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USMLE Road Map Pharmacology PDF
USMLE Road Map Pharmacology PDF
ECOND
ITID
VOR
Contents
I
2
3
4
II
5
6
7
8
9
Introduction to Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pharmacodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Drug Dosing and Prescription Writing . . . . . . . . . . . . . . . . . . . . . . .
3
5
12
17
Ill
I0
II
12
13
14
IS
16
17
18
19
IV
CARDIOVASCULAR SYSTEM
20
21
22
23
24
25
26
27
Antihypertensive Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antiarrhythmic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Drugs Used to Treat Congestive Heart Failure ....... ........ .
Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Antianginal Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Anticoagulant, Fibrinolytic, and Antiplatelet Drugs . . . . . . . . . . . . . .
Antihyperlipidemic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Drugs Used to Treat Anemia .... ........ .............. .... .
23
28
37
45
55
65
67
74
80
87
95
I02
I IS
I 19
125
135
148
161
167
174
179
188
195
xill
xiv
Contents
RESPIRATORY SYSTEM
28
VI
ENDOCRINE SYSTEM
29
30
31
32
33
34
VII
MUSCULOSKELETAL SYSTEM
35
36
37
VIII
GASTROINTESTINAL SYSTEM
38
IX
IMMUNE SYSTEM
39
Antineoplastic Drugs
ANTIMICROBIAL DRUGS
40
41
42
43
44
45
46
47
48
49
50
XI
TOXICOLOGY
51
Toxicology
XII
52
0.
0.
20 I
21 I
215
221
229
23S
241
247
255
262
267
277
293
297
303
31 I
320
323
328
335
350
357
369
377
397
Contents
xv
APPENDICES
A
B
C
Index
Section I
Principles of
Pharmacology
Introduction to
Pharmacology
What is pharmacology?
What is a drug?
1. Pharmacokinclics--<lescribes "what
the body does to tht> drug." This
includes topics such as absorption,
distribution, metabolism, and
excre tion or drugs.
2. Pharmacodynamlcs--<lcscribes
"what the drug docs to the body."
Specifically, it deals with the
biochemical and physiological effects
of drugs and their mechanisms of
action.
3. Pharmacothe rap eutics--<lescribes
the use of drugs for the prevention,
diagnosis, and treatment of disease.
4. Toxicology--<lescribes the
undesirable effects of therapeutic
agents, poisons, and pollutants on
biologic systems.
-ane
-azepam
-hi tal
-caine
-ciiJin
-cycline
-olol
-opril
-slatin
-zosin
2
Define pharmacokinetics.
Pharmacokinetics
distribution, biolmmfonnation
(metabolism ), and excretion.
ABSORPTION
De fine absorption.
Route of administration
Tlw
intravenous route is 111ost eflcclive.
Blood Oow- ll ighly vascularized organs
such as the small int<'stine haw tJ1e
greatest ab~orbing ;tbility.
Surface area available- Absorption of
a drug~ dirt'ctly proportional to the
surface area availablc.
Solubility of a drug- The ratio of
hydrophilic to lipophilic propertil.'s
(partition coefficie nt) that a dmg
halt will dt>ltrmirw ''hether the dmg
c;m permeate t-ell nwmlmmes.
11 Ai1 11 I"
Basic drugs arC' chal'ged >vlwn
protonated:
Bll rt B + II
5
Define bioavailability.
1. First-pass mctaboli~m
2. All of tlw factors that affect absorption
(
pH
pHfK,
JLI
pH< pKa
6I
J
10
11
pKa
Figure 2-1. The distribution of a drug between its ionized and un-Ionized form depends
on the ambient pH and pJ<. of the drug. For illustrative purposes. the drug has been assigned a pJ<. of 6.5. (Redrawn from Mycek MJ. Gertner SB, Perper MM (Harvey RA.
Champe PC, eds]: uppincott's Illustrated Reviews: Pharmacology, 2nd ed. Philadelphia, Uppincott-Raven Publishers. 1997. p 6.)
Chapter 2 f Pharmacokinetics
I. First-pas~ metabolism
2. All of the factors that affect ahsorption
(i.e .. p i I, blood flow , drug soluhilit).
dnag-dlllg interactions. route of
administration)
Alinapntaa)'
Pnrenteral
lnhalatio11
Topic; a!
Tmnsdrnaaal
Subcutaawous
Name the fom typ es of
alime ntary routes of adminis tra tio n and slate the
a d vantage of each.
hepatic first-pa"
nwtaholism.
<1. Htl'l;\l (:.uppository)-Useful "lwn
tlw cmJ route is tu1availahiP due to
vo a uitin~ or loss of comcious raess.
Adra11iage: Approxi m ate!~ 50% of
drug absorbed Crom the rectaam wi ll
bypa\~ the Li\er.
2. Jntramusculur-AdcontageN: Usually
more rapid and complete absorption
than with oral administration.
~1inimizes ha1.ards of intrav<l!>cular
injection.
3. Subcutaneous-Ac/V<mlages: Sam(' as
intramuscular.
-!. lntrathecai-Adranlage l nca.ses of
acute CNS infections or spinal
anesthesia, dngs can be more
effective if injected direct!)' into the
spinal subarachnoid space.
Pulmonary agents
When is topical
administration used?
When is lransdermal
ndmirustration used?
DISTRIBUTION
Define distribution.
Blood Oow
Capillary permeability- The structure
Chapter 2 I Pharmacokinetics
Glucuronate-Quantitatively, addition of
this substrate constitutes the most
important conjugation reaction.
Acetic acid
Glutathione
Sulfate
I0
Pncloplasmi(' rp!i('ulum.
II rtactions <X.'<.ur in tlw c~imol.
Phu.~e
Yl'!>.
Chapter 2/ Pharmacokinetics
II
What is excretion ?
Skin
3
Define pha rmacodynamics.
Pharmacodynamics
Ph:u-rnacodynamics clesclibes the actions
of a umg on the body. and includes tltc
principles of receptor interaction),
mechanisms of therapeutic and to\iC
action, and dose-response relationships.
llow is phannacodynamics
related to phannacokinetics?
RECEPTOR INTERACTIONS
What is a receptor?
1. Ligand binding
2. Activation of an e ffector systPm
(message propagation)
What is an effector?
mech,misms:
I . Tnmsmcmbrane-Some ligaml~
such us insulin bind to receptor:. that
Chapter 3 I Pharmacodynamics
13
Dose of drug
administered
ABSORPTION
Pharmacokinetics
ELIMINATION
J
Pharmacologic effect
~iJ\.
Toxicity
Pharmacodynamics
Efficacy
Figure 3-1. The relationship between dose and effect can be separated into pharmacokinetic (dose-concentration) and pharmacodynamic (concentration-effect) components.
Concentration provides the link between pharmacokinetics and pharm<~codyn<~mics and is
the focus of the target concentration approach to rational dosing. The three primary
processes of pharmacokinetics are absorption. distribution. and elimination. (Redrawn
from Katzung BG: Basic and Oinical Pharmacology. 7th ed. Stamford, CT. Appleton & Lange.
1998, p 35.)
14
Receptors as
Enzymes
Nicotinic
acetylcholine R G Protein-Coupled Receptor systems
Glutamate R
GABAA R
Glycine R
5HT3 serotonin R
Cell
Transmembrane
Effectors
G Proteins
receptors Catalytic Activities
Tyrosine kinases
Growth factor receptors
Regulated by a subunits:
Cytoplasm
Neurotrophic factor receptors
t Adenylyl cyclase,
Tyrosine phosphatases
t Ca2+ currents
Serine/threonine kinases
+
Adenylyl
cyclase,
TBF~-receptor
t K+ currents
Guanylyl cyclase
+Ca2 currents
ANF receptor
t Phospholipase cp
Guanylin receptor
+
Na+tw exchange
Nucleus
Cytosolic
t cGMP
Receptor
Regulation of
-phosphodiesterase
~
transcription
(vision)
Steroids
1~
~
Aetinoids
~
Thyroid hormone
Chapter 3 I Pharmacodynamics
IS
What is an agonist?
receptors
16
'I
Drug concentration
Figure 3-3. Effects of drug antagonists and partial agonist. EC50 = drug dose that shows
50% of maximal response. (Redrawn from Mycek MJ. Gertner SB. Perpecr MM [Harvey RA.
Champe PC. eds]: Uppincott's Illustrated Reviews: Phormocology, 2nd ed. Philadelphia. Uppincott-Raven Publishers, 1997. p 22.)
Wbati!. K,/
What is EC50?
3-3).
DRUG DOSING
What tlwee factors :ue
involved in dete rmining an
a ppmpriute drug dose for a
patie nt?
H ow is Vd calculated ?
What is important to
tcmc mbc r in pe rforming
Ulis calculation?
What is a loading dose?
plasma
18
Loading clo!>e -
Vd X
desired plasma
COllCl'lltration
intervals.
What variable affects these
concentnltion.'i?
Approximate!)
What is clearance?
..t~
half-lives. At 3.3X,
PRESCRIPTION WRITING
en'')' hour
qhl>
CWI)'
night
'2
:I
:e
.!.
.g
Injection of
2 U of drug
Injection of
1 U of drug
~y
~00}
19
.a
.5
en
'g
c
:I
<
1
0
Days
qd
every day
bid
twice a day
tid
qid
qos
stat
immediately
ac
at meal time
hs
at night
pc
20
po
orally
gtt
drops
pm
as needed
qs
pills)
How i~ a standard
prescript:ion written?
Riverside Hospital
1492 Columbus Ave.
Ashtabula, New York
(212) 613-5000
NAME - - - - -- - - - - - - -- - - --
AGE _ _ _ _ __
ADO!lESS _ _ _ _ _ __ _ __ _ __ _ _ _ DATE - - - - - -
T~~P~E~-------------------
REFill --TIMES
PRAC11110NEFI'S SIGNATURE
DEA REG~ - - - - -- - - - - -
Section II
Autonomic Nervous
System
Introduction to
Autonomic Nervous
System Pharmacology
llC I'VOU S
hody
Wh y is thh
sy~1:em
important?
tlw
V>
CD
S}11lpat.hetic
a.
=
0
:::J
Parasvmpathetic
)>
Effector Organs"
Eye
Radial muscle (iris)
Circular muscle (iris)
Ciliary muscle
Heart
SA node
A\' node
Contractility
Lung
Bronchial muscle
Blood vessels
Most (except skeletal muscle)
Skeletal muscle
GI (Stomach and Intestine)
Sphincter
~1otility and tone
Heceplor
Response
Rccf'ptor
Response
c:
8:::J
0
;:;
Contraction (wydriasis)
Ql
~2
Relaxation
Contractio n (miosis)
Contraction (accommodation)
~I
~I
~I
iHR
eonduction velocity and automaticity
i force of contraction (atria & ventricles)
J. IIR
J. conduction velocity
J. contractility (atria)
~2
Relaxation (bronchodilation)
a,
Contraction (hronchocomtriction)
~ 13
M3
Constriction
Relaxation
132
o:,
0:,
M3
Constriction (retention )
132
J.
Relaxation (defecation)
motilit) and tone
CD
...c:
~
;;
3
GU
Urinary sphincter
Bladder wall
Uterus, pregnant
Uterus, nonpregnant
Penis, seminal vesicles
Secretory glands
Sweat
Intestinal
Bronchial
Lacrimal
Metabolism
Adrenal med ulla
Kidney
Skeletal muscle
Pancreas (beta cells)
Fat cells
Ctl
132
et1; 13z
132
('(!
Constriction
Relaxation (retention)
Contraction; relaxation
He laxation
Ejaculation
MJ
Rehtxation
Contraction
E rection
M3
5"
a
Q.
a2
Localized secretion
Inhibition
M
M3
M
M
<X I
secretion (moderate)
Generalized secretion
i secretion
i secretion
Profuse secretion
5
::l
>
c
8::l
0
NN
131
132
('(2
133
Secretion of catecholamines
i renin release
Glycogenolysis, i contractility
! insulin release
Lipolysis
The parasympathetics system controls most organs except blood vessels, which are regulated by the sympathetic nervous syste m.
N,. = nicotinic; M = muscarinic receptors
(Adapted from Gallia G, Hann CL, Hewson WH: The Phannacology Companion. Ann Arbor, Ml, Alert & Oriented Publishing Company. 1997. )
i'i'
'"~
c
"'
~
..
..
"
3
-:T
n
0
g
....
"'
26
fiJ:'i
act upo n ?
27
2. Norepinephrine-adrenergic
transmission
Cholinergic Agonists
autonomic ganglia
2. Muscular uicot.inic (N~.1 ), 1ocated in
tlae nC'uromuscular junction
Prcg;tnglionic fibers of the autonomic
ganglia
Preganglionic fibers that terminate in the
adrenal medulla
Postganglio11ic fibers of the
parasympathetic system
Voluntary muscles of the somatic system
CNS
Sweat gland~ innervated by postgangliunic sympathetic nervous ~ystcm
Se<> Figure 6-1.
28
Somatic
Nervous System
$L
Sympathetic
Paresympathetlc
Acelylcholin&
ii!IIWII*'I,-~~
18'/"W~
Acetylcholine
Acetylcholine
iu-
i!.
~N'~cotinlc
~oooptor
....
~
receptor
.g
~ J<icotinio
(no gangha)
receptor
~t-
Adren~medulla
Epinephrine
{released
into lhe blood)
Niootinic
receptor
29
NOleptnephnne
AcetylchOline
....
~
receptor
~
receptor
Acetylcholine
Effector organs
Striated muscle
Figure 6-1 . Sites of action of cholinergic agonists in the autonomic and somatic nervous
systems. (Redrawn from Mycek MJ, Gertner SB, Perper MM [Harvey RA. Champe PC,
eds): Uppincott's Illustrated Reviews: Pharmacology, 2nd ed. Philadelphia. Lippincott-Raven
Publishers, 1997, p 36.)
l.
2.
3.
4.
Acetylcholine~prototype
Bethanechol
Carbachol
Pilocarpine
5. Methacholine
6. Nicotine (discussed in Chapter 17CNS Stinwlants)
ACETYLCHOLINE
30
Miosis
Bronchoconshiction
Excitation of skeletal muscle
Lacrimation
Salivation and sweating
DUMBELS
NOTE: These adverse effects are
typical of all direct and indirect
cholinergic agonists, not just
acetylcholine.
BETHANECHOL (Urecholine)
l'fM
\;X,
31
\"X,
CARBACHOL
PILOCARPINE (Pilocar)
An alkaloid
Is it cleaved by acetylcbolin-
estera~e?
32
METHACHOLINE
\\1hat
fm?
M uscarinic receptors
INDIRECT-ACTING AGONISTS
l.
2.
3.
4.
5.
6.
Why mc p h ysostigmine,
ne ostig m ine, c drophonium,
a nd pyrido~ligmine
considered to be eversible?
33
PHYSOSTIGMINE
w hen is physostigmine
administered ?
34
Phosphorylation of Enzyme
Enzyme inactivated
Pralidox1me (PAM) can
remove the inhibitor
II
C3 H70 - P- OC3 H7
I
F
Isoflurophate
,..0 - H
Active site of
acetylcholinesterase
Acetylcholinesterase
(irreversibly inactive)
,..0 - H
Acetylcholinesterase
(active)
Convulsions
Muscle paralysis secondary to
overstimulation
Cataracts
Generalized excessive cholinergic
stimulation
35
NEOSTIGMINE (Prostigmin)
Does this drug enter the
CNS?
Usually 2 to 4 hours
EDROPHONIUM (Enlon)
What is its clinical use?
PYRIDOSTIGMINE (Mestinon)
What is pyridostigmine's
duration of action?
36
Cholinergic
Antagonists
1. Muscarinic blockers
2. Neuromuscular blocking agentsinhihit the efferent impulses to
skelE>talmuscle via the nicotinic
muscle receptor (NM)
3. Ganglionic blockers- inhibit l11e
nicotinic neuronal receptor (NN) of
both parasympathetic and sympathetic
ganglia
MUSCARINIC ANTAGONISTS
l. Atropine (prototype)
2. Scopolamine
3. l lomatropine
4. Cydopentolate
5. Tropicamide
6. Pirenzcpinc
ATROPI NE
38
Bradycardia
Mydriasis and cycloplegia-beneficial
39
Organophosphatt' poisoning
When is the use of atropine
to effect mydriasis and
cycloplegia contraindicated ?
Mnemonic:
1'oxic Eff ect:
" 0 1y as a bone"
Dry mouth
Inhibition of ~-weating, " I lot as a hare"
especially in young
childnm
"Hed as a beet"
Tachycardia and
cutaneous
vasodilation
Blurring of vision
Hallucinations <tlld
"Blind as a baf'
" Mad a~ a hatter
delirium
l'fM
\;X,
SCOPOLAMINE
a c tion ?
1nuscarini<.:
rct'l'ptor\
PrevPntion of motion
"lotio11 for nwtion"
l'fM
\;X,
sickness
or
40
PIRENZEPINE
What is it?
l. Tubocumriru.'-prototypc
2. Pancuronium- longer duration of
action than tubo<-urarinc
3. Atracurium
4. Vecuronium
What is th e mute of
administration?
41
poor.
What arc tbc adverse effects?
Succinylcholine
Plasma cholinestcr;L~e
42
Phase r
Membrane depolari7.es. resulting io ao
initial discharge which produces transient
fasciculati ons followed by flaccid paralysis.
'
(!
'
Na
~~('\~
++ +
+ + +
Nicotin ic receptor at
neuromuscular junction
Na+
PhaseD
Membrane repolarizes but receptor is
desensitized to effect of acetylcholine.
Malign<Ult hyperthennia
How is malignant bypetthennia beate d ?
Do neuromuscular blocking
agents block autonomic
ganglia as weU?
43
GANGLIONIC BLOCKERS
1.
2.
3.
4.
Nicotine
Hexamethonium
Mecamylamine
Trimethaphan
44
Adrenergic Agonists
Pbeuylcphrinc
Methoxamine
Clonidinc
Melhyldopa
DobutnmiJte
Isoproterenol
Albuterol
Mctaprotcrcnol
Terbutaliue
Epinephrine
Norepinephrine
Dopamine
Epinephrine, norepinephrine.
isoprotere nol, dop<lmine, and dobutamine
46
PHENYLEPHRINE (Nco-Synephrine)
What are phenylephrine's
physiologic actions?
47
~ Receptors
Activation of receptor
decreases production
of cAMP, leading to an
inhibition of furth er
release of norepinephrine
from the neuron.
Membrane ~ D~
phospho ~
inosltldes
-v ca++
IP~
a, Receptors
Activation of receptor
increases production of
diacylglycerol and inositol
triphosphate, leading to
an increase In intracellular
calcium ions.
48
METHOXAMINE
Describe the lhe rape utic uses. Treatment of l)poteosion mld PAT
\Vhut mc m e thoxamine's
adver~c cfTcc~?
CLONIDINE
TreatmC'nt of hypertension
\\ 'ithdrawal from benzodiazepincs and
opiates
TrPatm<>nt of diarrhea in diabetic patients
whn have autonomic neuropalhit>s
Sedation
Dry mouth
Sex1 1al dysfmwtim1
Ortho~tatic hypotension
DIRECT-ACTING
When~
a rc the
located?
fl
fl SELECTIVE AGONISTS
receptors
posts)~1aptic
49
Wlm t is it ?
A dopamine a n a lo~ue
IV
Arrh) thmias
Headache
Hypertension
Palpitations
/\Jt~ina
Nausea
ISOPROTEREN OL
anrl
(13.,)
(13 2 )
50
1\
\rrll)tlnnhL~
Palpitations
Tachycardia
lleadadH'
ALBUTEROL, METAPROTERENOL, AND TERBUTALINE
pulmonary disease
TrPal nwnt of bronchitis
Tcrhutaline and ritodrine can be U\CU to
reht\ the ut(rus durin~ prPmatun
lahor.
Arrh) thmitt.s
Tachycardia
lleadachc
Nausea and vomiting
SI
Cardiac arrhythmias
Hypertension
Palpitations
Dizziness, am.iety, headache
Tre mor
Myocardial infarction due to increased
cardiac work
Pulmonary edema
NOREPINEPHRINE (Levophed)
J3 receptors.
Vasoconstriction
Reflex bradycardia
52
DOPAMINE
How is it administered?
IV
doses
Arrhythmias
Tachycarrua
Hypertension
Tissue necrosis can oc-cur if dopamine
extravasates during infusion.
INDIRECTACTING AGONISTS
TYRAMINE
What is tyramine?
ephline.
What is the mechanism of
action of tyramine?
No
53
AMPHETAMINE
When is it appropriate to
adm inister amphetamine?
Restlcssuess
Palpitations
Tachycardia
I mpole ncf'
EPHEDRINE
or
W h a t are ephedrine's
therapeutic uses?
Arrhythmias
Palpitations
Insomnia
H:1Jett cnsiott
54
METARAMINOL
Adrenergic
Antagonists
1. a hloektrs
2. f3 blocklrs
a BLOCKERS
Name
~ix
a blockets.
sdcctivc. revcrsihle
2. Doxazosin (Canlu ra)
sp]pdi\p .
a 1-atlrcncrgic
rpV('rsihJI'
55
56
Treatment of hype1tension
Prevention of u1inaryretention in
patients who have benign pn1slntic
hypertrophy
Gastrointestinal hnlermotility
Orthostatic hypertension. especially after
the initial dose
Orally
57
Orthostatie hypotension
Reflex tachycardia- If severe, it may
induce anginal pain; therefore
phcnoxyben;r.amine is contmindicated
in patients with coronary disease.
Inltibition of ejaculation due to lad. of
smooth muscle contraction in the vas
deferens
YOHIMBINE
What is it?
PHENTOLAMINE
What is it?
An imidazole derivative
Orthostat1c hypotens1on
Gastrointestinal stimulation which may
lead to peptic ulcers
Tachycardia, myocardial infarction, or
<lrrhytlrmias due lo reliex sympathetic
response
~BLOCKERS
58
2. Pmstssion of intrinsi<:
'' mpathmnimeti<: adhity
3 Capacit) to block a-adrenPr~it
r<<rptor~
13 1 SELECTIVE BLOCKERS
Name fom selective 13 1
blockers.
I. At1nolol (Tenormin)
2. E~ c llolol (Brt>vibloc)
3. Ac:dmtolol (Sectral)
4 . .Mttoprolol ( Lopressor)
In ~tneml. 13-blockers starting with 1\ or
M are tardtOselectin:.
Is the ir ~ 1 ~electivity
absolute?
What is the main advantage
of 13 1 selectivity?
132 I"('C'<ptor<..
Thest dmgs arP sometimes called
card ic>.~dcctive because tJH..Y lack tltl
unwmcted hronchoconstric.:tor and
h~11oglyct'mic d'fects of nonst>lccti\"(
bloC'k<'rs.
What c linical conditions
wananl t he usc of cardio
selective ~ blockers?
Atenuloi-Jl~lwrtension.
myoc<udial
infarction
Propranolol
blockc as.
pr<S\UJ'l'
59
The liver
Hn>ertension
Angina. tachycardia
Arrh)1:hmia
Thyroid storm
Acute panic syndrome
M igraine headache~
Bradycardia
Bronchoconstriction--cun result in an
asthmatic attack
May hide waming signs of hypoglycemia
such as tachycardia; therefore, it is
critical to monitor diabetics who are
receiving ~-blockt'rs.
Fatigue
Depression
Sexual dysfunction
~-adrenergic
60
a BLOCKING CAPACITY
Labeta lol
What is thh drug's mechani~m of action?
Carvedilol (Coreg)
What is it?
Tn'alnwnl of li)lltrttnsion
Treatnwnt of chronw (.II F- Ait hough il
may seem paradoxical tom< 13
blocktrs in the trealnwnt of CHF,
since the, can also worst'n S\ mptoms.
tht') appc:ar to ht.ncflt tht palitnt b)
rcdut'ing sy1npatht>tic acth it). Tlw)
ma) also impro\C' cli<L,tolit dy,hulC'lion
by prolonging dia\tolic: fillin~ timP
What a r c t h e mechanh-ms
of action?
Butoxamine
What is it?
61
They do not directly block ex- or 13adrenergic receptors. They do, however,
block the release of norepinephrine from
nerve endings- in e ffect, they antagonize
the e ffects of the ~ympathctic system.
GUANETHIDINE (ISMELIN)
Yes-treatment of hypertension
RESERPINE
What is it?
A Rauwolfia alkaloid
Section Ill
Central Nervous
System
10
Introduction to
Central Nervous
System Pharmacology
Atetyl<holiuP
Norcpilll'phrim
Dopan1inc
Scruton in
Gammn-a min nbut yric add (CABA) and
What ty p es of receptors a tc
most cornrnonlv fo und in
the CNS?
.
a rf'<Pplnr <llld .,uhscqtwntly
To hind
Wh at arc EPSPs?
C h e fhe e xamples of
excita tor-y neurobansmitters.
chan1wls
1. :\orcpllll'phrilw
2. D opamine
3. Act-l\.kholinp
-i. Clut:tul.lte
5. Aspartalt>
What are lPSPs?
Inhibitory posts),~<~ pi il.: potl'ntialsiniliated wht>n an inhihilof\ ncurotransmiltrr opPns ddoridc~cl ~:ulnels und
the cell mvmhnuw lw<'onws h)1Wrpohuizcd. lPSPs utukt il111ore difReult
For the lll'llron to lwtouc atlivatcd
(l"igun> H)- I ).
1. Gly<.'int
2. CABA
65
66
l l
Threst}.oj<! __ _
IPSP
Time~
Figure I 0-1. Interaction of excita[Qry and inhibitory synapses. On the left, 3 supra thresho ld stimulus is given to an excitatory pat hway (E). On the right, this same stimulus is given
shortly after stimulating an inhibitory pathway (I) , which preve nts the excitatory potential
from reaching thresho ld. (Redrawn from Katzung BG: Basic and Clinical Pharmacology, 7th
ed. Stamford, CT. Appleton & Lange, 1998, p 3-45.)
~torag<,
11
Anxiolytics,
Hypnotics, and
Sedatives
De 6nc anxiety.
Tachycardia
Tachypnea
Sweating
T rembling
Weakness
Wh at a te t he major classes
of drugs used to treat
anxiety?
BENZODIAZEPINES
68
Long-Acting(J-3 day'>):
Chlordiazcpoxitk(Libriunt)
Diazepam (Valium )
Flurazcpam ( Oalmane)
What is GABA?
llow do benz.odiazepines
work?
PO, lV, or IM
metabolized?
c 1
"' ~ +
li'Wn'niMJH!~ c:r-----1 1lr1Mfrlrrnlf1'
+
~M~ U~~~~
Benzodiazepine receptor
70
antagoni~t
overdose
~t>rotonin
(5-
HT1A) receptors.
diazepincs.
Minimal sedation
Low ahuse poteutial
No overdose fatalitirs rl-porled
No withdrawal symptom~
What toxic e ffects are
associated with buspirone?
lleadache, nauSl'a,
dizzine~~
71
CARBAMATES: MEPROBAMATE
\Vhat is meprobamate's
mechanism of action?
effPct
ll ypot('nsion
Shock
H l"art failure
BARBITURATES
rect>ptors.
\Vhat a.e the therape utic
indications for barbiturate
administration?
or
Induction
till('\( lt(~i;i-1 hiopt'ntal
Antic-orwttlsant..-'.)1;.. ph<'nol>arbital
Treatllll'llt of ;ulxicty
Induction of hypnosis
Why a re be nzodiazepines
favored over barbituratcs
liw the treatment of anxiety?
IV, PO, or IM
72
Barbiturates, alcohol
,
,,
,,
Coma
Medullary depression,''
,
,,
Anesthesia
- - - - - Benzodiazepines
Sedation, anxiolysis
Increasing d o s e Figure I 1-2. Comparison of dose-response relationships of benzodiazepines and barbiturates.(Redrawn from Gallia G, Hann Cl, Hewson WH: The Pharmacology Companion.
Alert & Oriented Publishing Company. 1997, p 33, Fig 3. 1.)
RPdis~ribution
to the other
OTHER SEDATIVES
ZOLPIDEM (Ambien)
ti.o;..~uPs
Treatment of insomnia
CHLORAL HYDRATE
llypnosis
Sedatiml (in childn11)
Gastrointestinal clistrt'ss
Uupleasant taste
73
12
What are antipsychotic
drug~?
Anti psychotics
or tlu brain.
Do antipsychotic agents
dilfe in potency?
Do antip,ychotic' differ in
c fficac\?
:ttl(]
haw a largt:
in tlw liv('r.
14
75
soxazolcs.
TRADITIONAL ANTI PSYCHOTICS
PHENOTHIAZINES
Pigmentary retinopathy
May cause cardiac arrhythmias and conduction block
BUTYROPHENONES
Haloperidol (Haldol)
Droperidol (lnapsine)
Tourette s syndromE'
Huntington\ disease
Phencyclidine overdose-drug of choice
DIBENZOXAZEPINES
Loxapine (Loxitane)
to this class.
THIOXANTHENES
Thiothixene (Navane)
76
to l'l'llll'mher are:
TrPal nwnt of any agitated or p~ychotit
statl', Sll(h as hi polar d isease or
sdizopltrenia (These ageuts an
tspecially effective ii1r the positil'l'
symptoms of schizophrenia. !>ueh as
ddusious. thought disorder~. and
halldnations. )
t\ntilnwtiC' tlwrap) due to bl<x:kmlP of
dopamine in the chemoreceptor
tri~gtr wnP (Thioridaiuc. ho" <'"cr.
cannot he uscJ for this p1111)ose.)
or
agents.
phcllothia7ines
Potency
HfCH
LOW
*l = low, 4 = high
Side EfTects
Antichonlincrgic
Effects
Sedation
Extrapyramidal
Effects
Haloperidol
Fluphenazine
Thiothixene
Trifluoperazine
Loxapine
Chlorproma7Jne
Thioridazine
Drug
a -Aclrenergie
Efl'ects
.....
.....
78
Is tardive dyskinesia
reversible?
nant syndro m e?
1. Clo7.apine (Cio7.aril)
2. Risperidone (Risperdal)
3. Olanzapine (Z)'prexa)
Chapter 12 I Antipsychotics
79
Like risperidone and clozapine, olanzapine blocks both dopamine and serotonin
receptors. Effective in the treatment of
schizophrenia, it can produce anticholinergic effects as well as sedation and orthostatic hypotension.
13
Drugs Used to
Treat Depression
and Mania
ANTIDEPRESSANTS
What is dcpre!>sion?
That
Tricn:lics
Serotonnl-'>p<'dfit nuptak< inhibitors
(SSR ls )
\l onamint' m.t<la.~<' inhibitors ( l\IAOis )
Atypical ;mtidl'prts\allt'>
SSRis
Atypk-al antidtpr<'\\anl\
TRICYCLIC$
Doxepin
81
psychosis.
What is the mechanio;m of
action of all the tricyclics?
or
P<U1ic disorder
Genemlized anxiely disorder
Posttraumatic strE~ss disorder
Obsessive-comp1 1lsive d isorder
(clomipramine)
Pain d isorders
En uresis in children (imipramine)
82
No! There is a chane<' that this combination can lead to sevNe convulsions and
t'()ma.
benefit?
What is their
mecbani~m
of
action?
Fluoxetine (Pro7..ac)-prototype
SertraJine (Zoloft)
Paroxetinc ( Paxi l)
Fluvoxaminc ( Luvox)
Inhibition of serotonin reuptake \vithout
significant eiTects on norcpinPphrine and
dopamine
Orally
Nausea
Diarrhea
Netvousness
Insomnia
Dizziness
Jm potence
Decreased libido
83
\Vhat
i.~
monoamine oxidase?