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Drug Mechanism Clincal Use Side Effects

ANTIFUNGAL Amphotericin -Binds ergosterol – DOC -Systemic mycoses Neurologic imbalance


B (animals sterol) Anemia – decreases erythropoietin
-Pores in membrane Broad spectrum Electrolyte imbalance
Antifungals
(increases permeability)
-Low therapeutic index Nephrotoxic
-IV (intrathecal in
meningitis)
Fever, chills, pain, N/V – pre-tx w/
steroid/NSAID
Flucytosine -Pro-Drug Combo w/ Ampho B to decrease BM depression
-Deaminate  5- toxic effects of Ampho B
fluorouracil -Synergistic b/c also increases
-Fxnal/strxral flucytosine penetrance
instability -Meningitis – crypto or candida
-Inhibits thymidine UTI- candida
synthetase Torulopsis glabrata
-Enters CSF
Nystatin -Structurally similar to Candidiasis Rare – lack of absorption
(topical) Ampho B -Vaginal N/V
-Same mechanism -Skin Topical b/c too toxic
-Not well-absorbed -Oral for topical tx of GI
fungi (thrush)
IMIDAZOLES Ketaconazole -All work by blocking DOC – non-meningeal -N/V, anorexia
(itraconazole fungi cyt P450 blastomycosis, -Allergic rash
) -Inhibits ergosterol paracoccidiomycosis, -Inhibits steroid synthesis
production coccidiomycosis -Decreased libido, gynecomastia
-Disrupts membrane -Mucocutaneous candidiasis -Liver dysfxn
-Increased permeability -Vaginal candida -Teratogenic
-Also inhibits -Cushings Syndrome -Increases cycloserine/warfarin
-gonadal/adrenal Testicular Ca (anti-androgenic levels (x-rxn w/ human Cyt P450)
steroid synthesis effect) -Nephrotoxic
Oral -
Fluconazole -Similar to -Esophageal candidiasis Steven’s-Johnson’s syndrome –
ketaconazole -Prevents relapse of bullous erythema formae
-Enters CSF cryptococcal meningitis -Thrombocytopenia in AIDS pt.
-Slow metabolism -DOC – cryptococcal -Co-administration w/ phenytoin,
-No endocrine side meningitis, candidemia, sulfonylurea, warfarin cyclosporin
effects coccidiomycosis increases plasma concentration
- Enters CNS readily
Clotrimazole Topical only -DOC – oral thrush
-Tinea
-Otomycosis
-Cutaneous/vulvar candida
-Versicolor
Econazole Water-soluble cream -Candida Local erythema
-Dermatophytes Burning/itching
Miconazole Dermatological & Tenia pedis (athletes foot),
(monistat) vaginal cream cruris, versicolor

Vulvovaginal candidiasis

Trichophyton
Griseofulvin -Microtubule interxn Dermatophytes - Superficial -Barbituataes decrease absorption
-Disrupts mitotic -Microsporum -Hepatotoxic – increase metabolism
spindles -Epidermophyton of warfarin, contraceptives (BC)
-Keratin-containing -Trichophyton -H/a post-discontinuation
tissues & may take -Peripheral neuritis
months -Teratogenic /carcinogenic
-Can be given IV to tx
Candidas if allergic to
ampho B
-Must given w/ fatty
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Drug Mechanism Clincal Use Side Effects

ANTIVIRALS Amantadine -increase endosomal pH Prophylactic for Reswpiratory -CNS affects


Bockage of Rimantidine (blockage of uncoating) viruses -teratogenic
adsorption, -enters CNS Antivirals
-Influenza A -contraindicated in psychiatric disorders,
penetration, & -oral -Rubella epilepsy, CAD
uncoating -Parkinson’s disease (amantidine) -renal failure  toxicity
Nucleic acid Acyclovir -activiated by VIRAL -HSV-1,2 -local irritation (topical)
synthesis thymidine kinase -VZV -h/a, diarrhea, n/v (oral)
-premature chain -DOC – HSV encephalitis -renal dysfxn(crystallization), seizure, delirium
termination -prophylaxis immunocompromised hypotension (hi IV dose)
-disseminated seropositive
throughout body – oral, -CMV resistant – no thymidine kinase
topical, IV
-irreversibly binds
template primer to
viral DNA polymerase
-competes w/
deoxyguanosine
-only viral infected
cells affected
Gancyclovir -acyclovir analog DOC – CMV (disseminated -reversible neutropenia
-inhibits Viral DNA Pol /retinitis) -thrombocytpenia
-prophylaxis in BM suppression -renal dysfxn
-seizures
Trifluoridine -phosphorylated by Topical only Ocular irritation
idoxuridine HOST kinases Edema
cytarabine -incorporated to host -HSV keratitis Photophobia
& infected cells Pain
-inhibit DNA to
DOC – keratoconjunctivitis w/
disrupt fxn Systemically
respect to HSV
-Bone marrow suppression
-renal damage
-acyclovir resistance (2nd line)
-AML
Vidarabine -adenosine analog -HSV keratitis/encephalitis GI irritation
-inhibits DNA pol Hepatic dysfxn
-topical or systemic -in immunocompromised Convulsions
DOC -neonatal herpes
-VZV, HSV-1,2
Azidothymidi -Phosphorylated inhibits HIV -BM toxicity
ne (AZT) RT -CNS – h/a, insomnia, agitation, seizure
-terminates DNA -toxicity – precipitated by acetaminophen,
synth/replication lorazepam, indomethacin, sulfa’s, probenecid,
cimetidine
Interferons -induce protein kinase -Herpes zoster -FLU-like (h/a, fever, muscle aches)
--oligoadenylate -CV – dysfxn
kinase, protein kinase, -HBV -neurotoxic
phosphodiesterase -Kaposi’s sarcoma -BM suppression
(blocks peptide chain) -Hairy cell leukemia -GI irritation
-inhibitory on -HPV – (genital warts) –gamma-INF
DNA/RNA synth
-glycoprotein
Foscarnet -inorganic phosphate -acyclovir – resistant strains Renal impairment
analog Tremors & seizures
-inhibits DNA pol w/o -CMV 2nd to gancyclovir Hypocalcemia
being phosphorylated – CMV retinitis-in immunosuppressed Anemia
Ribavirin -synthetic guanosine DOC – RSV – children – aerosol Interferes w/ AZT
analog Anemia in Lassa fever
-inhibits viral coded -Influenza A, B Elevates bilirubin
RNA Pol (inhibits viral Lassa/hemorrhagic fever Electrolyte dysfxn
mRNA synth) Contraindicated in pregnancy

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LATE Methisazone -late structural protein -small pox (eradicated)
PROTEIN/ synthesis inhibition
VIRAL -
ASSEMBLY
DDC -Converted to ddCTP AZT-resistant HIV Peripheral neuritis
(dideoxycytosine -Alters DNA synth
)
PROTEASE Saquinovir -Blocks aspartate -Given in high dose to completely
INHIBITORS indinovir ritinovir proteinase to prevent stop replication of virus
cleavage of gag-pol -too low or monotherapy 
precursor protein resistance
-Blocks packaging &
assembly

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o
Gaseous Anesthetics

Drug type Drug Mechanism Clinical Use Side Effects

Inhaled Nitrous oxide MAC 100 Potent analgesic!!!! -Safest


anesthetics -Weak; used w/ No anesthetic -Diffusional hypoxia
others Give w/ 20% O2 -Vit B12 def.
-Rapid onset, rapid -2nd gas effect (enhance solubility of
recovery 2nd)
-< CV & resp. -Little muscle relaxant
depression
Desflurane MAC 8.0 Ambulatory surgery Bronchial irritation
Irritating
Not very soluble
Rapid onset &
recovery
-Less potent
Isoflurane MAC 1.4 -No arrhythmias Irritating
-No problems w/ catecholes
Enflurane MAC 1.68 -More potent muscle relaxant SEIZURE (assoc. w/ hypercarbia)
-Rapid onset & Malignant hyperthermia
recovery Renal toxicity (fluoride ion)
<Hepatotoxic
Halothane MAC .75 Pediatric anesthetic – not Hepatotoxicity
-Resp. & CV hepatotoxic to kids Lo threshold for catecholamine-
depression induced arrhythmia
-Vasodilation  MALIGNANT HYPERTHERMIA
relaxing SM (uterine) Carcinogenic
-Increase intracranial Increased risk of miscarriage
pressure
Methoxymethane MAC.16 -Reserved for OB -Metabolism releases fluoride
-Excellent skeletal -Most potent inhalant (RENAL DAMAGE)
muscle relaxation
-Slow onset &
awakening

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Neuromuscular Blockers:

Two Types:

Non-depolarizing-Competitively inhibits the NMJ receptors by binding without activation of pre and postsynaptic
sites. These cannot enter CNS due the charge of thei ammonium ions.
Presynaptic inhibition- Release of Ach diminishes and contraction “fades”
Postsynaptic inhibition- Blocks Ach at receptor. This is a competitive block therefore increased Ach can reverse
this.
Depolarizing-Competitive agonist that binds to and activates the NMJ receptor but inactivates it by keeping the
ion channel open (IE the receptor is prevented from cycling back to it’s closed state).

Drug Mechanism Clinical Use Adverse Effects


Duration

Long Tubocurarie Nondepolarizing Muscle parplysis Histamine release


A Gallamine Nondepolarizing Muscle parplysis Vagal Blockade
c Pancuronium Nondepolarizing Muscle parplysis Indirect sympathomimetic effect
t
i
n
g

(
1
.
5

h
r
s
)
Medium Atracurium Nondepolarizing Short surgical Safe for organ failure due to
A procedure nonenzymantic
c metabolism
t Vecurium Vent patients (long Toxic metabolite will build up with
i term) long-term infusion in pts
n with organ failure.
g

(
3
0

m
i
n
)
Very Succinylcholine Depolarizing Intubations Muscle soreness
S
h Malignant Hyperthermia
o
r
t

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Mivacurium Nondepolarizing Not used due to favor
of
succinylcholine

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Nitrosurias
Drug Carmustine Liphophilic
Mechanism
(BBB-CNS -Malignant
Cancer therapy
glioma Clincal Use Delayed hematopoietic
Side Effects
dep.
Lomustine tumors) Brain cancers Aplastic marrow
CANCER Mechlorethamine Non-phase specific Hodgkin’s disease Severe vomiting
-Penetrates CNS Renal toxicity
THERAPY -Alkylation of N7 Solid tumors Bone marrow suppression
-Alkylate DNA CNS toxicity
Alkalating Guanine in DNA Latent viral infxn
inhibiting replication
Agents -Cross-linkage between Extravasation is serious
Methane Busulfam Methane sulfate -CML BMSAdrenal suppression
chains & depurination
sulfona Pulmonary fibrosis
-NO DNA duplication
tes
IV or IA
Other Cisplatin Alkylating-like -Testicular ca (Ondestron)
Cyclophosphamide Pro-Drug -Burkitt’s lymphoma -Hemorrhagic cystitis w/ fibrosis of
-Complexes w/ guanine --Combo -- vinblastine, bleomycin, Limiting: Nephrotoxic
Chlorambucil -Activated via -BRCA bladder due to acrolein (active
in DNA cisplatin, etoposide (mannitol/hydration)
hydroxylation via Cyt -Nephrotic syndrome metabolite)
-Binds to proteins – -Ovarian ca Acoustic nerve damage
P450 -RA (intractable -Tx w/ MESNA, hydration & mannitol)
cross-linkage -Bladder ca Lo Ca++/Mg++
-Covalent x-link BMS
-Cytotoxic to all cell Neurotoxic
guanine -oral/liver metabolism w/ toxicity @ all
stages Sterility
-Oral; dose levels
Carboplatin Newer form of cisplatin Same as platin Less toxic/nauseating than cis-platin
Slow-acting
-No protein binding Limiting – myelosuppression
(chlorambucil)
(thrombocytopenia)
ANTI- Methotrexate -Dihydrofolate ALL-children Bone marrow toxicity
METAB (W/ leukovorin) reductase inhibition Choriocarcinoma – w/ dactinomycin GI disturbances
OLITE -Decrease THF Burkitt’s Urticaria
INHIB -Inhibit conversion of -BRCA Alopecia
ITORS dUMP to TMP -Head/neck ca Renal damage-Hi dose - 90%unchanged in
S-phase -Hi doeses 7-OH  -Long-term use in psoriasis/RA  urine Lo—50%--liver can only detoxify so
specific crystaluria hepatic fibrosis/cirrhosis much @ a time – measure blood/renal fxn
-CSF only Hi doses -Abortion when used w/ misoprostol in Hepatic fibrosis – in low doses (mostly
3rd term long-term for immunosuppression)- also
Leucovorin Rescue recirculates in biliary stasis -
GI toxicity
5-fluorauracil -Pyrimidine analog that Slow growing solid tumors (colon, Ulceration of oral & GI mucosa
interferes w/ breast, ovarian, pancreatic, gastric) BMS
conversion of Superficial basal cell Anorexia
deoxuyurdylic acid  N/V/D
thymic acid Hand/foot syndrome
-F-dUMP competes w/
dUMP (thymidilate
synthetase)
Arabinosyl Pyrimidine antagonist
-Decreases TMP & AML-myelogenous N/V/D
MITOTIC Vincristine -Microtubule assembly -Vincristine – (childhood tumors) –some Neurotoxic (axonal transport)
Cytidine ara-CTPDNA
inhibits – competitive
synthesis Combo w/ t-TG+daumorubicin Myelosuppression
INHI (oncovin) inhibitor adult leukemias & solid tumors
(Cytarabine/ARA-
6-mercaptopurine inhibitor
Purine for DNA
analog – Pol ALL—maintain remissions Hepatic dysfxn
N/V
BITO vinblastin -Blocks mitosis Vinblastine – testicular ca((now Vincristine: neurotoxic
C) -Chain termination upon
activated by Thrombocytopenia
RS e M-phase specific etoposide preferred), (bleomycin & Vinblastine: BM suppression (blasts
incorporation
HGPRT Myelotoxicity
(Vinca alkaloids) cisplatin), lymphomas, Kaposi’s, breast marrow)
ANTIBIOTICS Adriamycin Broadest antitumor
-Inhibits Solid tumors Cardiotoxic – ECG changes – cumulative
Resistance: export (P-glycoprotein)
(doxorubic amidotransferase
spectrum ALL & granulocytic leukemias dose dependent (unique)(give Fe++
Paclitaxel (Taxol) M-phase spec. Breast ca Neutropenia
in) -Competitive
-Blocks Hodgkins chelator)
Hyperstablizes Ovarian ca, Hypersens. Rxn (dyspnea, urticaria,
substrate/DNA pol
IMPAMP/GMP Kaposi’s sarcoma (liposomal prep BMS
microtubule hypotension)
inhibitor – allopurinol
-CAREFUL decreasescardiac toxicity) Alopecia
--Good to give w/ dexamethosone,
-INTERCALATION—
—(xanthine oxidase)
diphenhydramine, & H2 blocker
topoisomerse
inhibits drug II
Cardiac toxicity
interference
metabolismtoxic
OTHER Epipidophyllotoxin Topoisomerase II Small cell ca Leukopenia – limiting
-Superoxide/ (via
levels)
(Etoposid inhibitor Hodgkins
quinone moiety) free
e) – VP16 -Strand breakage CNS malignancies
radicals fragmenting
Effecfts in S & G2 Testicular ca
DNA
-Now used in combo w/ Leukemia
-Preference for
bleomycin & cisplatin
Sphase (not specific)
Daunorubicin Same Acute lymphocytic & agranulocytic
leukemias
-Not as effective against solid tumors
Bleomycin Intercalates w/ GC or Small cell lung ca Pulmonary fibrosis – low levels of
GT Testicular ca (w/ vinblastine & deactivating enzyme in this tissue
-Free radicals cisplastin) -Tachypnea/dyspnea
-Splits DNA Lymphomas -Rash-hypertrophic skin change
G2-phase specific -Anaphylactoid rxn
-Complexes w/ Fe++ No BMS
Actinomycin D -Intercalates in small Childhood tumors BMS 36
(dactinomy groove
cin) -Interferes w/ DNA-
dep RNA pol
Immunosuppression
STEROIDS Prednisone (Also CANCER: Lymphomas Adrenal suppression
immunosupp General anti-lymphocytic DOC for: Growth inhibition
ressive) effect -ITP Decreased muscle tone
-Triggers apoptosis -Autoimmune hemolytic anemia Osteoporosis
IMMUNOSUPPRESSION: -Acute glomerulonephritis Cushing’s syndrome
Toxic to some T-cell G vs. H disease Immune suppression
lines
-Suppress immunity &
inhibits production of
mediators
-Ameliorate drug
toxicity/inflammation
Asparaginase Decreases rapidly-growing ALL – esp. childhood Hypersensitivity rxn
leukemias that show Decreases clotting factors
nutritional requirement Hepatotoxic
for asparagines Pancreatitis
Seizures, coma
IMMUNOSUPPRESSIVES Azothioprine Pro-drug Autoimmune disease BMS
-Precursor for Renal transplants Gi irritation
mercaptopurine **Caution allopurinol toxicity Skin rash
-Actively dividing cells Hypersensitivity rxn
-Amidotransferase
inhibition
(IMPAMP/GMP)
-Incorporated into DNA
Methotrexate Particularly active Prophylaxis against G vs. H in Hepatic fibrosis/cirrhosis (not
against lymphoid cells BMT BM suppression)
-See cancer Severe RA Abortion in combo w/ misoprostol
chemotherapy Psoriasis (PGE1 analog)
Leucovorin rescue
Cyclophosphamide -2nd line to azothioprine Autoimmune -doesn’t cause side effects of
-Hi dose  tolerance to -RBC hemolysis, Ab RBC steroids/anti ca drugs
new antigen dyscrasia, BM suppression
BM transplant @ hi doses
Cyclosporin A Interferes w/ early Organ transplants Nephrotoxicity is limiting factor
antigen response G vs H disease Neurotoxic – hi in liver transplant
Infxn
-Inhibits T-helper cells RA Lymphomas
-Inhibits calmodulin, Il- Glomerulonephritis Hirsutism
2, RBC dysplasia Gingival hyperplasia
-Cyt P450 Inflammatory bowel disease Hypertension
Psoriasis

FK509 (tacrolimus) Similar to Cyclosporin A Liver transplant NO gingival hyperplasia, less


-Higher potency & fewer -Rescue in other organ hypertension
side effects transplants -Otherwise similar to Cyclosporin
-P450 metabolism A
-avoid use w/ NSAID –
interferes w/ renal blood flow
-Antibodies Antilymphocyte Rxn against T-cell (poly or G vs. H disease Hypersensitivity rxn/serum
Globin monoclonal) Organ transplants sickness
-Serological immunity not
impaired
Anti-OKT-3 Monoclonal, mature T-cell- Renal transplant/allograft crisis Hypersensitivity rxn
(Muromonab-CD3) directed Ab
-Blocks killer T-cells
Mycophenotate Converted to Kidney transplant
mycophenolic acid (MPA)

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Mechanism Clincal Use Side Effects

Isoniazid -inhibits synthesis of -bacteriostatic/ -cidal Peripheral neuritis (inhibits pyridoxal


(INH) mycolic acid phosphate kinase)
-intracellular/ TB- resistance if used alone
extracellular organisms --given w/ pyridoxine (Vit. B6)
-acetylated -hepatotoxic (hydrazine metabolite)
M. Kanasii
-affects synth. Of -allergic rash/drug fever
lipids/ nucleic acids -potentiates effects of phenytoin & warfarin
Prophylactically – given alone
-hemolysis in G6PD deficiency
Rifampin -inhibits DNA-dep Bacteriocidal -GI irritation
RNA pol -TB -Hepatotoxic
-decreaase RNA synth -atypical mycobacteria -Thrombocytopenia
-CNS penetration -M. Leprae – in combo -induces P450 (increase metabolism of steroids
-prokaryocytes -meningitis – prophylactic (h. & oral contraceptives)
-red/orange urine, influenza, N. Meningitidis) -Flu-like syndrome
sweat, tears etc.
Ethambutol Mechanism u/k Bacteriostatic Decreased visual acuity/optic neuritis
-TB, M. kansasii (reversible)
-atypical mycobacteria -peripheral neuritis
-h/a, confusion
Second line Pyrazinamide Mech u/k Bacteriocidal GI irritation
drugs TB Hepatitis  death
Hyperuricemia  gout

Photosensitivity
Streptomycin 30s inhibitor TB (advanced & military) Optic nerve dysfxn
Tularemia, plague, meningitis
Ethionamide -Structurally similar to - GI irritation – due to dose
isoniazid Impotence
-diff mechanism Mental disturbance
-large doses required
LEPROSY Para-amino -competitive inhibitor GI irritation
salicylic acid for PABA in Folate Hemolysis in G6PD def
(PAS) synth Hypersensitivity
Cycloserine Inhibits cell wall 2nd line for TB/atypical Exacerbate epileptic seizures
synthesis by mycobacteria
competitively inhibiting -nocardia infection if sulfa’s fail CNS disturbance
conversion of L-ala to -renal TB – 70% excreted in urine
D-ala, then linking D-
Peripheral neuropathies
form
Dapsone Bacteriostatic agent Leprosy Allergic rxn
inhibiting folate – Alternate tx for P. carinii in AIDS
(PABA-antagonist) pt. Peripheral neuritis
dihydropterate --recommended therapy = dapsone
synthase (similar to +clofazimine + rifampin
Hemolysis in G6PD def
sulfonamides)
-acetylation
-excreted via kidneys Lepra rxn (erythema Nodosum; similar to
jarisch herxheimer rxn w/ penicillin & syphilis)
Clofazimine Phenazine dye binds to -dapsone resistant leprosy Discoloration of skin
DNA to inhibit bacteriocidal to M. leprae
template fxn anti-inflammatory effect Eosinophilic enteritis
tx lepra rxn of dapsone

GI irritation
Amithiozone Alternate drug to Dapsone-resistant replacement Hepatotoxicity
dapsone GI irritation
Thiosemicarbazone

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Primaquine 8-aminoquinolone 1. Liver stage 1. GI irritation
Tissue
-liver phase of Antimalarials
infxn (exoerythrocytic) 2. H/A
schozont -“Tissue shizonticide” 2. Primary Falciparum, 3. Agranulocytosis
-extensive metabolism Malariae 4. Pruritis
icide
Drug Mechanism (oxidation/ Clincal Use3. Secondary Vivax, Ovale 5. Methemaglobinemia
Side Effects
demethylation) (latent hypnozoite) – only 6. Hemolysis in G6PD def.
Blood Cloroquine -DOC for all types -DOC – prophylaxis of all types 1. Short term – GI disturbance
agent to cure b/c they
schizonticide except falciparum (except resistant falciparum)
remain in liver 2. Long-term – SIGHT, HEARING
-blocks enzymatic synth -persistent liver stage (w/
of RNA & DNA primaquine) 4. Gametocidal for all 4 DAMAGE

-buffers cellular pH to interrupted
-amebiasis (cemetine) amebic liver transmission
decrease cellular abcess
invasion -collagen disorders/autoimmune like
-concentration: liver, lupus & RA b/c anti-inflammatory
idney, lung, blood, brain effect
-RBC – bindsw/ -gametocide
ferriprotopphorphyrin
IX  damages
membrane  lysis of
parasite/RBC
- erythrocytic phase
Amiodaquine Similar to cloroquine 1. Agranulocytosis
2. Photosensitivity
3. Dermatitis
4. GI disturbances
5. H/A
Pyrimethamine Inhibits dihydrofolate Prophylaxis of resistant falciparum 1. Megaloblastic anemia
reductase of parasite (w/ cloroquine & pyrimethamine) 2. Sulfa-skin rashes
Decreases P. Malariae & toxoplasma (w/ 3. GI distress
purin/pyrimidine synth sulfadiazine) 4. Hemolysis
Works @ lower -synergistic w/sulfadoxine in folate 5. Kidney damage
concentration than pthway 6. Steven-Johnson syndrome
required for mammalian
enzyme
Fansidar: pyrimethamine
+ sulfadoxine
Quinine Inhibits DNA Gyrase P. falciparum infxn resistant to 1. Cinchonism (h/a, tinnitus, blurred
mefloquine - prevent DNA strand chloroquine vision)
separation Relieve leg cramps 2. Cardiac conduction disturbances
Blocks DNA replication Myotonia congenital 3. Black water fever, (intravascular
& RNA transcription Sclerosing agent hemolysis)
-20% excreted 4. GI distresss
unchanged 5. Hemolysis in G6PD def

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Aminoglycosides

Drug Mechanism Clincal Use Side Effects

AMINOGLYCOSIDES Gentamycin -Inhibits 30s AEROBIC ONLY Ototoxic (vestibular & cochlear)
Amikacin -enters microbe via Gram – Nephrotoxic
Tobramycin O2-dep active E. Coli
transport Proteus NM blockade
-interferes w/ Klebsiella
assembly of fxnal Serratia
Hypersensitivity rxns
ribosome Pseudomonase
Superinfxn
-misreading of mRNA Enterobacteriaceae
-No CNS action TB (streptomycin)
Amikacin: resistant to
aminoglycoside
inactivity enzyme
produced by Gram (-)
Streptomycin Not effective in Gram TB – advanced & military Optic nerve dysfxn
(-) rods
Tularemia

Y. Pestis – plague
Meningitis
Spectinomyci Very limited spectrum Penicillin-resistant gonococcal Not ototoxic or nephrototoxic
n
Allergic penicillin gonococcal (not
effective against syphilis)
Netilmycin -Similar to amikacin Good for gentamycin-resistant Less ototoxic & nephrotoxoc
-Slight resistant to organisms (as is amikacin)
-aminoglycoside
inactivating enzymes
Neomycin -too toxic for systemic GI infxn Cochlear toxicity
(topical) use Sterilization for bowel surgery Nephrotoxic
(paramomycin -only used topically & Hepatic coma to reduce ammonia Hypersensitivity
) (kanamycin) sometimes orally intoxication Allergic rxn
-kanamycin/Paramycin Pottentiates action of NM blockers
is antiamebic
POLYMYXINS Polymixin B, -interacts w/ Ophthalmic Nephrotoxicity severely limits use
E (Colistin) phospholipids Skin Neurotoxic – parasthesia, dizziness, ataxia
-penetrates Ear Acute renal tubular necrosis
-disrupts cell Mucous membranes
membranes
-lyses cell
TOPICAL only

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Drug Mechanism Clincal Use Side Effects

AMEBIASIS metronidazole -undergoes reductive -severe intestinal & extra- Teratogenic /carcinogenic
bioactivation intestinal amebiasis
-cytotoxic products binds -UG trichomonas Seizures
protein/DNA Pseudomembranous colitis Ataxia
- cell death via pyrvate, Amebiasis Disulfiram- like
ferridoxin Giardiasis N/V/D
oxodoreductase in Dry mouth/stomatitis
anaerobic infxn Insomnia
Gardnerella vaginalis
Anaerobic infxn – esp B. fragilis Weakness
Acute ulcerative gingivitis Urethral burning
Cancrum oris
Cutaneous leishmania

Decubitis ulcers

Anaerobic infxns – esp. B.


Fragilis
Emetine -Blocks Ribosome (prot. Intestinal & extra-intestinal Heart: cloudy swelling & necrosis, hypotension,
Dehydroemetine synth) amebiasis CHF , arrhythmia
-IM injection Balantidium coli
Narrow therapeutic Fasciiola hepatica Pain/abcess @ injxn site
range Pargonimus westermani
Only given in hospital
Urticaria/ pruritic eruption
Concentration: liver,
N/V/D
spleen, kidney heart
Weakness & fatigue
--cumulative effect
Disulfiram-like rxn w/ alcohol

Potentiate coumadin
Diloxanide Mechanism u/k DOC - asymptomatic carriers of Mild
furoate Oral cysts N/V
Hydrolyzed in gut Abd cramps
diloxanide Moderate/severe intestinal Esophagitis
-oral, - 90% amebiasis Dry mouth urticaria
absorbedconjugated Proteinuria
inliver, urine excretion
Iodoquinol Mechanism u/k Alternate in asymptomatic Nephrotoxicity – high doses
Oral carriers Optic atrophy
Peripheral neuropathy
N/V
Mild-severe intestinal amebiasis Thyroid enlargement
Agranulocytosis
ANTI- Mebendazole -inhibits microtubule DOC: Nematodes GI irritation
HELMINTHS synth 1. Whip worm (trichuris Contraindicated in pregnancy
Nematodes -depletes helminth trichuria); prolapsed Rapid metabolization
energy stores by rectum
decreasing glucose uptake
2. Pin worm (enterobius
-hi therapeutic index
vermicularis)
3. Eichonococcus granulosis
Also:
Ascaris
hookworm
Thiabendazole Congener of DOC: Vertigo
mebendazole Threadworm (strongyloides)
Larvicidal & ovicidal Trichinosis Crystalluria/hematuria
Inactivated by liver Larva migrans; ancylostoma
hydroxylation (creeping eruptions; cutaneous)
Hypotension
-excreted urine/liver
Note: killed parasites  fever, chills, rigors,
skin rash & lymphadenopathy (like Steven-
Johnson syndrome)
Pyrantel Depolarizing NM blockage DOC: Ascaris (Oxantel doesn’t Rash & fever
pamoate block of nicotinic work) GI irritation
Oxantel receptors  paralyze Hookworm H/A 42
pamoate worm expelled from GI Enterobius infection Dizziness
tract Weakness
Ivermectin -enhanced GABA- DOC – onchocerciasis (river Lymph node nelargement & tenderne
mediated blindness) Arthralgia
neurotransmission in Hypotension
nematodes (paralysis) Filiarisis tachycardia
-facilitates removal by Strongyloidiasis
RES Scabies
-doesn’t cross BBB

Other Diethyl Mech u/k DOC: filiariasis (w. Bancrofti) Mazzoti rxn – acute rash post-tx
carbamazine Violent allergic rxn Onchocerciasis (river blindness) –
(dying parasite proteins) alternate drug (tx w/ antihistamines or steroids)
Kills microfiliriae & adult -pyrexia
-resp. distress
-hypotension
-prostration
Albendazole -Blocks glucose uptake Alternate Teratogenic
 decreased ATP -Neurocystercosis BM suppression
production -Echinococcus
-inhibits microtubular Also: Hookworm, enterobius, Hepatitis
assembly (similar to strongyloides, trichuris
mebendazole )
Alopecia
Piperazine -paralysis of worm via Alternate: Contraindications:
Citrate non-depol blockade -Ascaris -Hepatic & renal insufficiency
-Enterobius -Epilepsy
Cestodes Niclosamide -Inhibits oxidative DOC: T. Solium (followed by Nausea
phosphorylation in purge) Abd pain
mitochondria t. saginata (tapeworm) Pruruitis
-ineffective against ova Diphyllobothrium (fish tape worm, Fever
present in segments B12 def)
Drug -follw by purge
Mechanism Clincal Use Side Effects
Trematodes Praziquantel Increased permeability to DOC: schistomiasis Increased rates of abortion
ANTIHELMINTHS LevamisoleCa++ Depolarizing NM Alternate: Vasculitis
blocker
-Muscular spasticity -Ascaris Agranulocytosis
DOC cystercercosis (larval T. H/a
/paralysis) of worm -Hookworm Proteinuria
Solium) Sedation
Improves of
Vacuolization T-cell Restores depressedT-cell fxn of:
fxn in Tapeworms
cells N/V
RA
death -RA
Paragonimus wetermani Fever/Rash
Broad spectrum -Recurrent apthous stomitis
-herpes etc
Niridazole Concentrates in the Schistosomiasis - alternate drug Carcinogenic/ teratogenic
worm to cause glycogen Causes hemolysis in G6PD def
depletion Anti-inflammatory effect Psychiatric problems
AMEBIASIS/ANTIHELMINTHS Pulmonary infiltration
Eosinophilia

Immunosuppression/anti-inflammatory
Metrifonate Organophosphate Alternate Cholinergic stimulation @ hi dose
compound inhibiting -Schistosoma hematobium
actylcholinesterase -S. mansoni
Nifurtimox T. cruzi; Chaga’s disease

Sodium Leishmaniasis 43
Stibogluconate
(pentavalent
antimony)
DIABETES:

Diabetes Type I (IDDM) Diabetes Type II (NIDDM)

Mechanism Insulin is defective or is never formed. Insulin resistance; down-regulation of insulin


Antibodies against pancreatic beta- receptors; failure of pancreas to release insulin even
cells. though it being formed.
Survival Insulin is absolutely required for Patient will survive without insulin
survival.
Synonyms Ketosis-Prone Diabetes Ketosis-Resistant Diabetes

Juvenile-Onset Diabetes Adult-Onset Diabetes


Onset Sudden, often discovered by Gradual, insidious. Often discovered incidentally, or
ketoacidosis. Childhood polydipsia, when chronic complications arise.
polyphagia, polyuria.
Nutrition Often thin. Failure of action of insulin. Usually obese.
Ketoacidosis Frequent Seldom or never
Treatment (order of Insulin always required Diet and exercise
importance)
Diet Oral hypoglycemics

Never oral hypoglycemics Insulin

44
Diabetes
Drug Mechanism Clincal Use Side Effects

RAPID ACTING CZI “Regular Insulin” -subcutaneous -hypoglycemia (poor dosing)


crystalline -pork, beef, human -IV (emergency) -general insulin allergy
zinc insulin recombinant -lowers blood sugar w/in minutes -local fat atrophy/hypertrophy
-4 hr. peak
-ONLY one IV
Semilente -suspension of -subcutaneous
insulin amorphous insulin
(portk/beef)
-supplement for
intermediate or
prolonged forms
Lyspro -doesn’t complex w/
zinc
-very soluble & rapid
acting
INTERMEDIATE NPH insulin -delayed absorption -sub cutaneous
-conjugation w/ -tx all forms of diabetes (except
protamine (less soluble) ketoacidosis or emergency
-16 hour peak hyperglycemia)
Lente Insulin Like NPH -previously untx diabetic who
(similar requires insulin Rx
onset/duration)
PROLONGED Ultralente -Poorly soluble
Insulin -Delayed onset w/
prolonged duration
-peak ~20 hours
ORAL Tolbutamine -enhance pancreatic Type II (NIDDM) Neutropenia
HYPOGLYCEMICS Chlopropamide insulin Neuronal (tinnitus/h/a)
1st generation Tolazamide -close ATP-dep K+ Cutaneous lesions
acetohexamide channels
-depolarization Chlorpropamide
-decrease serum -enhanced ADH secretion
glucagons -disulfiram-like rxn
concentrations -granulocytopenia
-cholestatic jaundice
-photosensitivity
2nd generation Glipizide -100x more potent Type II (NIDDM) Hypoglycemic crisis
Glyburide -longer duration
-shorter life -NO agranulocytpopenia
-LESS disulfiram-like rxn
Biguanidines Phenformin Metformin – new form -fatal lactic acidosis
Metformin -NO effect on insulin -contraindication in prior MI or other
production or release metabolic problems
-enhances peripheral
glucose utilization
Acarbose Starch blocker: -used in fat people Flatulence
inhibits alpha Osmotic diarrhea
glucosidase
-decrease starch
absorption from the GI

45
Drug Mechanism Clincal Use Side Effects

STRONG morphine -opioid receptor in CNS & GI GOLD STANDARD Addiction


AGONIST -hyperpolarizes nerve cells (inhibit -analgesia Respiratory depression
neuronal firing & presynaptic
inhibition of NT release)
Rx’s diarrhea (decrease GI Vomiting
-Mu receptors in substantia motility) Dysphoria
gelatinosa decrease(Sub P release) -relieves cough (suppress central Decreased blood volume
-inhibits release of excitatory
transmitters from neurons
cough reflex) Increases intracranial pressure
carrying pain stimuli -spinal anesthesia Urinary retention – in hypertrophic prostate
-Liver  6-glucuronide  kidney MI, Post-op pain Histamine release (hypotension, sweating,
excretion
Pulmonary edema itching)
Heroin Diacetyl-morphine No medical use Addiction

-3x more potent than morphine


-metabolized to form morphine
/acetyl morphine
-enters CNS better
-more exaggerated euphoria
Meperidine K receptors Analgesia (post-op) Less urinary retention than morphine
-enters CNS better than morphine -addictive
(Demero -metabolite (normeperidine) has -doesn’t cause pinpoint pupils (acts more like atropine)
l) extremely long t1/2 Pulmonary edema
-kidney/liver dysfxn, clonus
twitching & seizures -less peripheral effects
Methadone -Mu Post-op pain -
-potency = morphine Heroin addiction – maintenance
-<euphoria therapy
-longer action Helps w/ heroin w/d
-oral -prevents heroin high
-long duration of action
Fentanyl -80x potency of Anesthetic – decreased amt. cerebral vasodilation – increase intracranial
morphine Needed pressure (contraindicated in head injury)
-rapid onset, short -combo w/ droperidol -stiff man phenom; need to give succinyl
duration “dissociative/ neuroleptic Choline
-doesn’t release histamine analgesia”
(unlike morphine) -w/ dropieridol & NO “neuroleptic
anesthesia”
Diphenoxylate Very insoluble Anti diarrhetic Very little addiction b/c lack of solubility
Sometimes combined w/ atropine
Loperamide Decreases addiction even more
WEAK Propoxyphene -derivative of methadone Analgesia Constipation
Respiratory depression
AGONISTS (nalbuphine) -similar to morphine/ Anti-tussive (cough) Convulsions
(darvon) codeine Hallucinations
-only oral Confusion
-magnified w/ alcohol/CNS depressants
-weaker -high dose causes psychotic episodes

Codeine Methylmorphine Cough Itching

less potent than morphine Analgesia


w/ higher oral
efficacy

-low abuse potential


-less euphoria
Dextromethorp -replaced cough in cough Cough (OTC) Non-addictive
han -most non-prescription
cough meds
MIXED Pentazocine Partial agonist of k receptors Analgesia – chronic severe pain Respiratory depression
-weak agonst to m & d -given w/ naloxone – if used orally, then Constipation
ACTION -spinal chord to promote analgesia naloxone is destroyed but if injected will Nightmares
-preciptate w/d if user is addict induce w/d sx in abuser Tachycardia
-binds PCP site also Dizziness

Buprenorphine -partial agonist @ mu


-antagonize morphine
-long duration of action
-
OPIOID Naloxone Rapidly displaces all receptor Reverse coma & respiratory depression of Precipitates w/d sx in morphine & heroin users
bound opioid molecules opioid overdose
ANTAGONIST -enables reversal of heroin -decreases pain tolerance
overdose -blocks analgesic effect of placebo
-competitive antagonist of mu, k, -blocks stress-produced analgesia
receptors
46
Naltrexone Similar to naloxone Used in opioid-dependence maintenance
-longer duration of action programs(not as good as methadone)
-now used to reduce alcohol craving (fairly
successful)
Drug Mechanism Clinical Use Side Effects
ENDOCRINE Somatostatin analog that modulates 1. Acromegaly -Nausea, cramps, diarrhea
Growth Hormones Octreotide neurotrans- 2. TSH/ACTH secreting -low glucose tolerance
-more selective for GH over insulin tumors -fat malabsorption
3. Islet cell tumors including -flatulence
those secreting: VIP, glucagons -gall stones (w/ long term
4. Carcinoid therapy)
5. GI; variceal bleeding
Prolactin Bromocriptine DA receptor agonist -DOC: M & F -Cold induced digital
-D1 antagonist, D2 agonist Hyperprolactinemia vasospasm(at higher doses)
-1st pass -Parkinson’s Disease -nausea, constipation
-Breast engorgement (after -orthostatic hypotension
abortion) -neuropsychiatric prob’s
-Excess GH (octreotide better)
THYROID Iodide -inhibit Thyroid hormone release Presurgery – firm gland -angioedema
-rapid onset, but short duration -larynx swelling,
Problems: delay radioiodine tx, hemorrhage
action of thioamides serum sickness
Thioamides Propylthiouracil Peroxidase inhibitor Iodide PTU-1st drug in emergencies
(PTU) ===X==>iodine “thydoid storm” -Agranulocytosis
Methimazole (US) PTU: Hyperthroidism -Rash
Carbimazole -protein bound, used in pregnancy, -jt. Pain/stiffness
(EUR) avoid in lactation PTU is highly protein bound vs. -parasthesia
-pro-drug for -inhibits T4-T3 conversion methimazole which is not -h/a
methimazole -hair pigment loss
Methimazole – 10 hr. t ½ , not protein
bound, doesn’t affect T4-T3
conversion
Propranolol Beta blocker. -Hyperthyroidism – tx’s sx See autonomics
-blocks sympathomimetic
manifestations
-may reduce peripheral T4 T3

47
Prednisone Has extremely
Has low anti-inflammatory action with Samedisease
as above Same as above
Intermediate Hydrocortisone
ADRENAL- low anti-inflammoatory -Addison’s -Cushing syndrome
CORTICO- Prednisolone and mineralocorticoid
(Cortisol) extremely low mineralcorticoid
potentices. action.
-Replacement therapy for -Diabetogenic action
STEROIDS TriamcinoloneDuration
Duration
of actionof is
action
8-12 is 12-36 hours. secondary or tertiary
hours. -Protein catabolism with
Triamcinolone is not administered
Orally, i.m. or i.v. Higher excretion of I.V.
adrenocortical insufficiency sketetal atrophy
Long
Short Acting
Acting Betamethasone Ca and -crosses placenta
poor intestinal absorption. -Relieve
-Congenital inflammation,
adrenal hyperplasia -masks symptoms
-Perforation of ulcers
Dexamethasone -used for fetal lung maturation (RDS) hypersensitivity (RA,
-Immunosuppression -cushing’s syndrome etc…
-Osteroporosis
(betamethasone) osteroarthritis, skin
-Cancer see cortisol
-Cardiovascular
inflammation) -CNS-psychosis
-Diagnosis of Cushing’s syn. -Fluid retention (HPT, CHF)
(Dexamethasone Suppression-Cataracts& Glaucoma
Test)
Beclomethasone -inhalers Asthma - inhalation
Budesonide -hi first pass (no adrenal suppression)
-large anti-inflammatory w/ no
mineralcorticoid action.
Steroid synth Aminoglutethimide -Chol-pregnenolone conversion -estrogen-dep breast cancer GI & Neurological side
inhibitor blocked (cyt P450) effects
-aromatase blocked rash
-inhibits all sterid synth
Ketokonazole -inhibits P450 -hepatic dysfunction
Diethystilbestrol Very potent&effective synthetic Same as above. Associated w/ vaginal
(DES) steroid. Has less first pass -Prostatic carcinoma (clear cell) carcinoma in
metabolism. -Prevent abortion daughters of mothers who
took it during pregnancy
ESTROGENS Estrone -excreted as glucuronides -replacement -Nausea, breast tenderness
Estriol -pregnancy – made in placenta -contraception -vascular:
-puberty, secondary sexual charact., -menopause – hot flash, thrombophlebitis, embolism
reproductive cycle, brain development vaginitis -cholestatic jaundice
-suppress FSH preventing ovulation -osteoporosis -postmenopausal bleeding
-hyperpigmentation
-hypertension
-depression

Cancer:
-increased endometrial
(prevented by concomitant
progestin)
ANTI-ESTROGENS Clomiphene -antagonist Infertility assoc. w/ -Ovarian enlargement
-pituitary/hypothalamus anovulatory cycles (Reversible))
-blocks (-) feedback on GnRH/FSH
increased FSH release (follicular
stimulation)

48
Tamoxifen -estrogen receptor partial agonist -estrogen-dependent tumor
-prevent/treat breast ca cells

Raloxifene -supposedly better @


prophylaxis in postmenopausal
osteoporosis
PROGESTINS Progestin -secretory phase of menstrual cycle -Contraceptive component -Weight gain
-suppress LH & prevent luteal -Anovulation/oligoovulation; -Hair growth
changes induces bleeding -Depression, fatigue
-Early or mid-cycle
bleeding
CONTRACEPTIVES Ethinyl estradiol -cause same effect as pregnancy Long-term:
Norethindrone -derivatives of estrogen -same effects as pregnancy
-increase T4 binding, HT,
throbosis

Other:
-Nausea, breast
tenderness, edema
-mid-cycle spot bleeding
(decrease estr & increase
Prog)
-wt. gain, hair growth,
depression (decrease prog)
-excess bleeding in late
cycle (increase Prog,
decrease Estr)

-
ANTI-PROGESTINS Mifeprostone Binds to (antagonizes) the -Abortions -Uterine bleeding
(RU-486) cytoplasmic progestin receptor-lose -Cushing’s disease (NEW -Possibility of incomplete
support for the conceptus & lose therapy b/c of its anti- abortion
inhibition of uterine contractions; glucocorticoid action)
also blocks glucocorticoid actions.
CALCIUM Calcifediol (25OH) Calcifediol -kidney & skeletal muscle.
REGULATING Calcitrol (1,25 OH) Calcitrol - GI & bone
-forms of Vit D.
-Calcitriol - most potent - high Ca
transport across the brush border
membranes - enhance Ca resorption
from the kidney
Calcitonin -parafollicular -Paget’s disease No significant effects
-decreases renal Ca++/PO4- -Osteoporosis -Nausea
resorption & bone -Hypercalcemia -Hypersensitivity
-decreases serum Ca++
Glucocorticoids -antagonize Vit D stimulated GI -Intermediate Rx of
absorption hypercalcemia due to
-prevent bone resorption sarcoidosis, lymphoma,
myeloma, D-hypervitaminosis
Estrogens Prevent bone loss after menopause. -Prevent osteoporosis (no
Probably antagonists of PTH. enhancement of bone
formation)

49
Raloxifene -estrogen agonist in bone New
-antagonist in uterus/breast -have to see what fracture
rate is
Diphosphonates -Retard the formation and dissolution -Hypercalcemia -Osteomalacia
(Etidronate & of hydroxyapatite crystals in bone -Osteroporosis -Hypophosphatemia
Pamidronate) -Inhibits osteoclastic activity -High Arthralgia
Mithramycin -DNA-binding cytostatic drug -Paget’s disease Since it’s given in such low
(intereferes w/ osteoclasts) -Hypercalcemia due to doses, no real effects
-1/10 cytotoxic dose malignancies
Gallium Nitrate -inhibit bone resorption (decrease -ca (osteoporosis, pagets) nephrotoxic
hydroxyapatite solubility)
Fluoride -Stablizes hydroxyapatite crystals Osteroporosis
MINERALCORT- Fludrocortisone -Very potent
ICOIDS Deoxycorticosterone -Act similar to aldosterone in the
kidney
-Deoxycorticosterone is the
precursor to aldosterone
INHIBITORS OF Metyrapone Inhibits 11-hydroxylation (final step -Cushing’s Syndrome -Water retention
STEROID BIOSYN in cortisol synthesis & the synthesis -Tests adrenal cortex function -Hirsutism
of corticosterone—the precursor of -Ectopic ACTH syndrome -Transient citizens
aldosterone -Adrenal syndrome -GI disturbances
Ketoconazole Anti-fungal, strongly inhibits gonadol -Cushing’s
& adrenal steroid synthesis at high -Testicular Cancer, anti-fungal
conc.
Aminoglutethimide Blocks the first step (cholestrol- -Cushing’s
pregnenolone) of glucocorticoid -Breast Cancer (low estrogens
synthesis. ALL adrenal steroid and androgens)
synthesis is suppressed **Must be used in combo w/
dexamethasone
-Adrenal Cortex tumors
GONADO-TROPINS GnRH Stimulate the pituitary release of & -Hypogonadism or delayed
& SEX STEROIDS (gonadorelin) FSH. puberty, infertility
Must be in given in pulsatile fashion -Cryptochidism
to be therapeutic. If given in -Endometriosis
constant dosing, you get -Hypothalamic ammenorrhea
desensitization
FSH/LH Menotropin FSH & LH like actions. Menotropin is -Female infertility (IVF); -Multiple pregnancy
Preparations HCG derived from the urine of normally given in combo w/ -Ovarian
HMG postmenopausal women; it contains a GnRH or Clomiphen Hyperstimmulation
Urofillotropin mixture of FSH & LH. -pituitary insufficiency Syndrome: Massive ovarian
-cryptorchidism enlargement, vascular fluid
Urofillotropin: into the peritoneum,
-only FSH (from pregnant women) hypovolemia, ascites, death

HCG:
-LH-like

HMG:
-postmenopausal urine
Leuprolide -slow release Prostate Cancer
-suppress FSH/LH (estrogen &
testosterone)

Estradiol Naturally occurring steroids. High -Post menopausal therapy -Vascular


Estriol first pass metabolism. Given IM. (osteroporosis & hot flashes) (thrombophlebitis,
Estrone -Development of secondary pulmonary embolism)
characteristics -Nausea

50
-Breast cancer -Cholestatic jaundice
-Contraception -Depression
-Breast tenderness
-Post-menopausal bleeding
-Hyperpigmentation
-Hypertension

51
EPILEPSY DRUGS
Drug Mechanism Clinical Use Side Effects
EPILEPSY Phenytoin -alters ionic flux (Na, K, Ca) Grand-mal Gingival hyperplasia
Decrease Na+ -membrane stabilizing Partial Hirsutism, coarsening facial
current -prevents spread of discharge Status epilepticus (IV) feat.
-shifts from 1st to 0 order 2nd choice – trigeminal Megaloblastic anemia
neuralgia(1st carbamazepine) Osteomalia (increased Vit. D
digitalis-induced arrhythmia metabolism -interfere w/
Ca++ metabolism)

Pregnancy – fetal hydantoin


(cleft palate, microcephaly,
hypoplastic phalanges)
Carbamazepine -related to TCA Psychomotor, grand mal -hyponatremia
-antimuscarinic effects Trigeminal neuralgia -H2O retention enhancing
-enzyme inducer Psychosis (alternative to Li+) effect of ADH on DCT
-Neurotoxic
-Hypersensitivity –
photosensitivity, lupus,
agranulocytosis
Valproate -blocks Na & “T” channel -petit mal -neural tube defect
-blocks PTZ seizure better than ECT -2nd choice grand mal -fulminant hepatitis (<3 yo)
-plasma protein-bound (inhibits met of -akinetic epilepsy
phenytoin, phenobarbitone,
lamotrigine)
Lamotrigine -Na+ channel blocker -partial seizures

Chloride current Phenobarbital -too sedative -increased porphyrin synth


increase -anticonvulsant (genetically susceptible)
Barbituates -long t ½ (less addictive)
-alkalinization of urine CI: liver, kidney diseases,
-microsomal inducer pulmonary insufficiency
Primidone -prodrug (deoxybarbituate ==> -same as phenobarb
phenobarbitone + phenylethyl
malonamide (PEMA))
Benzodiazepine -short-term tx for epilepsy Thrombophlebitis
(sedation) Drop in BP
-DOC – emergency - convulsion, Resp. depression
status epilepticus, tetanus,
eclampsia, convulsant poisoning
Clonazepam -blocks PTZ (little sedation) -Petit mal Tolerance – <6 mths
clorazepate -adjuvant in myoclonic &
akinetic epilepsy
Vigabatrin -structural similar to GABA Partial seizure
-irreversible inhibition GABA
transaminase
-increases GABA concentration
-DOES NOT INDUCE MICROSOME
Tigabine -inhibits reuptake of GABA
-used in partial seizure
“T” Ca++ blockers Valproate -blocks PTZ seizure Toxic metabolite:
-potentiates GABA -hepatic biotransformation
-competes for phenytoin, phenobarb, ==>fulminant hepatitis
lamotrigine protein-bindings sites
Ethosuximide -antagonize PTZ - absence seizures GI intolerance
Neurological:

52
-tiredness
agitation, mood change
drowsiness
Excitatory Felbamate -blocks glutamate -intractable partial seizure -aplastic anemia
transmittor blocker -hepatotoxicity
Gabapentin -GABA analog -~GABA -sedation
-behavior change in children
-movement disorders
Topiramate -enhance GABA Partial seizures -sedation
-weak block of glutamate -mental dulling
-voltage sensitive Na+ channels -renal stones
-wt. loss
parasthesia
Acetazolamide CA inhibitor Absence -rapid tolerance
-produces acidosis
Bromide -useful in refractory cases Sedation

CHOICE OF Phenytoin Generalized tonic clonic (grand


ANTICONVULSANT Carbamazepine mal)
Valproate Absence (petit mal)
Ethosuximide
Carbamazepine Partial-complex
Phenytoin
Valproate
Vigabatrine
Valproate Akinetic
Primodone
Clonazepam
Diazepam Febrile seizure
Phenobarbitone
Diazepam
Phenytoin
phenobarbitone

53
ALCOHOL
Drug Mechanism Clinical Use Side Effects
ALCOHOLS ETOH -absorbed same as H2O -decrease fever -all the good/bad CNS
-some metabolization in gut -nerve block effects
-mostly in liver -antiseptic -hypoglycemia
-minor elimination via lungs -solvent -hyperuricemia
-may facilitate GABA -relaxes uterine SM
-Alcohol dehydrogenase – NAD-dep – -vasodilation ==>
==> acetaldehyde + antabuse + NAD ==> Withdrawal: hypothermia
acetic acid -physical dep . / DT’s -decreased cardiac
-MEOS (microsome ETOH Oxidizing -Tx – diazepam w/ tapering contractility
System) – mitochondria in liver -acute – glucose, thiamin -diuresis
-NADH shuttles pyruvate from glucose -antabuse – induces disulfiram
(hypoglycemia) rxn also, metronidazole, fulfas, Chronic
griseofulvin, cephalosporin, Liver – fatty ==> cirrhosis
phenylbutazone, phenothiazine GI – gastritis, nutritional
defects
-Naltrexone – opioid antagonist CVS/blood – HPT, MI,
– prevents craving cardiomyopathy
-poor immune response
-increase brca
P450 induction – testicular
feminization gynecomastia,
impotence, sterility
CNS – polyneuritis,
Wernicke’s, Korsakoff’s
(Thiamine tx)
Fetus – teratogenic, retard,
growth def
Methanol -competes w/ alcohol dehydrogenase Substitue for ETOH by Visual dysfxn
for elimination alcoholics GI distress
Coma
Toxicity – give ETOH w/ Acidosis - death
dialysis
Ethylene Glycol -also uses alcohol dehydrogenase Toxicity – ETOH Renal damage/death
-oxalic acid is elimination by-product

54

Drug Mechanism Clinical Use Side Effects
THROMBOLYTIC Streptokinase Bacterial culture DVT
AGENTS Generates plasmin PE
Coronary throbus
Urokinase Human kidney cells Same
Generates plasmin
TPA Recombinant Same
Generates plasmin
ANTI-PLATELET Aspirin Inhibits TXA2
Increases bleeding time

Dipyridamole Prevent thrombosis on artificial valves


ANTICOAGULANT Heparin Activates antithrombin III Can be used in pregnancy Bleeding  1st sign
Anti-thrombin inactivates IX, X, XI, Long-acting hematuria
XII Suppress aldosterone
Parenteral Antidote: Protamine Hypersensitivity
Renal excretion Osteoporosis
Doesn’t cross BBB or placenta Reversible alopecia
Immediate action Thrombocytopenia

A mucopolysaccharide B SHORT
CI:
Bleeding disorder
Ulcer, hemorrhoid,
threatened abortion
Surgery
Aspirin or antiplatelets
Warfarin Vit. K-dep. Clotting factors – II, VII, CI in pregnancy -GI Bleed
IX, X Prophylaxis use -Petechiae
Lipid soluble – oral -Adrenal insufficiency
Secreted in milk Antidote:give fresh plasma / -Low Therapeutic index –
Protein-bound Vit. K drug interactions
-Pregnancy

B PAL
Vit. K Causes synth. of clotting factors For Warfarin overdose & CI: Synthetic analogs
SYNTH. newborns
ANALOG Menadione – H2O soluble Hemolysis – G6PD
Phytonadione Kernicterus – newborn
Menadione (hyperbilirubinemia)
menadiol
Deficiency
-decrease prothrombin/
clotting factors
-ecchymoses, bleeding
PRO-CLOTTING VIII Hemophilia A
IX From dried human plasma Hemophilia B (Christmas)
Has several Vit. K-dep. factors
Tranexamic Inhibit conversion of plasminogen to
acid plasmin
Aminocaproic acid Post-tPA , urokinase,
streptokinase
i.e. bleeding due to fibrinolysis
Antihemophilic hemophiliacs
Globulin

55
Thrombin Clots fibrinogen Topical hemostat (capillary
bleeding)
OTHER Protamine Heparin antagonist
From fish sperm

56