facialflushing , nausea, vomiting , dizziness and

Bl Psychotomimetic Drugs CHallucinogensl

- Pharmaco/ooical Action : - ~: Hallucinations, temporary psychosis
andimpaireddepth, timeandspaceperceptions
- ~ ; Tachycardi a ,hypertensionand d il a tedpupils
- Mescaline and Psilocybin are naturally occurring hallucinogens
- Mescaline in certaintypes of cactus (Peyote), Psilocybin in certain
types of mushrooms
l[g!lllll\llll!!lll!lllmlD
- 69-Tetrahydrocannabinol (THC) is responsible for most of the
characteristicpsychoactiveeffects of cannabis
- THC binds to cannabinoid receptors (CB1 receptors}, causes
d/sinhlb/tion of Dopamineneurons,by inhibition of GABAneurons
- Pharmacological Action: m: euphoria, impaired time, distance and
soundperception(riskofaccidentduringdriving). m :increaseheart
rateandbloodpressure, eyerednessanddecrease iOP
- Phencyclidine (PCP) and Ketamine are hallucinogenic drugs w~h
dissociativeanesthetic effets.
- Mechanism Qf Action: - Ethanol affects a large number of membrane proteins that participate in signaling 1pathways, including neurotransmitter receptors
- Acute Ethanol exposure enhances the action of GABA at GABA... receptors and l lnhtbition of NMDA receptor activation
- Pharmacolooical Action :- ~: like othersedative-hypnotic drugs, Alcohol is a CNS depressant. AI high I blood concentrations, ~ induces coma, respiratory
depression, and death
- 50-100 mgldl; Sedation and re/iefanxlety - 100-200 mgldl; Impaired motor function,1, slurred speech and ataxia.
- 200-300 mg/dl; Emesis and stupor. - 300-400 mg/dl; Coma - > 400 mgldl ; Respiratory depression, death
-Isl.!illlt:A)Acute Toxicity;- Severe confusion and stupor. - Vomiting. -Seizures. -Respiratory ( depression. -Pale and clammy skin (insufficient oxygen).
B) ChronicToxicity; associatedwith an increasedriskofdeath (1iverdisease, cancer, accidents; and suicide)
- Treatmentg[dependence (Medications); li.J!l!IIB,~ n d ~

- Brainstemstimu/ants (Analeptics);~{Dopra m®) and -- {Daptazile®); are respiratorystimulant. Ba(non-competitivechannelblocker · forthe GABA...receptor); usedinresearch.
Cl Convulsants and Respiratory Stimulants - Spinalcordstimu/ants;a:B;is ahigh/ytoxlc (blockglycinereceptors, cause muscularconvulsions), usedas apesticide
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Non-steroidal Anti-inflammatory Drugs {NSAIDs)
D1flumsai (Oolob1d)
Overview Ketoprofen (K~t~ DexkeiO rofen (Dextrafast )
- NSAIQs; area group of chemicallydissimifar~gentsthat have ~ {pain-ki/ling) Naproxen (Aieve l
and ~ (fever-reducing)and anti·inflammatorveffec ts
·The term non-steroidal to differentiate these drugs from steroidalanti-inflammatory
(corticosteroids)
- Paracetamoi (Acetaminophen)is genera/fy not considered an NSAID becauseithas
onlylittfeanti-inflammatoryactivity
· The NSAIDs act by inhibiting the synthesis of prostaglandins. Thus, an
understanding of NSAIDsrequirescomprehension ofthe actions and biosynthesis
of Prostaglandlns (PGs) [Thesecompoundsreferredtoas eicosanoids]

Eicosanoids
1
Q::::::: ••m'~"' ,,~,.•"'" uni~2 (!~~i:!~s~~"~ve?.rb~7:.c~~~! ~c~ooxygenase
Aspirin is the prototype of the NSAJDs , is
(includingothersa/icylates), are all reversible inhibitors of cyclooxygenase.ltis now usedonly as anti·platelet (75-325mg/d)
(COX-1 and COX-2), ofherNSAtDs • ~~P,i~~~.T ,~,c!fdGIDb7,~:~~t!~~!en &
j ~!!Y. affeCts chi,ldren'l : ~~~;y%:! -:.~~;:;~~~ :~~r/~1) ~::::~:~~·~~~=~~:.'i!e;~~s: :;~~: ~~d::~~~~::~~t~~ ~:~~:~~~~ a~t ~c~~cd~~:, (> ~-~~hi\f:~::::: : : : :o: :t: ryus : :::it::::,a::

, '
NSAIDs Phosph oll paseA2 Jgld) ¢ block .
~ cooH UA reuptake ¢ 1" UA excretion. Therefore, /owdose Aspirin is avoidedin goutorin patientstaking Probenecid

X ~

~--~~~i~~~~
~::~~~~~%~c~f~~~J ~spirin isan irreversib/yinhibitor of COX, isanenzymerequiredfor prostaglandins and thromboxanes synthesis
0
1) Anti-inflammatory actions; Prostaglandins act as mediator for inflammation, NSAIDs decrease prostaglandins synthesis ¢ inhibits

inflammation .- N.B. ; COX-2 is expressed during inflammation and injury

• wit!@:higher cox. 1 selectivity, less potent than
Indomethacin, maximum dose is 300 mg/day

~~~~~=l~i:e ~:,::~:~:~· used for inhibition of

Prostaglandins
Prostaeyellns
. ~~c;;.~~~~~~ ~~~S:~~~~~~~{:;achidonic acid; AA) formation ;
• Eicosanoid biosynthesis begins when a cell is activated by; mechanical trauma,
cytokines, growth factors or other stimuli
. This triggers ¢ release of a phospholipase at the cell membrane
. The phospholipase catalyzes ester hydrolysis of phospholipid (by phospholipase
k_; PLA) or diacylglycerol (by phospholipase c ; PLC)
. This frees a 20-carbon fatty acid (arachidonic acid; AA)
2) Prostanoids formation (cyclooxygenase pathway);
·The cyclic pathway is initiated through the action of prostaglandin GIH synthase
(alsoca//edprostaglandin-endoperoxidesynthase)
·This enzyme possesses two activities, cyclooxygenase (COX) and peroxidase
. There are two forms of COX activity in humans, COX-1 and COX-2
.- (prostaglandin synthase-1 ; PGS-1) is expressed constitutively in gastric
mucosa, kidney, platelets, and vascular endothelial cells
- COX·2 (prostaglandin synthase-2; PGS-2) is inducible and is expressed in
macrophages & monocytes in response to inflammation
· :,~~a~~~-~. &i;c~~~~gca::~!~~~=n~~~~P (~o~;)~rsi;r~~~:;~~~id{~~bjci~n~
thromboxane (TXA2)
3)Leukotrienesformation (lipoxygenasepathway);
- Thelinearpathway is initiated throughtheactionof lipoxygenase (LOX) enzymes
ofwhich are 3forms, 5-LOX, 12-LOX & 15-LOX.
. The most actively investigated leukotrienes are those produced by the 5-LOX
·J1~e~e~:~~!~~enue:0:~e~t"~aes~i~~s~~u~~~~~!~~~;~i~e~~~re~~ncluding white
-Inhibition of Eicosanoids Synthesis;
2) ~=~:~:es~~:~!~~;~:r~=~~~~:~~~t~~~;;~~=:~~~~fD~e;:r~~:~n~~~2t~;n~~:~~s ~b;~;e~~~np:i~~;:,i~~i~~ other chemicals mediators • -~~:~;,~o~~AJD single enantiomer, has a ~
J) ~~t:.:~e:~~o~c!o~~c;::eg;~~s s~n~~r~~~!~~i~gth~g~=ot~!1~0~~:s~th:,~:;e as~:~:~~t ~f ~fe::p0o"fu~~~~~~~::~~%g:r!!~~a~:~teo; of CV events, Naproxen poses an intermediate risk of stomach
NSAIDs decrease PGE2synthesis ¢ thermoregulatory center ¢ 1' heat loss in patients with fever N.B.;!12 effect on norma/body temp - mparedtolbuprofen
• ~~tt~:~~(~::,~f~t~~t~:i ~l~:;::,b~~:t::t:fan::~~~~e~~~~~~~~~~~~::~: ~~~tv:~::~e~~g~~rw~~~~ea~~t~~:itAt~~~:~~~~!:::~ho~~:;~~:~~~ ~-'=·=·=·=h=as=mi=ld u=ric=os=un=·c ,=use=lu=l in=go=ut= = = = = i
· ~;. ; U~~=r~~i~~~ntda~~~~!~:~~~; nn~r~~~~;,N;~~~~h~~:i::::~: ~~~da~~~~~~t t:~~:;~ ;~~o;;;~~::t::~~~~~~~~:fa;~;:~v~f ~~~s in stomach .~;:!!~~,!~~~P~~~~r~Dt!.~!~oderate
and s":'all intestine (PGE2 and PGF2a). NSAIDs inhibitCOX·1 ¢ reduce beneficial effects of PGs in the GIT, resulting in increased gastric acid high risk of CV events, and has a ~ risk of Gl
secre!Jon , decrease mucus protection and increased~ for Gl bleeding and ulceration. complications
• !5k!!J.u; Decrease Renal Blood Flow; normally, PGE2 and PGh, are resoonsible for maintaining renal blood flow by vasodilation in the kidneys - ~ is one ofthe mostpotentNSAIDs , is morepotentanti·
NSAIDs inhibit COX-1 ¢ reduce beneficial PGs in the Kidneys ¢ decrease renal blood flow due to constriction of afferent arterioles inflammatory than Indomethacin with higher COX-2 selectivity,
NSAIDs decrease sodium and water excretion may cause edema in some patients (patients with a history of heart or kidney disease) it used widely in the treatment of pain associated with renal
· CVS; Risk of Cardiovascular Events; normally, there is a balance between; stone (first choice NSAID for renal colic), ~ risk of CV
· PGb (vasodilator&inhibit platelet aggregation) and TXA2 (vasoconstrictor & induce platelet aggregation) events and moderate risk of Gl complications. [Diclofenac and
· NSAIDs with a very high degree of COX-1 selectivity (such as Aspirin); have a cardiovascular protective effect, due to decrease TXA2 Indomethacin should be used with caution in CHILDREN
productionmediatedbyCOX-1 youngerthan3yearold ] -
• NSAIDs with a very high degree of COX·2 selectivity (such as Rofecoxib), have a high risk for card iovascular events (MI and stroke), due to · ~ has low Gl complications
decrease PGI2production mediated by - .Aspirin in high dose (> 325) inhibitPGb production mediated by COX-2 and may carry a rJ.g · ~ is the ~ and most effective NSAIDs (as
for CVS events. All NSAIDs (non-selective and selective COX-2) are not without CVS risk analgesic; 30 mg of = 10 mg of Morphine), it used widely in short·
- Jdmg ; Risk of Bronchospasm;normally; There is a balance between; Cyclooxygenase pathway (PGs and TXs) & Upoxygenase pathway (LTs) term in moderately severe pain, should not use for> 5 days, the
.
· NSAIDs cause shift in arachidonic acid from cyclooxygenase pathway [Qiipoxygenase pathway ~ leukotrienes formation ¢ bronchospasm
may occur {about 10% of people taking NSAIDs). NSAIDs should be used with caution in patients with asthma
rhe~:::~Z: J::;T:..
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oral formulation is ~ to be used as continuation to IV or IM
is a prodrug analog of Indomethacin, with less toxic,
Wm inhibiting PGs in the kidneys (Kidneys can reoxidize the
A) Anti-inflammatory and analgesic: NSAIDs are used in; rheumatoid arthritis (RA), osteoarthritis (OA) & gout. sulfide to the inactive sulfoxide prodrug), ~.it one of the safest
· Mild to moderate pain due to multiple causes; headache, toothache, backache, menstrual cramps (dysmenorrhea) and cold/flu drugsfortreatingosteoarthritisinolderpiOple
Combinations of NSAlDs and Opioids maybe effective in treating severe pain causedby malignancy. Ketorolac can used for severepain -~ isa non-acidic NSAID .
B) Antipyretic: NSAIDs maybe used to treat fever, Aspirin is contraindicated in children (under 20years) as antipyretic~ viral infections I \ = = = = = = = = = = = = = \
such as chickenpox or influenza), due to increased risk for Reye syndrome 4) Enolic Acid Derivatives
~~ ~~~~~~~a:;~~~~~i~~~:~::o~~i~:a~~~:~~i~~~~~~t:~~~c~nac:;::;:~~~~.h~:~Y:~~~~~;~a~eb~~~~o~~~~~~se~ ac~u~~~~~~~~~rrent Ml . rmd and lDim!lm; once~aily, ~ risk of Gl
· General~ effects for all NSAIDs (dose related); complications.

~ ~~~-~~:::~~!~sa~:f~n~~k~~7on~a~~~a:S;~:~:~~n;J:c:~n~~~i~rostaglandins ·v~~~;n~~~~~~~e~; ~~~~~;nd dizziness. ~ ~~~e7r:~:~~~~fr~~dn~~t,e~t~~~·f~;r~,ah~~~~~:~i~~ ~:t~ti~u-~~~:~~~~~~~~:i_n~ ~~~~:ar:i:h~:usea, ~ lah:a:~dh~;;:: ~~X~~~:~:::::ii~.· ~ has a fewer risk of
~P~~b~n~~r:i~=~~~:~~:t~~~o;;=~~;eb:ni;~:~tJ:~ ~e~~o~~!~~ receptor · Preanancy: i~::~~~:~~= ~~ek :t:~~n\O~ai~ t~~~e~~10~e~o~:~~~~~!~~~:~~~:~a~:r~o:,~s~~: ~~a1t~~Zc~Us~~:~~~~:~~~~~e~~:~k~~~ I ~G=tc=om=pl=ica=tio=ns=,h=igh=m=ode=ra=fe =CV=ev=en=ts n='sk= = = = i
(LTC,, LTD, and LTE.) {Zafirlukast, Montelukast & Pranlukast), are used in synthesisof PGE1& PGE2,whichare neededtokeepopenthe ductusarteriosus) 5) fenamic Acid Derivatives
- Maj~~o;~~~~~~~~~!anoids; • ~(mild fonn · ~ Wome~~~no~~~ST~~!:~:::~eA~!:~~ ~~~:~:t;~~t~~s~~~~~~uapnr~f~~;l~~~~~~:aa:~nd~~::r:::; ::;:~tt:~e~;~e!d~~n!~=~th - ~ (COX-2 » COX-1 ), act as prostaglandins
- ~~~~~~~d~~i~ .~~~~~mation and fever :::::::~~); 1===~======~==============~==11 ~::&!:~:~~a::~~~ ~;:~:~~~~~ea:also effectiveness inthe
• control acid secretion and mucus production in the GIT. • Nauseaand vomiting 7)
Selective COX -2
Inhi bitors (Coxi bs)
. Control renal blood flow & control uterine contractions · Hyperventilation. - ~ is a reversible selective COX-2 inhibitor (about 10-20 times more selective for COX-2than for COX-1) 6) Other Agents
. Prostacyclin (PGh); • Headache. · It is approved for the treatment of rheumatoid arthritis, osteoarthritis, and acute mild to moderate pain (has similar efficacy to NSAIDs in the • ~ is association with risk of hepatotoxicity , so it has
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- lnduceplateletaggregation &inducevasoconstriction · Iillrlitw (ears ri'lging). Paracetamol (Acetammophen ) san analgesic antipyretic of chosce lor ch1ldren pregnancy and breastfeedmg women pattents wsth CV nsk anafgesic, antispasmodic and antipyretic with minfmafanti·
- Leukotrlenes (LTs); or Gl complications ard asthmatiC pat1ents Contra1nd1cated m severe renal and hepatiC 1mpa1rment (used With caut1on m M1ld to moderate inflammatory effects, ~ is association with risk of
. Powerful bronchospasm & increase vascular permeability hepatlc lmpalrmentwlthglulalhloneanalogues) agranulocytosis , but it is still available in some countries
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Overview
- Anemia isa reduction ofthe hemoglobin concentration to /essthan130g/l (13 gldl)in malesor /essthan
120g/L(12g/dl)in females
- Anemia, likea fever,isa sign that requiresin vestigation to determine the under/yingcauses
>Morphologyflerminology:·
• Normochromic cells; normal concentration of hemoglobin. • Normocytic cells ; normal size of RBCs
• Hyperchromiccells ; higherconcentrationofhemoglobin. • Macrocyticcells; larger sizeofRBCs
• Hypochromiccells; /owerconcentration ofhemoglobin • Microcyticcefls; sma/lersizeofRBCs
Red Blood Cells (RBCs)
- Redbloodcells or redbloodcorpuscles (RBCs);alsoca//ed erythrocytes,areresponsiblefor de/iveringoxygen
to the body tissues.
- RBCs are rich in hemoglobin, aniron-containingbiomoleculethatcan bindoxygen.
· Structure; matureredb/oodcel/s; areflexible and ovalbiconcavedisks,they /ack a cellnucleus and most
organelles (to accommodate maximum space for hemoglobin)
- RBCsdeve/op inthe bonemarrow andcirculatefor about 100·120days
- Approximale/y 40-45%ofthe blood's volume is redbloodcells
-Approximate/y SmillionRBCsperoneblooddrop
· Approximate/y270million of hemoglobinperoneredbloodcell
·Approximately 2.4 million new RBCs are produced per second in human adults
- Each circulation takesabout 20 seconds
-The redbloodcells inadu/fhumanmalestoreabout 2.5grams of iron (about65%ofthetotalironin thebody).
· FormationofRBCs (Erythropoies/s);
-Kidneysrespondto a loweroxygenconcentration intheb/ood, whichthensecrete Erythropoietin
·Erythropoietin travels to the bone marrow and stimulates the production ofRBCs
· Damaged or old RBCs are destroyed primarily by the spleen
Hemoglobin
- Hemoglobin or haemoglobin (Hb or Hgb);isthe iron-containingoxygen-transportmetalloprotein in redcells
· Structure: hemoglobin has twoparts; heme (prosthetic group)and QQQ!in (Protein)
o Heme :consistsofan iron intheforumofferrous (Fe2•)heldina heterocyclicring, knownasa polllhYrin
This porphyrinring consistsof fourpyrrolemolecules linkedtogether(bymethinebridges)withthe iron
ion boundinthe center.The ironion,whichisthe site of oxygenbinding
o Globin:istheproteinpartandconsistof fourchains
Anemia
Glucose-6-phosphate Dehydrogenase Deficiency Anemia (Favism)
· Giucose-6-phosphatedehydrogenase (G-G..PD)is anessential enzyme for nonnallifespan
for RBCs, and prevent RBCs damage from oxidizing processes
• This enzyme deficiency may provoke the sudden destruction of RBCs and lead to hemolytic
anemia with jaundice in responsetoa numberof triqgers , suchas;infakeof favabeans,
infections and vario usdroo sthe followingareconsidered ~
- Primaquine , Pamaquine and Chloroquine (antimalaria/agenls)
- Sulfonamides (Antibiotics).
- Non-sulfaantibiotics (Nalldixlcacid,Ciprofloxacin ,Nitrofurantoin,Chloramphenicol )
- Giibenctamlde {anfidiabeficdrug)
- Rasburicase (recombinanturateoxidase)
· G-6-PD enzyme responsible for convert NADP" to NADPH which make detoxification of the
drugs or toxicagents lhrough glutathionesystem.
Thalassemia (Mediterranean Anemia)
· Thalassemia [tha1-uh--SEE-me-uh] is a !1fQ!m of inherited blood disorder characterized by
abnormal formation of hemoglobin. The name is derived from the Greek word "thalassa"
meaning"thesea" becauseitwas firstdescribed inpopulationslivingnearthe Mediterranean
Sea. lt is causedby mutation in genes that ma/ceshemoglobin, cause defectsin eitherthe
a or pglobinchain
-- -; LowMCV and MCHC
· Complications; Iron overload (due to frequent blood transfusions), heart failure and liver
fibrosis (duetoironoverload)andenlargedspleen (duetodestructionofa/argenumberof
RBCs)and bonedeformities (especiallyinthefaceandskull; ~ th a lassem iaface).
Megaloblastic Anemia
· Megaloblastic anemia ; results from inhibition of DNA synthesis.during RBCs production ;
When DNAsynthesis is impaired,the cell cyclecannot progressfrom the growthstageto
themitosisstage,this/eadsto continuing cellgrowth withoutdivision. The defect in RBC
DNA synthesis is most often due to deficiency ofVitamin Bu and/or Folic acid
-- ; HighMCV and MCHC
· Causes; For Vitamin 812 (Cobalamin ); Lack of vitamin Buin diet, Failure in intrinsic factor
:J.E: (pernicious anemia), Coeliac [see-L+ak] disease {autoimmune disease in small intestine;
malabsorptionofvitamins), Chronic pancreatitisand pro/ongedexposureto nitrousoxide
· For Folate (Vitamin Bt); Lack of folate in diet, increased demand (pregnancy),
alcoholism, intestinal disorders, medications (methotrexate).
· Treatments ; eating cobalamin/folate-rich foods or taking Vitamin Bu/Folate supplements
AplasHc Anemia
· Aplastic anemia; is a rare disease in which the bone marrow stops producing~ new
bloodcells. Thiscausesa deficiency of allthreebloodcelltypes (pancytopenia): redblood
cells (anemia), white blood cells (leukopenia) and platelets (thrombocytopenia)
- Causes;
·Idiopathic (Unknown). Genetics. Certain viral infections. Immune disease
- Pregnancy.Exposureto radiation . Exposureto certainchemicals (BenzeneorPesticides).
-Exposureto certaindrugs (Chloramphenicoi,Carbamazepine,PhenytoinandOuinine)
· Treatments ; Blood transfusion, stem cell transplant, immunosuppressants or bone marrow
stimulants
Iron Deficiency Anemia (IDA)
- lronDeficlencyAnemla;is anemiacaused bya lackof iron
-- -; LowMCV and MCHC. __ ...--,, ,__.._OS
· Signs;
. .. Koilonychia (spoon-shapednails)
. •• Pallor (reducedoxyhemoglobin in skinormucousmembranes .
- fig (hungerforice,dirtandpaper)and Crackedcorners of the mouth.
- Causes;
- Bioodloss;heavy menstrualperiods, Gibleeding, parasiticdisease and
-Lackofironindiet;examp/esofiron·r1chfoods;Chlckenliver,
meat, leafygreenvegetables, beans, seafood (especial/yoysters),
fortifiedbreakfast cereals and nuts
- Lackofironabsollllion
-Pregnancy;occursin manypregnantwomen
· Treatments ; eating more iron-rich foods or taking iron supplements (IV iron or blood
transfusions can be administered)
Sickle Cell Anaemia (SCA)
· Sickle Cell Disease (SCD);isa groupofgeneticblooddisorders,resu/fingfromthe presence
of a mutated formof hemoglobin (hemoglobin-S).
-Hea/thyRBCstypical/y functionfor 90-120days,but sickledcellson/y last 10-20days
· Complications; SCD may lead to various acute & chronic complications, with high mortality
rate; vasa-occlusive crisis, acute chest syndrome (ACS), anemia, aplastic crisis and
hemolytic crisis.
· Treatments ; There's nocure, treatments can re/ievepaln andhelp preventfurther problems
associatedwithsicklecellanemia

Symptoms of Anemia

Hematopoietic Drugs; Drugs for Anemia

· Anemia may be undetected in many people and symptoms can be minor.
• The symptoms canbe re/atedtoanemiacause. Symp\Omlof
• ~o~~~;:_(:;a!~::S~oms; ~~ - ~ ~ Ane~ia ~a!:
o Confus1on E~~H [)jzzjn_,
o Dizziness -v~ ·Faltltitlg 1) Erythropoiesis-Stimulating Agents (ESAs) 2) Iron Supplements
o Headache. ~ (Epiaoe)(Eprext) ~ (NeoRecormont) OrallronFormulations
o Dyspnea(shortnessofbreath)
o Decreasementalactivity
~ (Aranesp*) -tGjiijt\I (Mircera®) ~ltfflttTt!rl!!A'ff®dltfflttTt!#%MWJ!IilMtttt@if!Tjt:/;fiit.JIIH,Ird!ititie:m:mmmil
olossof energy · Recombinant human erythropoietin (rhEPO); produced by recombinant DNA technology · Common side effects (dose-relatedl; Gl disturbances caused by local irritation (nausea, abdominal cramps, constipation {if
o Pale{yellowish)skin · Administration (IV and SC); • Epoetin alfa ; three times a week. · Darbepoetin ; weekly. astringent} or diarrhea {if irritant}) and dark stools
o Fastorirregularheartbeat · Methoxy polyethylene glyco1-epoetin beta ; 2-week or monthly intervals Parenteral Iron Formulations
o Chestpain - ~ ; Anemiaassociatedwith ;e nd --stag e ren ald isease (notclearedbydialysis), HIV, bonemarrow ~ (CosmoFer®) ~ (Venofer®) fj'iti:mtfJiji!!#-l@)i.l@ilii {Ferr1eci!®)
o Coldhandsandfeet disordet's, prematurity and cancer ~ (Feraheme®J IMI!@ffM'ii®M (Ferinject®) l'f·hJMiti®!ftt1t•f:i!UiU@ (Monofer®)
- ~are adjusted to maintain a targethemoglobin upto, M notexceeding , 10-12g/dl - Parenteralirontherapy shouldbe reservedforpatients with irondeficiencywhoare;
Risk Factors and Complications · Most common side effects; hypertension and thrombotic complications •Unable to tolerate oral iron. •Unable to absorb oral iron. • Extensive chronic anemia (such as chronic kidney disease)
.> Bi§!s.Factors:· · ~~~s:a:~~% i~~~~:~~~:·i~h~~~i~~u~o~ew:~91~a~~~i~!~ ~~hr~~~~i%~:a~~~~~~~ ~sc:~~e~ • ~n~~:~a~~,Val~~~~:~;r:~a~~;:J~ ~~~dd~~~· fever, arthralgias, nausea and vomiting, back pain, flushing, urticaria,
• Poornutrition ;dietlowiniron,vitaminB12andfolate.
• lntestinaldisorders;,suchasCrohn'sdiseaseaffectstheabsorptionof thr=om=bo=tic=ev=eni=Q!=, in=
:= pa=tie=
nts=w=
rth=
ad=
van=ce=
dh=ea=
d a=nd=ne=
ck=ca=
nc=
ers=
,fa=ste=rtu=m=or=gr=
owt=h=~ . ~::~;fv~~ ~t~:~~~::~;s ~\:s~~s~~~~~r~sa~~~~~~r:~a~~~~~;- results when excess iron is deposited in the
nutrientsinsmallintestine 1

• Menstruation;duetolossofblood 3) VItamin 812 Supplements · Treatments ; the goal of therapy is to remove the iron before it can produce irreversible parenchymal damage;

• Pregnancy
• Chronlcconditions ;suchascancer,kidneyfailureorHepaticfailure.
• Familyhistory;inheritedanemia,suchassicklecellanemia
• Age ;peopleoverage65
• Otherfactors ;historyofcertaininfeclions,blooddiseasesandautoimmune
disorders, alcoholism, exposure to toxic chemicals, and the use of some
medicationscanaffectredbloodcellproduction.
> Complications:-
• Severe fatigue
• Pregnancycomplications (suchaspremalurebirth)
• Heartproblems (suchasarrhythmia,en/argedhearlorheartfaifure)
• Death (suchasinsicJdecellanemia)
·r"f:!,mt!! ~~~.~!::1; ~;c~;~e~~~·t~:~~~i~:e(:~~t~.,;~s o~:~' :~:i~:~~e t~: t~;~r~::~~~~~~: chelation~: ,:k[EJ~t£i~~fuft ~~~f:~~~~--l(~~;~:;~r~~Ftrhl'i!Mut (Exjade®J
·l!M
z::~::~i:~~c:1:e~i~a;~~~:~~:6~~n::!~:~aa!~~~:~~;:x®) to improveCyanocobalamin kinetics, : g:::~~~~~!n: =na::;~~t~r:~::~:.h;~::~;;o~~;i~:~~~~~:~~ ::~:~~l~c~~~:~ase or anuria
· Deferasirox isan oralironchelator, warning ; maycausesevere and fatalkidney or liverproblems
- ~ is another VitamlnB u prodrug , avai/able; ~ parenterallv (IM ), IV~ for li=========~=====~========i
cyanide poisoning. It is prefe"ed than Cyanocobalamin because it is rapid response and more 3) Folic Acid (Folate) Supplements
highly protein-bound and therefore has longer half-life • 1mg of folic acid orally daily is typically sufficient to reverse megaloblastic anemia (it may administrated parenterally; IM,
- ~ isthe activeform of VitaminB12, higherbioavailability (betterabsorbed) and /onger SCandiV). Usualadu/tdoseforfolicaciddeficiency; 400-800mcg
retention in tissues, it is the only form of Vitamin 812 that can cross the blood-brain barrier without . WAR.tiiH.G_; Folic acid should not be given a/one in patients with without knowing whether they also have a Vitamin 812
assistance or conversion, highdoses atsobeenusedto effective in multiplesclerosis - - deficiency.
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Bout and Hyperuricemia Disease Modifying Antirheumatic Drugs {DMARDs)
- Gout isa metabolicdisorder characterizedbysudden, severeattacksof Ri!D., rednessand tendemess in joints - DMARDs are used in the treatment of Rheumatoid Arthritis (RA) and have been shown to slow the course of the disease, induce remission , and prevent further destruction of the joints
(oftenthejointatthebaseofthe bigtoe) - DMARDs should be started within 3 months after RA diagnosis. NSAIOs or corticosteroids may also be used for relief of symptoms if needed
•• Definitions: - Rheumatoid Arthritis (RA); is the most common autoimmune inflammatory (chronic) arthritis in adults, characterized~~ inflammation of joints and may involve other organ
• Hyperuricemia; is an abnormally high level of Uric Acid (UA) in the blood; svstem (immune svstem mistakenlv attacks bodv's tissues)
· Reference range; Male; 3.5--8.0 mg'dl. Female; 2.5-6.5 mg/dl
- Gou~ is a crystal-deposition disease that results from chronic elevation of Uric Acid levels
"hyperuricemia" (serum urate level more than 6.8 mgldl or 7 mgtdl), resulting in tissue deposition of Mono-
Non-biologic (Traditional) DMARDs
.:.:.~u~euur:~uc;"o~h=~c~~~~~~~~eh::!'~f:~~::~i::'u~~~~~:~~u :~~osphate crystal~
0
Emi!mlml·(Methotrexat~) l!llil!!i!llilm(Arava<) (Avara<) !CMUz;;mnt.U•l•l!ild (Piaquenift)
;====================~ ~ - =~~~=a~a~~;~~ isa syntheticantimetabolite (Folic - l eflunomide, like MTX, is an immunomodulatory non- - Hydroxychloroquine isan antimalaria/drug.
biologic DMARD - Mechanism: unclear.
• Hyperuricemia causes; imbalance between overproduction of uric acid and/or decrease excretion of uric acid _11 was originally used as a chemotherapy treatment for - Mechanism: the active metabolite (Terifluoomide)
inhibits dihydroorotate dehydrogenase (DHODH)
- Mainadvantaqe: lesstoxicities onthe liver, kidney and immunesystem
>Gout Predisposing Factors; • • • • • • • • • • • • • • cancer, used in much lower doses for rheumatoid
• Alcohol Consumption arthritis and other rheumatic diseases enzyme, inhibits pyrimidine synthesis, leading to a than other OMARDs, which simplifies monitoring
• Dietary, - MTX now considered the first-line OMARD for decrease in lymphocyteproliferation and modulation : Serious~~ OCULAR TOXICITY);
•• Avoid, Organ meats, game (hunting) meats, fish, seafood ; and high-fructose drinks or foods
of inflammation ~ Monitorioo: Ophthalmoscopy every ~12 months and Amsler grid
.. Umi( Meat, poultry, dried peas, beans, legumes, mushrooms, some vegetables
- Onsetofeffect, within 3-6weeks of startingtreatment -Usedas monotherapy Of in combination testathomeeverv2weeks
•
(cauliflowerandspinach)and wholegrains
Drugs; Thiazide and loopdiuretics {~ of incident gout & higherrate of goutflares)
- Used as moootherapy or in combination
- MQ!f common~~ mucosal ulceration and
- Common side effects: Respiratory infection, diarrhea,
nausea, headache, hypertension , alopecia, rash,
I :====================i~ (Azulfidinee)
Low-dose Aspirin ~ bea riskfactor for gout)
nausea, leukopenia, anemia, stomatitis, Giulcerations weightgain, andabnonnalliverfunctiontests - Sulfasalazine (SSZ)isa prodrug,isa sulfadrug c/eavedby bacteria in
• Medical condilions; Hyperuricemia, obesity, diabetes, and alopecia (duetoinhibitingce//ularpro/iferation) , - P(AAnancr category X; should discontinuation at least 2 the colon into Sulfapyridine and Mesalazine (5-Amino-Salicylic Acid; 5-
hypertension, dyslipidemia &renalinsufficiency. years after treatment and plasma levels of A771726 ASA)
halitosis (badbreathodour).
• Otherconditions; Trauma,surgery, starvation, - Dose-related; hepatotoxicity. should be less than 0.02 mgll) Q[ Administer • Sulfapyridine is probably the active moiety in treating RA
dehydration and familyhistoryofgout Cholestyramine to ensure level less than 0.02 mg/L • Use of Sulfasalazine is often limited by its adverse effects.
- Rare; acutepneumonitis & kidneyfailure.
>Gout Symptoms and Signs:-
· Fever.- lntensepain. r-~~~~___j 1- ~~::~~:~~~:t:~~vo;r::~~~~~~~may decreaseseverity I ~-=_=
MTX=s=h..=ld=b=
e th=ep=re=ferred
=in=itia=ID=MA=RD=Io=rm=o=
stp:::Oat-'=
ien=ts ============~
::...._j---~~~~----. 1 - Monitoring, liver enzyme tests, CBC, and monitoring ~ In hepatitis B or Cpatients; using DMAROs otherthan MTX or leflunomide, such as Sulfasalazine QI Hydroxychloroquine
for signs of infection - Minocycline has been suggested as a treatment alternative fOf patients with RA who have low disease activity and without features
1) Nonsteroidal Anti-inflammatory Drugs (NSAIOs); All NSAIDs are likely to be effective in decreasing pain
and inflammation . 2) 0R Colchicine;seenext. Biologic DMARDs
3) OR Corticosteroids {oral, intramuscular or intra-articular routes);~ an appropriate alternative for
patients who cannottolerate NSAIDs or Colchicine, lntra-articularcorticosteroid (ICS)usedif one or two 1) TNF-a Inhibitors; Etanercept, lnfliximab, Adalimumab, Certolizumab and Gotimumab 2) T-Cell Activation Blockade; Abatacept. 3) 8-Cell Depletion; Rituximab
large joints 4) ll-11nhibit0fs; Anakinra 5) ll-61nhibitors; Tocilizumab 6) Janus Kinase (JAK) Inhibitors; Tofacitinib
• These drugs may be effective when other DMARDs (non-biologic) f1l1 to achieve adequate responses but are considerably mOI'e expensive to use
-im:m, isan antimitoticdrug,isa plantalkaloid, usedforthe treatrnentofacutegoutyattacksandfamilial • Precautions·Most of thesedrugs are increased an incidence of riskofinfection (especially tuberculosisinfection;tuberculinskintestingisrecommended)
Mediterraneanfever(FMF) · uvevaccines shouki !!.Q! be given topatientstaking biologicagents to avoid the riskof infection
- Colchicine relieves the ~ and inflammation of gooty arthritis in 12-24 hoors without altering the metabolism
or excretion of urates andwithout otherana/gesic.effects (notanana/gesic)
· Mechanismgf~ Colchici n e bindsto micro-tubularintracellularprotein called tu b ulin causingits I ) Tumor Necros1s Fac tor-alpha (TNF a) lnh1b1tors

-::o:::~~~;ii::.~~l~~~:~:~;~~~~2i~~:~~:~i~?!~~~~~~~~:a~:~~~~i~~\~~ :-~~~~~~~~~~~~~~G~~~~~~~;;_:~~~~~~?~~~;~~~~~y-~~~~~~~!~~~~.-;;~;~~~~~~~~~~~~~~~~~~~J
- c~;~~;:::i~)f~ r~~~~~~:::f:~p~trmC:~~~~;,eto~;~~tys::sn!cc:~~ 4
inhibitors (~ or mlimZ!m (Enbrett) lmiiE!Wml· (Remicadee) ~ mm&mmll (Simpon~) I@G'miitlil#®l (Cimzi~)
F======================i · Etanercept isa recombinant, - lnfliximab is a recombinant DNA- ( H umira~) _ Golimumab is a human - Certolizumab isa unique (notcontain
Drugs for Gout PrevenHon (Chronic) ~:~e~u~~~ ~~;;:',~ ~s:~:, :~~ii~~:Y ~~~~b~:s ~~:~lu:l~;o:F:al r::o~~~~~~~ is~ monoclonal antibody w~h
a high ~!l~niz:nt;~~~boday :ae:o::~~~nnti
Hyperuricemia Urate-Lowering Therapy (ULT) therebyblockingitsinteraction - lnfusionsitereactions mayoccur dueto human lgG, affinity for soluble anO conjugatedto a PolyethyleneGiycol
- Urate-loweringtherapy; usediftheyhave morethantwoattacksper year or theyhave chronickidneydisease, with cell surface TNF-a anti-infliximab antibodies formation monoclonal antibody membrane-boundTNF-a (PEG)
kidneystones or tophi{depositofuratecrystalsinthejoints,bones,cartilage,orother bodystructures) receptors (Methotrexate should be given to thatbindslo TNF-a
1) First-lineULT; AIIopuri nol or Febuxostat {XanthineOxidaselnhibitors; XOis) - Used alone or in combination decrease formation of antibodies - Alone or in combination. DON'T forget lhe biologic precautions
2) Aiternativefirst-lineULT; Probenecid (Uricosuric); lfXOis is contraindicated or nottolerated
2) T-Cell ActivatiOn Blockade 3) B-Cell Deplet1on
~ (Zyloric<) lllll!El!l:ili! IFeburic<)
- AIIopurinol,a xanthineoxidaseinhlbitor. -lsa xanthineoxidaselnhibitor, is structurafly
unrelated to Allopurinol ~ (Orencia*) ~ (R~uxant)
- Mechanism: Allopurinol decrease Uric Acid - Abatacept isa soluble recombinantfusionprotein of lgG, fusedto the extracellulardomain of - Rituximab is· a genetically engineered chimeric (murine/human) monoclonal antibody
- Mechanism· Selective direct non-competitively
production by competitive/yinhibitingxanthine CTLA-4 {cytotoxic T-Iymphocyte-associatedprotein-4), CTLA-4 (Abatacept)hasveryhighaffinity directed against the C020 antigen found on the surface of normal and malignant B
blocking the activesite of xanthineoxidase
oxidaseenzyme (duetostructuresimilarity)inthe for CD28 ontheT-cell, prevents the activationofTcells. lymphocytes, resulting in B-celldepletion
- Febuxostat and AIIopurinol are equa/ly effective in
/asttwosteps in Uric Acid biosynthesis - ~ Monotherapy(firu-fiM~ orin combination (notwithotherbiologicdrugs) - Uses: in combination with Methotrexate in oatients who failed to one or more aaents
preventing recurrent gout
- !fill; Chronlcgout &hyperuricemiasecondary
to chemotherapy
- §iJ;t§~ - UricosuricAqents· are substances that increase 4) lnterleuk1n 6 (IL-6) lnh1b1tors 5) Janus K1nase (JAK) Inhibitors
'* G/SideEffects; Nausea,vomiting,and diarrhea the excretion of Uric Acid inthe urine
•* AIIopurinolhypersensitivitysyndrome (AHS); - i:mEm and ~ are a uricosuric
drugs
~ (Ademra<) IIEil!!!lll!lll iXeijanz<)
- SBmce hypersensitivity reactions; Urticaria, - Tocilizumab isa humanizedmonoclonalantibodythat blockll-6receptor - Tofacitinib isan OI'al inhibitor of Januskinases (firstoralbiologic)
a5Wel/ as Stevens-Johnson syndrome, - !lill; lf XOis is contraindicated or nottolerated - ~ SJHXmd.-JjMtl.eil.tliHmt as monotherapy orin combination
- ~; Mono therapy(fi!;g-~~ orin combination (notwithotherbiologicdrugs)
hepatotoxicity and eosinophilia - SecondaryUricosurics; l osartan &Fenofibrate

- Pegloticase isa recombinanturateoxidaseenzyme usedinsevere, refractoryorresistantchronicgout, itacts

by converting Uric Acid to AIIantoin, a water-solublenontoxicmetabo/ite 6) lnterleuk1n I (IL-l) Inhibitors
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Gastrointestinal Drugs
Drugs Used to Treat Gastroesophageal Reflux Disease (GERD) and Peptic Ulcer Disease (PUD)
1) Antacids 2) H2-receptor Antagonists (H2RAs) 3) Proton Pump Inhibitors (PPis)
llt,·1mmtif!ftri~~:~M@M~·~·
I
·=t:.il~t!Jii~·~IW~··~"'414'~11,~P:M@M~·~·
~·~-h\M~·~-r·iE
ilfjitili!1jfilfflift1®1iJlii¥1 JifflM:fi.f.jr$11§1Ulili!Jil
_ Antacids; are weak bases that react with gastric acid to form water and a salt
l &mmmm (Tagame~J IIil1i!m!lml tzanta~JEI!m!mlmi (Uicfreee) o:mmmm {Antodine&J
-They are reduces the secretion of gastric acid by blocking Hzreceptors
- Cimetidine is largely replaced by other Hzreceptor blocker due to side effects

5
~ -::n~ac~~s a~~;e~c;.,:~~!~~c~/Z· ~~~u:~::~~ng~e~:~~~~~~ a~
(Maaloxt plus)to controlqas or ~Gavisco n*)toactasa ~ba"ier
to acid
- Mechanismgfaction; ~ gastricacid --+ decrease of pepsin --+ increase
LESpressure
- Advantages; Rapldonsetofaction
· Dfsadvantages; Shortdurationofaction (needfrequentdosing)
· §j1!Jl effects; Constipation (AI; hALts stool), diarrhea (Mg; magnifies stool),
~~~~~:~~t:~h~i~ s~~~;!,~ ~:e~~;~:l~i:~:~~i~i~~%~~~t:~~~~)are less popular
1
- .
4) Mucosal Protective Agents
l!!r!!lilll!!!I (Carafate')
- Sucratfate isa sucrosesulfate-a/uminiumcomplex that binds lothe ulcer, creating
a physicalbarrier that protectsulcer, a//owingthe ulcer to heal.
- Require acidicpH for actlvation, should!1Qt beadministeredwith PPis, H2RAs
-lts use is /imited duetothe needformultipledaily dosing
lllD!ll
- Bismuth has multiple actions; formation ofa protectivecoating , stimulation of
mucosalprotectivemechanisms and directantimicrobialeffects
- Bismuth maycausea blackdiscoloration ofthe tongue and stool
~ ~:::::tj~:i; t~:~~ired in moderate tosevere renal dysfunction and severe hepatic impairment
- Histamine re/easedfromenterochromaffin-like (ECL) cells in the fundus oflhe stomach by
Gastrin orvaga/parasympatheticstimulation (Acetylcholine)
- H2 receptorantagonists block the actions of histamine at parietalce11Hz receptorsand - MechanismgfAction;
suppressbasa/ and~stimulatedacidsecretion - Active drugs of proton pump inhibitors blocks proton pump by forms a stable covalent bond
- H2 receptorantagonists inhibit60-70%of tota/24-hoursacidsecretion Urreversib/e) withthe H•/K•-ATPaseenzyme
- H2 receptorantagonists havea markedeffect on nocturnalacidsecretion butontya modest - AI least 18 hours are required for resynthesized of new H•/K•-ATPase enzyme, and acid secretion is
effect on meal-stimulated secretion inhibited duringthis time
Th~~a;:~f~ ~;D isease IPUDl: PPis have largely replaced H RAs 2
- Therapeutic!L!u; AII PPis arethe mosteffectiveagents "gold-standard"
1 ) Gastroesophagea i Reflux Disease~) 3) Non-u1cer Dvspepsia
- H2RAs used in Zollinger-EIIIson Syndrome (ZES), ZES is a gastrin-secreting tumor of the 2) PepticUicer Oisease(E!.@ 4) AcuteStress Uicers
pancreas that stimulates the acid-secretingcells ofthe stomach, cause mucosalulceration
2) Gastroesophageal Reflux Disease IGERDl: H2RAs is less efficacious than therapy with
- §ll!JlEffects; PPis are extreme/ysafe.
- Respiratory and Entericlnfections; Gastricacid isan importantbarrier to colonization and infection of
3) Non-ulcerDyspepsia: Commonlyused fordyspepsianotcaused by pepticulcer the stomach and intestine fromingesledbacleria
4)AcuteStress Uicers: IVinfusion (PPis are favor forthis indication) - Long-terms/deeffects; riskforosteoporosis and maycause acuteinterstitialnephritis
- ~Effects ; Cimetidine inhibits binding of Dihydrotestosterone to androgen receptors (Anti· - ~lnteractions ; - Ciopidogrel (antipfate/et)isa prodrug that requires CYP2C19 . fn2009, the FDA i ssueda
androgeniceffect)and increaseserumprolactin , /ongtermuse maycause: public-health warning aboutthe possibleinteraction between Ciopidogrel and Omeprazole
- Preanancv ~ Enoughdata tosuggestthat PPis therapy is safe during pregnancy
-Impotence in male (Anti-androgenic effect). - Gynecomastia in male (Increase prolactin)
- Galactorrhea and amenorrhea infema/e(/ncreaseprolactin)
- fm!g Interactions; Cimetidine inhibits several cytochrome P450 isoenzymes (LME inhibitor) and can
interfere with the metabolism of many other drugs, such as Warfarin and Phenytoin 5) Prostaglandins
- ~ ~ FDAcategoryB
" • • ( C~otec')(Misota c<)

- Patients w~h PUD who are infected with H. pylori require antimicrobial treatment; Amoxicillin, Metronidazole , Tinidazole, Clarithromycin, -It is a PGE1 analogue, with oxytocic properties, it is approved for use in the prevention of NSAID·induced gastric
6) Antimicrobial agents Levofloxacin , Tetracycline and Bismuth ulcers; Off-labeluses: laborinductionandpostpartumbleeding

Antiemetic Agents Antidiarrheal Agents Laxatives

·azt·ne1s);
Phenotht
P.b,A"~'
::::.!!.:.:_: :m:ml~
o.ni~.
·a· . QQ
.tgfj s.
. . . 3)
Antihis tamines
- Used for motion sickness and vertigo (prevent nausea and
Antim~ 1)
mmmmmlJ (Imodium®) ~ (Lomoti~)
I 1) Stimulant (or Irritant) La x at iv es
- Stimulantlaxatives ac.tonth~ intestin~lmucosa ~r en~eric~ervoussystem, a/tering

- :,~~~~~h~i~~~~~n~n:~:~~hr::ro~~~e~;~i~n~r!o~~~~ecde~~:.ugh - a ·Navidoxinee), nmmJ(Emetrextl) and ~ : ~~~n~~tt;;;~~~~~~s~gh~;~}e0:e~~6,~~~!~~~· & children > 2 years . water ani i i l t :sec_re~t~n
anw.;; clw ; •on.. • •
Side effects· Extrapl i i i M I &oms (EPSm ;ivity (Diclegis*) are combinedwithVitamin B6 (Pyridoxine) to control of • Uses; - Short-1m!! relief of acute or interminentconstipation.
-Butyrophe~ones; _ , 1 • 1 , (Haldol*) 1 , 1 _ , , (lna~sinee) nausea and vomiting of pregnancy Qrle). I - Evacuation of the bowel before surgery or colonic examinations .
• Butyrophenones are antipsychotic agents, Antiemetic are mediated I i=============i 2) Antisecretory Age nts ~ Preventionofopioid-induced constipation
through block of D2in CTZ 4) Antimuscarinic I.:Miif.J!!MtitG'lElli (Pepto-Bismol*)
- Sid;:~~~:~~~~:~~~~~~~~7iiiM&ti(~rio:;~:~n - ~ is one ofthe bestagents formotion sickness ~===========~ 2) Bulk Forming Laxative
- :::~~~~~~a:~d~e~i:tede;hro;;;;~~~o~~do~:opamfne antagonist.
- Side effects; extrapyramidal symptoms (EPS)
5 ) Benzodiazepines
- Diazepam, Lorazepam, Alprazolam, Midazolam; /ow potency
~::::.. Ad,;;;;
...' _sorb. e n!. A .n_e. n t s..
(~:r;l]:~~~:i'l!~~;;;;;~;;:l~~-~ "'ii:Bm!!!ll
-Act by absorbs water in the intestines.
1 -Bulk-forming laxatives; absorb water, forming a bulky, emollient gel in the large
intestine ........ waterret~n~on Err@ifnmu..Jttmrl peristalticactivity
_Uses; Intermittent or chronic constipation
- Metoclopramide increases lower esophageal sphincter (LES) tone and - Kaolin-Pectin binds to bacteria and toxic substances in the GlT
improve gastric emptying , can be used in gastroesophageal reflux
6) Corticosteroids ;::::============::::; 3) Osmoti c Lax at iv e s
disease6~~=r b~n1~~:~~~:t~~ti&nM (Motilium*)
0
- ~nd ~re used in prevention 4) Others - Osmotic laxatives; are substances that increasesosmoticpressure, causing fluid
- Domperidone isa peripheral/vdopamineantagonist ofacuteand~nauseaandvo m itinginpatientsreceiving - Lactase; preventbloating, diarrhea, and gas oflactoseintolerance accumulation, colon distension, soft stools, and stimulates a bowel movement.
· S~
;::: id~
ee~
ffe~
cfs~
;.falal
~Q~ T p~ro~
lon~
ga~
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n ======:::; IO=m
=o= hi ~hl~em~et=
der=afe=fv=to!l!JI!!!t
= og=
en=
ic c~he~
mo=th~
era~
py=reg=im='"=
'==] -~~~~hti~~;~~:~:~i~o:::~;;~:~i:~~nction and suppresses the -~·upp. Uses; acuteorintermittentconstipatio.n
~ Uses ; lntermittentandchronic constipation

2) S-HT3:~%Mists ~ n nabinoids - ~i;:e~~~::;~~~~~~n~at~ ~!~es:~:unb~oe~~~~!~~=O:~~ation and

lilli!Ellllll (Zofran• ) · . · • (K~n~) (EM·EX• ) . ~~cer chemothe~!~ ~~~~~)~re nausea and vomiting

~ (AJox~) lllilE!IllZD (Anzemet<)

Gl!l!!!!lB (Navoban&)
11
I. oocusate ;,
6 .~
} .~~~~,~~f~~rf<~ebyr;,,~
P~~g tat ~nd water into
I
~ rokini~ ) Blockers ~================i
- 5-Hll receptorantagonist, used toprevent nauseaandvomitingcaused
by cancer chemotherapy, radiation therapy, surgery, or postoperative
Most common side effects; QT interval prolongation especially (Emend®) · ' · (Akynzeo®)
the stool mass to soften th.e stool (emulsified stool), prophylaxis
ratherthan acutetreatment
I
5) Lubric ant Laxatives
; lllll!l:m
·. •
LD_ot_
as_etr_
on_
and_h~
~-~_se_ s o_
f o_
nd_an_
set_ro_
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nd_Ne_
tu_
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•~_u_sed_fu_
r p_
~_""_oo_gc_IN_
v __~ L-----------------------------~
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬

UTS Drugs for Urologic Disorders

Drugs Used to Treat Erectile Dysfunction
I) Phosphodiesterase Type 5 (PDE5) lnh1b1tors

(Viagrao) - Pharmacoklnetics: -Absorption; rapidlyabsorbed (oral/y) - ~:- UsuaiAdultDoseforErectileOysfunction :

- Mechanism of Action; - Maximum plasma concentrations within 30-120 - 50-100mgorallyonceaday,as needed, 1 hourpriortosexualactivity
minutes - DoseAdjustments(erectiledysfunction)

~~NO
-Geriatric:25mg1hourpriortosexualactivity
-!lJ!.ri!lgsexualstimulation'*Stimulatereleaseofnilric - Metabolism; predominantly by CYP3A4
- Severe renal dysfunction (CrCIIess than 30 mUmin): 25 mg
oxide(NO)inthecorpuscavemosumin thepenis -Excretion; feces (80%) andurine {13%) -Hepaticimpairment(anydegree):25mg

Sti~:~aa~on }
-NO release '* Activate guanylate cyclase (GC) '* 1'
cyclic guanosine monophosphate (cGMP) '* .J.. Ca2·
· Therapeuric!li!!: -Treatmentoferectiledysfunction (EO)
- Treatment of pulmonary arterial hypertension
-With a-blockers or CYP450 3A4 inhibitors (Ketoconazole or Erythromycin): 25 mg
- Contraindication
influx '* Relaxationofbloodvesselssmoothmuscle '* (PAH):Hrelaxesthe arterialwall, leadingtodecreased -lnpatientswhotakingorganicnitritesandnitrates
eii •,. - $<n_. one..... . vasodilatation .,. Erection pulmonary arterialresistance&pressure -Severehepaticimpairmentorsevererenalimpairment
GT\P • ,G;: eoo:ic..'":'"" •..:~::.,•::-~-Ere<tion -Phosp~odie.st.erasetype-.5. respo
cGMP mlo GMP
. nsiblef.ordegra.datio·n. o
f -Hypotension,recentstrokeorheartattack
-Retinaldisorders(geneticdisordersofretinalphosphodiesterases)

jJ
- Mostcommon adverseeffects
- Sildenafil lsaselectlvephosphodlesterasetype-5 - ffM~
-Headache,flushing,dyspepsia, abnormalvision, nasalcongestion, -Patientsshouldstop Sildenafil ifa suddenlossofvision occurs inone or botheyes,
...... (PDE5)1nhlbltor '* accumulallonofcGMP .,. Erect1on
... ~ - Sildenafil hasnoeffectmabsenceofsexualsllmulatlon
back pain, myalgia, nausea,dizziness and rash
- Abnormal vision:due toinhibitionof PDE-6
whichcouldbeasignofnonarteriticanteriorischemicopticneuropathy(NAION)
GMP ~ -Patientsshouldstop SIIdenafil intheeventofsuddendecreaseorlossofhearing

(Cialis*) l'o'\!EIIE!iii (Stendra• ) 2) Prostaglandin Analogues

- Vardenafil and Tadalafil areselectivePDE-5inhibitorsusedforerectiledysfunclioo - Avanafil isaselectiveisaPDE5inhibitorapprovedfor
-Structurally Vardenafil issimilarto Sildenafil,while Tadalafil isverydifferent erectiledysfunctionbyFDAonApril27 , 2012
~ (Cave~ecf®)
- Vardenafil ismaybeeffective inthetreatmentofprematureejaculation!! - Onset of action: 15minutes( Fas~ - Alprostadil is a prostaglandin E, (PGE1) analogue used in male erectile dysfunction (second-line therapy if PDE-5 inhibitors tam, increases cAMP
- Tadalafil used for in treatment of pulmonary arterial hypertension and symptoms of benign - Durationofaction:upto6hours - smooth muscle relaxation
prostatichyperplasla(BPH) - Dosageform: Tablels:50, 100&200mg - Dosage form :- MUSEfl penile suppository; 125-1000 meg inserted into the urethra.- Cave~ect®; 2.5-40 meg injected directly into corpus cavernosum
- Vardenafil ismoreselectivethan Sildenafil and Tadalafil toPDE-5 - Onsetofact/on:5-10minutes
- Sideeffects sameas Sildenafil - Commonsideeffects: penilepain {p/aceofinjection)or urethralpain (suppositoryon/y), priapism and hypotension
~i'ij#n !Mi#"W-d@Mn
FDAapprovaldate March27, 1998 Augus\19, 2003 No...ember21,2003

Oosageform
2
5mg,=g~t00mg 2
.5mg,~b~~,20mg 5mg,10mg,20mgtablets Female Viagra (Pink Pill) Drugs Used in Nocturnal Enuresis
Efficacy 82-84% 80%
(Addy~)
25minutes(effectdelayed
by latty meal)
1645minutes(eHectNOT
dOOyedbyfood) - Fiibanserin isthe firstmedicationapproved (August, 2015)forthetreatment of HypoactiveSexual Desire
1) Vasopressin Analogues
Disorder (HSDD) in pre-menopausal women - Desmopressin is a synthetic replacement for antidiuretic hormone (ADH) or vasopressin,
10mg, maybeadjusted
10mg,maybeadjustedto201D'J thehormonethalreducesurineproductionduringsleep
to20mg - Fiibanserin was originally deve/opedasan antidepressant, before being using for HSDO. - Desmopressin isthe first-/inetreatment for enuresis in childreno/derthan5years
4to5hours - Fiibanserin isa multifunctiona/serotoninagonistantagonist (MSAA)
-~=t~:;ectivealterhigh-

ro
- Mechanism~action ;
-Lessetrectiveafterhigh- -Workswithoutregardlowhat
fat meal • Moderate-fat mea~ not
- Fiibanserin he/psrestorerebalancing of neurotransmitters that inffuencesexualdesire 2) Anticholinergic Agents
redi.ICeeffectiveness "' - F1ibanserin actas 5-HT,.., agonist and 5-HTv. antagonist - increases Dopamine and Norepinephrine - Such as Oxybutynin in a dose of 2.5-5 mg administered at bedtime, may be used in
(bothresponsibleforsexual excitement) and decreasing Serolonin (responsibleforsexual inhibition)
Mostcommonside Facialflushing,l\eadache, combinationwith Desmopressin to increasebladdercapacity duringsleep
Fadalflushing,headache Headache, indigestion - QQu; 100 mg orally once per day at bedtime (discontinue after 8 weeks if no response)
effects indigestion

E
s.....
l esscommon slde
effects

high-fat meal
AJ.eredvision,dizziness,
nasalcongestion
Indigestion, nausea,
dizziness, nasal
congestion
Backpain, muscleaches, nasal
coogest~~=~ftushing,

Vardenafil is alsoavai/ab/e inorally disintegratingtablet (ODT)formu/alion; notaffectedbya

- MQgcommon§isl!effects; dizziness, nausea, fatigue, sedation orinsomn iaand hypotension

- Fiibanserin and Aicohol intakeincreases the risk ofseverehypotension and syncope

- Contraindicated withstrongormoderate CYP3A41nhibitors.
- Contraindicated inpatienlswith hepatic impairment
3) Tricyclic Antidepressants
- lmipramine is usedmostoften inthe treatment of enuresis; decrease the amount of sleep,
re/ax the detrusormuscle (anti-muscarinic) and stimu/atevasopressinsecretion

ro Drugs used in Benign Prostatic Hyperplasia (BPH)

...c 1) at-Receptor Antagonists

(Minipress®)~ (Cardura®) lll!mmi (Hytrin®)
2Jjm<g;~eductase Inhibitors
.·o· (ProscarfJ) ~ ·(Avoda~)
3) Phosphodiesterase

a...
•
Type-5 (PDE5) Inhibitors
E!Il!lm!lll (Xatra~) llll!ll!l!lm (Fiomax®) llllll!m (Rapaflo") - Finasteride and Dutasteride area 5-a-reductasefnhfb/tors
-They are inhibits 5a-reductaseenzyme which convert Testosterone intothe morepotent
- Prazosin , Doxazosin and Terazosin arearum,-~ se/ectivea , blocker ; actsonbloodvessels (lowerbloodpressure)and prostate (relax - Tadalafil are selective PDE-5 inhibitors used for Erectile
androgen Dihydrotestostero'ne - reduction in prostatesize with improve in urinaryflow Dysfunctionanditis approvedfor use in BPH in 2011 or both
prostateandurethramusclesandrelaxbladderneck), usedin symptomsofBPH (LUTS)and hypertension
- Mostbeneficial ; in men wdh prostates/argerthan40g BPH and ErectileDysfunction
- Aifuzosin isa ~ se/ectivea1 blocker inthe prostate and bladder, approvedon/y for symptoms ofBPH , not indicated for hypertension - Onsetofbenefits;approximately 6months of therapy isrequiredto achieveclinicalbenefit
- Tamsulosin and Silodosin a rea ~ se/ectivea, blocker thathas preferential se/ectivity forthe a, A receptor inthe prostate versusthe a,s - Mechanism (exact mechanism unknown); is thought to be
- Doses; Finasteride;5mgdaily. - Dutasteride; 0.5mgdaily
receptorinthe bloodvesselsapprovedon/y for symptoms of BPH {LUTS), notindicated for the treatment of hypertension caused by phosphodiesterase-induced smooth muscle
- A//a-blockers can cause orthostatichypotension (non-sPecific»>specific); Therapywith non-specificagentsshou/d beginata lowdose and Side~~~:~"~~~~=; ~~%c&;mr:~'nw~~~::~:~~~~~i~~~art®) relaxation inthe bladder, urethra and prostate

23
•
thenbe titratedupward. Sildenafil (or otherPDE-5)indoses> 25mgshouldnotbetaken withinfourhours of a-blockeruse - Doses; 5 mg once daily. Combination of ladalafil and a,-
- /tcontains;Tamsulosin 0.4mg+ Dutasteride 0.5mg blockers is a risk of hypotension Q!!! ~ can safe in proper
-AI/a-blockers can causeejaculationchanges, headaches, nasalcongestion &weakness. Patientstaking Tamsulosin arepronetoa complication
known as floppyirissyndrome during cataractsurgery, shou/davoiduntiltheircataractsurgeryiscompleted. - /ndications; severesymptoms of BPH whoa/sohavean enlargedprostate /argerthan40g instructions
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Asthma and Chronic Obstruc ti ve Pulmonary D1sea se (COPD) Medic ations
- The Pragonists arethe mosteffectivebronchodilators availab/e.
- /ngenera/ activation of jb-adrenergicreceptors <r
- Smoothmuscles; bronchodilatation and uterinemusclere/axation
- Skeletalmuscles; vasodilatation and tremOI"s
- Heart; heartmusclecontraction
- Mastcells; inhlbition of mast celldegranu/ation
- Metabolic;glycogenolysis, gluconeogenesis, lipolysis,hypokalemia and increaselactate
- Side Effects; Tremor, Tachycardia, Hypokalemia, Hypomagnesemia and Hyperglycemia
2) Cort1costero1ds
- Benefits of cortlcosterolds in asthma;
1) /ncreasingnumber and sensitivity of jhreceptors.
2) Reducingmucusproduction and hypersecretion.
3) Reducingairwayedemaand exudation
4) Reducingbronchialhyperresponsiveness (BHR).
- Mechanlsms of cortlcosterolds in asthma;
- Suppress several proinflammatory cytokines - reducing inflammatory cell activation
andinfiltration - decreasingvascularpermeability
-Reducingproduction of leukotrienes by inhibitingphospholipaseA2
· Preventaction of proinflammatorycytokines onfhe cell
-/ncreasei32Receptordensity (wahin 4hoursofcorticosteroidadministration)and improve
responsiveness of ~2-agonists (within2hoursofcorticosteroidadministration) .
-Revera - l l i l 1 i i i wt lmemm
~ (HostacortinOI ~ IHostacortin-H')
~ (Solu-Medrote)
- Prednisone isa prodrug which converted via/ivermefabo/ismto Prednisolone {active)
- Olli are used jMiQijif.H;,Mii@MJG~#i.ili!~ijnplsodes.
j:@@@l;m::ti1i1'1 (0VARe) ~ (Fiovente)(Fi ixotidee)
~ (Asmanexe) l!l.!liiDmi (PulmicorteFiexhaler) (Miftooidee)
llm!iil!lil!lli iAzmacorl') lil!lill!!llm iAerospanO)
- ICS are the tiJ:sLiinj~ for long- termcontrol anydegree of perslstentasthma
- ICSaregivenas /ong-term to avoidadrenalinsufficiency, lwl highdoses of iCS maycause
adrenalsuppression. -
- Onset of improvement, 5-7 days (additional benefit may occur over several weeks)
- ICS have few systemic side effects (consider Calcium and Vitamin D supplements in adults,
particular1yinpremenopausalwomen)
- ICS ioca/ sldeeffects;duetoiCSdeposition on the oral and laryngealmucosa cancause;
1) 0ropharyngealcandidiasis(Thrush); duetolocalimmunesuppression
2) Hoarseness {Dysphonia);duetomyopalhyof thevocalcords
••• Patients should be gargle water and spi~ after each inhaled treatment to decrease the
chance ofthese localadverseevents
llili!DI!lll (AJvesco')
- Ciclesonlde is recent/yapprovediCS asa prodrug activatedbyesterases in lung to form its
activemetabolite (Desclclesonide)
- Because itis notactivateduntil it reaches the lung , Ciclesonide ~ fewerlocalside
effects
- Desciclesonide is tightlybound to plasmaproteins, andsohas fittleaccess to glucocorticoid
receptors in skin, eye and bone, minimizing its risk ofcausing systemicsideeffects.
3) Ant1chol1nerg1cs
-The anticholinergicagents blockvagally medialed contraction of airwaysmoothmuscle and
mucus secretion
- Side effects; Headache, flu~hed skin, blurred vision and tachycardia
smzm:mmml (Atrovente)
- lpratropium is a non-selective muscarinic receptor blocker. quaternary ammonium
derivatives (notcross888)
- lndications; Off-labei; Acutesevereasthma in patientsnotresponsive to !l2-agonlstsa/one.
Approved; Chronic Obstructive Pulmonary Disease (COPD)
~ (Spirivae Respimat)
- Tlotroplum is a selective muscarinic receptor blocker (mainly on M3), used in management
of COPD.
Respiratory Drugs
1) ~ 7 -ad renoceptor Agon1st s
12 hours
4) Leukotnene Mod1f1ers
r'----'---------,----,-------,--,------------,---,-----,----, j
- leukotrienes (l Ts) result from the action of5-lipoxygenase enzyme 2!1. arachidonic acid
- Bronchospasm occur bout 10% of people taking NSAIDs, because of a shift in
arac~ lE15j; ~
emm::!IIJ (Accolatee) ~ (Si ngulai re)
- Zafirlukast and Montelukast are se/ectiveantagonists ofthe leukotrienereceptors
- Zafirlukast and Montelukast used for the prophylaxis and chronic treatment of asthma
- Montelukast Mll!f. In exercise-Induced bronchospasm and allergic rtlinltls
~andPrecautions; Neuropsychiatricevents , Churg -Strausssyndrome
- Hepatotoxicity with Zafirlukast only (monitor symptoms)
- Qnig /nteractlonsQdMiili&li~£jij';I3~;Z@firlukast only.
~ (Zyflofl)
- ~andPrecautions ; Neuropsychiatricevents , Churg -Strausssyndrome
- Hepatotoxicity (monitor liver Function Tests)
- !ln!ginteractions; Warfarin , Propranolol and Theophylllne.
6) Monoclonal Ant1body
IIDI!l!lill!lli iXolair&l
- Omalizumab is a recombinant anti-lgE (human immunoglobulin E) antibody approved
for the treatment of allergicasthmanotwellcontrol/ed on oralcortlcosteroids or iCSs
- Mechanism Qf action; Omalizumab decrease binding of lgE to its receptor on the surface
ofmastcells and basophils
- §1M effects; Injection site reactions (urticaria, thrombocytopenia, malignancy & rare
anaphylaxis) · 8) Phosphodiesterase-4 (PDE4) 1nh1b1tors
- ~ {Daxase)(Dalirespe); isa phosphodiesterase-4/nhibitor, is an anti-inflammatory, notbronchodilator, reducelhe risk of COPDexacerbations in patients with severe COPD associated with chronic
bronchitis anda historyofexacerbations . ~; 500mcgorallyoncedai/y.
- §1M effects; Diarrhea, weight loss (monitoring body weight) or decreased appetite, nausea, headache, back pain, influenza. insomnia and dizziness
Allerqic Rhinitis (AR) Medicat1ons
I"""""~
- INCs are lhe drugsofchoice fortreatmenl ofmoderate tosevereallergicrhinitis.
- Affoft1Jeseagentsreduce; 1)sneezingf)itching~) rhinorrhea!)congestion
- ~ on/y Budesonide hasa categoryB and otiJers are categoryC
- Local~effects ; throatinitation , epistaxis, sti nging , burning and nasaldryness
- ~!fM.effects ; No or fimitedeffects on Hypothalamic-pituitary-adrenai(HPA )
axis suppressionanddecreasedverticalgrowth of children [allinb'anasal
corticosteroidscarry a warning that /ong-tennuse may restrictgrowthin children]
- SABA .shaulJ:L.Ils. used for acute asthma for symptomatic treatment of bronchospasm , providing quick relief of
acutebronchoconstrlctlon
- LABAshmillf..niH usefor acuteasthma
- LABAUSBII....fJJ! prevention (suchas; nocturnalasthma or exercise-inducedasthma)
- LABA awst..bB used in chronic asthma in combination with another long-term asthma-control medicine (e.g
lnhaledCorticosteroids (ICS)suchas fluticasone and budesonide); to prevent ASIH.MA-RE..L.AIE..D...
- LABA in COPD; ~ used as mono-therapy g£in combination w~h CorticosteroidS _ _ _
5) Methylxanth1nes
- The 3important methylxanthines are Theophylline, Theobromine and Caffeine
- Aminophylline is a Theophylline complex with Ethylenediamine is less potent and shorter-acting. Aminophylline
isthe pteferredinjectableproduct cmingto increasedsolubility.
- Mechanism Qf actions; Methylxanthines have several mechanisms, the main mechanisms are;
1) Inhibits phosphodiesterase enzyme - increase cyclic adenosine monophosphate (cAMP);
; !)smooth muscle - relaxation (bronchodilatation). -In cardiac muscle - contraction (increase heart
2) 8/ockadenosinereceptors; -ln heart - increaseheartrate. - /n brain - Stimulant effect
- Methylxanthines havebeenusedfor asthma for morethan50years, buttheir usein recentyears has dec/ined
markedly owing to the high risk of severe life-threatening toxicity and numerous drug interactions, as well as
decreased efficacy compared with ICSs and lABAs
~ (Quibroo@l)
- Theophylline is a methy/xanthfne bronchodilator agent
~ ~~:~~~~:::~: ~:~::::b~~~o~:~~~~:::;~~a~~~~n:,:~~~i~~~ decreases its symptoms.
- ~effects; at therapeuticlevels ; lnsomnia, Giupset and agitation
- ~ at high levels: Nausea, vomiting , CNSstimulation, headache, cardiacarrhythmias and seizures
- fJD!R. interactions ; Theophylline is metabolized in the liver by CYP1A2 and CYP3A4; It is subject to numerous drug
interactions; suchas Ketoconazole, Cimetidine and Erythromycin (increase Theophylline therapeuticeffect)
7) Mast Cel l Stabilizers
- Mast Cell Stabilizers act by stabilize the mast cell membrane, and inhibit the activation and release of mediators
~ (lntaJfl) l:@rmttmfi1 ..1WM (Tiladee)
- Cromolyn and Nedocromil are mastcellstabi/izers, widelyusedas eyedrops in allergicconjunctivitis, andthey
are used as inhaled anti-inflammatory agent for the prophylaxis and management of asthma
I'=== = ===================='
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Antimicrobial Agents
Antibiotic Introduction

M ICrObiOlogy • Classification of Antibiotics According to Mechanism of Actlon:-

Bacterial Cell Wall Classification of
- There are two main types of bacterial cell walls; gram-positive bacteria and gram-negative bacteria; Bacteria
- Grampositive bacteria ; ~ of peptidoglycan {about 90% ofcellwall ) - According to Gram Stain;
- Gram negative bacteria ~of peptidoglycan ( about 10% ofcellwall) ' Gram-positive;
! Gram-Positive j I
GrMt-Negative ( - Cocci~ ;
Staphylococcusspp
Streptococcusspp
Enterococcusspp
-Bacilli(~
Non-SporeForming(Aerobic)
Corynebacteriumspp
Erysipelothrixspp.
ListeriaandNocardiaspp
Non-SporeForming(Anaerobic)
Propionibacteriumspp
Actinomycesspp
Lactobaci/Jusspp
Peptostreptococcusspp
Bifidobacteriumspp
Mobiluncusspp
Spore-forming(Aerobic)
Bacil/usspp
Sporeforming(Anaerobic)
C/ostridium spp
• Gram-negative;
- Cocci
Neisseriagonorrtloeae
Neisseriameningitidis
- Peptidoglycan; -Bacilli~
- N-.eetylg luco..mlne(NAG) Escherichia coli
- N--.:•tylmu,.m lcacid(NAM) Vibriocholerae
Klebsiel/aspp
~ Skfe.clulln•mlno acld
Sa/mone/la spp
g Cro. .-brldge•mlno acld
Shigellaspp
Proteusspp
Pseuclomonasaeruginosa
He/icobacter pylori
Legionellapneumophila
Haemophilusinfluenza
Brucellaspp
Bordetellapertussis
• Atypical (Bacteria that do not
color with gram-staining);
Chlamydia
Mycoplasma
Rickettsia
• Mycobacteria (Mycobacteria a
genusof rod-shapedacid-fast
bacteria having twoslgnificant
pathogenic species);
Mycobacteriumleprae
Mycobacterium tuberculosis
1) Agents that inhibit cell wall synthesis or repair.
2) Agents that disruption of cell membrane functions .
Definitions 3) Agents that inhibit protein synthesis
· ~~ {basedonexperience); 4) Agents that inhibit of nucleic acid synthesis .
Initial or Blind or Umbrella or Empirical 5) Agents that act as antimetabolite.
therapy refersto the treatment ofan infection
withoutknowing the causativepathogen
* Definitive~ (Pathogen-specrlic); once
the infecting organisms has been identified,
the specific antibiotic should be narrow
spectrum to;
1) Reducecost
2) Reducetoxicity
3) Preventantimicrobialresistance
• Prophylactic !b!@Qy; Administration of
antimicrobials in absence of a known
infection, to decrease the risk of infection
• Bacteriostatic; A drug that inhibits growth
and replieation ofa bacteriawithoutkillingit
-Example; Sulfonamides, Tetracyclines and
Macrolides, act by inhibiting protein
synthesis
• Minimum~Concentration (Mig;
is the minimum concentration of drug which
ca n inhibit the ~ ofthe microorganism
• Bactericidal; A drug that directly kills a
bacteria. Example; Drugs thatprimarily acton
the cell wall (e.g. ; ~-lactams ), cell membrane
(e.g.; Daptomycin), or bacteri al DNA (e.g.;
Fluoroquinolones)
• Minimum Bactericidal Concentration
~; is the minimumconcentration of drug
which can!!1J1themicroorganism
• Narrow-~; Chemotherapeutic
agents actingonfy ona single or a limited
group of microorganisms. For example;
Isoniazid is active only against
Mycobacterium tuberculosis
• Extended -~; Antibiotics that are
modifiedto be effectiveagainstgram+ve and
also againstasignificantnumber of gram -ve
bacteria. For example; Ampicillin or
Amoxicillin isconsideredto havean extended
spectrumbecause it actsagainstgram+ve &
sornegram-ve
• Broad-~ ; Antibiotics that affect a
wide variety of microbial species. For
example; Ampicillin or Amoxicillin + ~­
lactamase Inhibitor, Tetracycline ,
Fluoroqulnolones and Carbapenems

Antimicrobial Resistance
-Antimicrobialresistance is the abilityofamicrobe to resist the effects of
antimicrobialprevious/yusedto treatthem
- MechanfsmofBacteria/Reslstance;
• Enzymatic inactivation; e.g. ~-lactamase enzyme (Penicillinase) which inactivate
• Peptidoglycan is made up of a polysaccharide backbone consisting of alternating N-Acetylmuramic acid (NAM) Penicillin by hydro/ysis of ~ - lactam ring
and N-Acetylglucosamlne (NAG) residues in equal amounts • lmpermeabilitv to antibiotic; Many antibiotics enter the cell through protein
-Peptidoglycanis responsib/efor the rigidity ofthe bacterialcellwall and for cellshape channels called 'Porin" absenceor mutation orloss ofaporinschannel can slow
- Penicillin-bindingproteins {PBPs) area norma/constituent of manybacteria,whichare essentialforfinai the rate ofdrug entry into acell or prevententry
• Efflux; Bacteriaalsohave effluxpumps thatcan transportdrugsout of the cell - Superinfection is asecondinfectionsuperimposed on afirstinfection
stage of bacteriaicell wallsynthesis (formthe bondsbetweenoiigopeptidecrosslinks in peptidogiycan) -Superinfection occur after using broad-spectrum antibiotic, this antibiotic alter the normal
• Mutation;is a change inthe DNAthat cansometimescause;
- PBPs are members ofa subgroup of enzymescal/ed Transpeptidases - Decreaseaffinity of targetenzyme bacterialflora and cause an imbalance of the flora
- Some antibiotics such as Penicillins and Cephalosporines interfere w~h the production of peptidoglycan by - Alterationoftargetsite - Example; Overgrowth of endogenous Clostridium difficile which occurs following
bindingto penicillin-blndingproteinsenzymes (Transpeptldasesenzymes) - Overproduction o! targetsite or metabolite treatment witha broad-spectrumantibiotic
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Il l) Monobactams N on-~- l actam Ce ll Wall lnh1b1tors
Bmm!iiiAzactam')
- Monobactams are {J-Iactam antibiotics wherein the ~-lactam ring is alone lmonocyclic P-lactam) and not fused to another ring, in
contrast to most other ~-l actams . Aztreonam, is the only commercially available monobactam
-It has antimicrobial~ primarily agains( Gram -ve, including Enterobacteriaceae and Pseudomonas aeruginosa (similar to
that 3 111 generationcephalosporins ). lt ~activity against Gram+veoranaerobes
-It ~ to treat serious infections such as pneumonia , meningitis, and sepsis caused by susceptible Gram -ve in patients with
hypersensiti vityto penicillins(NO cross-hypersensitivity). ~f!m!!J (Cayston•)is approved forcysticfibrosis -
I) Glycopep tide Antibio tiCS

- Vancomycin is activeg against Gram+ve bacteria ; ~effective against

Gram-ve; poorlypenetratephospholipidmembrane
- Vancomycin is notabsorbed after oral administration
II ) Othe rs
- (Monuri~)(Monuro~)
- Fosfomycin (Phosphomycin or Phosphonomycin ) is a broad-spectrum
antibiotic (against many Gram +ve and Gram -ve)
- Fosfomycin is /ndicated inthe treatment ofurinarytractinfections(UTis),asa

- FIRSHJNE for,
1) rt; complicated skin infections, bacteraemia, endocarditis, bone and joint
lnfectlons,andmeningitis ~ Methicillin-resistantStaphylococcus
IV) Carbape ne ms aureus (MRSA) & Methicillin-resistant Staphylococcus epidermidis (MRSE)
2) Qr!!; Pseudomembranous colitis ~ Clostridium difficile (Qr!!
~;notabsorbedalld Vancomycin act locally)
$111D.!§.!§u!Irii@Ujiirtj (Tienam•) - Mechanismofaction; Vancomycin /nhfbitscellwallsynthesis by binding firmly
~(Meronem•)~(Doribax8) ~ (1nvanzfl) emmmA:ii (Orapenem 8) to the 0-alanyi-D-alanine (0-Aia-D-Aia) in peptidoglycan, preventing further
- Carbapenems ares tructural/yrelated to ~ -lactamantibiotics elongation of peptidog/ycan andcross-/inking. The peptidoglycan isthus
-Theyexhibita broaderspectrum of activity comparedto Cephalosporins and Penicillins weakened,andthe cellbecomessusceptibleto lysis
- Vancomycin-resistant Staphylococcus aureus {VRSA); are a strains of
- Carbapenems in general have seizurerisk in highdoses
enterococci resist Vancomycin by modification of the 0-Aia-D-Aia binding site
- Most common side effects (more common with lmipenem); nausea, vomiting, diarrhea, skin rashes, and infusion site reactions. - Side Effects;
- Renal failure; Doses tnJW be adjusted (may lead to ~); Meropenem, Doripenem, and Ertapenem are much less likely to -Red Man Syndrome (RMS) or Red Neck; infusion reaction; usually appearing
cause seizuresthan liliTPenem -- rapidly after infusion. Non-specific mast cell degranulation ..... release of
· lmipenem is compounded !!l111 Cilastatin to protect it from metabolism by renal dehydropeptidase; Histamine - Redness and hotness in face and neck
- lmipenem is rapidly degraded by the Dehydropeptidase (Dipeptides) renal enzyme when administered alone - Nephrotoxicityand0totoxicity; increases thetoxicity of Q1hBrnephrotoxins
(Nephrotoxic Metabolite) or ototoxins suchas Aminoglycosides - usedONLY asa secondline intreattuberculosis.
- Co-administered with Cilastatin (Dehydropeptidase enzyme inhibitors)¢ Prevent this inactivation (prevents - (Targocid')- - ('jbativ<)
formation of toxicmetabolite and increaseurinaryconcentration). Telavancin is potentia//yteratogenlc ,and ~~ mustbe confirmed
- Spectrum of activity, aerobic and anaerobic, Gram +ve and Gram -ve including Pseudomonas (Except Ertapenem is !!Ql active - (Dalvance')(Xydalba')- - (Orbacliv")
agalnst, Pseudomonas , AcinetobacterandEnterococci).
Dalbavancin and Oritavancin ; Once-weekly iVdosing (singledose)
-
singleoralmegadose
• Mechanism , It blocks cell wall synthesis by inhibiting UDP-N-
acetylglucosamine enolpyruvyl transferase enzyme, which
cata/yzesthe firststepin peptidoglycansynthesis
- ~ ; active against Gram +ve bacteria (high molecular weight; poorly
penetrate Gram-ve phospholipidmembrane and poorlyabsorbed)
- Mechanism ; Bacitracin Inhibits cell wall synthesis by interfering with
dephosphory/ation incycling ofthe lipidcarrier that transferspeptidoglycan
subunitstothe growingcellwall
- Bacitracin is highly nephrotoxic when administered systemically and is ONLY
used topically
- (Seromycinfl)
- ~; Cycloserine inhibitsmany Gram+ve and Gram-ve bacteria,ll!tl itis
- Mechanism ; Cycloserine isa structura/analog of D-alanineandinhibitsthe
incorporation of D-alanineintopeptidoglycanpentapeptide
- Cycloserine causes seriousdose-related CNStoxicity; headaches , tremors.
acutepsychosisandconvulsions

- ~; ~tl,!,1t'liii'biG1IDBfii)i; - Polymyxins inhibitmanyimportant Gram-ve bacteria; includingPseudomonasaeruginosa, Escherichiacoli,Kiebsie/lapneumoniae,Acinetobacterspecies,and EnterobacterspeCies

- Polymyxins are re/atively neurotoxicand nephrotoxic,soareusually used ONLY asa /ast resortin treating infectionscausedby multipledrug-resistant bacteria
B) Cell Membrane
- ~;~is used inthetreatmentofsystemic and /ife..threateninginfections causedbyGram+ve bacteria. ~; S/mi/arto Vancomycin , ll!tl morerapidly bactericidaland activeagainst Vancomycin-resistant strains ofenferococci
Disruption Antibiotics (VRE) and Streptococcus au reus {VRSA). Mechanism ; Daptomycin binds to cell membrane via calcium-dependent insertion of ~s lipid tail. This results in depolarization of the cell membrane with potassium efflux and rapid cell death
. Myopathy and rhabdomyolysis have been reported in patients simultaneously taking statins; thereby statins should be temporarily discontinued while the patient is receiving Daptomycin therapy.

C) Protein Synthesis Inhibitors

- Bacterial cell (Prokaryotic) have a 70S ribosome (50S large subunit & 30S small subunit), but human cell (Eukaryotic) have a 80S ribosome (60S large subunit & 40S small subunit). Prokaryotic and Eukaryotic have a different structure to ribosomes so can use antibiotics for selective toxicity.

Tetracyclines Glyc ylc yclines

-:lltD!mmi (Sumycinfi)~(Terramycinfl); are rarelyusednow ~(Tygaci~)
Affected by food; chelation with metals e.g. Ca, Mg, Fe and AI (tooth bleaching). Fanconi Syndrome; nephrotoxic metabolite - Giycylcyclines area newc/ass of antibioticsderivedfrom Tetracyclines.
DJiiiii!I'MDlli!ifi&ijj;~ (Vibramycin®)~ (Minoin®); are common Tetracyclines used - Tigecycline primary excreted via biliarylfaecal ~ dose adjustments in patients with renal impairment).
Less chelation. Notcause toothbleaching. Absence of nephrotoxicmetabolite - They are specifiCally designed to overcome 2 common mechanisms of Tetracyclines resistance ;! ) Efflux pumps andlor Z.) Ribosomal protection .
- Pharmacokinetics ; - ~ ;- Broad~~ inc/udingthose of multi-drugresistance ; Methicillin-resistantStaphylococcusaureus(MRSA) , Vancomycin -

- Tetracyclines chelate cations, and their oral bioavailability is decreased significantly when administered with Calcium, Iron, Antacids , or Multivitamins resistant strains of enterococci (VRE), P-lactamase-producing Gram -ve bacteria and many anaerobic organisms
- Doxycycline alld Minocycline are available as oral and IV. Only Doxycycline and Minocycline achieve therapeutic levels in the cerebrospinal fluid (CSF). -lim active against; P.roteus, f!.rovidencia or f!.seudomonas species (due to; it contains chromosomal efflux pumps}
- Minocycline reaches veryhigh concentrations in tears & saliva, makes it useful foreradicationofmeningococcalcarrierstate
- Tetracycline iseliminatedrenallyand shou/dnot be used in renalinsufficiency
- Doxycycline doesn't need doseadjustment in renal or hepaticdysfunction
- Mechanism; Bacteriostatic; Tetracycllnes enter susceptible organisms via passivediffusion andalsobyanenergy-dependent of activetransport
Oxa zolidinones
- Tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome and prevents binding of !RNA to the mRNA-ribosome complex, thereby
inhibitingbacterialproteinsynthesis. I!EmJ (Zyvox8)(Averozolidtl)mmmJ(Sivextro®)
- Indications; Gram +ve and Gram -ve bacteria, protozoa, spirochetes, mycobacteria, and atypical species; - Linezolid isa syntheticoxazolidinone deve/oped tocombat resistant Gram+ve strains,suchas;
. High effective against (Drug of choice); Rickettsia infections, Mycoplasma pneumonia, Chlamydia! infections, Lyme disease, Cholera and Brucellosis - Methicillin-resistant Staphylococcus aureus (MRSA). • Vancomycin-resistant Streptococcus aureus (VRSA).
. Also effective against, Acne vulgaris. Acne rosacea, Syphilis, Anthrax, Plague, He/icobacter pylori, Malaria and Filariasis - Vancomycin-resistantenterococci(VRE) - Penicillin-resistantstreptococci
- Demeclocycline ( Declom~ci nfl) inhibits the action of antidiuretic hormone (ADH) in the renal tubule and has been used in the treatment of Syndrome of - Mechanism ; Linezolid binds to the bacterial 235 ribosomal RNA of the 50S subunit, thereby inhibiting the formation of the 70S initiation complex
Inappropriate Antidiuretic Hormone (SIADH) (Hyponatremia) - Resistance; by mutation ofthe Linezotid binding site on 235 ribosomal RNA.

-~Effects; ~=:~::~~:i;i:~~~;.;e;:~~!!!~h~aand
norexia,
effectnausea, vomitinginchildrenlessthan8years
on bonegrowth and diarrhea andfetusduringpregnancy
- ~ ; Linezolid iseffectiveaga i nst allimportant Gram+ve
- ~effects ; · MQ!!~; Giupset , nausea , diarrhea , headache and rash
articularlywith Minocycline · Hematologic (re versible and generally mild); due to bone marrow suppression (related to Linezotid-induced inhibition of
. Photosensitivity; Severe sunburn may occur and more frequently w~h Tetracycline and Demeclocycline mitochondrialproteinsynthesis);· MSl.§lf2!l!!WU!; Thrombocytopenia(main/yoccurif used longerthan 10days)
- Hepatotoxicity; rare,!;M fatal ;mayoccur withhighiVdoses, particular/y in pregnancy or patientshepatic or renaldysfunction - Anemia and neutropenia maya/sooccur.
• Renal Toxicity (except Doxycycline); Acidosis and azotaemia; particularly in patients with impaired kidney function - Qtt!.m; Serotoninsyndrome (Linezolid possesses non-se/ectivemonoamineoxidaselnhibitor)optic andperipheratneuropathy
-Fanconisyndrome; expiredTetracyclines ; convertedlo 4-Epitetracycline &Anhydrotetracycline which damageproximaltubule (irreversible andmainlyoccur if used /ongerlhan 28days)and tacticacidosis(dueto mitochondrialtoxicity andmain/yoccur
- Pseudotumorcerebri; rare; benign, intracranialhypertension (headache and blurredvision)mayoccur. if used longerlhan severalmonths)
- Contraindications ;- Chlldren/essthanByear .- Pregnancy ~ ; CategoryD ) - fm!a~; Monoamine Oxidase lnhibitors (MAOts)andother Serotonerg.ic Drugs
--------------------~
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Aminoglycos1des Macrol1des

ll!IBimDIED.iBI!!m!ii (Amikin*) "(Garamycin&) •• . (Tobrex®)

- Aminoglycosides are used most widely in combination with a P-lactams in serious infections with Gram -ve bacteria, in combination with
Vancomycin or a P-lactams for Gram +ve endocarditis, and for treatment of tuberculosis
- Absorotion; absorbed ~ poorly from GIT (polycationic), and almost the entire oral dose is excreted in feces after oral administration
- AI/Aminoglycosides ~ Neomycin ; due to severe nephrotoxicity ) !!!!!!!~ given parenterally (IM or IV infusion)
-Qui Aminoglycosides such as Neomycin can be used for preoperative bowel preparation and for hepatic encephalopathy or hepatic coma
- ~-~~ ; - Aminoglycosides have concentration~!!l1Ji.!1g {spectrum and bactericidaleffectdependingon their concentration )
-T hey also havea significant ~-antibioticeffect ( continuedsuppression of bacterialgrowthafterremoval ofthis agent)
· fxcretion: Morethan90% ofthe parenteral aminoglycosides are excretedunchanged inthe urine
- Mechanism ; Bactericidal (concentration deoendent1 ; Aminoglycosides enter susceptible organisms by passive diffusion via porin channels, and
then activelytransportedacross the cellmembraneintothecytoplasmby an oxygen-dependentprocess; Anaerobicbacteria such
as Bacteroidesfragilis are innatelyresistant
- Bacterial Resistance;
1) Enzymatic Inactivation; production of a transferase enzyme or enzymes inactivates the Aminoglycoside by adeny/ylation, acetylation,
or phosphorylation (Amikacin is lessvulnerable to theseenzymes)
f ) lmpairedentrv ; mutation or deletion ofa porins or proteinsinvo/ved in transport oralteration in oxygen-dependenttransportprocess
- Erythromycin, Clarithromycin and Azithromycin are the !!!Q!! fQ!ll!!1Qfl. Macrolides
- Spir~mycin has Antiparasitic activity (Antipl-otozoal) and it is used to treat toxoplasmosis during pregnancy
- Pharmacokinetics ;
- Erythromycinbase is destroyedby gastricacid and mustbegiven aseither enteric-coated or more-stablesalts or esters. Erythromycin
- Ciarithromycin and Azithromycin are stab/e in stomachacid andare readilyabsorbed
- Food interferes with the absorption of Erythromycin and Azithromycin (Azithromycin capsules and extended release suspension should be
administered 1 hour before or 2 hours after meals, ~ Azithromycin tablets and immediate release suspension can be taken with or without food)
- Azithromycin have relatively low serum concentrations and penetrates into most tissues (except CSF); neutrophils, macrophages, and fibroblasts,
with tissueconcentralionsexceedingserumconcentrations by 10-100-fold (tissuehalf-/ife of 2--4 days)to produce an e/iminationhalf-life approaching
3 days (For example, a single 1-g dose of Azithromycin is as effective as a 7-day course of Doxycycline for chlamydia! cervicitis and urethritis)
- Spiramycin crosses the placenta and reachesconcentrations in the placenta uptoStimes higherthanserum
- Erythromycin ~liver microsomal enzyme inhibitor; CYP1A2, CYP3A4) is extensively metabolized by CYP450 system; Interference with the
metabo/ism of drugs, suchas Theophylline, Statins and numerous Antiepileptics
- Ciarithromycin is ~ metabolized by CYP3A4

~ ) Impaired ribosomal binding ; mutation or deletion in receptor protein on the 30S ribosomal subunit.
- Spectrumofactivitv;
- Aminoglycosides are effective against majority of aerobic Gram -ve bacilli including those that may be multidrug resistant , such as;
Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter species
-In combination~ a ~-lactam or Glycopeptide (Vancomycin ): Aminoglycosides are effective against staphylococci (including; MRSA),
streptococci and enterococci (Enterococcal endocarditis) (Gentamicin and· streptomycin are the ~); ~-lactams and Aminoglycosides
are administered in f~ syringe dueto acidlbase chemicalinteraction .
- Azithromycin does not inactivate CYP450 enzymes; because it has a 15-member !11M 14-member lactone ring like Erythromycin and Clarithromycin
- Erythromycin and Azithromycin are primari/y excreted inthe bile via feces
- Clarithromycin and its metabolites are eliminated by the kidney; Dose should!?§ adjusted in patients with renal impairment
- Mechanism ; Bacteriostatic (mu !?§bactericidal, particularly at higher concentrations); Macrolides bind irreversibly to the 50S subunit of the bacterial
ribosome, thus inhibitingtranslocationsteps of proteinsynthesis
- Bacterial Resistance ;
1) ~influx or increasedefflux

- Gentamicin and Streptomycin is also useful against Francisel/a tularensis (Tularemia; is a pneumonia acquired during rabbit hunting season 2) Enzymaticinactivation; production of esterases (by fnterobacteriaceae)that hydrolyze Macrolides
by huntersskinninginfectedanimals), Yersiniapestis (Piague) and Mycobacterium (Tuberculosis) ~) Ribosomal~ ; by modification of the ribosomal binding site by chromosomal mutation or by a macrolide-inducible or constitutive
~ (post-tra nscri ptiona l methylation of the 23S bacterial ribosomal RNA); ~incosamides and .§.treptogramins
- Side Effects ;
sharesome cross-resistance with_Macrolides(M!,..§.-resistant).
- Nephrotoxicitv (dose-relatecf); Oiiguricacutenephrotoxicity is oftenreversib/e, but itmaybe fatal , witha rise inthe serumcreatinine
- ~ ; - Mycoplasma pneumoniae and Pertussis (whooping cough) (Bordetella pertussis).
- Risk of nephrotoxicity are increasedby;
- Otitis media , sinusitis and bronchitis (Moraxe/la, Streptococcus pneumoniae and Haemophilus influenzae) ·
-Concurrent use of NSAIDs, Diuretics , Cisplatin , Cyclosporine , Cephalosporins , Amphotericin and Vancomycin
-Pharyngitisandtonsillitis (Streptococcuspyogenes)
- Eiderly, renalimpairment and pregnancy.
-Pyogenicskininfection (Staph. aureus or Streptococcuspyogenes)
- Ototoxicitv (dose-related) ; can be temporary but is usually irreversible and common symptoms of inner ear damage are: tinnitus, hearing loss,
-Acnevulgaris (Propionibacteriumacnes)
vertigo, trouble with coordination and dizziness
- Chlamydialnfections; Azithromycin
- Neuromuscular paralysis; Aminoglycosides inhibits ACh release from cholinergic nerves by competing with calcium ions
- Campy/obactergastroenteritis ; Erythromycin - Azithromycin
- Allergic reactions: Contact dermatitis is a common reaction to topically applied Neomycin
- Helicobacterpylori; Ciarithromycin
• Diphtheria (Corynebacterium diphtheriae) Erythromycin
-ToxoplasmosisduringPregnancy (Toxoplasmagonditl; Spiramycin
Chloramphenicol - Macrolides mayalsobe used lo preventbacterialendocarditis (rheumaticfeverprophyfaxis)in palients who cannot take Penicillins
- Erythromycin is the most potent prokinetic drug when given IV and may be ~ to improve delayed stomach emptying in patients with severe
- Chloramphenicol isa broad-spectrumantibiotic gastroparesis; byactingas motilinreceptoragonist. . . I
- Mechanism ; Bacteriostatic (may be Bactericidal ; depending on the dose and organism)
-ltbinds reversib/y to theSOSsubunit ofthebacterialribosome and inhibitspeptidebondformarion (inhibitpeptidyltransferase) - ~~~~. ~~!c~lnu~e~~~~1f5~~~::sc~l:~~.~~adi~~=~~~~nac::i:e~~~~~~~n.~=~:~~~~~~eg:~::~;~:~~~fection {gono.rrhea} (or; 2 g ora.fly once), n.on·
- Due to some similarity of mammalian mitochondrial ribosomes to those of bacteria; high circulating Chloramphenicol , producing bone - SideEffects; .
marrow toxicity - GIT discomfort; Anorexia, nausea, vom1ting and diarrhea; due to a drrect stimulation of gut motility (especially with Erythromycin IS a prokinet1c)
- IVinjection of Chloramphenicol only used as altemative - Cholestatichepatitis (fever, jaundice andimpairedlivertunction ); especiallywith Estolate form of Erythromycin
- Typhoidfever ()'lgenerationCephalosporins &Fiuoroquinolones are drugofchoice) - QT interval prolongation; Macrolides may prolong QT interval and should be used with caution in those patients with proarrhythmic conditions or
- Meningitis (3RigenerationCephalosporins are drugofchoice) concomitant useofproarrhythmicagents
- Rickettsialinfection (Tetracyclines are drugofchoice) - Ototoxicity; especially Erythromycin at highdosages alsobeen associatedwith reversibfe hearingloss
- Metabolism ; Chloramphenicol is metabolized by the liver to Chloramphenicol glucuronate by glucuronidation (which is inactive) - Others ; Azithromycin maycause taste/smellperversion and/or loss
- Anemias (dose-related);
- Hemolyticanemia; in patients wilh glucose-6-phosphatedehydrogenasedeficiency
- Aplastic anemia (bone marrow suppression ); rare, idiosyncratic reaction, irrevers ible, independent of dose and highest risk with guj
Chloramphenicol andcanbe fatal.
Ketol1des
- Otheranemias ; reversiblesuppression of redcellproduction
- .G.ru~~ ; Neonates havea lowcapacityto glucuronidation , andlheyha veunderdevelopedrenalfunction ;w h ich accumulates (Ketek<)
active Chloramphenicol leve/sthat interferewiththe function of mitochondrialribosomes . This leadsto poorfeeding , - Telithromycin is a semi-synthetic Erythromy.cin . Similar antimicrobial coverage of Macrolides , However, the Ketolides are active against many Macrolide-
depressedbrealhing, cardiovascularcollapse, cyanosis (graybaby) and death resistant Gram + ve strains (Methylase-mediated & efflux-mediated resistance). YHst. m.t. Community-acquired pneumonia
- Telithromycin inhibits CYP450system (fike Erythromycin & Ciarithromycin);druginteractions
- FDA WARNINIG; fatal breathing problems may occurred in patients with myasthenia gravis . ~ effects; like Macrolides ;
L1ncosam1des
(Dalacin®-C) Fusidic Ac1d Streptogram1ns
- Clindamycin !1M. Erythromycin, inhibits protein synthesis by interfering with the formation of initiation complexes and with aminoacyl
translocation reactions. Resistance to Clindamycin, which generally confers cross-resistance to Macrolides
(Xifaxan®)(Gastrobiotic®) 1 (Synercid®)
- ~ ; Ciindamycin is ~ primari/y totreat ~ Gram+ve ~ & some of Gram -ve ~
- ~ ; Primarilyagainst Gram+ve - Theyare bacleriostalic, but incombination theyare
- Clindamycin highly concentrated in bone , teeth and urine bu1 poor entry into the CSF even with inflamed meninges - Rifax.imin is anewGiantibiotic
- Fusidicacid isQ!Wl usedtopically synergistically bactericidal
- Indications ; Otitis media, sinusitis, bone or joint infectionS,d"ental infections, pelvic inflammatory disease, bacterial vaginosis, intra-abdominal - ~ ; traveler's diarrhea, irritable
- ~ ; VRE and MRSA , flQ! active against
- - anaerobicinfections, pneumonia, endocarditisprophylaxis,bitewounds, inhalational/gastrointestinalanthrax, CNStoxoplasmosis, - Systemic Fusidicacid shouldnot be givenwith bowel syndrome and hepatic Enterococcus~
acne and malaria Statins because ofa risk ofserious and encephalopathy, ithas poororal
- ~effects ; .D..iilrrb.ta (pseudomembranouscolitis ) nausea and skinrashes potential/yfatal rhabdomyofysis absorption (actloca//y) - ~~; P~~:~~~~~~ arthralgias and
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
D) Nucleic Acid Synthesis Inhibitors

Qu1nolones and Fluoroqu1nolones Antifolates

- Dil!I!!!I!!IINegGramO) -Common Sulfonamldes ~;
· Nalidixicacid isthe ffrst ofthe synthet/c quinoloneantiblotlcs, usedforurlnayb'act lnftctiont,it iseffect/veprimarilyagainsf - Systemic; -Wellabsorbed;
gram-ve bacterla. - ~ Sulfanilamide (Prontosilt), Sulfaeytine, Sutfisoxaz~e (Sulfafurazole), Sulfamethizole, Sulfadimidine and Sutfaisodimidile.

MNMM# ~ICipro') - ~-tlli!l'l!!!!ll(Tarivkl')lmm!li-lil!l'i!lll'!l - -- -/ntermediate· Sulfamethoxazqft, Sutfadiaz:ine and Sutfapyridine

- L2mz; Sulfadoxine, Sulfamerazine and Sutfamethoxydiazine.
- Ciprofloxacin, Enoxacin, Lomefloxacin, Ofloxacin, Levofloucin and Pefloxacin possessing azo11m1 Gram -ve activity and
- Poorly absotbed; Sutfasalazine (for Inflammatory Bowel Disease), Sulfaguanidine & Sulfathalidine

-=··1~~
ll!CI:deata to llJMMl aetlvityagafnst Gram+ve bacterla. --
- Topicat. - Ophthalmic; Sulfacetamide (lsopto Cetamidee)
· Ciprofloxacin (~ and levofloxacin arethe ~~ actlvityaga/nst Pseudomonasaeruginosa
- Sk/n ; ~Sulfadiazine (Dermazi~)forsklnbumsand ~ (Sulfam)'ion').
iiiiiiiiMMI!III ~ (TavanicO)~(Parox<)~(Raxa,e) j¢1U!.U.f£&;. MOffll@jftllitifMMfjfjjf§IA®I (Septrine) $yrllhue ~
- Levofloxacin has superior activity against Gram +ve organisms, including Streptococcus pneumoniae - Cotrimoxazole OR Sulfamethoxazole (SMX)fTrimethoprim (TMP) is the !!12!1~ used antifolate antibiotic
i@IIQ@i!@hii# li!!Iimii(Trovan-)~(Avame)lmm!mm(F~~(Tequin') - Mechanismofsctlon· Cotrimoxazole blocks 2consecutivesteps inthe biosynthesls of nuclelcacids inmanybacterla Dihydrololieacid

"'==1~
1) Due to structural similarity between Sulfonamldes & P·Amino-benzoic acid (PABA) Q Compete w~h PABA
- Moxifloxacin ~. Gatifl oxacin & Gemifloxacin Improved activity against Gram +ve organisms, particularly
Q /nhibftionof Dihydropteroatesynthase.
Streptococcus pneumonfae and some staphylorocci.
2) Trimethoprim /nhibitsDihydrofolatereductase
- Moxifloxacin islhe on/yapprovecl has t!HHlm activityagafnst anaerobic bacteria • From1 and 2 Q inhlblt ofFolicacid synthes/s whichis essentia/for synthesisof DNA.
- Phannacoklnptics: · Advantaqeofcombina!ion (SMXITMP);
Tetrahydrololieaeid
- Catcium, lron, nnc, Sucralfate and Antaclds reduce the absorption; ora/Fiuoroquinoiones shou/dbetaken2hoursbeforeor - Synerglstlceffect. -Decrease lhe dose of eachone.
4hoursafter any productscontainingfhesecations
· ~urine concentrations are Moxifloxacin and Gemifloxacin (MfM.HJ!. inUTis)
- Decreasethe bacterialreslstance.
- Bactericidal action.
-lncreasethespectrumofactivity.
,L
- Ciprofloxacin and Ofloxacin have goodpenetrat/on into cerebfospinalfluid inpatientswlthinflamedmeninges - Res/stance; mayoccur asaresult ofmutationsthatcause; I
· Moxifloxacin is excreted primarily by the liver (no dose adjustment is required for renal impairment, while dosage adjustments !) Overproduction of PABA. DNA
are needed in liverdysfunctlon) 1) Production of a folic acid-synthesizing enzyme that has low affinity for Sulfonamides
- Mechanism· Bactericidal; 1j lmpalrpermeability tolhe Sulfonamlde
• Fluoroquinolones block bacterial DNA synthesis by Inhibiting bacterial Topoisomerase II (DNA Gyrase) and Topoisomerase - Spectrum of activity, Staphylococcus au reus (including many MRSA strains), Streptococcus pneumoniae, Streptococcus pyogenes Haemophilus influenzae, Escherichia
IV. coli, Salmonella, Shigella, Klebsiella pneumoniae, Nocardia, Stenotrophomonas mattophi/ia, Usteria monocytogenes & Pneumocystis jirovefii
• Inhibition of DNA Gyrase prevents the relaxation of positively supercoiled DNA that is required for nonnal transcription and - Side Effects; - Dgrmatologic: Rash (much more common in AIDS patients and severe in elderly). Stevens-Johnson syndrome also occur Q1l1 rare
replication , promoting DNA strand breakage (more significant in Gram -ve) - ~; Nausea , vomiting and diarrhea
• Inhibition of Topoisomerase IV Interferes with separatlon of newly replicated DNA (more s/gnlflcant in Gram +ve). - Hematologic; - Bone-marrow suppression (do&Hependent). Hemolytic anemia; may occur in patients with G6PD deficiency.
• Agents with higher affinity for Topoisomerase II (such as Ciprofloxacin' and levofloxacin) more potent activity against - Renai; Crystalluria (bioodureaandcreatinineeievations), acutelnterstlllalnephrltls andcan/eadto acuterenalfallure (veryrare)
Pseudomonas aerugfnosa and should not be used for Streptococcus pneumonlae Infections. - ~; Hyperkalemia
· Agents w~h higher affinity for Topoisomerase IV (such as Moxifloxacin ", Gemifloxacln and Gatifloxacin) more potent activity - ~; Kemlcterus (Bi.-obin-nducedbraildysfmcOOn; Neuroloxichwerbilirubinemla).
against Streptococcus pneumoniae and should not be used for Pseudomonas aerugfnosa infections - Contralndicatlons; hypersensitivity to sulfa, Age <2 months, CrCI <15 mUmin, G6PO deficiency (Favism), hepatic impairment, pregnancy and nursing mothers
l ;1!ilijrmrmtjiMttifiWtrtijm f'f!!!@t!t!tjij:mtijQI®Mitl (Fansida~)
1)~ influ x or increasedefflux. - Sulfadiazine/Pyrimethamine is used forToxoplasmosls. • Sulfadoxine/Pyrimethamine is used as antimalarial drug
~Chromosomal~ both TopolsorMrase II and Topoisomerase IV may undergo mutations (alteration of the target
sites);
• Mutation in Topolsomerase IV will occur first in Gram +ve organisms.
·Mutation in Topolsomerase II and active efflux wilt occur first in Gram -ve organisms
· SOectrum of activity; Fluoroqulnolones were~ developed because their excellent activity against Gram -ve aerobic
bacteria; Escherichia coli, Pseudomonas aeruginosa, Haemophilus inffuenzae, Klebsiella pneumoniae,
Antimycobacterial Drugs
Legionelfa pneumophila, Proteus mirabilis, Shigella species and Enterobacter species.
Anti-Tubercular Drugs Ant1-Lepral Drugs
· Mostcommon sideeffects are nausea, vomltlng and dlarrhea.
- ~~
• CNS; · Common; Headache, dizziness and insomnia
111!11;lsoniazid, Rifampin (orother Rifamyclns), Pyrazinamide & Ethambutol liilimill
. .;are ~ used to treatdisease thatis t:Hli!!m to first-l inetllerapy (Multl-Drug - Dapsone is structurally related to the sulfonamides and used in
- Lesscommon; Hallucinatlons and depresslon
Resistant TB ; MDR·TB); Streptomycin , Amikacin , Kanamycin, Ofloxacin, comblnatlon wth Rifampicin &Ciofazimine fortreatmentofleprosy.
- Rare; Neurotoxicity (Seizures) inhibit GABA; [especially with Norfloxacin and Ciprofloxacin); only in
levofloxacin , Moxifloxacin, Capreomycin, Ethionamide, Prothionamide, p-
patientsunderlyingneurologlcdiseases (epilepsy), renallnsufficiencyorconcomitantuse of
aminosalicylicacid , Cycloserine and Terizidone
neurotoxic drug.
~(orlilmlill!!lilll!illiliRimaclane•)
lmll!Diiml
- PNS; Perlpheralneuropathy cana/so occur. -ltis never glven asasingleagent inthetreatmentofactivetuberculosis,
- Cardiovascular· • - Rifampicin is ~CYP450inducer, leadinglo lli!!!:!!!2!!! ~1nteractions becauseresistantstrainsrapidfyemerge during monotherapy
• QT Interval prolongation jespecja//y wth levofloxacin, Gatifloxacin, Gemifloxacln and Moxifloxacin]. - !l!!!;- Mycobacterial Infections, !!!!ill~ administered wlh Isoniazid or other ·- lsoniazid isa drugof cholceforthe treatment oflatenttuberculosis
antltuberculousdrugs to patients wilhactlvetubercuiosistoprevent - Metabol/sm ; byliver (by ~; fastacety1atorsishigheramongpeople
- Moxffloxacin carr/eslheQ[!!f!!lrisk, m ciprofloxacin appearsto be associatedwithltlelowestr1sk
emergenceofdrug-resistantmycobacteria. of Asian origin (& NativeAmericans) thanthoseofEuropeanorAfricanorigin
- Dermatologic·
-NelsseriaMenlng!tidisCarrlerandHaemophlluslnfluenzaeTypeBProphylaxls. (Fastacetylatorsmayrequirehigherdosage)
· Photosensltivlty; Severesunbums mayoccur;canbe avoided or prevented byavo/ding exposuretosunllght · Mechanism; lsoniazid preventsthe synthesis of mycollcacids inthe celiwall
- ~Effects; - Nausea, vomiting and rash are the most common
or s~ouldbe advisedto usesunscreen whiletaking Fiuoroqulnolones
- Orange-red disco/oration of urine - ~~; - Peripheralneuropathy (dose-related);canbe prevented by
· Musculoskeletal· administering 25-50mgld of Pyridoxine(VitaminB6)
- Hepatotoxicity incidence/ncreased when Rifampicin usedwith lsoniazid
· ArtlcularCartllageEroslon (Arthropathy)has beenobserved. Thus , thesedrugsa re !!Q!~
- fm!glnteract/ons; Rifampicin isa lMlJ!!1l.liver microsomal enzyme Inducer. lM!!HJ. • Hep:r;awi~ill~io&(~.v.=~~ensitivity reactions.
recommendedfor patientsunder18years ofage~ Ciprofloxacln and levofloxacin insomeindications ).
metabolism of otllerdrugs, feadlng to numerous s!IY.g~
- Tendon rupture; ararecomplicationlhathasbeenreportedinelderly, patientswithrenaldysfunction and - Pyrazinamide ~ used in combination with INH , Rifampin & Ethambutol.
those taking Corticosteroids li!IBllliiMycobulinO)
- Gl ucose Metabolism; - Rifabutin is preferred for Mycobacterium avium complex (MAC); is an infection most - ~effects; - Hyperul#lm@fi,ejBc(i~-bje)
common in patients with human immunodeficiency virus (HIV), who are often taking
- Gatifloxacin hasbeeo associatedwith hyperglycemia in diabetlcpatlents aodwith hypoglycemla in patlents - Mechanism; Ethambutol inhibits arabinosyl transferase Ill enzyme
antiretrovi raitllerapy thatis metabolizedbyCYP450. 8ecause Rifabutin ~QQWtl
alsorecefvingoralhypoglycemicagents - §JM.effects; QR!jfNeurltls OR Retrobulbar~; Et hambutol = Eyes
CYP450inducer than Rifampicin; Rifabutin isusually preferred inMAC.
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Antifungal Drugs
A) Syste m1c An tifungal

Polyene Ant1fungals Azole (Tnazole) Ant1fungals

li'!ii!BiimiliJI: (Fungizone«>) (AmBisome®) - Azoles thatareavai/ab/efor clinicaluse are classifiedas either lmidazoles or Triazoles according tothenumberof nitrogenatoms
· Amphotericin B remains the drug of choice for the treatment of several life-threatening mycoses (broad antifungal spectrum and a lack of alternatives) - lmidazoles ~. ·· and ~ are ~used.Q!!OCin topicaltherapy
- Amphotericin B isnearly inso/uble in water and it have renal & infusion toxicity, therefore prepared in a several formulations; to irnprove~ and - Triazoles ·, • ,, and • • • , ;are used systemically
decrease~. lli!J. may show different pharmacokinetic characteristics compared to Conventional Amphotericin B such as Liposomal Amphotericin 8 - Although these drugs have similar mechanisms of action and spectra of activity, their pharmacokinetics and therapeutic uses~ significantly
- Mechanism , - Ketoconazole isthe first azole-based oral treatmentof systemicfungalinfections,inthe ear/y1980s, but nowhas/argely been rep/aced duetorisk
- Amphotericin B binds to ergosterol forming pores in the cell membrane. of severeliverinjury, antiandrogenic (Ketoconazole shampoomaybebeneficial alopecia)and antiglucocorticoid and adversedrug interactions
- The pores disrupt membrane function , allowing electrolytes (parlicularly potassium) and small molecules to leak from the cell , resulting in cell death ~. Triazoles suchas Fiuconazole and ltraconazole ,withimprovedsafety profilewere developed

- Antifungal soectrum; Amphotericin B in general is fungicidal; depending on organism & concentration - Mechanism; Azoles in general are fungistatic; Azoles are inhibit C-14 a-demethylase {a cytochrome P450 enzyme), thereby blocking the
- It is broad antifungal spectrum; Candida albicans, Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces demethylation of Lanosterol /o Ergosterol,the principalsterol of fungalmembranes
dermatitidis,andlJN11lstrainsof Aspergil/us -The inhibition of Ergosterol biosynthesis disrupls membranestructure and function,which,intum, inhibitsfungal cell growth
-ltisalsousedinthe treatment ofthe protozoalinfection leishmaniasis -The se/ectivetoxicity of Azoles results fromtheir ~~ for fungalthan for humancytoc hrom e P450enzymes

- Fungalresistance; OecreasedErgosterolcontent ofthe fungalmembrane · lmidazoles exhibila /esserdegree of selectivity thanthe Triazoles, accountingfortheir higherinciden ceof drug interactions and
- ~ · Antifungal; Life-threatening mycoses, such as Mucormycosis , Cryptococcal meningitis and certain aspergillus and Candida! infections adverse effects
· Resistance ;Speciall yin~~ Mutations inthe C · 14a ·demethylasegene that/eadlo decreased Azoles binding
- Antiprotozoal; Visceral Leishmaniasis and Amoebic Meningoencephalitis
- Side Effects; - Antifungalspectrum; Broadspectrum, inc/uding;
A) Infusion-Related Reactions (shake & bake syndrome); Fever, chills, muscle spasms, vomiting, headache & hypotension. Can be attenuated by, - Many species of Candida and Cryptococcus neoformans
-Siowing the infusionrate - Dermatophytes (endemic) mycoses (Blastomycosis, Coccidioidomycosis & Histoplasmosis)
- Usinginitialdosingregimen. - ltraconazole and Voriconazole are effectiveagainst Aspergi/tus infections.
- Pre-medicating wi th Acetaminophen, Hydrocortisone and Antihistamine - Drug Interactions; M Azoles inhibit the hepatic CYP450 isoenzymes (especiaHy CYP450 3A4) to XHll!!g degrees; decrease metabolism of other
· Liposomal Amphotericin B has the lowest incidence of infusion-related reactions, white Amphotericin B Colloidal Dispersion has the greatest drugs, leadingto numerous mMginteractions
ID Nephrotoxicitv; Renal tubular acidosis and ~ hypokalemia and hypomagnesemia (Caution when coadministration with other drugs that cause - PotentCYP450inducers (e.g.; Rifampicin )canleadto decreaseeffect of Azoles
hypokalemia; e.g., corticosteroids, digoxin). Liposomal Amphotericin B, have less nephrotoxicity than Conventional Amphotericin B - PotentCYP450inhibitors (e.g.; Ritonavir)canleadlo increasedadverseeffects of Azoles
~) Others ; Hepatotoxicity, Anemia & Thrombophlebitis (thrombophlebitis can decreased by adding heparin to the infusion)
• • · (Diflucan* )
- Fluconazole is !1JJID1:i bioavailable (available in both oral and IV formulations), with fewer hepatic enzyme interactions (feast CYP450 effec~ . with
betterGitolerance and widesttherapeuticindex of ai/ Azoles
Antimetabolite Antifungals - Antifungalspectrum ; ~ spectrum of ai/ Triazoles (/eastCYP450effect ofruJ. Ihe Azoles );
- !::!ls1!:!!Y. active against most Candida species (lllif HQ.I Candidakrusei or Candidaglabrata)
- Good activity agains/ Cryptococcusneoformans{e:Q.; Cryptococcalmeningitis)
(Ancobon") - ~ active against ~ Dimorphic fungi w~h !1.9. activity against Aspergillus species
- Flucytosine is specifically used , together with Amphotericin B, for serious Candida infections and Cryptococcosis; Amphotericin B increases cell · Mostcommonsideeffects; b..ead.acbe: ..nausea, vomiting and skinrashes
permeability, al/owing more Fiucytosine to penetrate the cell and /eadingto synergisticeffects. • • (Sporano~)
- Mechanism;
- ltraconazole hasa broader spectrum of activity lhan Fiuconazole (Mnotas broadas Voriconazole or Posaconazole);ltis activeagainst
- Flucytosine enters the fungal cell via a cytosine permease enzyme (not found in mammalian cells)
Aspergil/us,which Fiuconazole is CJJl/.
- Fiucytosine is convertedintracellular1yfirst to 5-fluorouraci1 (5-FU) and then to S-fluorodeoxyuridinemonophosphate (FdUMP)and Fiuorouridine
- ltraconazole is the drug of choiceToi-; Blastomycosis , Sporotrichosis, Histoplasmosis , and Onychomycosis. It is rarelv used for Candida and
triphosphate (FUTP),which inhibitDNA, RNA and proteinsynthesis
Aspergiltus species becauseoflhe avai/abifity of newer and moreeffectiveagents {Voriconazole or Posaconazole)
- Resistance; Decreased enzymes that convert of 5-FC to 5-FU (commonly in monotherapy)
- Ora/dosaqeforms (capsules have lowerbioavailability than oralsolution )
· Antifungal spectrum; Flucytosine is fungistatic; it is effective against ~ strains of Candida and Cryptococcus - Oral solution; shouldbe taken onan emptystomach , as fooddecreases the absorption
- ~;- Fiucytosine is lW_used asa singleagent becauseof; - Capsules; shou/dbe takenwithfood, and ideal/y an acidic beverage (orange juiceor cola)to increaseabsorption
- Uhas synergisticeffect withother agents - Antifungal spectrum;
-To avoid the development of secondary resistance · !::!iJJ111x. active against most of Candida and Aspergillus species, Cryptococcus neoformans, and many dimorphic fu ngi (ltraconazole is the
· Fiucytosine is used in combination with; azoleofchoice for ~infections )
A) Amphotericin B for treating Candidiasis and Cryptococcosis. B) ltraconazole (or Fluconazole) for treating Chromoblastomycosis - Good activity against Candidakrusei and Candidaglabrata
- Side effects; - Mostcommonsideeffects; DaUSei, VOmiting and rash
- Gidisturbances (nausea, vomiting,and diarrhea);are common • •. • (Vfend®)
- Bone marrow suppression (anemia, leukopenia and thrombocytopenia); result from metabolism of Flucytosine to 5-fluorouracil by intestinal flora - Voriconazole is simifar to ltraconazole inits spectrum,having excel/ent activityagainst Candida (inc/uding Fiuconazole resistantspecies suchas
-Reversib/e hepaticdysfunction {elevation of serumtransaminases and alkalinephosphatase) Candida kruse!), Cryptococcus neoformans, Aspergillus, Scedosporium and Fusarium species {Voriconazole is the drug of choice for invasive
aspergillosis; /esstoxic than AmphotericinB),and many dimorphic fungi
- Voriconazole IV admixture wrth Sul(obutylether ~-Cyclodextrin SBECD is restricted in patients with renal insufficiency
Ech1nocand1ns Systemic for Cutaneous Infections • ·~ . • • (Noxafil®)
- Posaconazole is the broadest spectrum member of the azote family, with activity against most species of Candida, Aspergittus and Zygomycetes
li!!!!il!ll!lii iCancidas•) ~ (Mycamin..) ~ (Uitragriseofulvini')(Grifulvin V*)
• NOW Griseofulvin has been largely replaced by oral Terbinafine for the
lt'!iml!lli!l!! IEraxis<)
-They have potentactivityagainst Aspergiltus and most Candida spp treatmentofOnychomycosis ,although itis stil/used for Dermatophytosis B) Topic al Antifungal
- Echinocandins havean excellentsafetyprofile. Theycancause mi/d llliDili!l (Lamisi~)
Histamine-mediated infusion-related reactions (flushing}. - Terbinafine isa synthetic ~ (SqualeneEpoxidaselnhibitor)thatis
- Echinocandins inhibitssynthesis of glucan inthe cellwall,via non· availableinan .Q!]J_ and ~ formutations
competitive inhibition of 1,3·P·D-glucan synthase enzyme. This - AIIylamines actby inhibiting squaleneepoxidase enzyme,thereby b/ocking
resultsin disruption ofthe fungalcellwall and celldeath the biosynthesis of Ergosterol,an essentia/component ofthe fungal cell
- Anidulafungin is the 9.!!fl Echinocandins can be administered in membrane (not act on CYP450). Accumulation of toxic amounts of squalene
severe hepatic dysfunction resultsin increasedmembranepermeability anddeath ofthe fungalcell
• Co-administered of Caspofungin with Cyclosporine OR Micafungin - Terbinafine isthe drugofchoice for treatingOnychomycosis;
with Sirolimus cany highincidence of elevatedliverenzymes -Bettertolerated. -Shorterduration of therapy. -Moreeffective
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Antiviral Drugs Chemotherapy
- Viruses cannot reproduce ontheir own, they are use host's metabolic processes, andsoa
fe wdrugs areselectiveenough to prevent viratreplication An t1 v 1rals for He rpesvirus Infectio ns Antivira ls for V1ral Respiratory Infections (V Ri s)
- Replicationcycle; The virusreplication occurs in 7stages,namely;

-u
1) Adsorption (Attachment), 2) Entry, 3) Uncoating, 4) Transcription/mRNA production,
S) Synthesis of viruscomponents, 6) Virion assembly (Maturation), 7) Release.
d'LW.f#,IM@iji!!t@TMiiijiJIIIQI!!IMfiTiitmlift4§14iiiilldti.f)
~ (Zovirax<) - Neuraminidase Inhibitors (NAis) are a class of drugs which block viral neuraminidases of the
- Acyclovir (Acycloguanosine)isthe prototypicantiherpeticdrugs influenzavirus, by preventingreproduction and re/ease of newvirions fromcell to cell
l!'l!!l!ml'lll (Tamiflu") flllml!lll (Relenza")
::::::r
- 8/oavai/abi/ity is /ow, Valylester of Acyclovir (Valacyclovir)has greateroralbioavailability

h~-~·· &~f?
~-·--a ~~
- Mechanism: (AntiherpesDrugs)
- Oseltamivir and Zanamivir are effective IHUb. typeAandtypeBinfluenzaviruses
- Activation; Acyclovir (ACV) isa Guanosine ana/og requires 3phosphorylationsteps for activation;
- Oseltamivir isan ora//y is raPiiiif hydrolyzed bythe liver toits active form
Virus-infectedcells are mostsusceptible;
- Zanamivir is notactive I via inhalation
• Acyclovir is converted to Acyclovir Monophosphate by Thymidine Kinase (TK) enzyme
fl\ '\.
~
•
• AcyclovirMonophosphate isconverte<ltothe iD- & ldphosphate by hostcellkinases damantane Derivatives

~~~ratus \~ J =--
- Acyclovir Triphosphate competes with Deoxyguanosine Triphosphate as a substrate for viral DNA
polymerase and is itself incorporated into the viral DNA, causing premature DNA chain termination
- !hM; Genital Herpes, Herpes Simplex Virus (HSV Encephalitis), Neonatal HSV Infection, HSV
Mucocutaneous Infection (Hsm.i@fi/Jf~:~~:~~ster (Shingles and Chickenpox)
Amantadine • · Rimantadine 11l!'m·
• ! ·!•! D I-

......,
).1.1

~ . ""
lmm
····· ~i)
- Valacyclovir isthe L-valylester of Acyclovir. lt is rapid/y converledlo Acyclovir, serumlevelsare 3 to
Stimesgreaterthanorai Acyclovir and oralbloavailability is -55%
~ (Denavir")
- Penciclovir is absorbed l11!il!i.f. whengiven orally it is used only as a topical treatment for Herpes
lil!lmll!il
- Ribavirin [rye-ba-VYE-fin] isa syntheticguanosineanalog, iseffective against a broadspectrum of
RNA and ONAviruses; -RespiratorySyncytiaiVirus (RSV) infection
-HepatitisC (incombinationwithotherantiviraldrugs) 3
ru
-ViraiHaemorrhagicFever
- Antiviraldrugs may targetspecific stepsof viralreplication; SimplexLabialis. Un/ike Acyclovir, Penciclovir notcausechaintermination • Mechanism· Ribavirin is phosphorylatedintracellularly by host cell enzymes. Ribavirin triphosphate
- Vi ral attachment and entry are blocked by; Enfuvirtide {HIV), Maraviroc (HIV); lllli!l!m (Famvir") appearsto interferewiththesynthes/sof guanosine triphosphate,inhibits the replication
"-. Oocosanoi (HSV)and Palivizumab (RSV} - Famciclovir isthe di-acD G i i@ j & =& J ralbioavailability (77%) ofa widerange of DNA and RNAviruses
- Uncoating areblockedby; Amantadine and Rimantadine (influenza) · ~~ - Dose-dependent transient anemia; monitoring is essential.
- Nucleicacidsynthesls areb/ockedby; NucleosideReverseTranscriptaselnhibitors; - Cytomegalovirus (CMV) is a commonvirus that infectspeople of al/ages and can cause serious - Nausea, fatigue, headache, myalgia, arthralgia and insomnia
NRTis (HIV, HBV}, Non-nucleoside Reverse-transcriptase Inhibitors; NNRTis (HIV}, problems in advanced immunosuppression patients {organ transplant or HIV infection) and neonates - Pregnancy; FDACategoryX

G)
Acyclovir (HSV}and Foscarnet (CMV} infected withthe virusbefore theyare bom (congenitaiCMV) · - Effectivebirthcontrol method m!&_f2j taken to avoidpregnancy during therapy &for 6months
after completion of treatment in bQ1b. female patients & in female partners of male patients who
- Protelnprocessi ng areb/ockedby; Proteaselnhibitors (HIV} ~ (Cytovene')
- Viralrelease are b/ockedby; Neuraminidaseinhibitors (influenza) are taking Ribavirin therapy -
- Ganciclovir isan acyc/icguanosineanalog (ana/ogof Acyclovir thathas greateractivity against CMV - FDA Warning;
- Retrovirus; A virus that is composed of RNA, b.ul have an enzyme, called reverse

up to 100 times greaterthan thatof Acyclovir). Like Acyclovir, Ganciclovir requires activation by
transcriptase,thatgivesthem the uniqueproperty Oftranscribing lheir RNAintoDNA afler triphosphorylation before inhibiting vi raiDNApolymerase
enterin g a cell. The new DNA is then incorporated into the host cell chromosomal DNA by
- Side effects: Myelos uppression (Neutropenia , Thromboc~openia). Ganciclovir is teratogenic (embryotoxi c).
c
' Shou/dnot be usedalone for chronichepatitisC(noteffective)
' Hemolyticanemia; Shouldnot be used in unstab/ecardiac disease (monitoring is essentian.
· Teratogenic (Category X); Avoid in W2Dlill who are pregnant and in m.al.e: partners of women who

-·
an integrase enzyme, at whichpoint the retrovira/DNA is refe"ed toasa provirus. HIV is
~ (Valcyte') are pregnantduring and after6months of therapy -

10[@1 ~1
- Valganciclovir, is an L·valyl ester prodrug of Ganciclovir, to improve oral bioavailability of

c...
Ganciclovir; it is rapid/y convertedlo Ganciclovir after oraladminlstration
Hl!lli!!lii iVistide')
- Phosphorylation of Cidofovir to tlie active diphosphate is independent of viral enzymes
An t1wals for Hepa titis B V1rus (HB V)
- lntravitreal of Cidofovir is assoc/atedwlthrisk of hypotony and uveitis
-MJl§l administer Probenecid oral/y & IV normalsaline with eachdose of Cidofovir to reducerisk of -As of 2010; 7drugs were approvedfor treatmentof chronicHBV infection;

- Reverse-transcriptaseinhibitors (RTis) areac/ass of antiretroviraldrugs usedto treat HIV

infectlon orAIDSandsomecaseshepatitisB
nephrotoxicity
IDili!3 (Foscavir")
- Foscarnet is not a purine or pyrimidineana/og, ~isa Phosphonoformate (a pyrophosphatederivative)
and doesnot requireactivation by viral (or cellular) kinases
- 2injectab/e; lnterferons (PEG-interferonalfa-2a and lnterferonalfa-2b)
- Sora~ Nucleoside/NucleotideAna/ogues (Lamivudine, Adefovir, Tenofovir, Entecavir & Telbivudine)

1Gi®&®f1@tli!@~@l
-The se/ective antiviralaction of iFN-a is primari/y dueto activation ofa hostcellribonuclease that
CD
An t1wals for HIV lnfect1on (Ant1retrowal Agents)
preferentially degradesviralmRNA
- Polyethyleneglycoi (PEG)is/inkedlo lnterferon to malceit (PEG-interferon) fastlonger inthe body
- lnterferon is notactive orally and administerediM , SC, or iV
- !hM; Hepatitis C (NOT USED ALONE\ & Hepatitis B
- Common§Jsli!effects; - f!M-!!M~ (fever, chills, myalgias, arthralgias & GI disturbances}
s:
~ (Zeffix«') (Epivire) · · •·•••• (Hepsera*) ::::J
• Lamivudine and Adefovir are Nucleoside Reverse Transcriptase Inhibitors (NRTis) works by
b/ocking the HIVreversetranscriptase and HepatitisBviruspo/ymerase
- Unlike Adefovir, Chronic therapy of Lamivudine may cause emergence of resistance
c..
administration al low doses
increasesthe bioavai/abi/ity ofthe secondPI, ofl.ena/lowingfor fongerdosinginterval s.
- Druginteractions area commonproblem for a//Pis, because theyare noton/ysubstrates
butalso~inh i bitors of CYP450isoenzymes
-Forexamp/e dangerousinteractions with Pis inc/ude;
- Rhabdomyolysisfrom Simvastalin or l ovastatin
- Precautions; Lacticacidosis, hepatomegaly & severeacuteExacerbation of hepatitisB may resu/1
l3l!mJI (Ba;.clude') l1!liBIIill(Tyzeka") (Sebivo<) (Viread<)
- Entecavir appearstohavea higherbarrier tothe emergence of resistance than Lamivudine
- Precautions; Lacticacidosis and severeacuteExacerbation of hepatitisB mayresu/1
s:
Q)
- Excessivesedation from Midazolam or Triazolam. - Respiratory depression from Fentanyl A ntiv irals for He patitis C Virus (HC V )
- SideEffects; Nausea, vomiting and diarrhea
- 0/sturbances in glucosellipidmetabolism;diabetes, hypertriglyceridemia &hypercholesterolemia
""C
- Chronictherapy results in fatredistribution; buffalohump &breastenlargement tmmm;mrnttll'*"mt• · ··
l!)i!iifli1fiiiili ~ (Fuzeone). ~ (CCR5antagonis~ (Selzentry*) ~ (Victrelis*)OR IDElD:JI (Incive~)are NS314AProtease Inhibitor

N~~::~~~r ph~s~~~~~~ ~~:~beia~ctiive,i]NiRjT~Isijhaiffis.hig~h!lllin~cid!eni!l

ll ce
31
~ (Oiysi()Cl) is NS3/4Aproteaseinhibitor
- Unlike the req uire
hypersensitivitv~ inc/uding s.kinras.h
of amw.+m••ammmuUilll5l
lililllll!lmll ltsentress') ~ (Vite~ao) lil:ll!!!!liDIZ ITivicay<)
~ (Sovaldi®)isa nucfeotideanafog actby b/ockingNSSBRNA-dependentRNApolymerase
- All NNRTis are substrates for CYP3A4andcarlact as inducers {Nevirapine), inhibitors (Delavirdine}, - INSTi doses shouldbe separatedfrom Antaclds and other polyvalentcations mrmtttt?f#iilffill!!WJ (HaNoni®) l•@ffi@fflil:tttJM!ftWW·M.MM•t!t!!Mrt® {Viekira Pak®)
or mixedinducers & inhibitors (Efavirenz.Etravirine} - ~fQmmQ!!~effects; Nausea and d i arrhea lt@Mfi!ftti@li!t.!. l§'jjh·N.ptifl" (Qurevo®) (Technivie®)
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Antiprotozoal Drugs
Chemotherapy for Amo eb 1os 1s (Arn eo1c d es ) Chemotherapy for Molano (Ant1molonol Drugs)
- Amoebiasis (Amoebic Dysentefy) is an Infection caused by !Dl Ofthe amoebas of the Entamoeba group, commonly by Entf~ histolytia - IIIIW is a mosquito-borne acute Infectious disease caused by • species ci lhe protozoal genus Plasmodium
· Amoebiasis can be acute or chron ic, with varying degrees of illness, from asymptomatic !52 mild diarrhea l2 dysentery :diarrhea with blood). -The disease is most commonly transmitted by an infected female Anopheles mosquito.

- Enta~hr:J&iiiiffi@ittestF::;~iitiii~F::"~)twiai~=~~== (~~aze)
· Metronidazole is a nitroimldazo/e, is the mixed amebicide of choice for treating amoebic infections (kills Trophozoites !.lll!not Cysts).
· 5-Nitroimidazoles include Metronldazole ,Tinldazole and Secnidazole used to combat ~ bacterial andprotoze>a tlfections.
- Metronidazole is alsousedinthe treatmentof,
-Giardiasis(Giardia/amblia)and Trichomoniasis (Trichomonas vagina/is) -Infections causedby ~coci:i , and ~gram-negativebacilli
-Helicobacterpy/orl-associated peptlculcerdisease
- Drogofcholce for thetreatment ofbacterialvaginosis.
· Drug of choice for the treatment of pseudomembranous colitis caused by Clostridium difficile
· Mechanism 21 action; Inhibits nucleic acid synthesis by disrupting DNA and causing strand breakage; ameblcldal , bactericidal and trichomonacidal ; The nitro
groupof S-Nitroimidazole isableto serve asan electronacceptor, andchemica/fyreduced in anaerobicbacteria (onlyinanaerobic ce/ls) and sensitive protozoa ,
forming reduced cytotoxiccompounds that bindtoprotelns and DNA, resulting in death of anaerobicbacteria andTrophozoites
• !:i:.J!; to kill cysts confined to the Intestine; Jodoquinol , Paromomycin and Oiloxanide ; One of these drugs may use along with Metronidazole
· Side Effects ;
· Unpleasant metallic taste, nausea, vomiting and abdominal pain
· Disulfiram-/ike reaction; Occur when Metronidazole ingested with Alcohol cause severe flushing, tachycardia and hypotension (Disulfiram -like rNCtion)
- Metronidazole alone rarefy causes Stevens-Johnson syndrome, ruJ1 is reported to occur at high ra tes when combined with Mebendazole.
- fnfrequentsideeffects; diarrhea, insomnia, weakness, dizziness, thrush, rash, dysuria, darkurine, vertigo, paresthesia aod neutropenia
- Pregnancy, Metronidazole FDA Category B (No evidence of harm to the fetus due to Metronidazola)
- Lactation; excreted in human milk; not recommended (Concentration in the milk similar to maternal serum levels)
I!IIMI•@P§ •••• • (Yodoxine)~ (Humat~l i•HM§Mtj(Amoebyl'l)
- Theyare poorlyabsorbed from GIT and isusedasa luminalamebicide
- Symptoms lhat typ ically inc/ude fnn,~~ and~; usua/lybegln10-15daysafterbeingbitten.
- Most deaths are caus«< by Plasmodium falciparum ~ Plasmodium vivu, P11smodium ovale & Plasmodium malariae gentnlty
cause mllder formofrna&aria
- P11smodium falciparum {most dangerous) may cause; ~.!lJAbflm, ~ hyeotenslon, and~~
{abnormal elevation in the number of red blood cells accompanied by swollen, reddish limbs). Plasmodium falciparum infection can lead toaa!!!Jil
obstructJon&~withoutprompttreatment
~
~ (Ara~n")
- Chloroquine hasbeenthe drugofchoice forboth bD!!!maod ~ofmalariasincethe 1940s {EXCEPT in reslstantstralns
ofP. fl/cipllrum ).
- AntlmalarlaiActlon; - Highlyelfectivebloodschlzonticlde
- Modetately effective against gametocytes of P. vivax, P. ovate and P. malariae (not against P. falciparom)
· Notactiveagainstliverstageparasltes
- Mechanism 21 action; - Chloroquine binds to heme, preventing its polymerization to hemozoin.The increas«< pH and the KCUmul•tion of
heme result in oxidative damage to the phospholipid membranes, leading to lysis of both the parasite and the red
blood cell
• Resistance to Chloroquine in P. falciparum can result from dectMsed accumulation of the drug in the food vacuole caused by the ICtivity
ofatransportersystem encodedbythepfcrt gene
- SideEffects ; - Giupset, pruritus and headaches
- BiurredvisionlChloroquineretinopathy); Ophthalmologicaxamination shouldbe routinelyperformed.
- Chloroquine ~~ associated hemolytic anemia in patients with glucose-6-phosphate dehydrogenase delfclency.

- Oehydroemetine also used in Leishmaniasis

ILMlJ1ll!l'l!lli!1Lli iPiaqueni~) ·
- Hydroxychloroquine has similar pharmacokinetics to Chloroquine , w~h rapid Gl absorption, used for the prevention and lr'Ntment of
malaria
Chemotherapy for Trypanosomiasis - Otheruses; Rheumatoidarttvitis and Systemiclupus Erythematosus
rmm!ll!ll!ll DDI!II!II
- Amodiaquine is a 4-aminoquinolone similar in structure and mechanism of action to Chloroquine. Amodiaquine + Artesunate as a
· African bypanosomiasis {sleeping sickness) and American trypanosorriasis {Chagas disease) are two chronic and, eventually, fatal caused by of Ttypanosoma
recommended therapy forfaldparum malaria in ~nas with res/stance to older drugs.
-In African ~mnru ; · Causes; Ttypanosomabruceigambiense (TbG) and Trypanosomabruairhodesiense (TbR). TbG causes over98%ofcases.
- Piperaqulne has been combined with Oihydroartemisinln in co-fotmul1ted tablets (Artekln•, Ouo-eotecxin') that have shown excellent
- ln ~disease; - Causes}:::~~:nsmiHedby the bite ofan infected. nd are mostcommon in ruralareas. ~ efficacy and safety forthe treatmentoffalciparummalaria.
- Transmittedby insects knownas Triatominae {kissingbugs). Gm!!llill
· Primaquine is !he drug of choice for the eradication of dormant liver forms of P. vivax &P. ovate and can also be used inchemoprophy\uis
mmlll!m (Pentam') (NebuPent>) for all malarial species.
- ~ ; Trypanosom i asis in!J!;M!!!@ (hemolymphatic); · First line in West African Trypanosomiasis; Trypanosoma bruai gambiense
- Second line in East African Trypanosomiasis; Trypanosoma brucei rhodesiense {Suramin is a first line) fQIQiie"i' lff.l§
· Because it does not enter the CSF, ais Ineffective against the second stage {CNS involvement) of trypanosomiasis. El!llilli!l and ~
ll!!ll:ll!ll - Quinine and Quinidine remain important therapies for faldparum maliN ; ~ mere d.iiuii, although toldcity may complicate
thetapy, resistance to Quinine is uncommon .b!.!1 may be increasing
• Suramin is a sulfated naphthylamine used primarily in the tiru_ ~ {without CNS involvement) of East African Trypanosomiasis (Trypanosoma btucei
rhode_siense) as first line. Suramin is less effective than Pentamidine for early West African Trypanosomiasis - Quinidine acts as a class I antianflythmic agent PAl in the heart {l QRS complex and l QT int&fVal).
- Mechanism !1f action ; (ike Chloroquine , interl'eres w~h IMme polymerization, resulting in death of the erythrocytic form d parntte.
lll!!lllmllB (Arsobat>) - Antimafaria/A£fi2a; Quinine isa rapid-acting , highlyetrect#ve ~~ lflalnstthefourspectesofhumanmalariaparasltes.
• Melarsoprol , a trivalent arsenical compound , is used for !he treatment of African Trypanosomiasis in the .second.~! (C!!S_ involvement); The drug is Gametocidal against P. vivax and P. ovale .b!.!1 not P. fllciparum . It is not active against liver stage p.-asites
- First/ine and on/y avaltable in ~ ~ of EastAfric:anTrypanosomias is ; Ttypanosomabroce/rl!odes/ense - Side Effects;
- Secondline in ~ ~ ofWestAfrlcanTrypanosomiasis ; Trypanosomabrucefgamblense (Eflornlthine is a first line agent) - Clru:honism~ ; Tinnitus, t.eadache,nausea , dizziness , flushi ng, and vlsualdlsturbances {reversible)
llil!llllllli!I IOmidyt>) llllll!lilliEI ILampito) ~ (RochaganO) - ~memia {especiallyinG&PDdeffciency),Ihmm.b.o.c'ttopenla &Leukopenia .
- Eflornithine is a fi!;g-~ for neo.n.d ~ ofWest African Trypanosomiasis; Trypanosomabruceigamblense (Metarsoprol is a second line agent) - ~~ ; rashes ,angioedema & bronchospasm .
- Nifurtimox is a nitrofuran, is used as a second line {Benznldazole is a first line agent) for American Trypanosomiasis {Chagas' disease) and may use in -lt must be used with greatcaution in patients with cardiacabnormalitles
combination with West African Trypanosomiasis; · ~ (Lariam•)
- Benznidazole isusedas i ittends tobe - Mefloquine is one of the lecommended chemoprophylactic drugs for use in most malaria-endemic regions with Chloroquine-resistant
strains (Chloroquine - resistant P.falciparum).
• A~J=:~:~g~~~=~ blood schizonticidal 'l:rirt}mm ~':;{m and P. vivax, M ~is !!2! active against hepatic stage

- Lumefantrine (or Benflumetol ) is an antimalarial drug. It is 2!t!f used in combin1tion witi! Artemether (Coal'tem").
t·hlijUI§!.i!,p M4i ~~i·fi@lffiit.fi@ffiihi1WtfflfflN 11 1Mim,e
- Artemisinin or Qinghaosu and its derivatives (Artemlslnin-combination therapies, ACTs) are now standard treatment worldwide for P.
talclparum malaia . To prevent the development of resistance, these agents should !!2! be used alone, companion drugs include;
Lumefantrine , Mefloquine , Amodiaquine, Sulfadoxlne/Pyrimethamine , Piperaqulne and Ch10foproguani1JOapsone .
J'¢ittTtft!.iijfit1liip.ptltj !IMft!nmtfjfj.jjj!ii,t.ir'#BJ Pentavalent Antimonial Agents ; - Side Effects; Nausea , vomiting , anorexia & dizziness . fJ1gh 22m may cause QT prolongation. Hypersensitivity ructions may occur.
Chemotherapy for For cutaneous and visceralleishmaniasis ~ (-ffil@@ift#l@!iitffiftj (Fansida~) - (Malaronee) ~
~ {lmpavido8); firstorally activedrug forvisceralleishmaniasis
Le1sh m on10S1S mE!Ii!IBii!E!m'D~
-; ~~~ ~liDml!l • Atovaquone , inhibits mitochondrial processes such as electron tnnspOI't, as well as ATP and pyrimidine biosynthesis
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Drugs for the Treatment of Nematodes (Roundworms )
phylum in the animal kingdom, encompassing up
~(Vennox<)
- Mebendazole is asynthet/c benzimidazole a broad-spectrumantihelminthlc agent.
- Benzimidazofes (Albendazole, Mebendazole and Flubendazole) are act against Nematodes by
inhfbiting the assembly ofthe cytoplasmicmicrotubule inthe paraslte& b/ockingglucoseuptake
- Benzlmldazoles are kills hookworm, Ascaris, and Trichuris .@9.9!; not need dose repeated {in Pinworm
(Enterobius vermicularis =Oxyuriasis; Oxyuris); <!: 2 years; 100 mg orally once as a single dose; this
doseshouldbe repeatedin 2 weeks}.
- Absorption; less than 10% of orally administered Mebendazole is absorbed; absorption is increased
withafatty meal
- Mebendazole is a first-line agent for the treatment d ~ ~ of Nematodes such as; pinworm alld
hookworminfections, ascariasis, trichuriasisandstrongyloidiasis
- Mebendazole is an alternative to Metronidazole in-Giardiasis; Stevens-Johnson syndrome can occur
when Mebendazote is combined with high doses of Metronidazole
~ or lil:lll!li!!m:m(Mintezoro)
- Thiabendazole asynrhetic benzimidazole is apotent broad-spectromanthelminticagent.
- Because ofHs toxiceffects, Curret~ tuseof Thiabendazole as alternative to lverme ctln or Albendazole
for Strongyloidlasis andCutaneouslarvaMigrans; CLM (creepingerupt/on)
!Mtffj1MI#ifljftMtfj(Pin-X•)
- Pyrantel pamoate is a broad-spectrum anti_ helminthic highly effective for the treatment of Pinworm,
Hookworm, Ascaris and Trichostrongylosis
-ltis poorlyabsorbed orallyand exerts itseffects locally intheintesti nal tract
- Mechanism· Pyrantelpamoate actsasa depo/arizingneuromuscularblockingagent, causingrelease
of Acetylcholine and inhibition of cholinesterase, thereby causing sudden contraction,
followedby paralysis,cR the helminths; thishasthe resultofcausingthe worm to "loseits
grlp"on theintestinal wall andis expe/lednaturally.
~(Stromecto~)(lverzin..)
- lvermectin isthe !l!MJl~choice forthe treatme nt of; CutaneouslarvaMigrans , Strongyioidiasis , and
Onchocerciasls (riverblindness)causedby Onchocercavo/vulus
-ltis hl9..!11teffective againstHeadllce, ScabiesandlymphaticFilariasls, amongothers.
- Mechanism~~ lvermectin act by binding to glutamate-gated chloride channels (GiuCis)
Chloride /nffux is enhanced&hyperpolarization occurs, resultingin paralysis&death of worm.
- lvermectln kil/lng dthe microfilaria inOnchocerciasiscanresultina dangerous M.az.mttt Be.acti.on.
- ~ ~ - Onchocerciasis; Mm.o.tti. Bu.ction; fever, headache, dizziness, somnolence and
hypotension; severity re/atedtoparasiteload; Antihistamlnesor/and Corticosteroids
maybe gfvento decreasethesymptoms.
!ittftUiMt:ffl•M"Mirlj(Hetrazane)
- DJethylcarbamazlne is the drugofchoice forFilariasis; ~Lymphatlc FIIarlasis (Eiephantiasis ;
Wuchereria bancroft/, Brugia malay/ and Brugia timon), Loiasis (Loa loa) and Tropical Pulmonary
Eosinophllia (Wuchererfabancroftf).
- Diethylcarbamazine is commonly used in combination wHh Albendazole in Filariasis
Antihelminthic Drugs
Drugs for the Treatment of Cestodes (Tapeworms)
_Cestodes {Tapeworms) are long, segmented worms
- Cestodes and Trematodes arewonns/ack anintestinaltract andinstead can absorbnutrients through
their integument
-Adult Cestodes surviveinslde their humanhosts,wheretheyare /imitedto theintestinaltract
-Larvae of Echinococcus speciesexistwithinthe tissues and rnigrate throughdifferentorgansystems,
two mostimportantformsofthe disease inhumansareCysticEchinococcosis (Hydatidosis)and
Alveolar Echinococcosis
- Niclosamide n.o.w:isa second-/inedrug (altemativelo Praziquantel)forthelreatmenlofmostCestode
infections, ilOfongeravailable in USAaccordingtoCDC (using Praziquantel;as single do~e)
- Niclosamide rapid/y killadultworms (but notova)bycausing necrosis ofthe head and adjoining
segments of the tapeworm, due to inhibition of oxidative phosphorylation or stimulation cl ATPase
activity.
- Qill; 500mgChewableTablet (in foilcover);
· Beef tapeworm (Taenia sag/nata), Pork tapeworm (Taenia solium) and Fish tapeworm
(Diphyflobothriumlatum); Onesing/edose is sufficient.
- Dwarf tapeworm (Hymenolepis nana); 7 days is recommended; Praziquantel is superior.
- Precautions; • Don't remove from foil until immediately before administration
• Tablets should be administered in the morning on an empty stomach
• Tablets should be chewed before swallowing and washed down with a little water
• Patientsshou/d receivea salinepurgative (e.g. Sodiumsulfate, Magnesiumsulfate) 2
hoursafter theYomesant; to ensure a rapid and compfeteexpulsionofthe wonn
• Atcohol shou/dbe avoided within1day ct Niclosamide use
••• •· · · (,>Jbenz..)
- Albendazole, is a broad -~ benzimidazole antihelminthic (Beruimidazole Carbamate)
effectiveagainstl!!lflt~ inc/uding, .c.estod.es_ and Nematodes
-lt isthe drugofchofce of HydatidDisease and Cysticercosis(TissueCestodes)
- It is also used in the lreatment of ffi!1!t ~ of Nematodes such as; Pinwonn and Hookworm
infections, Ascariasis, Trichuriasis and Strongyloidiasis
- Aibendazole isan alternative or adjunct to Metronidazole inGiardiasisespecia/ly in children
- Benzimidazoles (Aibendazole, Mebendazole and Fiubendazole )arethoughttoactagainst ~
by inhibitingcytoplasmicmicrotubulesynthesis and glucoseuptake
- Albendazole also has larvicidal effects in Hydatid Disease, Cysticercosis, Ascariasis and Hookworm
infectionand ovlcldal etfects in Ascariasis, Ancylostomiasis and Trichuriasis
- Albendazole is used i.n combination wHh Diethylcarbamazine or lvermectin in Filariasis
- Pharmacokinetics;
- Absorption; ~~ after oraladministration ,!M absorption is enhanced bya h/gh-
fatmeal (upto4-5times)
- Distribution; wide/ydistributed; insidehydatidcysts and CSF
- Metabolism; E.xtensivefirst-passetfecl (rapidsulfoxidation ); Aibendazolesulfoxide ~.
- fxcretion; Activemetabolites areexcreted in the urine.
- ~ -Neurocysticercosis ( TaeniaSo/ium Cyst inthe brain )
-Hydatid Disease
- Ancylostoma, Ascariasis, Hookworm, Trichostrongylus; 400 mg orally ooce.
- Pinworm; 400mgorallyonce, repeatin2weeks
- l:Qngoom~ (Hydatid Disease; 3 months); risk of hepatotoxicity and, rarely, agranulocytosis
or pancytopenla (dropinwhitebloodcells,redbloodcellsandptatetets)
Drugs for the Treatment of Trematodes (Flukes)
· Trematodes (Flukes) are leaf-shaped Flatworms that are generally characterized by the
tissues they infect (forexamp/e, liver, lung, lntestinal or blood).
~ (Bi~ricid..)
- Prazlquantel isa drugofchoice forthetreatmentr:lalfforms of Schlstosomiasis ,other
Trematode Infections and Cestode Infections such as Taeniasis including
Cysticercosis
- The drug's Htm: and effectiveness as a single oral dose have also made it useful in
mass treatmentofseveralinfections
- Praziquantel acts by Increase cell membrane permeability to Calcium , causing
contractureandparalysisoftheparasite
- Prazlquantel shou/dbetaken with food (notchewed duetoa bittertaste)
-lt is rapidlyabsorbedafteroral administration and distributes into CSF
-Thedrugis exte'!_sivelymetabolized,andlhe inactivemetabolitesareexcretedprimarily
in the urine
-J.!H!;
- Schistosomiasis;20mglkg/doseorallyin3doses(4-6hrs)for1day
- Ciooorchiasis, Opisthorchiasis and Paragonimiasis; 25mglkgldose3timesdaityfor2d
- Taenlasls and Diphyllobothriasis; S-10mg/kgorallyonce(nearty100%curerates)
- Tapewonns; 5-10 mg/kg as single dose or 25 mgfKg if Hymenolepis nan a
- ~~;- ~; Dizziness , malaise , headache and GITdisturbance
-Mildandtransient elevations of liverenzymes wQgJJf.
- Low-grade fever, pruritus and skin rashes, may associated wnh
eosinophilia(probablyduetothereleaseofproteinsfromdyingwormsrather
lhandirectdrugtoxicity)
- lln!IJ.Interactlons; - Corticosteroids , Phenytoin , Rifampin and Carbamazepine may
increasethe metabolism of Praziquantel ; decreased Praz.iquantel
levels
- Clmetidine causes fncreased Praziquantel levels
- Contralndications; Praziquantel is contraindicated for the treatment of Ocular
Cysticercotis, becausedestruction ofthe organism inlhe eye maycause irreversible
damage
· (Vansil')
- Oxamniquine is a semisynthetic Tetrahydroqulnoline used as alternative to
Praziquantel for the treatment of Schistosoma mansonf Infections. The drug may
cause seizures
.: or
- Metrifonate isan irreversib/eorganophosphate (cholinesteraseinhibitor; paralyzesthe
adult worms) used as alternative to Praziquantel for the treatment of Schistosoma
haematobium
• (Ergamisoi')(Katrex')
- Levamisole is an anthelminticlimmunomodulator drug , used as alternative for the
treatment of Ascariasis and Hookworminfections
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
ChBmothBrapy Cancer Chemotherapy
- Cancer is characterizedby the development ofabnormal cells that divideuncontrollably andhave the abifitytoinfiltrateand destroy
I) Ant1metobol1tes, Part l

..
normal body tissue; Neoplasm or Tumor is a group of cells that have undergone unregulated growth and will often form a mass or
lump, butmaybe distributeddiffusely
- Cancer oflen hasthe ability to spread throughoutthe body(Metastases); - Antimetabolite is a substances structurally similar to normal compounds that exist within the cell

,,.•..,
0.. - These contrastwith benigntumors; which ~!lQJspread to otherparts ofthebody
• Cancer or Neoplasm, is ll1m!gf]J.Io develop from a cell in which the normal mechanisms for k2n1r.ol of growth & proliferation are altered.
- They generally interfere with the availability of normal purine or pyrimidine nucleotide, and inhibit synthesis of DNA or RNA. Their maximal cytotoxic effects are in S-
phase and are,therefore, cellcyclespecific

ro • Cancer is caused by both internal factors (such as inherited mutations, hormones and immune conditions) and
environmentallacquiredfactors (suchas tobacco, diet, radiation and infectiousorganisms);
· The majority of cancers (90-95%) are due to genetic mutations from environmental factors lii!iilllililfi
~
- The remaining (~10%)areduelo inheritedgenetics .
- Twomajorclasses of genesareinvo/vedin carcinogenesis;
I?Q!.i.jj'4fHJ161f31 mwtJ!iS!l!liliij(illiJJ(PurinethoJe)
-Is a chemotherapy agent and immune suppressant, it is used to treat · 6-MP wasthe first of the thiopurineana/ogs foundtobe effective incancertherapy
- Oncogenes ( OCGs); ~ to causecancer
· Tumor-Suppressor Genes (TSGs) or Anti -Oncogene ; ~ cell from path to cancer Cancer, Autoimmune Diseases, Ectopic Pregnancy & Medical Abortions with immunosuppressant activity. Azathioprine is an immunosuppressant, exerts
- Metabolism; by liver and intracellularly to poly-glutamated forms which its cytotoxiceffects aflerconversionto 6-MP via metabolism
- Cell Cycle;
""'0 can be convertedback to MTX by hydrolase enzymes. A
- Metabo/lsm;inthe liver; 6-MP is converted inthe liver to 6-methylmercaptopurine

c -Many types of cancer are

caused by mutations that
small amount of metabolism to 7-hydroxymethotrexate;
lesswatersoluble than MTX andmay leadtoCrystalluria
- Mechanismg!Action;
- For cancer MTX is structurally related to Folic Acid and competitively
derivative orto Thlourlcacld (an inactive metabolitethis reaction is
catalyzedby xanthineoxidase; AIIopurinol increasedlevelsof 6-MP ,
thereby /eading to excessivetoxicity)

~
allow the cells to speed inhibitsdihydrofolatereductase (DHFR),an enzyme that converts • 6-MP dose should be reduce by 75% (quarter dose) when used with Allopurinol
through the vanous Dihydrofolate to its activeform, TetrahydrofolicAcid;
checkpoints or even skip · Affinity of MTX for DHFR is about 1000-fo/d that of Dihydrofolate. - Pharmacoqenomics ;
them altogether. Going from · Folic Acid is neededfor the denovosynthesis ofthe nucleoside - ThiopurineS-methyl-transferase (TPMT) enzyme is responsible, in part, forthe
S to M to S phase almost Thymidine,requiredfor DNAsynthesis. /nactlvation of 6-Mercaptopur1ne
consecutively. Because these
Q) cells have
checkpoints,
lost
any
their
DNA
· - Resistance;- Decreaseddrugtransport via the reducedfolatecarrier
- Decreasedformation of cytotoxicMTXpoly-glutamates
- /ncreasedlevels ofthe targetenzyme DHFRthroughgene
- Certain genetic variations within the TPMTgene can lead to decreased or
absent TPMTenzyme activity.

-o
mutations that may have
occurred are disregarded and
passed onto the daughter
ce!ls.This isone reasonwhy
cancercellshaveatendency
to exponentially accrue
Interphase / Mn:otic Phase M-Phase
amplification
-Altered OHFR protein with reduced affinity for MTX
- Decreased accumulation of drug through activation of the
multidrugresistancetransporterP170glycoprotein.
-.JlW;
· TPMT screeningshou/dbeperformed priorto administration in al/ patients
prescribed Azathloprine or 6-Mercaptopurine
- Mechanism gf Action; 6-MP competes with the purine derivatives Hypoxanth ine
and Guanine for the enzyme Hypoxanthine--Guanine
Phospho-Ribosyl-Transferase (HGPRT)& itself converted

::J
mutations
-Rapidly dividing cells (cancer
cells) are generally more
DNA Synthesis Phase sensitive to chemotherapy,
s-F~;;
(.9
whereas slowly proliferating
cells(nonnal cells)areless
sensitive to chemotherapy
-Non-dividingcells(those inthe
Gophase)usuallysurvivethe
toxic effects of many of
- ln combination with otherdrugs,inacuteLymphocytic Leukemla, to Thio-lnoslneMonophosphate(TIMP);
BurkitrsLymphoma in chi/dren, Breast Cancer, BiadderCancer &
- TIMP can inhibit the firststep of denovopurineringbiosynthesis.
Head & Neck Carclnomas
- TIMP also b/ocks the formation of AdenosineMonophosphate and Xanthinuric
- Low-dose;is effectiveas a singleagent against certain Autoimmune
Dlseases; Psorlasis, RheumatoldArthrltisandCrohn's Disease. Acld from lnosinicAcid .
- TIMP isconvertedto ThloguanineMonophosphate ,whichafter phosphorylation
- Side Effects ,
----: Common Side Effects; Nausea, vomiting, diarrhea, mucositis can be incorporated into RNA. The deoxy-ribonucleotideanalogs thatarealso
(mucosal ulceration), stomatitis and myelosuppression (anemia, formedare incorporated into DNA.This results in nonfunctionaiRNA and DNA
leukopenia and thrombocytopenia)

co
- Dose-related Side Effects ; hepatotoxicity, acute pneumonitis and - Resistance;
chemotherapeutic agents
kidney failure - Decreasedlevels of HGPRT.
- ~ ~; MTX isan abortifacient andis commonly usedin - Increased dephosphorylation
-Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a category of cancer treatment that uses one or more anti- combination with Misoprostol in Medical Abortions and Ectopic - lncreasedmetabolism to ThiouricAcid or othermetabolites
cancerdrugs (chemotherapeuticagents)as part ofa standardizedchemotherapy regimen

E
Pregnancy
-Many of'the sideeffects of chemotherapy canbetracedto damage to normalcells that divideWlli!.!Y andarethus sensitive to anti- -!!m; AcuteLymphatic Leukemia, Crohn's Disease and UicerativeColltis
mitotic drugs; such as Cells in . Bone marrow; - Myelosuppression (decreased production of blood cells, hence also immunosuppression) - MTX shouldbe givenwith Folinicacid (leucovorine); 24hoursafter each
- Digestivetract Mucositis (inflammationofthelining ofthedigestivetract) weeklydose orby the useof daily Folicacid (notin thesameday; off-
llil!llll!Z!Im 1Fiudara8)
- Hairfollicles; Aiopecia (hair loss) days),although thismay decrease the efficacy of Methotrexate byabout

s..... - Irulnl<nl ~;
A) Induction Chemotherapy; is the first line treatment of cancer with a chemotherapeutic drug
10%, !lJ!!.this reducesseverity ofadverseeffects.
.Q!!:!Q Interactions; NSAIDs, Penicillins, Cephalosporins ,
·It is ~ in non-Hodgkin'& Lymphoma & Chronic Lymphocytic leukemia (CLL)

co
Amlnoglycosldes, Proton-pumpl nhlbitors and Valproates are increase - Fiudarabine isa potentimmunosuppressant and increaserisk for opportunistic
B) Combined Modality Chemotherapy; is theuseofdrugs with other cancer treatments, suchas surgery, radiationtherapy or infections,including fungi, herpes,and Pneumocystisjirovecipneumonia (PCP);
hyperthermia therapy plasmaconcentrations of MTX
Patients should receivePCPprophylaxis with Co-Trimoxazole
C) Consolidation Chemotherapy; is given after remission in ordertopro/ongthe overal/disease-freetime and improveoverall ll:lii!!!!ml (I'Jimtao)
survival. The drug that is administered isthe ~n the drug that achieved remission Qnduction Chemotherapy) liEmZ!m (leustatin€1):
...c - Mechanism; is antimetabolite similar in mechanism to' MTX, in addition to · (Arranon")
D) Intensification Chemotherapy; is identic alto Consolidation Chemotherapy bJ!1. a differentQnm than the Induction Chemotherapy
inhibitingDHFR,italso inhibitsthymidylatesynthase
is used • Cladribine is used in Hairy Cell Leukemia , Chronic Lymphocytic Leukemia (CU) &

a...
E) Combination Chemotherapy; involves treating a patient wah a number of dffferent drugs simultaneously. The drugs differ in · .JlW;Malignant Mesothelioma and non- small Cell Lung Cancer non-Hodgkin's Lymphoma .
their mechanism and side-effects; - Is also recommended in combination with Carboplatin for the first-line
- ~; · Minimizing the chances of resistancedevelopingto anyoneageot treatment of advancednon-sma(I Ceii LungCancer - Nelarabine is used in T-cell acutelymphoblastic leukemiaflymphoma
• used at lowerdoses, reducingtoxicity - Folic acid and Vitamin 8 12 QM) shouldbe givenbeforefirstdose and
• providemaxima/cellkilling wdhinthe rangeoftoleratedtoxicity f!!!ti!l!Itherapy and ~therapy lo reduce hematologic and Gitoxicities
F) NeoadjuvantChemotherapy (preoperative); Chemotherapy given prior tolhesurgica/procedure in an attemplto shrink the - Dexamethasone shouldbe given to avoidinfusion skinrashes - It is used in Acute Myeloid Leukemia {AML) &Acute Lymphocytic Leukemia (ALL)
primary tumor
G) Adjuvant Chemotherapy; Chemotherapy given ~ a local treatment (radiotherapy or surgery), used to decrease risk of
~ (Folotyn")

34
- Mechanism;isa newer antimetabollte thatalso inhibitsDHFR IMtff-iMUif.fj•tnMg!\t.JlnlG4i (Nipentfl)
recurrence andalso useful inkilling any cancerouscells thathave spreadto other partsofthe body (micrometastases)
H) Maintenance Chemotherapy; is a repeated low-dose treatment to prolong remission -.JlW;Relapsed or Refractory PeripheraiT-cell Lymphoma (PTCL) -ltis used as single-agent for alpha-interferon-refractoryHairyCeii Leukemia and
I) Salvage Chemotherapy or Palliative Chemotherapy; is given without curative intent, but simply to decrease tumor load and - Folic acid and Vitamin Bu QM) shou/dbe givenbeforefirstdose and may alsobe used incertainnon-Hodgkin's Lymphoma
increaselifeexpectancy andgiven after the cancer has notresponded to otherchemotherapyregimens f!!!ti!l!Itherapy a nd ~therapyto reduce hematologic and Gitoxicities
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
.......
I) Ant1metabol1tes, Part 2

mi!!!:Z!!!ImiJ(Adruci~)
- Administration; IVonly (notusedorally due to severeGitoxicity)and topicalty
- Pharmacogenomics; '
- Dihydro-p~rim! dine Oehydr~enase (DPD) enzyme is responsible for the detoxifying metabolism of
II) Alkylat1ng Agents
- Aikylatlngagents exert their cytotoxiceffects by covalentlybinding ci alkylgroups to nuc!eophilicgroups on variouscel/constituents
• Alkylation of DNA within the nucleus probably represent the major interactions that lead to cell death
- Aikylatingagents areusedin combination with otheragents totreata widevariety of tymphatic and solldcancers.
-Aif alkylatingagents are mutagenic and carcinogenic andcan /eadtosecondarymalignancies suchas acuteleukemla

Fluoropynmldmesdrugs thalindudes 5-fluorouracii, Capecitabine and Tegafur (prodrug of S-Fiuorouracil)

-Genetic variat!ons w~hin the DPD gene can lead to reduced or absentDPD activity, DPO deficiency have a
signlficantlymcreasedrisk of severe oreven fata/drugtoxicities. (Mustargerr<)
- Mechlorethamlne is the prototype of AikylatlngAgents
- MechanismQ!Action;
- Mechanism; it works by binding to DNA, crosslinldng two strands and preventing ce11 duplication. It
- 5-Fiuorouracii (S-FU)is/nactiveandrequiresactivation via a complexseries of enzymaticreactionstoribosyl
anddeoxyrlbosylnucleotidemetabolites; binds to the N7 nitrogen on the DNA base guanine, causing miscoding breakage and llm!l!l!ll!I IBiCNLJO):
1) S..FU is convertedto 5-Fiuoro-OeoxyuridlneMonophosphate (S..FdUMP),which/nhibits thymidylate subsequently DNA replication failure
~ynthase enzyme ( thereducedfolateisrequired ; so Leucovorin isadminfsteredw ith S.FU ); th isresults -!l!!!; Hodgkin's Disease, Lymphosarcoma, Chronic Myelocytic Leukemia, Polycythemia Vera and
minhibltlon ofDNAsynthesisthrough'Thxm.i.!:l!!.u~" Bronchogenic Carcinoma
2) S.FU is conve~edto 5-Fiuoro-DeoxyuridineTriphosphate (5-FdUTP) ,which ca n be incorporatedinto - ~~E!t!sl§.; Severenausealvomlting (90%), myelosuppression and alopecl a
DNA, resu/tlng minhibition of DNAsynthesis and function "'fflU¥1ifu¥i®Mftfj (Cytoxan*) (Neosare) (Endoxan*) : • · (lfex')
3) 5-FU is also convertedto 5-Fiuoro-UridineTriphosphate (5-FUTP),whichisthen incorporated into • Cyclophosphamide is the most widely used Alkylating Agent with broad spectrum, being used either
RNA, resu/tlng ininhibition of RNAsynthesisand function.
singly or as partof a regimen inthe treatment of awidevariety of neoplasticdiseases. lfosfamlde is
- Resistance· - Decreased 5-FU conversion into 5-FdUMP - /ncreased thymidylatesynthase /eve/s an ana/og ci Cyclophosphamlde
· llH!; -primari/y in~ (for examp/e; Colorectal, Breast, Ovarian, Pancreatlc and GastricCarcinomas). - Mechanlsm2f.A£fl2n;
- 5-FU rema/ns the mostwidelyusedagentin the treatment of ColorectaiCancer · Active metabolites are delivered to both tumor and normal tissue, where non-enzymatic cleavage
~(Xelod..) tothe cytotoxlcforms; PhosphoramideMustard and Aao!ein
· Capecitablne is an .2@ fluoropyrimidine carbamate with 70-80% oral bioavailability, which is enzymatically - Cytotoxic metabolites Interfere with malignant cell growth by cross-linking tumor cell DNA
converledto 5-Fiuorouracil insidethe tumor. - Cytotoxicmetabolites cmtspecific for anyphase ofthe cellcycle; also has ~
immunosuppressive activity
- Capecitabine is used inthetreatmentct colorectaland metastatic breastcancer
- Res/stance;- /ncreasedDNArepair - Decreaseddrugpermeability. - /ncreasedexpression or
· WMnfng; Capecitabine may increase the anticoagulant effects of Warfarin
activity of Giutathione and Giutathione-associatedproteins
liBI!I!IIFUDR<) -Mill;
• Floxuridlne or 5-Fiuorodeoxyuridine is a prodrug, which Is converledto 5-FU, it is used in the treatmentofGI
Adenocarcinoma with Metastasis to Liver, Gallbladder, Bile Ducts.
- Fioxurldine is given by rap/d intra-arterialinjection ONLYby or underthe supervisionof aqua/ifiedphysician
• Cyclophosphamide is used in combination wfth other antineoplastic agents to treat a wide variety
of ~ a nd~~; such as Lymphoma, Multiple Myeloma, Leukemia, Ovarian
Cancer, Breast Cancer, Small Cell Lung Cancer, Neuroblastoma and Sarcoma
- Cyclophosphamide is an immunosuppressant and used for autoimmune diseases .
• ffosfamide is used incombinat/on is used incombinationwfth otherantineoplasticagents to treat
llll!!!!!1llm
- Nftrosoureas are !JiJl!11!LJlRjjl-l21l!.R!J andareableto cross the blood-brain
barrier, making them effective inthe treatment of braintumors
- Thesedrugsappear tobe non-cross-res/stant with other alkylatingagents
• · (CeeNu<): m'!lmJii (Zanosar<
- Carmustine is used to treat certaintypesof BrainTumors , Hodgkln'sDisease,
non-Hodgkin's Lymphomas and Multiple Myeloma
- Lomustine are used in Bra!nTumors and Hodgkin'sDisease;ltis given 2r!!lv
OltLY ONCE EVERY 6 WEEKS (both physician and pharmacist slHllili1
emphasize to patient that ~onedose ofthedrugistaken evety6weeks;
SevereMyelosuppression]on emptystomach (no foodordrinkfor2hours
aftertodecreaseincidenceofnausea); ltis given JY andalso avaifab/eas an
Implantable brain wafer (Giiadel'); wafer as an adjunct to surgery &
radiation
- Streptozocin is used to treatislet cellcancer ofthe pancreas; llis given .!Y'
M~i'Mfi
(Mylerarr<)(BulsulfexO)
• Busulfan is ~sed in combination with Cyclophosphamide as a conditioning
reg i m~n p~ to Allogeneic Hematopoletlc Progenitor Cell Transplantation,
espectaf/y sn Chronic Myelogenous Leukemia (CML)
- Toxicity, Myetosuppression, lnterstitiai Putmonarv Fibros/s fBusulfanluna),
Seizures, Hepatic Veno-Occlusive Disease (HVOD),
.
Hyperpigmentation and
- Antiepilepticagent isusedas proph•ylaxi•:againosi BU!oulfan<nduo:ed
·

Germ Cell Testicular Cancer

- lfosfamlde is a/soused in BoneSarcomasandSoftTissueSarcomas.
- ~~ ;
· Mechanism; Cytarab~ne {ara-C) is I (ara-CMP) to the diphosphate and triphosphate - ~.cntill!.whichcanleadto BiadderFibrosis ; Biaddertoxicity !ileto Acrolein other
metabo/ttes (ara-CTP). ara-CTP can be/ncorporatedintoDNAand RNAresulting in inhibition of ToxlcMetabolites in the urine;
DNA and RNAsynthes/sandfunction - Biaddertoxlclty canbe reducedby,
- lt is ~oteffective whe~ g/ven orally (becauseofits deamination tothe non-cytotoxic uracil arabinoside; ara-U by - Slow IV Infusion.
cyt•dlnedeaminase mthe lntestinalmucosaand liver). - Adequateh~ration
· ~; Acute Myeloid (non-lymph~~c) Leukemia (AML), Acute Lymphocytic Leukemia (ALL), and Meningeal • Mesna should be administered concomitantly with Ifosfamide.
Leukemia (intrathecai; IT adm•mstration). - Nausea and vomiting, myelosuppression and alopec:ia
- ~~; Conjunctivitis , fever , myalgia , bonepain , rash and malaise • High dose d Ifosfamide can cause Neurotoxicity and CNS Toxicity due to chloroacetaldeh~e
- ~~ when given in highdoses ,which mayleadto ataxia. metabolite.
l!l!mlm!!l!i!IIGemzar<) l!llll!!!I!!DIILetJkerarr<): ~(FiudaraO)
-!l!!!;
- Pancreatic Cancer [first-line treatment fbr patients w~h locafly advanced (oonresectable Stage II or Stage Ill) or
- Chlorambucil is used to treat Chronic Lymphocytic Leukemia (CLL), Hodgkin Lymphoma and non-
Hodgkin lymphoma
iiliiillillWiif
metastatic(StageiV)j. - Fiudarablne isan effecrlve treatment forChronicLymphocyticLeukem!a (CLL) that doesnotrespond (Piatinott)
- BreastCancer (in comblnationwfth Paclitaxel) toinitia/treatment with Chlorambucil - Mechanismgfaction;is unc/ear, butsamemanner as atkylatingagents
- OvarianCancer (in combinat/onwfth Carboplatin) lml!llm!II !Aikeran>) - Cisplatln is used in ~Ilml2t:l (testl cularcancer , ovar!ancancer , bladder
- Non-smai/CeiiLungCancer (incombinationwith Cisplatin). cancer,breastcancerheadandneckcancer,cervicalcancer,lungcancer,
· llis used to treat~~(MMJ [plasmacell cancer]
-BiadderCancer (in comb/natlonwfth Cisplatin); Off-labe/. mesothelioma,esophagealcancer &braintumors)
- CholangiocarclnomaandotherBiliaryTractCancers; Off-/abe/. - Other uses; . Melphalan (Evomela*); high-doseofconditioningtreatment prior to Hematopoietic
Progenitor (Stem) Cell Transplantation in Multiple Myeloma (MM). · §JJ1!Effects;
• BM1 ~ Effects; Renal mlcroangiopathy syndromes (including hemolytic-uremic syndrome), hepatic and
-Ovarian Cancer, Retinoblastoma, Ocular (uveal) Melanoma and Neuroblastoma - Severe , ~ vo m iting (atleast1hourafteradministrationandmaycontinue
pulmojffiiffim(llidazaeJ -limmlm(oa:ogen*J forasbogas5days)
lml!l!ll!!!!lii !Treand..): lilll!!l!l!!I (ThioplexO)
- Mechanism; 1) Hypomethylation d DNA and 2) Direct cytotoxic effect on hematopoietic cells in bone marrow by : Nephrotoxicitv; Oose-related and cumulative
- Bendamustine is used to treat Chronic Lymphocytic Leukemia (Cll), Multiple Myeloma, and non-
/ncorporationlntoDNAandRNA. Hodgkln'slymphorna. - Ototoxicity; Tinnitus and/or hearing/oss.
· !l!n; Mvelodysplast!c SyndromH (MDS) and Acute Myeloid Leukemia (AML) - Thiotepa is used in Adenocarcinoma of the Breast & Ovary, and as Intravesical in Bladder Cancer - Neurotoxicitv; Peripheralneuropathy and opticneuritis
- Myelosuppression and Hypersensitivity Reactions
lil!II!!!Eil!ii iEioxatirr<) (Para~alin")
- Oxaliplatin is a third-generation platinum analog whose mechanisms of cytotoxic action and clinical - 1:lM Ci~p!atin; Carboplatin h~s broad-spectrum activity against a wide range
pharmacology same as Cisplatin and Carboplatin . However, mechanisms of msiJ.1an1 to Cisplatin or of ~!M..!n2!l.However,m contrast to Cisplatin, Hexhibits significantly
Carboptatin are lJllla:QJH esl.s.tant to Oxaliplatin -- l!!§. Nephrotoxicitv and Gi toxicity .
. !l!!!; OxaiiplatiniSused for treatment of Colorectal Cancer, typicalfy in combination with Fluorouracil - ~effects and ~ · MiJsl Nausea and Vomiting
and Folinicacid (Leucovorin)
- ~effects and ~ - ~; Peripheralneuropathy .
- Neurotoxicity, Myelosuppression, Hepatotoxicity
- Nausea, Vomiting and Myelosuppression & Hypersensitivity
- fil!; Nephrotoxicity and Ototoxic\ty /essthan Cisplatin and Carboplatln . - ~ Nephrotoxicity and Ototoxicity.
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Ill) Cytotox1c Antib1ot1cs IV) M icrotubule ln h1b1tors
-The Cytotoxic antibiotics or Antitumor Antibiotics owe their cytotoxic action primarily to their interactions with DNA, leading to disruption of DNA · Mitoticspindle ;isan intracellularskeleton {cytoskeleton)thatisessentialforthemovements ofstructuresoccurTinginthecytoplasmofalleukaryoticcells
function. -The mitoticspindle consistsof chromatin and microtubules composedoftheprotein tubulin.
- Cytotoxicantibiotics inhibittopoisomerases (l and ll)and producefreeradicals also p/ay a majorrole intheircytotoxiceffect -The mitoticspindle isessentiafforeukaryoticcelldivision
-Severaf plant-derived54Jbstances usedas anticancerdrugs disruptthisprocessbyaffectingtheequilibriumbetweenthepotymerizedanddepolymerized
forms ofthe microtubules,therebycausingcytotoxicity
~
IU1Ml!iif®ijU611!.1,UHW (Cerubidine®) t • • • · • . {Adriblastin~)
llllli!l!lm lldamycin<) • • (EIIence<) lfl!ll!lll!mi (Valstar") ~
- Anthracyclines are used to treat various cancers and most important and widely used anticancer drugs (Doxorubicin ; ~ of the most important • Mechanism Qf action; inhibition of tubulin polymerization, which disrupts assembly of microtubules; This inhibitory effect results in mitotic a"est in
anticancer drugs) metaphase (M-phase), causingcelldivisiontoastop, whichthen/eadslocelldeath
- Mechanism !2[ Action; The Anthracyclines exert their cytotoxic action through 4 major mechanisms (cell cycle nonspecific); · Administration and EQA~ ; Vinca alkaloids Vincristine - Vinblastine - Vinorelbine;• N..Otii.Y; FATAL if given intrathecally
1) /nhibitionof topoisomerasell (anenzymeresponsibleforcutbothstrandsoftheDNAhelix) " Extravasationmayoccurs
2) High-affinity binding to DNA through intercalation, with consequent blockade of the synthesis of DNA and RNA
3) Generation ofSemiquinonefreeradicals and Oxygenfreeradicals · NEUROTOXICITY (Peripheral neuropathy, autonomic nervous system dysfunction with orthostatic hypotension, urinarv retention , and paralytic ileus or
4) Sinding to celfularmembranestoalterfluidityand iontransport
constipation , cranialnervepalsies,ataxia, seizuresandcoma); Vincristine > Vinblastine > Vinorelbine
- Pharmacokinetics ,
. All Anthracyclines must be administered IV (due to inactivated in Gl tract) - Syndrome of Inappropriate Secretion of Antidiuretic Hormone {SIADH); too much ADH and hyponatremia impaired water excretion .
-Mye losuppression (Vinblastine >Vincristine ) Nausea/vomiting & ~
• Extravasation can leadtotissuenecrosis
• Because of the dark red color; the veins may become visible su"ounding the site of infusion , and red discoloration of urine may occur
~ {Oncovin€1)
· They donot penetratetheSBB ortestes
- Anthracycllnes are metabolized e:densive/yintheliver and upto50% of drug is eliminated inthefecesvia biliaryexcretion ; -ltis used inthetreatmentof,
" Dosereduction is required in liverdysfunction. ·Acute Leukemia ·Hodgkin's Lymphoma -non· Hodgkin's Lymphoma • Neuroblastoma
· ~Effects ; · Irreversible , dose-dependent CARDIOTOXICITY; · Rhabdomyosarcoma -Wilms' Tumor. ·Ewing's Sarcoma . Multiple Myeloma
-Dueto freeradicalformationandothermechanisms - Ml!n.~effects ; Peripheralneuropathy , hyponatremia , constipationandalopecia
· More common wrth Daunorubicin and Doxorubicin than with ldarubicin and Epirubicin
- Addition of Trastuzumab to protoco/s with Doxorubicin or Epirubicin increases congestiveheartfailure l!lllll1Wllilili (Velban")
- Dexrazoxane {ZinecarcP)isa cardio-protectiveagent usedwith Anthracyclines andalsoavai/ab/eas extravasationantidote ·It is used in treatment of Hodgkin Lymphoma, non-Hodgkin's Lymphoma , Testicular, Kaposi's Sarcoma , Head and Neck, Bladder, Breast and Lung cancer
(Totect®)(Savene®)for treatmentof extravasation resultingfrom iV Anthracyclines. - Comrnon§.kt!effects; Myelosuppression and alopecia
-Liposomal-encapsulated Doxorubicin is/esscardiotoxic thanthe usuafformulation ~j (Navelbin~)
· Other Side Effects; Nausea, vomiting, arrhythmias, injection site reaction , urine dis~oloration , myelosuppression & alopecia -ltis lessneurotoxic than Vinblastine and Vincristine(Vinorelbine < Vinblastine < Vincristine)
• Doxorubicin or Adriamycin is QD! of the most important anticancer drugs in clinical practice, it also called I Red Devil Chemo ~ partly due to • Vinorelbine is used as first-line in treatment of advanced or metastatic non-Small Cell Lung Cancer {NSCLC ) as a single agent or in combination with Cisplatin
its red color. lthasa broadspectrum ofactivityand Q!l!t ofthe iD.Q!!effective anticancerdrugs forSolidTumors; -ltis off-labeluse inBreastandOvarianCaOcer.
-It is used to treat ~ Tumors; Cancers of Breast. Bladder, Stomach , Lung, Ovaries , Thyroid , Soft Tissue Sarcoma, Multiple Myeloma, - Vinorelbine like olher Vinca administeredparenterally; " l.'i..O.tii.Y; FATAL if gWenintrathecally
Liver and Others
-It is used to treat Leukemias , Hodgkin's Lymphoma and non-Hodgkin's Lymphoma
- DoxorubicinUposomai {Doxil«>);isa polyethyleneglycolcoatedliposome-encapsulated formo! Doxorubicin used to treatA!.Q§.-related
Kaposi's Sarcoma, Ovarian Cancer, ~.mW.Qm!and offlabe/for Breast Cancers other Solid Tumors; Doxorubicin Liposomal is · Taxanes are act as a mitotic spindle poison through high-affinity binding to microtubules with enhancement of tubulin polymerization.
lesscardiotox.ic lhantheusua/formulation
- Taxanes areactiveinthe G21M-phase ofthe cellcycle
- ldarubicin isa 4-demethoxy semisyntheticanalog of Daunorubicin , andthis increases its llpophillcity.ltis used in combination wlth Cytarabine · illlf11r. Hypersensitivitvreactlons, Neurotoxlcity (peripheralneuropathy), Myelosuppression and Alopecia .
asa flrstline treatmento!AcuteMyeloidLeukemia
· Taxanes like Vinca alkaloids are concentrated and metabolized in the liver by the CYP450 and eliminated in bile and feces; Doses must be modified in patients
- Epirubicin is approvedasadjuvanttherapy in patientswithaxillarynodetumor after surgeryremoveofprimarybreastcancer(node-positive with impalredhepaticfunction
patients). It is also used in Breast and Ovarian Cancer, Gastric Cancer, Lung Cancer and Lymphomas
liml!li!:!3 1TaxoP)
-Valrubicin enterscellsmorerapidly than Doxorubicin .lt isused inthe treatment of BiadderCancer (byinfusiondirectlyintothebladder;intravesical)
-lthassignificantactivityina broadrange of~ Tumors ; Ovarian , advanced (metastatic) Breast , Lung , Heada nd Neck , Esophageai , Prostate , Pancreatic
• • (Novantronel>); strucrureresembles the Anthracycline ring andBiadderCancersandAIDS-relatedKaposi'sSarcoma
. ~; · Advanced, hormone-refractory Prostate Cancer {combination with Predn isone)
· Premedication with Dexamethasone, Diphenhydramine and an H2 blocker to decrease Hypersensitivltv Reactions (Fatal anaphylaxis ) to Paclitaxel
·Low-grade non-Hodgkin's Lymphoma · Breast Cancer and Acute Myeloid Leukemias · Albumin-bound Paclitaxel (Abraxane®) form is also available and used in metastatic Breast Cancer, Lung Cancer and Pancreatic Cancer.
- Abraxane®is notassociated with Hypersensitivitv Reactions and Neurotoxicity morereadilyreversible than Paclitaxel
mm {Bienoxane®)
(Taxotere®)
- Docetaxel or Taxotere isasemisynthetictaxane used in advanced BreastCancer, LungCancer, Head &NeckCancer, GastricCancer and ProstateCancer
- Bleomycin is a small peptide that contains a Q!M·.!Wlf!i.!!g region and an l.r2n:.!Wlf!i.!!9 domain at opposite ends of the molecule; form DNA- - Abnormalliverfunction increaserisk of Docetaxel -associaled mortality
Bieomycin-fe2• complex. A DNA-Bieornycin-fe2• complex appears to undergo oxidation to Bleomycin Fel' . The liberated electrons react - Docetaxel shouldnot be used if neutrophilcount<1500cells/mm3.
withoxygen toform superoxideorhydroxylradicals,which,intum, attackthe phosphodiesterbonds of DNA,resultingin strandbreakageand
- Severe HypersensitivityReactions mayalsooccur.
chromosomalaberrations; Bieomycin is ce/lcyc/especific {G•phase).
• Metabolism ; Bleomycin is inactivated by hydrolase enzyme ; • the enzyme is widely distributed in normal tissues with the ~ of the !hln (Jevtan,.)
andl.Y.n.Q§;, bothtargets of Bieomycintoxicity - Cabazitaxel was approved by FDA for the treatment of hormone-refractory Prostate Cancer in 2010
· Resistance; ~ Increased levels of Bleomycin hydrolase or deaminase or glutathione S transferase enzymes - Cabazitaxel shou/dnot be used if neutrophil'count <1500cells/mm3
- lncreasedefflux oflhe drug. -DNArepairalsomay occur
- Severe HypersensltivltvReactions mayalsooccur
· ~; -Squamous Cell Carcinoma.-Hodgkin's disease -non-Hodgkin's lymphoma.-Testicutar Carcinoma.· Pleural Sclerosing
- ~Effects ;- Mucocutaneo u s {and iDill!) ~ (>50%);inc/uding rash , erythema , hyperpigmentation , urticaria andhypertrophicskinchanges
• Pulmonarv illi£l.!y !Bleomycin Lung); Pneumonitis w~h cough , dyspnea and pulmonary fibrosis (10%)
-Others; Mucositis, alopeciaand allergicreactions
.1:o , (lxempra«>)
(Mutamycin~)
- lt is used in aggressivemetastatic or /ocal/yadvanced BreastCancer.
-lt is used inthelrealmenlof Cancer ofthe Stomach orPancreas
-ttacts to stabilizemicrotubules.ltishighfypotentagent,capab/eof damagingcancercells in verylowconcentrations,and retainsactivity incaseswhere
• It is a/so used in treatment of Cancer of Anal , Bladder, Breast, Cervical , Colorectal , Head and Neck , and non-Small Cell Lung Cancer
tumorcells areinsensitiveto Paclitaxel (TaxaneResistance)or Anthracycline (AnthracyclineResistance)
. Common §.lst! effects; . Hemolvtic Uremic Syndrome {.!::!.Y,§)
- txabepilone shouldnot beused ifneutrophilcount<1500cells/mm3
I , I
- Severe Hypersensitivity Reactions mayalsooccur
• It is used in Wilms' Tumor (cancer of the kidneys that typically occurs in children), Ewing's Sarcoma, (is a rare type of cancer that occurs in bone~)
Gestational Trophoblastic_Neoplasm , Metastatic Testicular Tumors, Childhood Rhabdomyosarcoma, Trophoblastic Neoplasm and certam (Halaven®)
typesof OvarianCancer - Eribulin isa microtubu/einhlbitor usedin metastaticBreastCancer&Liposarcoma
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬

....
- AHormone-SensitiveCancer orHormone-Dependent Cancer; isatypeofcancer that is dependentonahormonefor growth.
- Examples; Breast Cancer, which is dependent on Estrogens, and Prostate Cancer, which is dependent on Androgens like Testosterone.

- Giucocorticoids interferewiththeconcentration, distr/bution and function of leukocytes

- Giucocorticoids promlnentlyusedin the treatment of BioodCancers.
mmm:m:l (Hostacortin")
V) Endocnne Therapy

-
!1&§1GfUtiii·W!jf#IN€H\ (Megace*)
- ltisa Progestin wffh antiandrogenactivity thatis lesscommonlyused inbreastand endometrial cancer .
• MGA is also commonly used as a supportive to treat severe loss of appetite (Morexia) and muscle wasting (cachexia) in patients with cancer or HIV/AIDS
· ~~ - Weight gain. · Edema (swelling, usually in the feet or hands).

~
- Breakthrough menstrual bleeding and spotting

...
- Prednisone is a potent synthetic, anti-lnnammatory corticosteroid with less mineralocorticoid activity than Cortisol.
- Prednisone is inactive and extenslvelymetabolizedinllver viahydroxylation to Prednisolone (active metabolite)and excretedrenaliy.
- Prednisone is primarily employed to Induce remission in patients wffh Acute l ymphocytic leukemia & both Hodgkin & non-Hodgkin lymphomas,
Multiple Myeloma&otherBioodCancers
- Prednisone also he/psto decreasenauseaaswellaspromote anappetite
· Estrogens, such as Ethinyl Estradiol, had been used in the treatment of Prostatic Cancer. However, they have been largely replaced by the GnRH
analogs because of fewer side effects (Thromboemboli, myocardial infarction, strokes, hypercalcemia, gynecomastia & impotence.)
- Estrogens /nh/b/t thegrowth of prostatlctissueby bfock/ng the productlon oflH, thereby decreasing thesynthesis of androgens in the testis
- Gonadotropin-Releasing Honnone (GnRH) is normaffy secreted by the hypothalamus and stimulates the anterior pituitary to secrete the Gonadotropic
Honnones (Gonadotropins); 1) LuteinizingHormone (lH); stimu/atesecretion of Testosterone
2) Follicle-stimulatingHormone (FSH); stimulatesecretion of Estrogen
• GnRH Analogs binds to the GnRH receptors and thus desensitizing the GnRH receptors and indirectly downregulates the secretion of Gonadotropins; lH
and FSH, /eading to hypogonadism andthusa dramatic reduction in Estradiol and Testosterone /evels regardlessof sexand, particularly usedinthetreatmenl
of Breastand Prostate Cancer.
jt!llitti11#M!G!!l1!i1®1 (l upron") ; llm!lil (Zoladex<) ;lii!BIIil (Decapeply~)
- Qlli; -AII GnRHAnalogs are used in; Prostate Cancer
- Leuprorelin and Goserelin are used in; BreastCancer, Endometriosis, uterine fibroidsandearlypuberty
- TriptorelinPamoate is off-labelused in; preparationfor lnVitro Fertilization (IVF)
· Common~~ Impotence, hot flashes, fatigue and depression

Bllllll.lll
Selective Estrooen Receptor Modulators ~ llillll!ll!!!tl
lmu:TiiiN~vadex<) lil!l!ilil!I:!I!Eulexin"):lliii!!miilll!IIAriandron"):IDI!!l!lliii!II(Casodex<)
·II is a Selective Estrogen Receptor Modulator (SERM); Estrogen antagon/stwith some estrogenic activity; selectively an~estrogenic in the breast - They are synthetic, no~steroidal antiandrogens (NSAA) used in the treatment of Prostate Cancer; are compete with the androgen for the androgen receptor
but estroge~like inbonesandendometrlum. · They are also used in Feminizing Hormone Therapy for Transgender Women and also used to decrease acne and excessive hair growth in women
- Tamoxifen is taken ora/ly dai/y for 5years · Common~~ Gynecomastia, breast tenderness, hot flashes, impotence & decreased libido

· It is metabo//zed intheliverby theCYP450 ~and CYP3A4) into active metabolites;

- Tamoxifen isan/nh/bltor ofCYP503A4, 2C9and2D6andP-glycoproteln
• Patients with variant forms of the CYP2D6 gene may not receive full benefit from Tamoxifen (because of too slow metabolism of the tamoxifen
VI) Monoclonal Ant1bodles
into its activemetabolites). SelectiveSerotoninReuptakeinhibitors (SSRis)can decreasetheeffecttveness of Tamoxifen
· f,/jg · First-line therapy in treatment of both early and advanced Breast Cancer. • Prevent Breast Cancer in women at high risk. • Monoclonal Antibody therapy is a form of immunotherapy that uses Monoclonal Antibodies (mAb) to bind mono-specifically to certain cells or proteins
• Ductal c.-clnoma in Situ (DCIS); abnonnal cells in of milk ducts in the breast - Prevent Estrogen-related Gynecomastia - MonocionaiAntibodies are d/rected at specifictametsandoflen have feweradverseeffects.
- mAbs canbe useda/one orto carrydrugs,toxins,or radloacttvesubstances directlyto cancercells. - 4majorantibody types thathavebeen deve/oped;
- Q!f~ Ovulatl on /nduction.
1) Murine (mouse); (suffix -omab); ' Cause allergic reactions and sometimes anaphylactic shock 2) Chimeric (65% human-mouse); (suffix -ximab)
• ~~ - Tamoxifen has thepotentla/ tocause Endometrial Cancer. -Hot flashes -Nausea and vomiting 3) Humanized (95%human); (suffix -zumab) 4) Human (100%fully human); (suffix -umab)
-Vaginalbleedinganddischarge. - Bonepaln. - Thromboembolism lil!l!!!!liimli iRHuxan")
_ li!ll'l!l!!miFaslodex<) - It is a genetically engineered, Chimeric Monoclonal Antibody directed against the CD20 antigen that is found on the surfaces of normal and malignant B
- It is a selective Estrogen Receptor Degrader (SERD), ~ works by binding to the estrogen receptor and destabilizing it, and down regulates estrogen lymphocytes.
receptorsandfnh/bltJbreasttumorgrowth. - ~ non-Hodgkin's l ymphoma, Chronic Lymphocytic Leukemia and Rheumatoid Arthritis
-ltisg/ven iM forHormoneReceptor-Positiveaclvanced BreastCancer. • Severe §lsi!~ Severe Infusion Reactions~ and TuilfliMin5:Ji7~~rceptine)
- Sideeffects; l/ke Tamoxifen.
-It is a humanized Monoclonal Antibody, specifiCally targets the extracellular domain of the HER2 growth receptor that has intrinsic tyrosine kinase activity
lilill!l:!!m !Evista<)
- lt is used in BreastCancer, Gastric Cancer and off-labe/ in PancreaticCancer.
-ltis a SelectiveEstrogenReceptorModulator (SERM); estrogenic in bone, but anti-estrogenic in breastand uterus.
- Severe~~ ~Failure ( worsenedwifh Anthracycl i nes) and AIIergicReactions
· Raloxifene is given oraffy for, - Osteoporosis in postmenopausal women
·Reduce th_e risk of Breast Cancer in postmenopausal women wffh osteoporosis. ~(Pe~eta<)
·Reduce the risk of Breast Cancer in women with high risk for breast cancer.
-ltis a humanizedMonoclonaiAntibody,specifica/ly targetsagainst HER2growthreceptor.
- Sideeffects; l/ke Tamoxifen -It is used as first-line in combination with Trastuzumab and Docetaxel for the treatment of metastatic HER2-Positive Breast Cancer
- Severe~~ ~Failure (worsenedwith Anthracyclines)and AIIergicReactions .
Aromatase Inhibitors (8!§)
~IAvaslin")
• Aromatase is an enzyme responsible for the extra-adrenal synthesis of Estrogen, which convelfs Androgens info Estrogens by a process called
- ltisan angiogenesisinhibitor (itworksbyslowingthegrowthofnewbloodvessels;withoutnewbloodvessels,tumorsdonotreceivetheoxygenandessential
Aromatizatlon;which takesp/ace inliver, fat, muscle, skin&breasttissues.
nutrientsnecessary for growthandproliferation).
- Peripheral aromati.zation is an Important source of Estrogen in postmenopausal women
- ~ · first- line in metastatic Colorectal Cancer. · Lu ng Cancer, Glioblastoma, and Renal Cell Carcinoma.· AgfHelated Macular Degeneration; AMO
- Aromataseinhibitors decreasethe productlon of Estrogen inthesewomen
• Aromatase is a member of the cytochrome P450 enzymes; It is CYP19A 1 - severe~~ Hypertension and highrisk i@ffiWij!ij(Erbituxe): ~ {Vectibixe)
- Aiscan be classlfledeitheras steroidal (typellnhlbitors)or non-steroidal (typellinhibltors), based oo theirchemicaistructure; -Theyare an epidennalgrowthfactorreceptOf (EGFR) inhibitor; oncogenes; inCreasedresponseto EGFRinhibitor -7 acne likerash
- TypeiiAromatasetnhibitors; suchas Anastrozole and Letrozole are !!2l~and work by /nterfering~ wilhthe hememoiety of Aromatase
- ~ Metas taticCol orectaiCance rand Head&NeckCancers .
enzymeoccupy its substrate-blndlng slte,thereby preventlngbindlng of androgenstothecatalytlcsite
- Common~~ Skin rash fatigue, nausea, diarrhea, fever and hypomagnesemia.
-ln contrast, TypeiAromataselnhibitors; Exemestane isananalogue ofthe natura/aromatasesubstrate.lt act.sas afalsesubstrate forlhe Aromatase
enzyme,and is processed to a n lntermedlate that b/nds~ tolhe activeslte of the enzymecausingits inactlvation ; suicideinhibition

~(Arimidex<J:I!!m:rl (FemaraO) limiZ!rlim (Cyramzae); Gastric Cancer, non-small Cell Lung Cancer and Colorectal Cancer - ~ (Arzerra~); Chronic Lymphocytic Leukemia (CLL)
· ~ · Hormone Receptor-Positive Breast Cancer of postmenopausal women . ~( KeytrudCfC); Metastatic Melanoma, non-small Cell Lung Cancer, Head & Neck Squamous Cell Carcinoma and classical Hodgkin Lymphoma (cHL)
- Prevent Estrogen-related Gynecomastia ~(lartruvoe); Soft-tissueSarcoma (STS). - ~(Gazyvae) ; Chronic LymphocyticLeukemia(CLL) and Follicular Lymphoma
- letrozole has been used for OvarlanStimulation. IIDl!rll!f! (Opclivoe); Metastatic Squamous non-small Cell Lung Cancer, Metastatic Melanoma, Renal Cell Cancer, Urothelial Carcinoma & Hepatocellular Carcinoma
- ~~ Hotflashes , jolntpalnand Osteoporosis ( Bisphosphonates are prescribedj - (Portrazzae); Metastatic Squamous non-small Cell Lung Cancer. -ll!lr&il!llllil (Yervo~); Metastatic Melanoma
lmlll!!l!D (Aromasin") - Zevaline); non-Hodgkin'slymphoma -~(E mplic~it);MultipleMelanoma -- lmfinzif>); UrotheliaiCarcinoma
- ~ -HormoneRecepto r-Positlve BreastCancer of postmenopausa/women . ~Da rzalexC);M u lti pleMyeloma -~Adcetris~); Hodgkin LymphomaandAnaplastic Large-cell lymphom a
·Reduce the rlsk ofBreast Cancer in women with highrlsk for breast cancer as an ~to Tamoxifen or Raloxifene. ~ B iincyto*); Precursor B-ceiiAcutelymphoblastic Leukemia - ~Bavenciot);MetastaticMerl<eiCeiiCarcinoma
- ~~ Hotflashes , nausea , fatlgue, jointpainand insomnia ~ecentriqe);UrotheliaiCarcinomaandMetastaticnon-smaiiCeiiLungCancer - ~Campath®); B-ceiiChronicLymphocyticLeukemia
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
VII) Tyros1ne K1nase Inhibitors IX) Non-C ioss 1f1ed
Chemotherapy - Tyrosinekinases area fami/y of enzymesthatareinvolvedinsevera/importantprocesseswithinacell, irdlding signaltransduction &celldivision wmm;mmt·11t)'H (Roferon~-A): iffitifi@if,ilt)'MI (lntron~ A)
- lnterferon-a-2a is approved for, Hairy Cell leukemia , Chronic Myelogenous Leukemia and AIDS-related Kaposi Sarcoma
• )Gieevec<) (Giivec<) - lnterferon-a-2b is approved for, Hairy Cell leukemia, Melanoma , AIDS-related Kaposi Sarcoma , and Follicular Lymphoma
- It is a Tyrosine Kinase Inhibitor, specific for abnormal BCR-ABL tyrosine kinase produced by Philadelphia chromosome in CMUALL -fxact mechanism bywhichthe lnterferons are cytotoxic is unknown
- lmatinib is ora/fy active and high/ybioavailable, metabolized viaC YP450 andexcretedinthefeces - Common~ Effects ; Flu-like symptoms and Gl upset

Cl... - lmatinib used to treat Philadelphia chromosome positive (Ph+); Chronic Myelogenous Leukemia (CML) &Acute lymphoblastic Leukemia (ALL}
- Other~; · Gastrointestinal Stromal Tumors (GIST). • Myelodysplastic/Myeloproliferative Diseases (MDS!MPD) I : D m m m (Kidrolasee)

co -Aggressive Systemic Mastocytosis {ASM)

- DermatofibrosarcomaProtuberans(DFSP)
- Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL)

- Common~ Effects ; Edema, skin rash, headache, fatigue, myelosuppression and arthralgia
-Someneoplasticcellsrequireanexternalsourceof Asparagine becauseof /imitedcapacity to synthesizesufficientamounts tosupportgrowth and function
(Cytotoxic)

~
- Asparaginase worksby breakingdown Asparagine
- Severe~Effects ; FiuidRetention andriskof severeCHF - Pegaspargase isa PEGylatedformu/ation of Asparaginase
• 1 (Tasigna«') - Asparaginase is used to treat childhood Acute Lymphoblastic
-It is a Tyrosine Kinase Inhibitor, stroctural/y related to lmatinib , it was approved to treat lmatinib-resistant Ph+ Chronic Myelogenous Leukemia Leukemia
-ltisalso used lolreat new/ydiagnosedPh+ CML

"'C - It is off-label use in Ph+ ALL and Gastrointestinal Stromal Tumors (GIST)
- Common~ Effects ; Skin rash, headache, fatigue, nausea, diarrhea and arthralgia
~ (Matulane•)(Natulan8)

c - Severe§.lst§.Effects; FiuidRetention and QTprolongation

•- 1 (Sprycel®)
- It is a Tyrosine Kinase Inhibitor, like lmatinib, it is used orally to treat Ph+; Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic
-ltis used totreat Hodgkin's Disease and Brain
Cancers (Cytotoxic)
-It inhibits MAO enzyme, patients should be
warned against ingesting foods that contain

~
Leukemia (ALL)
high levels of Tyramine , and ft may cause a
- Common~ Effects ; Edema, skin rash, headache, fatigue, diarrhea and myelosuppression
Disulfiram-/ike reaction
- Severe~Effects ; PulmonaryArteriaiHypertension
- Common ~ Effects ; Nausea, vomiting,
• • (Tarceva*) myelosuppression and alopecia
- It is Tyrosine Kinase-Epidermal Growth Factor Receptor (EGFR) Inhibitor, rt is used orally to treat non-small Cell Lung Cancer and Pancreatic

Q) Cancer.
- Common~ Effects ; Skin rash, anorexia, fatigue, nausea, diarrhea and arthralgia
- Severe~Effects (rare); Pneumonitis and Pulmonaryfibros i s
IM®Mt.lrfi'P§!!it!j (Zytiga• J
-II is a steroidal CYP17A1 inhibitor (Androgen

"""C • (Nexavar'l):
' (Tykerb")
- It is a Tyrosine Kinase Inhibitor, used to treat metastatic HER2-positive Breast Cancer (in combination with Capecitabine or Letrozole)
- Common~ Effects; Rash , diarrhea, fatigue , hand & foot syndrome and myelosuppression
• · (Sutent®)
synthesis inhibitor) which is used in
combination with Prednisone in metastatic
castration-resistant
(honnone-resistant or
Prostate Cancer
honnone-refractory
-Theyare ora/TyrosineKinasetnhibitor,used main/y in RenaiCeiiCarcinoma prostatecancer);thedrugis veryexpensive

:::J - ~; - Sorafenib ;- Advanced Renal Cell Carcinoma - Advanced Primary Liver Cancer
- Radioactive Iodine Resistant Advanced Thyroid Carcinoma
- Sunitinib;- Renal Cell Carcinoma - lmatinib-resistant Gastrointestinal Stromal Tumor (GIST) - Pancreatic Neuroendocrine Tumors
-ltisa stronginducer of CYP3A4 anda moderate
inducer of CYP2C9 and CYP2C19
- ~Effects ; Hypertension . hypokalemia , fluid

<.9 - M.Qg Common~ Effects ; Rash , diarrhea, fatigue, hand & foot skin reaction syndrome , hypertension and myelosuppression
- OtherAge~ts are used in RenaiCeiiCarcinoma {RCC );
-lil!mm!l (Votrient®); Advancedlmetastatic; Renal Cell Carcinoma & Soft Tissue Sarcomas
- ~ (Torisei');AdvancedRenaiCeiiCarcinoma
- ~ {Afinrtor'I);Renal Cell Carcinoma, Breast Cancer and Neuroendocrine Tumors
retention , urinary
hepatotoxicity
tract

lm!l!l!lmi!!I IXtand~)
infection &

ro
-mm!C!(II or • • (Proleuki~); Metastatic Renal Cell Carcinoma and Metastatic Melanoma
is an oral synthetic non-steroidal
-: (Avastin®); Renal Cell Carcinoma, metastatic Colorectal Cancer, Lung Cancer, Glioblastoma, and Age-related Macular Degeneration
antiandrogen
-It is used in metastatic castration-resistant

r~
ProstateCancer;thedrugis veryexpensive
V III) Topoisomerase Inhib ito rs

E
L...
- Inhibition of topoisomerase enzymes (which aids in DNA unwinding), prevents re-ligation of the DNA strands, and by doing so causes DNA strands
to break (Cancercellsrelyon thisenzymemorethanhealthycells,sincetheydividemorerapidly)
- Side effects ; Gynecomastia, asthenia, back
pain, hotflush, fluidretention and riskof

'
0
'

ro (Toposar®) · (Vumon•)
- They are semisynthetic derivative of Podophyllotoxin from the rhizome of the wild mandrake (Podophyllum peltatum)

..c
-Theya~ Cytotoxic ( lateS-to G2phase ; inhibitTopo i somerasell )andavai/ab/ein Ora l and iV formu/ations
- Etoposide is used for refractoryTesticularCancer and Smaii-CeliLungCancer
B LEOMYCIN/
- Teniposide is used for refractory childhood AcuteLymphoblasticLeukemia
~~

a...
- Common~ Effects; Nausea, vomiting, myelosuppression and alopecia

~
lllll!m!li!!III 1Hycamtin8) : (Campto&)
-Theyaresemisyntheticderivatives of Camptothecin .Theyare Cytotoxic (Sphasespecific; inhibitTopoisomerasel )
- lrinolecan avai/ab/e !V formu/ation,while Topotecan avai/ab/ein Oral and iV formu/ations

38
- Topotecan is used in metastaticOvarianCancer, CervicaiCancer and Smaii-CeiiLungCancer
- lrinotecan is used with 5-FU & Leucovorin for treatment of Colorectal Carcinoma
- Common~ Effects; Diarrhea, nausea. vomiting, myelosuppression and alopecia
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
ImmunE!
Immune System
SystBm Hypersens1tiv1ty Immunosuppressants
- Hypersensitivity isanundesirab/ereactions producedbythe norma/immunesystem

c.. -Theyare usua//yreferred toasan over-reaction ofthe immunesystem andthesereactionsmaybe

damaging , uncomfortable,or occasiona//yfatal
l) G lucocortico1ds 2) Caloneunn (CaN) lnh1b1tors

co - Hypersensitivity canbe c/assified~;

- Antibody-mediated; threetypes ofhypersensitivity(types l- 111)
- Cel1-mediated ; onetypeofhypersensitivity{typeiV)
-The corticosteroids werethe firstpharmacologicagentstobeusedas immunosuppressives,both
intransplantationand in variousautoimmunedisorders
- Glucocorticoids aredescribedin EndocrineSystem chapter.
- Calcineurin (CaN ) is a Calcium & Calmodulin dependent Serine/Threonine protein
Phosphatase
· CaN is responsible fordephosphorylating NFATc (cytosolic Nuclear Eactor of Activated I s;ells),

~
- Hypersensltivity occursin !wQR!l!m - /mmunosuppressioneffects;(anti-inflammatoryeffectsseeendocrinechapter) which is necessary for the activation of aT cell- specific transcription factor (NFATc are
-Sensitizationphase; initia/encounterwithan antigen (firstencounter) importantinthe transcription of ll·2genes)
-Effectismainfydecreases inthe functionand numbers of lymphocvtes (Bcellsand Tcells)
- Effectorphase ; immunologicmemoryand resu/ts in tissuepathology . ~-Calcineurin-NFAT~~;

-c Type-----'----AI~e;~:~ ___l_~~::l:~ Mediators Description

-Symptomsusuallyoccurringwijhin minutes
- Giucocorticoidssuppress~·mediated !mm!ml!vbyinhibiting genes that code forthe
cytokinesll-1 , 1L·2, 1L·3, 1L-4, 1L·5, 1L-6, 1L·8and1FN·y(themostimportantofwhichisll·2)
-IL-2alsopromotesthedifferentiationof Tcells intoeffectorTcellsandintomemoryTcells
-Ca2•entryviatheopeningofCa2•releaseactivatedCa2•(CRAC)channels
-SubsequentelevationofintraceffularCa2•1evelsresultsintheactivationofalargenumber
of Calmodulin (CaM)-dependent enzymes including the serine-threonine phosphatase

c
- Giucocorticoids alsosuppress the humoral !!:!l!mmily calcineurin
·Free antigens cross link !he lgE on mast
Atopy · Glucocorticoids cause 8 cells to expresssma/Jeramounts of IL·2 and of ll-2 receptors. This -The transcription factorNFAT is dephosphorylated and activatedbycalcineurin andin
"Allergy" cells and basophils which causes a
Anaphylaxis lgE diminishes both Bcellcloneexpansionandantibody synthesis tum controlsexpressionofnumerousgenes (suchas ll·2genes)
(immediate) releaseofinflammatorymediatorssuchas
Asthma · Giucocorticoidsinhibitsprostaglandin and leu kotrienesynthesis, and increases the catabolism ~ (SandimmunNeoralf>)
histamineandleukotrienes

~
-TestingbyskintestforspecificlgE
·Anlibody (lgMorlgG)bindstoantigenona
targetcell, whichisactuallyahostcelllhat
lgMorlgG
"Cytotoxic' is perceived by the immune system as
foreign, leadingtoce!lulardestructionvia
of lgGantibodies
-ltisused(orallyoriV)for;graft.versus-hostdisease(GVHD) in bonemarrowtransplantation ,
prevent organ rejection in organ transplantation .(Kidney, Liver and Heart), rheumatoid
arthritis, psoriasis, Crohn'sdlsease and nephroticsyndrome
3) MechoniSflc Torgel Of RopomyCin (mlORIInhlbllors
- Cyclosporine eyedrops (Restasis~)usedfor KeratoConjunctivitls Sicca (severe dry eye)
- Metabolism ; primarily by CYP3A4 and is a substrate of the P..glycoprotein (P·gp) efflux pump

Q) "lmmu11e
Autoimmune
the MAC
·Antibody (lgG) binds to soluble antigen,
formingacirculatingimmunecomplex
• mTOR inhibitors are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR),
which is a serine!threonine·specific protein kinase that belongs to the family of
phosphatidylinositol-3kinase (PI3K) relatedkinases (PIKKs).
• Toxicity; NEPHROTOXICITY, hypertension , hyperglycemia , liver dysfunction , hyperkalemia,
alteredmentalstatus , seizures, gingivalhyperplasia and hirsutism
ll!Zlllmi!!!I (Prograf')
(Nephritis, · mTOR regulates cellular metabolism. ~. proliferation and angiogenesis.

"""C
Complex lgG -Thisisoftendepositedinthevesselwallsof -ltisa macrolide (23-memberedmacrolidelactone) ca/cineurininhibitor.
Arthritis, · PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell
Disease" the}ointsandkidney, initiatingalocal • II is nQ! chemically related to Cyclosporine , f2Y1 their mechanisms of action are similar,
Vasculitis) cycle; There are many known factors that enhance the PI3KJAKT pathway including; Epidermal
inflammatory reaction. -Cyclosporinebindstocyclophilin,tacrolimusbindstotheimmunophilinFK·bindingprotein (FKBP)
growthfactor(EGF),Sonichedgehog(shh), lnsulin·likegrowthfactor·1 (IGF-1 ), insulin, andcytokines
"Delayed-type -Responses occur2-3days (like iL-2) • Tacrolimus is preferred over Cyclosporine because; increased potency (10-100 times),
hypersensitivity -HelperTcells(specif!CallyThtcells)are decreasedepisodesofrejection
• mTOR inhibitors include; Sirolimus (Rapamycin) as well as its analogs (called ' rapalogsj such as

::J (DTH)"
'Cell·
mediated'
'Antibody·
activatedbyanantigenpresentingcell
Whentheantigenispresentedagaininthe
future,thememorylht cells will activate
macrophagesandcauseaninflammatory
Everolimus and Temsirolimus
(Rapamune•)
· lt isa macrolide, avai/ableon/y asanoraldrug (high-fatmealscandecreaseabsorplion)andhasa
· Metabolism ; primarily by CYP3A4 and is a substrate of the P·glycoprotein (P·gp) efflux pump
·It is used (orallyoriV)for preventorgan rejection in organtransplantation (Kidney, liver and
Heart). It is NOW considered a standard prophylactic agent (usually in combination with
Methotrexate or Mycophenolate Mofetil ) for GVH disease

<.9
indeoendent• resoonse.Thiscanleadtotissuedamaae longha/f-/ife (57to62hours) . Jacroiimus ointment (Protopite);usedfor atopicdermatitls , psoria.sls and vitiligo
· Met~bolism ; primarily by CYP3A4 and is a substrate of the P..glycoprotein (P·gp) efflux pump. · Toxicity; NEPHROTOXICITY, NEUROTOXICITY, hyperglycemia , hypertension and
- Sirolimus is used in renal transplantation and for LymphAngioleioMyomatosls (LAM). hyperkalemia
Immunoglobulin Therapy -ltalso used in coronarystentcoating ; Antiprofiferativeaction; inhibitrestenosisofthe blood
vessels by reducing proliferation
~ (Elide~)
· Like Tacrolimus.lt is available as a topical cream; usedfor atoplcdermatitis, psoriasis and
·It has been used effectively alone and in combination with other immunosuppressants

ro
- Immunoglobulin therapy; is the use of a mixture of antibodies (immunoglobulins) vitiligo
- lmmunoglobulinformulations arealsoavai/able inc/uding (.!!QlVaccines)
• Immune Globulin Intravenous (IGIV) • Rho(D) Immune Globulin
_~d~~~i~~~~~~~nri1~e~~;:;~u;i:1m~~~~~::ni~ l;:a~~:~:i~r~~:~~~tic
- Side effects; HYPERUPIDEMIA, headache, nausea, diarrhea, leukopenia and thrombocytopenia
• Hepatitis B Immunoglobulin (HBIG) • Rabies immunoglobulin (RIG)
- Combination of Cyclosporine and Sirolimus is more nephrotoxic than Cyclosporine alone. 4) Mycophenolates
. Tetanus Immune Globulin IG . . VZV aricella Zoster Virus) Immune Globulin

E therapy~is~u~sed~in~a$va~rie~ty~of~col!!!nd!Jl1itio~ns~.ra~ngj~:~~m=u~~~~~~~:~eficiencl es
(Zortress~)
-ilisan mTORinhibitor. - Mycophenolicacid (Mycophenolate) inhibitsanenzyme neededfor growthotT cells &Bcells
• IGIV tQ
- Mechanism and sideeffects; Like Sirolimus f2Y1shorterhalf·life andrequirestwice-dailydosing · Mycophenolate Mofetil {MMF) is a semisynthetic derivative of Mycophenolic acid
autoimmune disorders to HIV disease to bone marrow transplantation -ltreversiblyinhibitsinosinemonophosphatedehydrogenase,theenzymethatcontro/sthe
-It is approved for renal and liver transplantation , advanced renal cell carcinoma, breast cancer
• t (RhoGAM' )(Rhophylac®) and neuroendocrinetumors (NET)of GI , Iung or pancreas rate of synthesisof guaninemonophosphate inthe denovopathway of purinesynthesis
5-. . Rho(D) Immune Globulin contains human lgG antibodies against the Rho(D) antigen of red cell
- ~ in Rh-negativemotherwithin24-72hoursafter the birth ofanR h-positiveinfant, to preventRh
usedinthe proliferation of B & Tcells
·The salvage pathway of purine synthesis in lymphocytes is less active than the de novo

ro hemolyticdisease ofthe new-borninsubsequentpregnancies

5) Cytotox1c Agents
6) Immunosuppressive Ant1bod1es synthesis of purines .
im'tifflilMMt)VJifflHi (CeiiCept®) im'tiffliljftftfflM§iffiM (Myfortic®)
- Mycophenolate Mofetil and Mycophenolate Sodium are hydrolyzed to Mycophenolic Acid

..c E!'.!!lJll!!l!l (lmuran')

(synthesized and administeredas Mofetil and Sodium saltstoenhancebioavailability).
• Mycophenolate Sodium (Myforti te); ~.releaseenteric..coated tablets ; to minimize the Gl
sideeffects associatedwith MycophenolateMofetil

a... -ltwasthe firstagent to achievewidespreadusein orga.n transplantation

-llisa prodrug of Mercaptopurine and, /ike Mercaptopurine,functions asan antimetabolite (seecancer
chemotherapy).
• II has been more widely used than Mercaptopurine for immunosuppression
· Metabolism ; inthe liver; Azathioprine is convertedto &.MP andthenconverted inthe liver tothe S.
methylmercaptopurine derivative orto lhiouricacid (an inactivemetabolite this reaction iscatalyzed
by xanthine oxidase; Allopurinol increased levels of S.MP, thereby leading to excessive toxicity);
- Mycophenolates has,forthe mostpart,replaced Azathioprine because ofits safety andefficacy,
Mycophenolates is 15timesmoreexpensive than Azathioprine
- MycophenolicAcid is used in solidorgantransplant (Kidney, liver & Heart)in combination
with Corticosteroids and Cyclosporine or Tacrolimus
-N.QW; Mycophenolates are increasing application in autoimmunediseases ; systemiclupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis &
psoriasis.

39
Azathioprine dose shoufdbereducewhenusedconcurrentfywith AIIopurinol
. ~ ; Kidney Transplantation and Autoimmune Diseases (such as rheumatoid arthritis, Crohn's
diseaseand ulcerativecolitls)
• Common~ Effects ; Nausea, vomiting, diarrhea, myelosuppression and hepatotoxicity
. Toxicity; Gl DISTURBANCES (nausea, vomiting , diarrhea and abdominal pain ) headache,
DD.RillflD~~~-ii#~l:mmil!li (ATGAM') hypertension and reversibfemyelosuppression (primari/y neutropenia)
-Theyareaninfusionof animal.antibodies against humanTcelis whichis used inthe treatmentof • Pregnancy ; Mycophenolic acid is associated with miscarriage and congenital malformations
acuterejection in organtransplantation and aplastic anemia • Antacids (Magnesium or Aluminium), or wrth Cholestyramine, can decrease absorption
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
HypDthalamic Pituitary HDrmDnes
lntroductron Hypotholmnrc Ho rm o r1 es
>llajorendocrine glands inc/ude:-
-Pineatgland -Pituitarygland -Parathyroid gland - Thymusgland
-Thyroidgland - Adrenalglands -Pancreas -Ovaries alld Testes
> Typesof glands:- · GrowthHormone isa large polypeptide (191-aminoacid)thatis releasedbysomatotroplccells
A) Exocrine Glands; Release their cellular secretions through a ~ which empties to the outside or inthe anteriorpituitary inresponseto GrowthHormone-releasingHormone producedbythe
into the lumen of an organ .Suchas; sweatglands, salivary and pancreaticgtands hypothalamus
andmammaryglands. !ifl!considered a part ofthe endocrinesystem. - Stimulators of GH secretion;
B) E ndocrineGian ds; - fj!l!contain~ and re/ease their secretions!iJ!!£1!.i: intothe bloodstream · Growth Hormone-releosing Hormone; GHRH (Somatocrinin)
-Cof/ection of endocrineglands makesupthe endocrinesystem - Ghrelin (hungerhormone)via bindlng to growthhormonesecretagoguereceptor (GHS-R).
> llechanismofActionofHonnones:- - Deepsleep, fasting, hypoglycemia and vigorousexercise
L p d solub lr Horrnonf'~ Water-soluble Hormones - Sex hormones.
(Cell Mem brane Receptors) - Arginine, Clonidine, L-OOPA, Nicotine and Niacin (Vrtamin & )
- Genomic action; by dlffuse through the cell • Non-Genomicaction; by binds toa receptor - lnhibitors of GH secretion;
membranesoftargetcells then binds loa protein on the cell membrane of the cell -o - Growth Hormone-inh~Jiting Hormone; GHIH (Somatostatin)
receptor protein that activates DNA stimulates production of second meuengers - Circulating concentrations of GH & lnsulin·6ke Growth Factor-1 UGF-1) via negative
transcriptlon of specJffcgenes -o mRNA -+ -Second messengers such as cAMP, IP3, feedback on pituitary and hypothalamus
syntltts/s ofenzymes -o regu/lfespeciflc Calcium-calmodulin system and cGMP - Giucocorticoids and hyperglycemia
physiological cell activity - ~; Protein, Polypeptide and moslof - Mechanism of Action; after binding to GH receptors -> activate variety of signaling molecules
- ~; SteroidHormones. Amino Acid Hormones. -> increase in the production of Insulin-like Growth Factor 1 (IGF-1) (Somatomedin C)
-~
- Effect on Growth; lncreaseproteinsynthesis and celldivision -o lncreasenumber and!i!f!
of cell -+ lncreasesize of tissue and organs
· Effect on bone;
A) Before and duringpuberty {beforeunionofepiphysis);
0
==-
=
- /ncreaselineargrowth ofbone
- /ncreasethickness of bone
B) Afterpuberty (afterunionofepiphysis)-o lncreasethickness of bone
- Effect on Metaboiism;- f!QIDn; anaboliceffect

==
0

=- o :;;=-
~R 16 fH
A)Con!rolofHo rmorwSccretro rl
Negafrvefeedback ( )
-lncrease inhormonel!1h.llH1! further secretlon -/nCfNiein hormone111lmlJJJ!.furthersecretlon
-~;-t TJ& T•-+! T SH -o! TJ & T.
· ! TJ& T.-oj TSH- i TJ& T•
8) Receptor Rcgu l ~tron
Oow;;reguia-ho-n- -
- Prolongedl!1&!!JD. in hormonesecretion -Prolonged~inhormonesecredon
~number of cellreceptors and
lhereby ~cellresponse
:> Hypothalamic Hormones:-
ThyrolroprnreleasrngHormone TRH
Oopamme
ProiactrnrnhrbitmgHormone PIH )
Growth Hormon~~~~asrng Hormone
Somatostatrn (SS)
(Growth Hormone lnhrbrtm Hormone GHIH )
Gonadotroprn rcleasrngHormone GnRH
CortrcotropmreieasmgHormone (CRH )
Vasopressm
(AnlrdruretrcHormone ADH )
Posrttve feedback (+)
-~; Uterine contractions~r~~
11 contractionHt!Oxytocin
Up regulatiOn - - Dopamineagonists (Bromocriptine and Cabergoline).
1M!J.u! nurnlw of cell recepton and
thereby 1!Jm1H cell mponoe.
- Stimulate Thyroid-stimulating Hormone (TSH)
re/use from anteriorpituitary.
-Inhibit Prolactin (PRL) release from anterior
pituitary
- Stimulate Growth Hormone (GH) release from
anteriorpib.Jitary
- Inhibit Growth Hormone (GH) release from
anteriorpib.Jitary.
- Stlmulates follicle-stimuiatingHormone (FSH)
and luteinizingHormone (lH) re/use from
anterlorpib.Jitary
Stimulates Adrenocorticotropic Hormone
(ACTH) release from anteriorpituitary
-StlmulattsYIIrtnt..!Illl..mt~a nd
!!I!IH of m!!!!by !!Y!!!!!!ml!llnn (storedand
secrered into bloodstream by posterlorpttultary)
- Stimulates~reabsomtlonby kldneys
(stored and secreted into bloodstream by
posterior pituitary)
Proloctrn (PRL) Hormone
- Carbohydrate· Diabetogeniceffect; lnsulin-antagonistic
- Fat Increase lipolysis
- Disturbance of GrowthtiOOOOne ~
A) Hypofunction (Dwarfism); Adult height of less than 147cm; ! size of trunk & all extremities
B) Hyperfunction; · Aaomegaly; increaseGH secretion after puberty ~union of epiphysis)
- Gigantism; increaseGH secretionbeforepuberty {~unionof e piphysis)
- Pro/actin (PRL)isa 198-amino-acid peptidehormone produced inthe anteriorpituitary AI Growth Honnone Analogues
- Its structure/mechanism resembles that of GH ~ (Humatropee)(Norditropine)(Genotropin*)
- Prolactin is primary function is to stimulate and maintain lactation. in addition, ~ decreases sexual - it is a recombinant human Growth Honnone, is administered by SC or IM injection.
drive and reproductive function - ~;- GrowthHormoneDelfci&ncy.
- Stimulators of Prolactin secretion; -Short-bowel Syndrome
· Dopamineantagonists (suchas ChlorpromaDne) -HIV-assoclatedWastlngorCachexia
- lnhibitors of Prolactin secretion; - Off/abet. -Enhanceperformanceby athietes
---:oopamine {Prolactin-inhibitingHormone; PIH) · -As Anti-agingHormone inantl-aglngprograms
~ {lncreiex®): $M§bH§wij,p ·Jmt1fifitjl (tplex®)
- C/rcu/atlngconcentrations of Prolactin via negativefeedback on pituitary and hypothaiamus - Mecasermin isa recombinant human lnsulin-likeGrowth Factor·1 (rhtGF-1)
· Disturbance of Prolactin ~ - Mecasermin Rinfabate is a combination of rhiGF: 1 and insulin-like growth factor binding
A) Hypoprolactinemia; serum Prolactin levels below than normal, it is ~rare condition. protein-3 {1GFBP·3). 1GFBP-3 serves to pro/ong theaction of iGF-1.
B) ~; abnormaiiyhighlevels of Prolactin inthe blood - ~ Long-termtreatment ofgrowthfallureinchildren withsevereprtmaryiGF-1deflciency
- ~; (Primary IGFD) or with GH gene deletion or GH insen sitivity (La ron syndrome)
· M2!!£2!!1!Wl!!~Effects; hypoglycemia
- ~;
- Oligomenorrhea or Amenorrhea and Galactorrhea Bl Growth Hormone Antagonists !Somatostatin Analoquul
- lnhibitovulation;duetohypogonadism(!gonadotropin;FSH& LH)-oinferlility.
- Loss of libido; iossofsexdrive
l!l!mm {Sandostatine)
- Octreotide isthe mostwide/yused somatostatinanaiog
- Painfulintercourse; duetovaginaldrynessduetotestrogen
- ~; - Acro megaly , Carcinoid Tumors and Vasoactive Intestinal Peptide Tumors
-.M!!!; .
- Qff~!!lli; Esophagealvariceaibleedlng
- Loss of libido & lmpotence (erecti/edysfunctlon);hypogonadism (!testosterone) • V"rtamin Bn deficiency may occur with long-term use of Octreotide
- lnfertility and Gynecomastia;benigneniargementofbreasttissueinmaies -M2!1 Common~ effects; Gallbladder problems (reduction of bile production and gallbladder
- Treatments· ~~ oontractiiity,whichieadstoincreasedvisoosityofbiieandincreasedincidenceofgallstones)
~ (Lactode~)(Parlode~) ~ (Dost;nex<) I ! ! D m !Somatulin.. Depot)
- lanreotide reducing GH and normalizing IGF-1 levels (Octreotide decrease GH and IGF·1
- Bromocriptine is an ergot derivative, is used in the lreatment of Parkinson's disease,
levels)
Hyperprolactinaemla, Neuroleptic Malignant Syndrome (NMS) & Type 2 Diabetes
- Ha/,.life; 23 to 30days (Usuailydose;90-120mgSCevery4Week)
- Cabergoline isa long-acting dopamineagonist witha highafflnity for 02reeeptors, is used in
- ~;Acromegaly and Gastroenteropancreatic Neuroendocrine Tumors
Hyperprolactinaemia
- ~effects;Uke Octreotide
- Common !ilJ!.!. Effects; drowsiness, nausea, headache, dizziness and vertigo ~ {Somavertt)
• Bromocriptine and other ergot derivatives, used with caution in patients with history of myocardial - Pegvisomant isa GH receptorantagonist usedinthetreatment ofacromegaly
infarction or perlpheralvasculardisease - ltisthe polyethyieneglycoi {PEG) derivative ofa mutant GH ,Iike native GH.
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Endocrine
Hypothalamic Pituitary Hormones
System Ac::renocortlco 1rop c Hormore (ACTHJ
- Adrenocorticotropic Hormone (ACTH ) or Adrenocorticotropin or Corticotropin is a
Ant1d1uret1c Hormone (ADH) or Vosopress1n
Cl.. po/ypep6de honnone(39amlnolclds)~and~byCortk:ob'ophcellsinthe
anterior pituitary in response to Corticotropin 1'eleasing Hormone (CRH ) from the
Oxytoc1n

cu hypothalamus
- ACTH increased~and!!ftiHof Cortisol bythe cortex ofthe adrenalgland .
- Plasma ACTH & Cortisol ~vels uhlblt TIIUI!I (6-1 AM) & I !!J!!!!l (11 PM)
- Antidiuretic Hormone (ADH ) gr Vasopressin !;! Arginine Vasopressin (AVP ) Qf Argipressin are
peptide hormone consisting of 9 amino acids (nonapeptides), and is structurally related to
- Oxytocin isa 9-amino-acidpeptide w~hani ntrapeptidedisulfidecross-link like Vasopressin ,
aminoacidsequencediffersfrom thatof Vasopressin at positions3and 8
rut!

~
Oxytocin
- Stress and during circadian regulation - tctlvationof neurosectefoty CRH from the - Vasopressin is re/easedby the posteriorpituitary inresponseto; - Function ;
hypothalamus -+ stimulate ACTH release from the anterior pituitary -+ stimulltes the -t plasmatonlclty (hypertonicity) = f plasmaosmolality (hyperosmolality).
~glabour(UterineContraction );
secretionof Giucocortlcoids fromtheadrenalcortex. -/n sma//doses ; incrNses both the ~a ndthe~of uterinecontractions
-! bloodpressure
-Ai higherdoses ; produces ~contraction
~ -Bmsll51!1: - Oxytocin also stimulates the release of Prostaglandins and leukotrienes that !!l91!!!!1!
"'0 ~ or~(Synacthen<)
- WaterRetention(Anti-diuretic) Effect ;
- Vasopressin binds to the V2 receptor - increase formation of cAMP which causes uterine contraction.

c IG'Mt.tfGMI ·ft'Mlst (synacthen' Depot)

- Cosyntropin use as diagnostic agent in achnocortical insufftcleney (ACTH stimulation test);
dffferentiatlngbenreen ~adreoalinsufficiency (Addison's diseasewhicha:lreoalglands
donotproducesufficientglucocorticoidsandmineralocorticoids)and ~adrenal
lnsertionproteinwaterchannelscalled Aquaporin -2 inthe tubularcell - increase
permeability d these cells - incrHse water reabsorption by passive diffusion
(osmotic gradient)
- Duringlactation/Suckling(MilkEjection );
- Oxytocin also causes contraction of myoepithelial cells surrounding mammary alveoli ,
which/eadsfo milkejection.
- .Mi.!..!!.~~ ; Suck/ing bytheinfant atthe nipple is relayedbysp lnal nerves tothe
- Vasoconstriction Effect ;

~
insufficiency (caused by the inadequate secretion ofACTH bythepituitary); f!!:i!:!J!rtadrenal - High ccncentration rJ Vasopressin can cause vasoconstriction by binding to V1a hypothalamus,causing; Oxytocin and Prolactin re/ease fromtheposterior pituitary
insufficiency gaagJ be stimul•ted by ACTH where a ~ adrenal insufficiency wiD receptors {viaactivation of phospholipaseC; PlCandconsequent releaseofCa2• fromthe - Without Oxytocin -inducedcontraction, norma/lactationcannotoccur
!Dil!l!Hl to adequ•testimulatlonwith ACTH . - DuringSexuatlntercourse (Orgasm );
sarcoplasmic reticulum)
- Oxytocin (loveHormone) is nowbe/ieved tobeinvolved inawidevariety of physiological
- Other Effects ;
l@fiM@htf•tl'M•iU•folliiliftitfiJ (HP Adhare Gel)
- V1 (V1A); Vasoconstriction, stimulate gluconeogenesis, platelet aggregation and and pathologicalfunctions suchas sexualactivity , orgasm , and ejaculation , maternal
- Uses; Infantile spasms, muttiplesclerosis, rheumatk:disorder, inftammatorydennatologic behavior, socialbonding, stress ancl probab/ymanymore

(]) diseases,inflammatofyophthalmicdiseases,symptomaticsarc:oidosis&edematousstate.
release of factorVJII andvonWillebrand factor.
- VJ (V1B); Stimu/ate ACTH secretion from pituitarygland.
- Disturbance of Vasopressin Function ;
- Other;
-At highconcentrations , Oxytocin has ~antidiureticandpressoractivity dueto
activation of Vasopressin receptors
A)~; Syndrome of lnappropriateAntidiureti c H ormoneSecretion (SIADH )

"""C Thyro1d-St1mulot1ng Hormone (TSH)

· Thyroid -stimulating Hormone (TSH ) or
B)~; Diabeteslnsipidus .

v...,..essini!!J!!J!!~
~i!!!!!l!!~
~ (Pitocin•) (Syntocinon•)
- Oxytocin injection is a synthetic Oxytocin hormone for IV intJ.Lsiim or iM use
Thyrotropin isa g/ycoproteinhormone l'l.'li!ll'!lZm(Vasostrid")lllEi!l!l!!!lli(DOAVP')(MinirinO) - ~ ;-Laborlnductlon --

::::l synthesizedandsecretedbythyrotrope
cellsintheanteriorpltultary,inrr!sponseto
Thyrotropin-releasingHormone (TRH )from
the hypothalamus.
- ~.
- Desmopressin ;- Diabeteslnsipidus
-Hemophilia A and von Wilebrand chease (Type 1).
-Bedwetting (NoctumaiEna.esis) andNighttimellrination .
- PostpartumHemorrhage
- Adjunctive therapy in the management of incomplete or inevitable abortion .
- Nasal spray (Off-label); Promote Lactation, Autism , Delayed Orgasm &Intensifying Sexual ArOllsal

(.9
- WARH!.N1G; fxcessive stimulation of uterinecontractionsbeforedelivery cancause fetafdistress ,
- TSH regulates the endocrinetunctlon rJ ihe - Vasopressin ; placental abruption , or uterine rupture; Oxytocin injection in Labor Induction is
thyroidgland -to synthesize anclrelease - IMISC; Diabetes Insipidus, Abdominal Distention and Abdominal Roentgef1C9aphy administered Qti!.1 by the IV infusion & with adequate medical supervision in a hospital.
Thyroxine (T, )anci Triiodothyronine (Ts); - IV/nfusion;Esophagealvaricealbleedingandcolonicdivertiadarbleeting
- Sideeffects; -Headache, nausea, abdominal cramps and agitation. mmmli!lii(DuratodnO)~ (Sandopart')
-The effects of Ts34 times!!!Q!J:potent than
r •. - Overdosage can resu~in hyponatremia and seizures -Theyare notapproved by USFDA, but approved insomecountries for Y§§!!. toinducelabor,promote

ro
lactation , andpostpartumhemorrhage.
~ ~~~ ~~
~ (Thyrogen") l!!lml!lill!!il lllll!li!'m
- Thyrotropinalfa isa recomblnantTSH
(Vaprisol') (Sams<:a")
- Conivaptan and Toivaptan are approved bytheFDA for treatmenrfor hyponalremia associated
l.m!!m (Tractodl..)
- ~; asadjunctivediagnostictool -Atosiban isan Oxytocin receptorantagonist thalhasbeen approvedoutside lhe UnitedStates asa

E
wlthCHF, drrhosisandSlADH
treatment (tocotysis) forpretermlabor (tocolyticagent)

Gonodo·rop rs
L... - Gonadotropins are g/ycoproteinpolypeptidehormones secretedbygonadotropecellsoflhe ~~ -O!!i....-naHonnonel!1!!R!!}i!!!!!l!!~

ro l!lmlll!lZll!l! (Fo~imon<) ~ (Gonal-10) mJllZ!l!ll!lm (Puregon")

anterior pituitary in response to Gonadotropin-releasing hormone (GnRH ) from the
~ (Factreft); GnRH
hypothalamus
-lllammalian Gonadotropins lncludes;
- Urofollltropin extractedfromtheurineof postmenopausalwomen , Follitropins are recombinant. l!ll!lmii !Lupron") ~ (Suprefact<) lllli!lll!llii (Vantas<)
-l/m; -Aisis1ad ReproductiveTeehnotogy(ART);suchasln Y11JoFertilization(IVF)
- FoiUcle-stimulatingHormone (FSH)and luteinizing Hormone {LH); Producedbythe lilllll!lllil(Z~adex") lm!mll!il
(SynareJO) lillBII!I (Oecapepty~)

...c
anteriorpitultary in maleandfemale, theyare actonthegonads, control/lnggMlete
andsexhormoneproductJon
- Human Chorionic Gonadotropin (hCG); Produced by the placenta after implantation
·- Owlationlnduclion. -Spennatogenesis/nduclion(Gonal-1• ).
- GnRH analogues areeffecttvein suppressing production of the Gonadotropins ; Initial increase in
ll!!mil!li!E!Il (Luvertse) FSH and lH secretion - sustalnedstimutatlonofGnRHreceptors - hypogonadaieffect
- ~ ; Follde Stinallation; Only in combination with Follitropin .
- ~ ; Prostatecancer ,brtastcanc:er , endometriosis , uterinefibroids , eartypubertyandiVF .

a...
in pregnancy, hCG is detected in pregnancytests , hCG is nearlyidentic::al with LH ; its
actions are mtdiatedthrough lH receptors.
- Function;
- Maie;- FSH ; - Stimu/atesspermatogenesis (primaryfunction).
- Stimu/atesSertollcelis to produceandrogen-bindingprotein (ABP)
- Stimulates Sertoll cells to convert Testosterone !o Estrogen that is also
required for spermatogenesis
- Common Side Effects (FSH and LH) Headache and Ovarian Hyperstimulation Syndrome (OHSS)
- ~Effects ;- Hypersensitivitydermatitis and sinusitis canoccurin nasa/spray.
ll@®iiQI§·!.!. ;!i?f i ltbtiftG(.jU·TM~ or ~(Pergonrut)
- l!lfllla thefn!.!!l2ntbof~ Ovariancysts
- hMG are obtllnedtomtheurine of menopausal women and cont.lns FSH and LH .
- !J!!g g YH: causes typical symptoms of menopause (hot flushes , sweats and headaches),
-l/m; -Asois1ad ReprodudiYeTeehnotogy(ART); suchaslnY11roFertilization (IVF);
depression , diminishedlibldo, genera/izedpain ,osteoporosis and vaginaldryness .
- lnfwfllty in women and men.
- Common Side Effects; Headache, OHSS and multiple births GnRH~~
l lpt;ml!tt.m,y,fti§f·»Mtt®Mt !B (Pregnyl') e m i ! J (Cetrotidee) mll:lii!:I (Orgalutran<)Eml!l - l!!!llm!li!I IF'""90"'1

41
- LH ; Stimulateleydigcelis (lnterstltialcelis)to produce Testosterone
- Female; - FSH ; - Stimulates the growth of Immature ovarian follicles to produce Estrogen
-Stimu/atesGranulosacellstoconvert Androgens to Estrogen .
- LH ; -Inducesovutation
- hCG producedbyhumanplacentaanducreftdlnto the urine. - Uses; - Ganirelix and Cetrorelix are approved for use in controlled ovarian stimulation, In Vrtro
- ~ ; - Prepubertalayptorchicism -Hypogonadotropichypogonadisminmates. - Fertiizatjon(IVF); InhibitionofprematurelHsurgesundergoingcontrolledovarianstimulation.
-inductionofovulationandpregnancy. - Oegarelix and Abarelix are approvedformenwithadvancedprostrtecan<:er
- ~~Effects ; Ovarian cyst, OHSS, abdoninalpain, nausea and vomiting. - Common~ Effects; Nausea and headache
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Thyroid Hormones
Introduction Thyroid Hormones
- Biosynthesis of ~Hormones : IBi!'JZ!!:!!i!l or - (Euthyrox<) l!l:lliiDii!l (C~ome~)

- Thyroxine {T.)and Triiodothyronine {TJ)aswellas reverseTriiodothyronine (rTJ)are naturalthyroid hormones and · Mechanismg!Action;actby activatesgenetranscription ,which
they are levo (n isomers: synthetic dextro (d) isomer of Thyroxine, Dextrothyroxine, has approximately 4% of the leadsto alteration inproteinsynthesis and cellularphenotype.
biologicactivlty ofthe levothyroxine. · Function ,
· Levothyroxine or L·thyroxine,isa synthetic form of Thyroxine (T.) · Thyroid hormones are responsible for optimal growth,
- Uothyronine isa synthetic form of Triiodothyronine {TJ). development , function ,and malntenanceof ~bodytissues
- Liotrix {ThyrolafCl)isa 4:1 mixture of T. and TJmade synthetica//y · Thyroid hormones is critical for the development and
- Pharmacokinetics, functioning of nervous, skeletal and reproductivetissues
· Absomtion; Soth T, and TJare absorbedafteroraladministration - Thyroid hormones Stimulate Basal Metabolic Rate (BMR)
- 0ralbioavailability; T,; 70-80%. TJ; comp/etelyabsorbed (95%) - lmportance in fetal fornormalmentaldevelopment
- Food, Calcium preparations and Aluminum-containing antacids can decrease the absorption of T4 {Fatty meal - Calorigenic (thermogenic) effect
and coffeelowers its absorption): - lncreasecardiacoutput ani:l heartrate {tachycardla).
- Thyroidhormones mustbetaken inthe fastingstate (3().6()minutesbeforebreakfast) -/ncreaseGIMotillty (increaseappetite and foodintake)
- Absorption is not to be affected by mils! hypothyroidism but may be impaired in severe hypothyroidism; · Therapeutic~; Treatment of Hypothyroidism .
switching from oral to parenteraltherapy {IVispreferred) - Levothyroxine {T.)is prefe"edover liothyronine {T3)or T{r 4
- Distribution; combination;nis bettertolerated andhasa /ongerhalf-life
- More than 99% of circulating thyroid hormones are bound to plasma proteins; primary to Thyroxine-binding (Levothyroxine isthe drug of choice in Hypothyroidism)
Globulin (TBG) and some to Thyroxine-binding Prealbumin (TBPA); T. has higher affinity than T, - ~ (symptoms of hyperthyroidism );suchas Nervousness ,
- Unbound (Free) T, and T, arethe activeforms and gain entry intothe cellbyan ATPdependentprocess palpitations, tachycardia, heatintolerance,and unexplained
- Metabolism; weight loss.
1) Sequential Deiodination (major route of metabolism); About 80% of circ ulating T3 obtained from T. - Oisturbance of ThyroidHormonesFunction;
deiodination mainly in the liver & kidneys; Amiodarone, Propranolol & Corticosteroids - inhibits conversion A) Hypothvroidism;
of T4to TJ · -Common Causes; Autoimmune (Hashimoto's Thyroiditis)
1) 1odide:ill!m!!!g; - CongenitaiHypothvroidism (cretinism)
- lodide trapping throughthe follicularcell by Sodium/l odideSymporter (NIS ); tJ!l1 ~ -Myxedematous facies. ·Largetongue{Macroglossia)
- NIS can be inhibited by large doses of Iodide as well as anions (e.g., Thiocyanate (SCN·), -Umbilicalhemia -Widenasalbridge
Pertechnetate (TcO,·)and Perchlorate (CIQ,-) - Myxedema: is a dermatological change that can occur in
- Secondtransport; atthe apicalcellmembrane a second l· transportenzymecal/ed Pendrincontrols the hypothyroidism and some forms of hyperthyroidism,
flow of lodide across the membrane results in swelling ; texture ofthe skin like"orangepeel•
- MyxedemaComa or Crisis;isa rarelife-threateningc/inical
2) 0xidation of lodide (l·) to lodine (12); conditfon that representsseverehypothyroidism
- lnthe colloid, 2 1odide (l·)is oxidizedto lodine (l2)by ThyroidPeroxidaseOxidizes (TPO) enzyme. TPO is B) Hyperthvroidism;
stimufatedby TSH • Common Causes; Autoimmune (Graves' disease); bulging
3 ) 1o d ination of ~; eyes (exophthalmos )and thyroidenlargement~
- lodideOrqanification (organicbinding); iodinates Tyrosineresidues within the Thyroglobulin mo/ecu/eto - Management of Hyperthyroidism: Antithyroid~
form Monoiodotyrosine (MIT) and Diiodotyrosine (DIT) - Propranoloi OR DIItiazem areusedto contro/tachycardia

4) ~:
- 2 molecules of OtT combine within the Thyroglobulin molecule to form Thyroxine {T4)
- 1 molecule of MIT & 1 molecule of DIT combine to form T1
Antithyroid Agents
- 1 molecule of DIT & 1 molecule of MIT combine to form reverse T1(rT1); Coupling in the opoosite order and
is biologically inactive
- T., TJ, MIT,and DIT are re/eased from Thyroglobulin by exocytosis and proteolysis of Thyroglobulin Thioam~des [Thyro1d Perox1dase lnh1b1tors) Anion Inhibitors (Sod1um 10d1de Symporter lnh1bilors)
- Notes,
- PiasmaProtein.6lru!ln.q; T, and TJln plasma are reversib/ybound to protein, primarily Thyroxine-binding l@ft'M!!;mnttfiiii~ (Thyrocii') ~ (Tapazole') l#'§tffftMMMijffltj (Perchloracap®)
- Potassiumperchlorate is rarelyused (associafedwhh aplasticanemia).
Globulin (TBG): Only about 0.04% of total T. and 0.4% of T1exist in the free form (as FT. and FT1) ~ {Nea..mercazolee); Methimazole pro-drug -lt bfockthyroidalreuptake of l· inpatientswffh lodide-inducedHyperthyroidism suchas
- The 00 of T. to T1 within Thyroglobulin is approximately 5:1, so that most of the hormone released is - Thioamides are major drugs for treatment of Thyrotoxicosis and Hyperthyroidism
Amiodarone-inducedHyperthyroidism
Thyroxine · Methimazole is about 10 times more potent than Propylthiouracil and is the drug of
- ~metabolism(Oeiodination ); T. is converted fo TJ asrequired inthe peripheraltissues by choice inadultsand children (dueto Propylthiouracil has highrisk of hepatotoxicity)
lodothyronine Deiodinase enzyme (80%of TJcirculating in the blood is derived from peripheral metabolism - Mechanism of Action;
of Thyroxine). . · Mm£ Mechanism; Inhibit thyroid peroxidase enzyme and blocking iodine
lodtde Therapy (Blockade of Hormone Release)
- Q.r..y_g§. suchas Amiodarone , p-blockers and Corticosteroids, aswe//as severeillness or starvation ; inhibit organlflcatlon - preventhormonesynthesis.
the Deiodinaseenzyme necessaryfor the conversion of T. to T3 - OtherMechanisms:· Biockcoupling ofthe lodotyrosines
- Propylthiouracil (rug Methimazole) also inhibits the ·They are used for Thyrotoxicosis and as preoperative preparation for surgery {decreasethe
- Endocrine Regulation ; peripheraldeiodination of T4and h vascularitvsize and fragilitv ofa hyperplastic qland); notuseful for long-term therapy
- Thyroid -stimulatingHormone {T SH ) stimu/ates ~ and re/ease of T. and TJ - Propylthiouracil and Methimazole are classified as FDA pregnancy category 0 - Mechanism; -M!iR!action ; lnhlbltion of hormonerelease.
- Propylthiouracil is preferab/e during the firsttrimester of pregnancy because itis more · Otheractions; /nhibitorganification , decreasedthyroidalsize and vascularity
- Moreactive T. to lJ, actsina negativefeedbackinhibition inthe pituitary lo block the action of TSH andin -Improvement in thyrotoxic symptoms occurs rapidly, within 2-7 days
strong/yprotein-bound andtherefore, crosses lhe placentalessreadily (Methimazole
the hypothalamus to inhibit the synthesis and secretion of Thyrotropin ReleasingHormone {TRH )
may use in 2"dand 3nl trimesters)
- Side Effects,
· Autoreaulation of ~Giand ;
-The thyroidgland also regulates its uptake of lodide and thyroidhormonesynthesis (fndependent to TSH) --:Skin (MQ!f~sideeffects); Dermatologicreactions wffh fever Radioactive Iodine (RAI) - lodlne-131 (1311)
- GIT {Occurearly); Nausea and Gidistress
in responseto the level of lodine inthe blood - Liver; - Severehepatitis wifh Propylthiouracil (blackboxwarning) . 1J11isthe on/yisotopeused for treatment of Thyrotoxicosis and sometypes of thyroid cancer
- Hypothyroidism canbe causedby lodine Deficiency or lodine Excess!! - Cholestatic jaundice (commonly with Methimazole) . 1311rapfd/yabsorbed , concentrated inthe thyroidfollicles - radioactive lodine becomestoxic
- Excess of lodine inhfbltlodideOrganification {Thyroglobulinlodination);knownasthe Wolff-Chaikoffblock · Blood (Dangerous complication; rarely but fatal); Agranulocytosis. to cells (emission of~ rays) - thyroid parenchymal destruction occurs within a few weeks
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Endocrine
Parathyroid Hormones
System - Parathyroidglands are sma/lendocrineglandsinthat produce ParathyroidHormone{PTH ) Bisphosohonates IBPsl l1!!llmll!ll [Forteo8)
-Humans usuallyhave 4parathyroidglands ,variably /ocated onthe back ofthe thyroidgland
- ParathyroidHormone(PTH)and Calcitonin (producedbyC-cells in thyroidgland) have keyroles inregu/ating
~ (Fosamax®) llmll!li!i!li (Bonwa") ~ (Actonel•) -lt isa recombinantform of humanparathyroidhormone(PTH ).
~ [Zometa0) ~ (Aredia 0) Eill!llilili.!l (Loron°) - ltisthe smlr available anabolicagent (bonegrowing) forthe treatmentofosteoporosis
the amount of Calcium inthe blood and within the bones
-lt is increasesboneformation, boneremodelingrate, osteoblastnumber & activity
Q.. - Hyperparathyroidism and hypoparathyroidism , characterizedby alterations inthe blood Calcium /eve/s and IGIIiiZ!lililll [Didrone~) lll!!ll!lmil!ll (Nenxia• ) mmm!!!l (Skelid") - ltis shou/dbe resetvedforpatients at highriskoffracturesandthosewho have fai/ed
bone metabolism • Bisphosphonates are potent bone resorption inhibitors and most commonly prescribed

co
or cannottolerateotherosteoporosistherapies
- VitaminD , ParathyroidHormone (PTH) and Calcium ; antiresorpti vemedicati on sand remain fn!~ treatmentfor osteoporosis
- Teriparatide administrationnotrecornmendedmorethan2years
- Vitamin D and Parathyroid Hormone (PTH ) work together to maintain Calcium homeostasis • Absomtion of oral bisphosphonates isU!r ll22[ (<1 -1 0%) by passive diffusion in the stomach and
- Vitamin 0 is a fat-soluble vitamin , responsible for increasing intestinal absorption of Calcium , Iron, uppersmaflintestine. food and othermedications(such asCalcium&lron ) significantly decrease
Bl!!l!mll [Miacalck;<)
~
Magnesium, Phosphate and Zinc absorption
- VitaminDactivation , - Mechanism of Action; Bisphosphonates decrease osteoclastic bone resorption through an - ltis produced eitherbyrecombinantDNAtechnology orby chemicalpeptidesynthesis
- Vitamin D in the liver, is converted by vitamin D 25-hydroxylase to 25-hydroxyvitamin D [25(0H ) D]. increase in osteoclasticapoptosis {programmedce/ldeath) and decreaseosteoclastactivity. of SalmonCalcitonin (Sa/monfish)
- Thisform[25(0H) D]of vitaminD isbiologica/ly inactive and mustbe converted in the kidneys by 25- - Side Effects ; · Calcitonin-Salmon , is more potent and longer lasting than the Mammalian Calcitonin
hydroxyvitamin D1 1a-hydroxylase to the biologically active form 1a,25-hydroxyvitamin D - Oral bisphosphonates ; - Indications;
""C [1a,25[0H)> D[[Calci1riol) - Stomachupset , inflammatj on and mJiQilS ofthe e._~phagu_s ; -PostmenopausaiOsteoporosis (>Syearsofpostmenopause)

c - ParathyroidHormone (PTH ) increasesactivity of 25-hydroxyvitamin0,1a-hydroxylase

-Calcitriol binds to the intestinalvitaminDreceptor andthen increases Calcium bindingprotein. P-s
aresult, increaseintestinalabsOfption of Calcium and Phosphorous
- ~Remodeling ; is a process where mature bone tissue is removed (bone resorption ) by osteoclast cells
- Each oral dose should be taken alone on an empty stomach [morning] with at feast
240mL of tapwater atleast 30 (60for lbandronate) minutesbefore consumingany
food , supplements {Calcium ) or medications
- Thepatient shouldbe remain upright {slting or standing) for at/east30minutes (60
·Acute management hypercalcemia
- Symptomatic Paget's disease

for lbandronate ) lilm!l:l!lim!I IProlia•) [Xgev")

~
and newbonetissue is formed (boneforrnation)byosteoblastcells
- Musculoskeletal pain - Denosumab is amonoclonalan6body withaffinity for nuclearfactor-kappaligand
- Parathyroid Hormone; - Indications;
- ~ ; enhancerelease of Calcium fromthe /argebones ( boneresorption ) by osteoclasts
- IVbisphosphonates;
- Fever and flu-like symptoms (acute inflammfioryresponse) after the firstinfusion - Proliae; Postmenopausalosteoporosis {withhighrisko/fraclure) and boneloss
- ~ ; enhancereabsorption of Calcium and inhibitreabsorption of Pho s phate
- Osteonecrosis of the jaw (ONJ) especially with higher IV doses for the treatment of cancer. - Xgevae; Hypercalcemia of malignancy and bone metastases
- Intestine; enhanceabsorption of Calcium in the intestine by increasingproduction of activated
vitaminD (Calcitriol )
Q) - Calcitonin Hormone;
- /nhibitsosteoclasticboneresorption
li!illll:llm1E~s1a<)
- Raloxifene is aselective estrogen receptor modulator (SERM) approved for the prevention and
4iQM·®tnfft (Protelos®)
- StrontiumRanelate iscomposedof Ranelicacid andStrontium

-c
- Decreasesserumcalciumopposing the effects of PTH treatment of osteopOfosisinpostmenopausal women - lt increasescollagen and non-collagenicproteinssynthesis by matureosteoblast
- An ~ between boneresorption and boneformation , resultsin many metabolic bonediseases ,such -lt has estrogen.fikeeffects on bone and estrogenantagonisfeffects on breast and endometrium enriched cells
as osteoporosis - FDA black box warning ; risk of venous thromboembolism and death -Effectsonboneformation were confinned by enhancedpre-osteoblasticcellsreplication .

::J Mineralocorticoids Blucocorticoids

<.9 - Mineralocorticoids area c/ass of SteroidHormones characterizedbytheirinnuence on salt and waterbalances
- The primarymin&ralocorticoid is Aidosterone
- Adrena1Cortex is formed by 31ayers;
! ) ~ Glomerulosa (Outer layer); about 15% of the cortex; Producing Mineralocorticoids; Aldosterone
- Glucocorticoid Functions ;
• Metabolism; - Carbohydrate; Hyperglycemic, Diabetogenic and Anti-insulin effects.
- Protein ; Catabolic Effect
- Fat; Lipolytic and Ketogenic
Short~ [ <12houffi )
l!l!liJI!!!li~ (Solu-CorteP) mm!!li!I (CortoneAce1ate')
lntennediate~ [ 12-36houffi)
~ (Hostacortine) ~ (Hostacortin-H*)

ro
2J ~Fasciculata (Middle layer); about 75% of the cortex; Produc/ng Glucocorticoids; such as Cortisol
~) ~ Reticularis (Inner layer); about 10% of the cortex; Producing Adrenal Androgens such as
Dehydroepiandrosterone (DHEA), DHEAsulfate and Androstenedione {precursor toTestosterone ).
- Regulation;
- Angiotensin II (Major role); 1 plasma level of Angiotensin II -+ Stimulate secretion of Aldosterone
- Potassi~m ; 1serum K• level (Hyperkalemia)-+ 1Aldosterone secretion
- Redistribu6on of fatdepot inthe facio-cervical-trunk region; moonface
and buffalohump andin the abdomen ....... purple striae (stretchmarks) lliDm!l!imil tKenacort-A•) ~ [Solu-Medro~)
• Skeletal Muscles; Catabolic -+ weakness & muscle atrophy (! protein synthesis) 1!!!!g~ [>48houffi)
• m ; Hypertension; +veinotropic effect and Na• &waterretention
~ (Diprofos®) ~ (Dexamethasone®)
*Biood~ ; - ! lymphocytes , Monocytes , Basophils and Eos i nophils
· Cortisol or Hydrocortisone and Cortisone are natura//y occurring Giucocorticoids.
- j Neutrophils, Piatelets and RBCs

E
-Prednisone isa prodrug that convertedto Prednisolone , the active compound in the liver
- Sodium;t serum Na• /eve/ (Hyponatremia)-+ i Aidosterone secretion • ~ ; - l Glomerular Filtration Rate (GFR) & l reabsorption of Water, Na•, Chloride.
• ~ ; Osteoporosis ; Anti-vitamin D, l bone formation and l bone resorption · Hypothalamic-pituitary-adrenalaxis,circadianrhythm, stress and lowbloodglucose level
- ACTH (minor role); l ACTH - 1Aldosterone secretion arethe mostimportantfactors in glucocorticoidssecretionregulation
- Mechanism ; Mineralocorticoids such as Aldosterone binds to cytoplasmic Mineralocorticoid Receptors (MR), * S!in; SkinAtrophy or SteroidAtrophy and SkinThinning
* Q!I; SteroidUicers; j gastric-acidsecretion - P/asma ACTH & Cortisol levels exhibit l peaks (6-SAM) & ! nadirs (11 PM).
andactivatedreceptorsaffectgenetranscription. -!fill;
· ~1!!ng ; FetallungMaturation ;j produ ction of surfactants .
~ • Function ; Reabsorption of Na•, water and Cl· and Excretion of K• and H•
- SURVANTAe (Beractant); pulmonary surfactants intratracheal injection; used for - Replacement Therapy for;

ro
- Disturbance of MineralocorticoidsFunction; Respiratory Distress Syndrome (RDS) in premature infants · eflmm (Cortisol deficiency) adrenocortical insufficiency (Addison's disease)
A) Hyperaldosteronism; * i l l;t seizurethresho/d and j lntracranialpressure (pseudotumorcerebri) - ~ (ACTH deficiency)or ~ (CRH deficien cy) adren ocorticalinsufficien cy
- Primary Hyperaldosteronism (Conn's syndrome); is excess production of Aldosterone , (adrenal adenoma) *lli; Giaucoma (duefo increasedocularpressure) and Cataracts. - Congenitai AdrenalHyperplasia (CAH )
- SecondaryHyperaldosteronism ; isdueto overactivity of renin-angiotensin- aldosteronesystem • Arui.-inflammatorv Effects ; · Diagnosis of Cushing's syndrome ; Dexamethasone suppression test

...c:
B) Hyooaldost6ronism; - Suppress PhospholipaseAJ. activity -+ !prostaglandinsand leukotrienessynthesis • Anti-inflammatorynmmunosuppressive Therapy
- Addison's Disease ; adrenalglandsdonotproduce enough steroid hormones (Cortisoi, Aidosterone and -Suppress Cyclooxygenase (COX) activity - t prostaglandinssynthesis - Treatment of AllergicReactions
Androgens), most often due to adrenal glands damage by the immune system • Suppress proinflammatory cytokines, and other inflammatory mediators release · Accelerate of Fetal lung Maturation ; Betamethasone OR Dexamethasone

a...
- Congenital Adrenal Hyperplasia (CAH ); is mutations of genes for enzymes mediating the biochemical steps
of production adrenal hormones;! cortisol production resulsin rising levelsofACTH via feedback inhibition
- r overgrowth(hyperplasia)andoveractivityof thesteroid-producingcells -+j adrenalandrogens
-Thetreatment isto administer aglucocorticoid , suchashydrocortisone (ininfants) orprednisone, which
wouldrestorethefeedbackinhibition
~ (Astonin-H~)
-Stabi/izingmastcell and basophilmembranes -+ ! Histamine release
- Decrease capillary permeability -+! inflammatory edema
* Am!.~Effect ; -Decreaseantibodyformation a nd antibody/antigenreactions
- Decreasetissue response to allergicmediators
- Mastcell and basophilstabi/iza6on - ! Histamine re/ease
*lmmunosuporessantEffect;
· Cancer Therapy (Prednisone ); such as Acute Lymphocytic Leukemia and both Hodgkin
and non-Hodgkin Lymphomas, Multiple Myeloma and other Blood Cancers
- Prednisone also helps to decreasenausea asweUas promote an appetite
- Nausea and vomiting ; A large dose of Dexamethasone reduces emetic effects of
chemotherapy and generalanesthesia
Glucocorticoid Synthesis Inhibitors & Glucocorticoid Antaaonists

43
- Fiudrocortisone isa synthetic esll!!l.t mineralocorticoid (250pa rtssatt-reta ining)with ~ glucocorticoid
activity (10 parts anti-inflammatory). Used orally to treat Adrenocortical Insufficiency/Addison's Disease,
congenitaiAdrenaiHy&i!ma(I:J:!~::rnw (lns~)
-Theyaresynthetlcsteroid thatactsas acompetitiveantagonist to Aidosterone at mineralocorticoidreceptors
- lnhibitfunctions of Macrophages andother antigen-presentingcells;
- PreventsT-cellsproliferation;
* Am!.-shockEffect;j CRH -+j ACTH -+j Cortisoi ; Hypervolemia & Hyperglycemia
*WithdrawalEffect; Giucocorticoids cannot be stoppedabruptly and m!t!! be stopped
gradually to avoid Cortisol deficiency resullingfrom hypothalamic-pituitary-adrenalaxis
(HPA) suppression (Adrenallnsufficiency)
- ~ is an anti-steroiddrug actby block the conversion of Cholesterol to
l ; reduction inthe synthesis of a/lhormonallyactivesteroids.
-
·
isa pot.entnon-selectiveinhibitor of adrenal & gonadalsteroidsynthesi~
san antiprogestogen, aswellasan antiglucocorticoid and antiandrogen; ls
used to control hyperglycemia in patients with endogenous Cushing's syndrome

-
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Antidiabetic Drugs
Pancreatic Ho rmone s Ant1d1abet1c Drugs
- Pancreatic Tissues;
A) Pancreatic acini;

---
- Exocrinepart {About 80%ofthe pancreas volume)

---(1.--*"1(- --
- Secrete pancreaticjuice fnto the duodenum.
B) Pancreaticislets or islets of langerhans;

---
- -(H""*" RI

....
- Endocrinepart (1-2%ofthe pancreasvolume).
-A!Rhi {a) WI! (20% of total islet celts); Glucagon
- ~ ~~~ ~ (•70%); Insulin & Amylin (100:1)
- ~ (6) ~ (<10%); Somatostatin
- NPII ( -
.__
.._(L-

---
- fe (y or F ) ~; (<5%); PancreaticPolypeptide -Oiqlnt(l.nll'l

- IJotilol loc(T- -(T"""""'

......-(T-
~
-~-
- Glucagon effect is opposite to that of Insulin, which lowers the
extracellular Glucose
- Glucagon acting through G protein-coupled receptors (via cAMP) in
heart,smoothmuscle and liver
- Function; increases heartrate and fOfce of contraction, increases
hepaticglycogenolysls and gluconeogenesis, andre/axes
smoothmuscle particu/arlyinthe gut
- ~ lt is u sediM or iV to treatseverehypoglycemia ( Hypoglycemia
Antidotes), ~-blocker and calcium chan~ blocker toxicity
(increases cardiac cAMP without requiring access to~ receptors), . _. . . _
and GIRadlography (decreaseGimotility).
1. -ls,mtl'!
~ V)Giycosuncs
- ltisa synergisticpartner to lnsulin ,it regulatebloodglucoseby slowing
gastric emptying, promoting satiety (via hypothalamic receptors), and
lnhibitlnginappropriatesecretion of Giucagon

llili!!!IDI
· lnsulin is synthesized asthe prohormone Proinsulin, anBS.amino-acld
single-chain polypeptide.
- Proinsulin = lnsulln {A + Bchain; 51aminoacids)+ Cpeptide (31amino
acids).
- lnsulin isa d/mer of S1aminoacids; an A-chain anda B-chain, whichare
linkedtogether by disulfidebonds
• C-peptide has no inffuence on Glucose or Lipid metabolism, 1M have
beneflcialeffects on peripheralnerves, kidneys, and brain (protection
from diabetescompllcations;retinopathy, nephropathy &neuropathy)
- Mechanism of lnsulin Release;
- Giucose isthe P!iJ!!msUmuli for lnsulin re/ease
- Glucose enters the ~-cells through the glucose transporters, GLUT2
via facilitated diffusion
• Glucose is phosphorylated, high-energy ATP closes the ATP·
sensitivepotasslumchannel, /eadingto depotarization
-Upon depolarlzation, voltage-gatedcatciumchannelsopen
-An increasedlntracettular Ca 2• /eadingto increase lnsulin secretion

,.mfi.~~=~~~~.et")
- They are inhibit the intestinal a-glucosidase enzymes,
delaying the digestion and absorption ofstarch and
disaccharides, resultinginlower postprandlalglucose
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Gonadal Hormones and Inhibitors
Androg e ns
- Androgens are sterolds ; haveanabolicand/or masculiniziogeffects inbothmales and females
- Androgens are syntheslzed inthe testes ,the ovaries andthe adrenal~
- Themostimportantandrogen secretedbythe testes is Testosterone
-Thetestesalsosecretessmall amounts of;
- Potentandrogen; Dihydrotestosterone (DHT)
- Weak androgens; Androstenedione and Oehydroepiandrosterone (OHEA)
IHl2!l!r.2nt
- Testosterone,the mostimportantandrogen inhumans,issynthesizedby;
-Leydigcellsinthetestes in ma/e - Thecalcells intheovaries in fema/e (smallamounts)
- Adrenalglands in bothsexes
-About65%ofcirculating Testosterone isboundto SexHormone-bindingGiobulin (SHBG).
-Aboul33%isboundto Aibumin
-On/y 2%remainsfreeandavai/ab/etoentercells andbindtointracellularreceptors
· Testosterone isconvertedto Dihydrotestosterone (DHT)by Sa-reductase enzyme
-Some tissues; Testosterone is converted to Estradiol by P450 aromatase enzyme (aromatization)
I -fn11!n;littleeffectonproteinmetabolism
1 ~ (Deca-Duraboli~)
- A/ky/ation of Testosterone atthe17aposition suchas Methy1testosterone , Ffuoxymesterone and
Oxymetholone allows oral administration of the hormone
· !l..Hl;sincethediscoveryandsynthesisof Testosterone inthe1930s, AAS havebeen !l.llS!. as;
A) Androgenic; Androgen Replacement Therapy, Induction of Male Puberty and Masculinizing
Hormone Therapy
B) Anabolic; Bone Marrow Stimulation (especially aplastic anemia), Growth stimulation ,
Osteoporosis in postmenopausal women and Aging males
C) Ergogenic ~~ ~i!:!~); In the adult male, large doses of testosterone-when
givenalone--oritsderivativessuppressthesecretionofgonadotropinsandresultin
someatrophyoftheinterst~ialtissueandthetubulesofthetestes
D) Others; BreastCancer and Postmenopausal and TransgenderWomen
- §JJIJ_5flli!!; -
· .M!Ii·~priapism , gynecomastia , azoospermia , testicularatrophy, prostatehype rtroph y
and prostate cancer
- f.tm.!lt-~:masculinization, voicedeepening , hirsutism , menstru aldisturbances, clitoral
en/argement, breastatrophy and uterineatrophy. Testosterone should not be
used by pregnantwomen becauseofpossib/evirilization ofthe femalefetus
- ~-~: prematureepiphysealclosure (shortstature ), precociouspuberty in boys , defayed
puberty and contra-sexualprecocity ingirls
- ~;
- Dermatoloaicat, oily skin, acne, stretch marks (rapid muscle enlargement), hypertrichosis
(excessivebodyhairgrowth), androgenicalopeciaand fluidretentionfedema
-Endocrine:libidochanges, infertility and hypogonadism
-~:e/evatedliverfunctiontestsandhepatotoxicity; exclusively with 17a-alky latedAAS
suchas Methyltestosterone, Oxymetholone
- Cardiovascular: dyslipidemia, atherosclerosis, hypertension (sodium and water retention)
thrombosis, myocardialinfarction andsuddendeath
Antlandroaens
Androgen Receptor (AR) Antagonists
lii!!DII IEulexin") lliii!!Diii 1Nilandron°) I D D ! J ;casodex")
~ (Xtand~) ~ (Erlead,.)
-Theyare used forthe treatment of ProstateCancer
fi1ifli@@"i'Mt:itj (Androcuj®) (Dianee 35)
-Usedinacne, seborrhea , hlrsutlsm , earlypuberty, prostatecancer andin blrthcontrot
~ (AJdactone•)
- Usedinandrogen-dependentconditions; hlrsutism, acne in women&androgenlcalopecla
AndrogenSynthesislnhibitors
~~ (Z~iga 0 )
-Theyare17a-hydroxylaseinhibitor. Abiraterone used in ProstateCancer
lililim!ll!II IProscar') ~ (Avodart")
-Theyareare Sa-reductase/nhibltors,theyare used in Benlgn Prostatlc Hyperplasla (BPH )
h lr oqc ns Progest1ns
-The major Estrogens produced by women are Estrone (E,), Estradiol (~ ) and Estriol (E.,). Another - Progesterone isthe mostfmportantprogestin in humans
type ca!led Estetrol (~ ) isproducedon/yduringpregnancy - Progesterone setvesasa~tothe Estrogens , Androgens and AdrenocorticaiSteroids
- Estradioi (E1)isthe majorsecretoryproduct cithe ovary -ltissynthesizedinthe~(corpusluteum), ~(/argeamountsduring pregnancy), testis
- Estradiol (~ )isthestro ngest, whereas Estriol (E.,)isthe weakest. and adrenalcortex in responseto LH
- Micronized Progesterone is rapid/yabsorbed afteroraladministration .
- Estrogens arebound to SexHormone-bindingGiobulin (SHBG)and Albumin
- Function ;
Function.
A) FemaleRepl'oductiveSystem ;
~ale Reproductive System ;
. uterus;-Helps implantation and formation ofplacenta
1) During Intrauterine Uft; Development of the female sexual organs (uterus and vagina)
-Maintains pregnancy by·
2) BefortPubtrty; LowEstrogen /eve/s-o inhibitsGnRHre/ease priorto puberty.
- Preparing theendometrium for implantation
3) Durlng/AhtrPuborty; - Inhibit uterine contraction
· Qym: - Facilitate growth of immature ovarian follicles.
- Decrease myometrium sensitivity to Oxytocin
- Surge inEstrogen levef inducessurge of LH --essentia/for ovulation
-~I.!!.Qj; Stimulatemucussecretionfornutritionofthefertilizedovum
- Uterus;- Endometrium -of pro/iferationand growth
· ~;Stimulate thick secretion, making it thick and impenetrable to sperm
-Myometrium - T proliferation & T sensitivity to Oxytocin
B) Metabolism ;
- Cervix;fsecretion ofthinalkalinemucus - promotespermtransport
-~; f basalinsulinlevelsandtheinsulinresponsetoglucose
-~; - /ncrease vaginaflubrication
-Thickenthevaginalwall
-fil;stimulateslipoprotein lipaseactivity-ofatdeposition
- FallopianTubes; /ncreaseactivity on tubalmotility.
C) Other Effects ;
-Responsible of Secondary SexCharacteristics.
- DecreaseNa• reabsorption;bycompetewnhaldosteroneforthemineralocorticoidreceptors
B) Metabolism ;- llpld;-t HDL,f triglyceride andt lDl and! totalplasmacholesterolleve/s - Increases body temperature
- Bone;-t boneresorptionand t boneformation ProaestlnPreoaratlons
C) BioodCoagulation ; - t Factorsii, VII, IX&Xandf Piasminogen. and Derivatives
- ! Antithrombinllland ! Piateletaggregation.
D) Others;- Fiuldbalance; Sodium andwaterretention
- Gastrolntutlnai ; Reducebowelmotility;
- Cancer;Estrogensareimplicated invariousestrogefMependenlconditions
- MedroxyprogesteroneAcetate injections isusedonce every 3monthsas birthcontrol andin
~Preoaratlons endometriosis
Natural - HydroxyprogesteroneCaproate is usedonce weekly toprevent pretermbirth inpregnanl
· Megestrol Acetate is used mainly as an appetite stimulant to treat wasting syndromes and also
usedinthetreatmentof advancedbreastcancer and endometrlalcancer
First Generation Progestins
~ (Primolut«' N) • · · (Primolut-Nor'l)
~ (Enovid"l ii!DDI IExluton") - (Demulen')
· Low progestationalactivity, s/ight estrogenicactivity& more androgenicactivity.
Second Generation Progestins
(Ovraf®) (Microlut®)
- levonorgestrel isthe mostwidelyprescribed contraceptive progestin worldwide
- ~;- HormoneReplacementTherapy ; -llhas high progestational and androgeniceffects
-Menopausalsymploms(Hotflashes,vagillBiatrophyandosteoporosis) - II is Used in birth control has also been FDA approved for emergency contraception
- Underdevelopedfemalesecondarysexcharacters (Hypogonadism)
Third Generation Progestins
· Birth control; aloneorincombinatioow~hprogesteroneasconlraceptives.
- Prostatecancer;bysuppressingtestosterone levels l i D I ! D ICerazette') · (Cilest')
· (Gynera®) (Nexplanonfl)
- ~Effects ,
- High progestationalsefectivity, minimizing or no androgeniceffectsandestrogenicactivity.
- Most Common; Nausea, headache & breast tenderness (fluid retention)
- Uterinebleeding (toavoid;usesma!lestamountofestrogenpossible) FourthGenerationProgestins
- Risk ofthromboembolicevents and myocardialinfarction (Visannefl) I • • · • · (Yasm i ~)
- Risk ofbreast and endometrialcancer; - Dienogest has high progestational selectivity with some antiandrogenic activity, which may help
-Shou/dllQ! be used inpatientswithestrogen-dependentneoplasms to improveandrogen-dependentsymptoms /ike acne
- Drospirenone has high progestationalse/ectivity wnhantimineralocorticoideffects, leadingto
decreasedsalt andwaterretention causedbythe estrogen in birthcontrolpills
Selectlve~~ModulatorslllB!!!)
- ~ ; Birthcontroi , HormoneReplacementTherapy , Supportpregnancy , Dysfunctiona luterine
l!!l!lil!!!ll!! ICiomid") bleeding , Endometriosis , Endometrial Cancer, Breast Cancer and Appetite Stimulation
-llis used to induce ovulatlon in lnfertllity in women - ~Effects ; Most Common; headache , depression , weight gain and changes in libido
-ltisactbyincreaseproductionofgonadotropins(FSH&LH)by inhibitingnegativefeedbackof - 19-nortestosterone Progestins suchas Norethindrone & levonorgestrel ;possess some
estrogen on the hypothalamus (b/ockestrogenreceptor in hypothalamus)
androgenicactivity(structuralsimilaritytotestosterone)andcancause acne and hirsutism
- Side effects; Reversible ovarian enli?iifi'm~~~~~~~r flushing - Drospirenone maycause hyperkalemia duetoantimineralocorticoideffects
- The FDA recommends that Medroxyprogesterone Acetate by injection llQ! be used for longer
-It is a SERM approvedfor lhe preventlon and treatment of osteoporosis In postmenopausal than2years,duetoconcemsoverbone loss
womenand approvedforreductlon in risk of lnvaslvebreastcancer
-lthas estrogen·likeeffects on bone & estrogenantagonisteffects on breast &endornetrium
Selective Proaesterone ~ Modulators IRBM)
. FDA black box wa;mm;ijje(~o~:a~:~7boeiWm~~~r:~~o~~troke -, • - (Mifeprex®)
-Theyhave estrogeniceffects in bone and uterus and estrogenantagonisteffects on breast -ltisa Progesterone receptor antagonist and partialagonist activitywithpowerlu/ glucocorticoid
· Tamoxifen is taken ora/ly dai/yfor 5years for breastcancer receptor antagon/st effect
- ~ (Faslode~)isase/ective EstrogenReceptorDegrader (SERD), inhibitsbreast - !l..Hl; Medical abortion, Emergency contraceptive and Cushing's syndrome (treatment of
tumorgrowth.ltisgiven iM for HormoneReceptor-PosltiveadvancedBreastCancer hyperglycemia)
 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬

Deposit Number
International Standard Book Number (ISBN) 978-977-90-5610-4

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Copyright © By Dahshan Hassan Dahshan
All rights reserved, No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without
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 ‫ﺇﺫﺍ ﺍﻧﺗﻔﻌﺕ ﺑﻬﺫﺍ ﺍﻟﻛﺗﺎﺏ ﻟﻁﻔﺎ ﺍﺩﻋﻡ ﺗﺣﺩﻳﺛﻪ ﺑﺷﺭﺍء ﻧﺳﺧﺗﻙ ﺍﻟﺧﺎﺻﺔ‬
Full branch coverage
Saving pre-exam time Pharma Guide® ••
Presented in full colour
Side page for notes
Bas ic and Clini c al Pharmaco l og!:J
•
Just Open it
•
General Pharmacology •
Parasympathetic Drugs
16 Opioid Analgesics
17 Anesthetics
Antiviral Drugs
•
Sympathetic Drugs
Antiprotozoal Drugs
•
Autacoids
18 CNS Stimulants
19 NSAIDs
Antihelminthic Drugs
Cancer Chemotherapy-1 ••
Antihypertensive Drugs 20 Anemia Cancer Chemotherapy-2
Antianginal Drugs 21 Gout and DMARDs 36 Cancer Chemotherapy-3 •
Heart Failure Medications 22 Gastrointestinal Drugs Cancer Chemotherapy-4 •
Antiarrhythmic Drugs 23 Drugs for Urologic Disorders Cancer Chemotherapy-5 •
Antithrombotic Drugs 24 Respiratory Drugs Immunosuppressants •
Antihyperlipidemic Agents 25 Antibiotic Introduction ,4 U Hypothalamic Pituitary-1 •
Sedative-Hypnotic Drugs 26 Cell Wall Inhibitors 4 1 Hypothalamic Pituitary-2 •
Antidepressant Drugs 27 Protein lnhibitors- 1 42 Thyroid Hormones •
Antipsychotic Drugs 28 Protein lnhibitors-2 43 Parathyroid & Adrenocortical •
Neurodegenerative Diseases 29 Nucleic Acid Inhibitors 44 Antidiabetic Drugs •
Antiepileptic Drugs 30 Antifungal Drugs f\ tJ Gonadal Hormones •
Pharmacology Fast Review For Pre and Post-Graduate