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PHARMACOLOGY REVIEWER
Class Drug Indication Mechanism Adverse effects No
Cardiovascular drugs
Alpha2-selective
agonists
Clonidine Hypertension
Activation of alpha2 receptors in CNS -->
decrease NE release --> decrease TPR,
cardiac output, renin activity
Salt and waterretention,
severerebound
hypertension,sedation, dry
mouth CNS+ (enter
Methyldopa Hypertension
Activation of alpha2 receptors in CNS -->
decrease vascular resistance
Salt and waterretention,
sedation,positive Coombs
test, hemolytic anemia,
hepatitis --> fulminant
hepatic failure CNS+
Ganglion blockers
Hexamethonium,
trimethaphan Hypertension (obsolete)
Nicotinic blockers that act in the ganglia -
-> block the predominant tone of the
arterioles (sympathetic) and the heart
(parasympathetic) --> lowers blood
pressure, increases heart rate
Sympathetic and
parasympathetic blockade
(decrease in cardiac
contractility and output,
increase in heart rate,
postural hypotension, dry
mouth, mydriasis, urinary
retention, constipation,
severesexual dysfunction)
Postganglionic
neuron blockers
Reserpine Hypertension
Deplete adrenergic nerve terminal of NE
stores Depression
CNS+; adjun
agents
Guanethidine Hypertension
Deplete and block release of nerve
terminal NE stores
Orthostatic hypotension,
sexual dysfunction
(retrograde ejaculation) CNS-
Alpha1-selective
antagonists Prazosin,terazosin Hypertension
Alpha1-selective antagonist --> decrease
vascular resistance First-dose syncope
Decrease TG
increase HD
Beta-blockers
Propranolol
Hypertension, angina
prophylaxis, arrhythmia
prophylaxis after MI,
supraventricular
tachycardias,
hypertrophic
cardiomyopathy,
migraine,tremor,thyroid
storm,thyrotoxicosis
Nonselective cardiac beta blockade -->
reduction in cAMP --> reductionofboth
sodium and calcium currents and
suppressionofabnormal pacemakers -->
reduce heart rate, cardiac output; reduce
renin secretion
Sleep disturbances,
sedation,sexual
dysfunction, bradycardia,
AV block, asthma
(bronchoconstriction)
Slightly elev
and TG; red
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Carvedilol Chronic heartfailure Combined beta and alpha blockade Others: labe
Esmolol
Acute arrhythmias(AV
nodal arrhythmias, etc.)
Very short-acting beta blockade; slows
AV conduction --> increased PR interval Administere
Vasodilators
Hydralazine
Hypertension, heart
failure
Release of nitric oxide --> stimulates
guanylyl cyclase --> increases cGMP -->
smooth musclerelaxation --> decrease
vascular resistance (afterload)
Salt and waterretention,
marked reflex tachycardia,
lupus-like syndrome
(lacking renal effects)
Minoxidil
Hypertension,topically
for baldness
Prodrug --> minoxidilsulfate --> opens K+
channels --> hyperpolarizes/relaxes
smooth muscle cells --> reduce TPR
(afterload), reflex increase of heart rate,
cardiac output, renin activity; acts by
unknown mechanism to reverse effects
of testosterone in patients with
androgenic alopecia
Marked salt and water
retention,very marked
tachycardia,
hirsutism/hypertrichosis,
pericardialeffusion
Nitroprusside
Hypertensive
emergencies,acute CHF
Release of nitric oxide (from molecule
itself) --> stimulates guanylyl cyclase -->
increases cGMP --> smooth muscle
relaxation in arterioles and venules -->
decreases preload and afterload Cyanide toxicity
Diazoxide
Hypertensive
emergencies,
hypoglycemia dueto
insulin-producing tumors
Opens K+ channels -->
hyperpolarizes/relaxessmooth muscle
cells; reduces insulinrelease
Hypotension,
hyperglycemia,salt and
waterretention
Calcium channel
blockers
Nifedipine
Hypertension, angina,
Prinzmetal's angina
Block voltage-gated "L-type" calcium
channels (smooth muscle) --> reduce
intracellular calcium and muscle
contractility --> decrease vascular
resistance (afterload)
Constipation,edema,
nausea,flushing, dizziness
Alsoused in
preterm lab
and Raynaud
Verapamil
Hypertension, angina
prophylaxis,coronary
vasospasm,AV nodal
arrhythmias, arrhythmias
involving calcium-
dependent cardiac tissue
Block voltage-gated "L-type" calcium
channels (cardiac/smooth muscle) -->
reduce intracellular calcium and muscle
contractility; slows AV conduction,
reduce TPR
CHF, AV blockade,sinus
node depression,
constipation,edema,
nausea,flushing, dizziness,
meningeal vasodilation
(headache)
Alsoused in
preterm lab
and Raynaud
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Diltiazem
Hypertension, angina
prophylaxis, AV nodal
arrhythmias, arrhythmias
involving calcium-dependent cardiac tissue
Block voltage-gated "L-type" calcium
channels (cardiac/smooth muscle) -->
reduce intracellular calcium and muscle
contractility; AV conductionvelocity
decreased --> increased PR interval,effectiverefractory period increased;
Constipation,edema,nausea,flushing, dizziness
Alsoused in
preterm laband Raynaud
Nimodipine Hemorrhagic stroke
Block voltage-gated "L-type" calcium
channels (cardiac/smooth muscle) -->
reduce intracellular calcium and muscle
contractility; conductionvelocity
decreased,effectiverefractory period
increased
ACE inhibitors
Captopril,enalapril Hypertension, CHF
Inhibit ACE --> reduced AT II (decreased
afterload) and aldosterone (decreased
preload) --> increased K+, compensatory
increase in renin and AT I; inhibit
degradationofbradykinin --> increase in
bradykinin; decreased TPR (afterload)
Cough, renal damage in
patients with bilateral
renovascular disease,renal
damage inthefetus,
hyperkalemia
Renal-prote
diabetic kid
(decrease ef
on efferent
tone); lesse
blacks and o
patients; oth
benazepril
Angiotensin II
receptor blockers
Losartan Hypertension,CHF
Competitively inhibit AT II at its AT1
receptorsite
Renal damage in patients
with preexisting renal
vascular disease,renal
damage inthefetus,
hyperkalemia
Nitrates
Nitroglycerin
Angina, acuteCHF,
Prinzmetal's angina
Denitration withinsmooth muscle cells -->
release of NO --> stimulates guanylyl
cyclase --> increases cGMP --> smooth
muscle relaxation, venodilation
Reflex tachycardia,
orthostatic hypotension,
meningeal vasodilation
(throbbing headache),
tolerance especially with
skin patches
Interaction w
sildenafil (Vi
others: isoso
dinitrate,iso
mononitrate
(metabolite
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Nitrites
Amylnitrite,sodium
nitrite Cyanide poisoning
Treatment of cyanide poisoning: (1)
immediate amylnitrite, (2) IV sodium
nitrite, (3) IV sodium thiosulfate; nitrite
convertsferrous iron in Hbtoferric form -
-> methemoglobinemia (higher affinity forCNthan iron in cytochromeoxidase) -->
thiosulfate converts
cyanomethemoglobintothiocyanate
(excreted) and methemoglobin; also
relaxes smooth muscle and produces
venodilation
Methemoglobinemia,
orthostatic hypotension
Must be adm
by inhalatio
Cardiac glycosides
Digoxin
CHF, rapid atrial
(fibrillation, flutter,paroxysmal tachycardia)
or AV nodal arrhythmias
Inhibit Na+/K+ ATPase --> increases
intracellularsodium --> increases
Na+/Ca2+ exchange --> increased
intracellular Ca2+ stored insarcoplasmic
reticulum --> releaseleadstogreater
contractile force; slows AV conduction inAV nodal arrhythmias, accelerates
ventricular repolarization (shortened QT)
Arrhythmias (extrasystoles,tachycardia,fibrillation),
nausea,vomiting, diarrhea
Quinidine, v
reduce cleardigoxin; dig
inhibited by
extracellula
Mg2+,facilit
extracellula
primarily de
renal cleara
1.6 days; digantibodies u
digoxin pois
Loop diuretics
Furosemide
Hypertension, CHF,
ascites, acute pulmonary
edema,severe
hypercalcemia
Inhibit the cotransport of sodium,
potassium, and chloride in ascending
loop of Henle --> sodium chloride
diuresis (hypertonic loss; decreases
preload); increased calcium excretion
Hypokalemic metabolic
alkalosis due to potassium
wasting and excretion of
protons, hypovolemia,
ototoxicity, sulfonamide
allergy (furosemide)
Others: etha
bumetanide
Potassium-sparing
diuretics
Spironolactone
CHF; potassium wasting
with loop or thiazide
diuretics; aldosteronism
Combines with and blocks intracellular
aldosterone receptor in late distal tubule
and collecting tubule --> reduces
expression of genes controlling synthesis
of sodium ion channels and Na+/K+
ATPase
Hyperkalemic metabolic
acidosis, gynecomastia and
anti-androgenic effects
Others: ami
triamterene
sparing, but
aldosterone
antagonists
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intractable
supraventricular
arrhythmias
ventricular cells; no effect on ventricular
action potential duration or QT interval,
increase QRS
Class II
antiarrhythmics Discussed above
Class III
antiarrhythmics
Sotalol Arrhythmias
Blockade of potassium channels
responsibleforrepolarizationofaction
potential --> prolongationofaction
potential duration, increased effective
refractory period; increased QT
Torsade de pointes,sinus
bradycardia, asthma
Ibutilide
Atrialflutter and
fibrillation
Blockadeofpotassium channels
responsibleforrepolarizationofaction
potential --> prolongationofaction
potential duration, increased effective
refractory period; increased QT Torsade de pointes
Class IV
antiarrhythmics Discussed above
Miscellaneous
antiarrhythmics
Amiodarone
Arrhythmiasresistantto
other drugs
Blockssodium, calcium, and potassium
channels and beta adrenoreceptors
Microcrystalline deposits in
the cornea and skin,blue-
gray skin discoloration,
thyroid dysfunction,
paresthesias,tremor,
pulmonary fibrosis
Extremely lo
-> requires m
to achieve s
levels, even
loading dose
Adenosine AV nodal arrhythmias
Slows conduction in AV node (high doses)
probably by hyperpolarizing thetissue
and reducing calcium current Flushing, hypotension
Short durati
(15 s) --> IV
Potassium ion Digitalistoxicity Depressesectopic pacemakers
Magnesium ion
Digitalistoxicity,some
casesoftorsade de
pointes
Drugs with important actions on smooth muscle
Histamine H1
antagonists Diphenhydramine
(first-generation)
IgE-mediated allergies
(hay fever, urticaria,
atopic dermatitis);
motion sickness;
Competitive antagonists at the H1
receptor; moreeffective ifgivenbefore
histaminereleaseoccurs; antimuscarinic
actions, alpha-blocking actions
Sedation; antimuscarinic
effects (dry mouth, blurred
vision, tachycardia);
orthostatic hypotension;
Ineffective i
others effec
motion sickn
(dimenhydr
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chemotherapy-induced
vomiting; OTCsleep aids,
Meniere disease
excitement in children cyclizine, me
promethazi
Cyclizine, meclizine Motion sickness, vertigo Same as diphenhydramine Less sedating
Promethazine
Motion sickness,
antiemetic Same as diphenhydramine Marked sedation
Chlorpheniramine
(prototype),
fexofenadine
(second-generation)
IgE-mediated allergies
(hay fever, urticaria,
atopic dermatitis) Same as diphenhydramine Sedation Ineffective i
Terfenadine,
astemizole,
loratadine
IgE-mediated allergies
(hay fever, urticaria,
atopic dermatitis) Same as diphenhydramine
Arrhythmias (long QT)when combined with azole
antifungal drugs,
erythromycin
Withdrawn
market; littl
sedation
Histamine H2
antagonists
Cimetidine,
ranitidine,
famotidine,nizatidine
Peptic ulcer disease,
Zollinger-Ellisonsyndrome, GERD Blockade of histamine H2 receptors -->reduction of gastric acid secretion
Inhibits hepatic drug-
metabolizing enzymes
(primarily cimetidine),
cimetidine: gynecomastia
and other feminizingeffects in men
Serotonin 5-HT1D
agonistsSumatriptan
Acute migraine and
cluster headache attacks 5-HT1D agonist
Chest discomfort, mild
tingling
Serotonin is
mood, sexu
anxiety, slee
Serotoninantagonists
Ketanserin Carcinoid tumor
Competitive5-HT2 antagonist; also has
alpha-blocking effects Toxicitiesofalpha blockade
Cyproheptadine Carcinoid tumor
Competitive 5-HT2 antagonist; also H1
blocking effects
Ondansetron
Vomiting associated with
cancer chemotherapy
(most effective
treatment)
Selective5-HT3receptorblockers; central
antiemetic action in area postrema ofthe
medulla Diarrhea, headache
Ergot alkaloidsBromocriptine
Hyperprolactinemia and
parkinsonism
Potent dopamine agonists; alpha
adrenoceptor and 5-HT2 antagonist GI upset
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Ergonovine Obstetric bleeding
Selectively stimulates uterine smooth
muscle; alpha adrenoceptor and
dopamine agonist; partial5-HT2
antagonist
Severe prolonged
vasoconstriction (ischemia,
gangrene), GI upset, marked
uterine contractions
Ergotamine
Migraine,obstetric
bleeding
Stimulatesuterinesmooth muscle; alpha
adrenoceptor and dopamine agonist;
partial5-HT2 antagonist
Severe prolongedvasoconstriction (ischemia,
gangrene), GI upset, marked
uterine contractions
Methysergide Migraine prophylaxis Serotonin antagonist/partial agonist
cardiac,retroperitoneal,
and pleuropulmonary
fibrosis
Prostaglandins
PGE2(dinoprostone)
Ripen cervix atterm;
abortion in secondtrimester
Activationofcellsurfacereceptors
coupled by G proteinsto adenylyl cyclaseorthe phosphatidylinositol cascade Nausea,vomiting, diarrhea Vaginal supp
PGF2-alpha
Ripen cervix atterm;
abortion insecond
trimester
Activationofcellsurfacereceptors
coupled by G proteinsto adenylyl cyclase
orthe phosphatidylinositol cascade -->
increases cardiac output, constricts
bronchial smooth muscle, initiates
uterine contractions, and causes
contraction of gastrointestinallongitudinal muscle Nausea,vomiting, diarrhea
Latanoprost
alpha deriva
glaucoma (in
outflow ofa
humor)
PGE1 (misoprostol,
alprostadil)
Abortion with
mifepristone (RU 486) or
methotrexate; maintain
PDA; PUD prevention in
patientsonNSAIDs;
impotence
Inhibitory effect on cAMP --> decreases
acid secretion in stomach
Should not b
pregnant wo
women atte
conceive
Prostacyclin
PGI2 (epoprostenol)
Activationofcellsurfacereceptors
coupled by G proteinsto adenylyl cyclase
orthe phosphatidylinositol cascade -->
potent inhibitor of platelet aggregation
Leukotriene
inhibitors
Zafirlukast,
montelukast
Exercise- and antigen-
induced bronchospasm;
aspirin allergy Inhibitors at the LTD4 and LTE4 receptors
Churg-Strausssyndrome
(rare)
Notrecomm
acuteepisod
asthma
Zileuton Exercise- and antigen- Selecitve inhibitor of 5-lipoxygenase Elevationofliverenzymes
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induced bronchospasm;
aspirin allergy
Corticosteroids
PrednisoneModerate to severeasthma
Inhibit production of arachidonic acid by
phospholipases; inhibitsynthesisofCOX-
2; inhibitreleaseofmediatorsby mastcells
Adrenalsuppression,oralcandidiasis (inhalers)
Others: bud
dexamethas
flunisolide, mometason
Hydrocortisone
Moderate to severe
asthma
Inhibit production of arachidonic acid by
phospholipases; inhibitsynthesisofCOX-
2; inhibitreleaseofmediatorsby mast
cells
Adrenalsuppression,oral
candidiasis (inhalers)
BeclomethasoneModerate to severeasthma, allergy
Inhibit production of arachidonic acid by
phospholipases; inhibitsynthesisofCOX-
2; inhibit release of mediators by mastcells Oral candidiasis (inhalers)
COX inhibitors
Aspirin Fever, inflammation, pain
Discussed below; nonselective,
irreversible inhibition of COX-1 and COX-
2; permanent inhibition of thromboxane
synthesis in platelets
Diversion of
acid to leuko
synthesis in
allergy (mor
with nasal p
asthma])
Celecoxib,rofecoxib Fever, inflammation, pain SelectiveCOX-2 inhibitors
Beta2-selective
agonists
Terbutaline,
albuterol,
metaproterenol
Asthma (acute
bronchospasm)
Beta2 agonist --> stimulates adenylyl
cyclase --> increases cAMP in smooth
muscle cells --> bronchodilation more
than cardiac stimulation
Skeletal muscle tremor;
tachycardia; tolerance
Inhaled; sho
no use in tre
allergic rhin
Salmeterol,formoterol Asthma (prophylaxis)
Beta 2 agonist --> stimulates adenylyl
cyclase --> increases cAMP in smooth
muscle cells --> bronchodilation morethan cardiac stimulation
Skeletal muscle tremor;tachycardia
Inhaled; lon12 h)
Methylxanthines
Theophylline Asthma
Inhibit phosphodiesterase --> increase
cAMP --> bronchodilation; block
adenosine receptors --> bronchodilation;
stimulate diaphragm muscle activity
GI distress (nausea,
anorexia), tremor,
insomnia, nervousness,
headache
Inhibits met
theophylline
cimetidine,
erythromyc
allopurinol;
metabolism
barbiturates
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tobacco, ma
Muscarinic
antagonists
Ipratropium Asthma; COPD
Competitively blocks muscarinic
receptors in airways, prevents
bronchoconstriction mediated by vagal
discharge
Cromolyn and
nedocromil Cromolyn andnedocromil
Asthma/allergy
prophylaxis (especially inchildren)
Decrease in release of mediators
(leukotrienes, prostaglandins andhistamine) from mast cells
Cough, wheezing, and
irritation of airway when
given by aerosol,
gastroenteritis in somepatients
Of no value an acute ast
Drugs used in gastrointestinal disorders
Antacids
Magnesium
hydroxide PUD
Antacid; reacts with protons in the
lumen of the gut Strong laxativeeffect
Aluminum
hydroxide PUD
Antacid; reacts with protons in the
lumen of the gut; may alsostimulatethe
protectivefunctionsofthe gastric mucosa Constipating
Calcium car
(gastric anta
constipating
Sucralfate Sucralfate
(aluminum sucrose
sulfate) PUD
Small, poorly soluble molecule that
polymerizes in the acid environment of
the stomach --> polymer binds to injured
tissue --> forms protective coating over
ulcer beds Low toxicity
Mustbetak
times daily;
pH required
incompatibl
blockers and
Proton pump
inhibitors
Omeprazole
Zollinger-Ellison
syndrome, GERD, non-
NSAID-induced peptic
ulcers (H. pylori)
Inibit H+/K+ ATPase located in the
luminal membrane of gastric parietal
cells
Hypergastrinemia; carcinoid
tumors inrats; low toxicity
in humans
Used with b
tetracycline,
metronidaz
courseofam
plus clarithr
eradicate H.
Drugs that promote
upper GI motility
Metoclopramide
Gastroparesis; emesis
following surgical
anesthesia, emesis
induced by cancer
Acetylcholine facilitator and dopamine
receptor antagonist in the enteric
nervous system
Inductionofparkinsonism
and otherextrapyramidal
effects
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chemotherapy
Cisapride Gastroparesis, GERD
5-HT4 agonist in the enteric nervous
system --> increase release of Ach from
motor neurons that innervate GI smooth
muscle --> increase GI motility and lower
esophageal sphincter tone
Long QT syndrome,fatal
arrhythmias
Limited avai
to adversee
Drugs withantiemetic actions
Ondansetron,
granisetron,
dolasetron
Nausea and vomiting
after general anesthesia
and in patients receiving
cancer chemotherapy
5-HT3 inhibitors in chemoreceptor
trigger zone
Metoclopramide,dexamethasone,
some H1
antihistamines,
several
phenothiazines,
dronabinol
Pancreatic enzyme
replacements
Pancrelipase Steatorrhea Pancreatic lipaseobtained from pigs
90% ofan ad
dose destroystomach unl
raised by an
drugsthatre
secretion
Laxatives
Castoroil, cascara,
senna Constipation Irritant actiononthebowel wall
Benign melanotic
pigmentationofthe colon
(melanosis coli)
Saline cathartics,psyllium Constipation
Bulk-forming actiononthestoolthatevokesreflex contractionofthebowel
Dioctylsodium
sulfosuccinate
(docusate) Constipation
Softening action on hard or impacted
stools
Mild cramping, rashes,
nausea
Mineraloil, glycerin Constipation
Lubricating actionthateases passageof
stoolthrough therectum
Bisacodyl Constipation
Stimulant laxative: activates neural
plexuses in intrinsic nervous system
Abdominal cramps, atonic
colon with prolonged use Others: phe
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Lactulose
Portal-systemic
encephalopathy,
constipation
Synthetic disaccharide (galactose plus
fructose) metabolized by colonic bacteria
--> low molecular weight acidsthattrap
ammonia that diffuses intothe colon
from theblood by converting ittoammonium ion (notreabsorbed); also
retains water and stimulates colonic
peristalsis
Cramps, diarrhea,
flatulence, electrolyte
disturbances
Antidiarrheal agents
Diphenoxylate andloperamide Diarrhea
Meperidine analogs with very weakanalgesic effects
Difenoxin is
metaboliteo
diphenoxyla
blood-brain
poorly --> loeffects
Drugs that inhibit the
formation of
gallstones
Chenodiol
Inhibitformationof
cholesterol gallstones Reducesecretionofbile acidsby theliver
Ursodiol
Inhibitformationof
cholesterol gallstones Unknown mechanism
Endocrine drugs
Hypothalamic
hormones
Growth hormone-
releasing hormone
Determine causeofGH
deficiency
Acts on somatotropes to produce a rapidincrease in plasma growth hormone
levels
Octreotide
(synthetic
somatostatin)
Acromegaly, carcinoid,
gastrinoma,
glucagonoma, and other
endocrinetumors
Activates Gi protein --> decreases cAMP -
-> inhibitsreleaseofgrowth hormone,
thyrotropin, glucagon, insulin, and gastrin
Corticotropin-
releasing hormone
Diagnosisofabnormal
ACTH secretion
Stimulatessecretionofboth ACTH and
beta-endorphinfrom the pituitary;
increases synthesis of
proopiomelanocortin from anterior
pituitary
Thyrotropin-
releasing hormone StimulatessecretionofTSH from pituitary Tripeptide:
Gonadotropin-
releasing hormone
Diagnosis and treatment
ofhypogonadalstates
Stimulate gonadotropinrelease when
given in pulsatile doses (resembling
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physiologic cycling); steady dosing causes
a marked inhibitionofgonadotropin
release
Leuprolide
Suppress gonadotropin
secretion in prostaticcarcinoma or other
gonadal steroid-sensitive
tumors, endometriosis,
or precocious puberty
GnRH analog; stimulate gonadotropinrelease when given in pulsatile doses
(resembling physiologic cycling); steady
dosing causes a marked inhibition of
gonadotropin release
Bone pain, gynecomastia,
hematuria, impotence,
testicular atrophy
Ganirelix Infertility GnRH antagonist
Dopamine Inhibits prolactin release
Only nonpe
hypothalam
Bromocriptine HyperprolactinemiaDiscussed above; inhibits prolactinrelease
Anterior pituitary
hormones
Growth hormone
(somatotropin),
somatropin,
somatrem
GH deficiency in children
and adults
Growth hormone acts atliver and other
tissuesto increasesecretionofinsulin-
like growth factor I (somatomedin C;
peptide that circulates bound to carrier
protein); IGF-1 acts in hypothalamus to
increase secretion of somatostatin -->
decrease GH release (negativefeedback)
Thyroid-stimulating
hormone (TSH)
Distinguish primary from
secondary
hypothyroidism
Made up of two subunits (unique beta
subunit) --> increases iodineuptake and
productionofthyroid hormones in
thyroid cells
Cosyntropin
Diagnosisofabnormal
corticosteroid production ACTH analog,stimulates adrenal cortex
Follicle-stimulating
hormone (FSH)
Made up of two subunits (unique beta
subunit) --> stimulates gametogenesis
and follicle development in women and
spermatogenesis in men
Urofollitropin Infertility
FSH-like activity (stimulates
gametogenesis and follicle development
in women and spermatogenesis in men)
Luteinizing
hormone (LH)
Made up of two subunits (unique beta
subunit) --> major stimulant of gonadal
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steroid production; regulatesfollicular
development and ovulation in women
Human chorionic
gonadotropin Infertility
LH-like activity (majorstimulantof
gonadalsteroid production; regulates
follicular development and ovulation in
women)
Menotropins Infertility FSH plus LH activity
Posterior pituitaryhormones
Oxytocin
Induceorreinforcelabor,
stimulate milk let-down
Effectivestimulantofuterine contraction;
causes contractionofsmooth muscle in
the myoepithelial cellsofthe mammary
gland
Desmopressin
Pituitary diabetes
insipidus
Sele
ctive
agon
ist
of
V2
re
ce
ptors
(increasessynthesisor insertionofwater
channelsby a cAMP-dependent
mechanism --> increase in water
permeability inthe collecting tubulesof
the kidney --> waterreabsorption)
Thyroid hormones
T4 (synthetic
levothyroxine) Hypothyroidism
Binds to receptors in the nucleusthat
controlexpressionofgenesresponsible
for many metabolic process --> proteinsincludeNa+/K+ ATPase,specific
contractile proteins insmooth muscle and
the heart,enzymes involved inlipid
metabolism, developmental components
inthebrain,etc. Thyrotoxicosis
Form ofcho
cases; TSH le
suppressed
gland inactiv
131I uptake
T3 (liothyronine) Hypothyroidism
Binds to receptors in the nucleusthat
controlexpressionofgenesresponsible
for many metabolic process --> proteinsincludeNa+/K+ ATPase,specific
contractile proteins insmooth muscle and
the heart,enzymes involved inlipid
metabolism, developmental components
inthebrain,etc. Thyrotoxicosis
T3vs. T4: ab
times more
faster-acting
shorter half-
moreexpen
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Prednisone,
prednisolone,dexamethasone,
triamcinolone
Congenital adrenalhyperplasia and above
indications for cortisol
Synthetic glucocorticoids with the same
action as cortisol
Adrenalsuppression (from
ACTH suppression),
metabolic effects (growth
inhibition, diabetes, muscle
wasting, fat redistribution,osteoporosis),salt
retention, psychosis
Betamethasone
Hastens fetal lung
maturation
Glucocorticoid with low degreeofprotein
binding See cortisoltoxicity
Beclomethasone Discussed above
Mineralocorticoids Fludrocortisone
Replacementtherapy
after adrenalectomy
Mineralocorticoid (synthesisofsodium
ion channels and Na+/K+ ATPase) with
significant glucocorticoid activity Long duratio
Corticosteroid
antagonists
Mifepristone (RU
486) Cushing'ssyndrome
Inhibitor at glucocorticoid receptors as
well as progesterone receptors
Spironolactone Discussed above
Ketoconazole
Adrenal carcinoma,
hirsutism,breast cancer
Antifungal drug; inhibits the P450
enzymes necessary for the synthesis of
all steroids (e.g., testosterone)
AminoglutethimideSteroid-producingadrenocortical cancer
Blocks conversionofcholesterolto
pregnenolone and also inhibitssynthesisofall hormonal activesteroids
Metyrapone
Diagnostic testsof
adrenalfunction
Inhibitsnormalsynthesisofcortisol,but
notthatofcortisol precursors
Ovarian hormones
Estrogens
Primary hypogonadism
in young females;
hormone replacement
therapy; component of
oral contraceptives
Growth ofgenitalstructures during
childhood; secondary sexual
characteristics and growth spurtof
puberty; metabolic effects: modifies
serum proteinlevels and reducesbone
resorption,enhances coagulability,
increases plasma triglycerides; constant
low level prevents LH surge; increases
HDL,reduces LDL; suppresses FSH
Premature closureof
epiphyses in hypogonadal
girls; increased risk of
endometrial cancer in HRT(prevented by use of a
progestin); nausea, breast
tenderness, migraines,
thromboembolic events,
gallbladder disease,
hypertriglyceridemia,
hypertension
Others: estr
ethinyl estra
mestranol; e
HRT: reduce
flushes, sweatrophic vag
urinary urge
incontinenc
frequency; l
osteoporosi
in coronary
disease; ma
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mood depre
Progestins
Component of oral or
implantable
contraceptives; HRT;
produce anovulation andamenorrhea in women
with dysmenorrhea,
endometriosis, or
bleeding disorders
Cause developmentofsecretory tissue in
thebreast and maturationoftheuterine
endometrium; affect carbohydrate
metabolism and stimulatefat deposition;
arrests proliferative phase and inhibits
LH and midcycle LH surge; high dosessuppress FSH; progestin implants
containing levonorgestrel believed to
inhibit sperm transport and embryo
implantation
Weight gain, hair growth,
acne, and decreased HDL
Others: prog
medroxyprolevonorgest
norethindro
norgestimat
desogestrel
Oral contraceptives
containing both
estrogen and
progestin Oral contraceptives
Seeestrogens and progestins; act by a
negative feedback inhibition of
hypothalamic and pituitary function -->
suppression of gonadotropin secretion
and ovulation
May increase risk of breast
and cervical cancer
Oral contrac
render cervi
hostile to sp
decrease tudecrease inc
ovarian and
endometria
iron deficien
and PID
Postcoital
contraceptives Mifepristone (RU486) Postcoital contraceptive
Progesterone antagonist, partial agonist;
when administered before the LH surge,
they inhibit ovulation; also affectimplantation and possibly fertilization
Given as a si
dosefollowe
prostaglandanalog
Selective estrogen
receptor modulators
Tamoxifen
Hormone-responsive
breast cancers, after
breast cancer surgery in
patients with estrogen-
dependent tumors
Acts as an antagonist to prevent receptor
activation by endogenous estrogens; acts
as an agonist atendometrialreceptors -->
hyperplasia, increased risk for
endometrial cancer
Hotflushes, increased risk
of venous thrombosis,
depression, dizziness,
thrombocytopenia
Preventsost
women who
the drug for
cancer
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Raloxifene
Preventionof
osteoporosis in
postmenopausal women
Partial agonisteffectsonbone and
increasesserum HDL; antagonisteffects in
breasttissue,reduces incidenceofbreast
cancer in high-risk women; noestrogenic
effectsonendometrialtissue
Hotflushes, increased risk
ofvenousthrombosis
Estrogen and
progesterone
agonists,
antagonists, and
synthesis inhibitors
Clomiphene
Induce ovulation in
anovulatory women who
wish to become
pregnant
Selectively blocks estrogen receptors in
the hypothalamus --> reduces negative
feedback and increases FSH and LH
output from pituitary via GnRH -->
stimulates ovulation
Diethylstilbestrol
Estrogen agonist activity (synthetic
nonsteroidalestrogen)
Associated with infertility,
ectopic pregnancy, and
vaginaladenosis/adenocarcinoma
in daughters of women
treated with high doses
during pregnancy
Nolongerus
commonly
Mifepristone (RU
486) Discussed above
Danazol
Endometriosis,
fibrocystic diseaseofthe
breast
Weak partial agonist that binds to
progestin, androgen, and glucocorticoidreceptors in cells (blocks progesterone
stimulation of uterus in endometriosis)
and tosteroid transport proteins inthe
blood; also inhibitsseveral P450 enzymes
involved in gonadalsteroid synthesis
Anastrozole Breast cancer
Inhibitorsofaromatase,theenzyme
required forestrogensynthesis
Nausea, diarrhea, hot
flushes,bone and back pain,
dyspnea, peripheraledema
Androgens
Testosterone
Replacement therapy in
hypogonadism
(impotence, decreased
libido); stimulate RBC
production in certain
anemias; weight gain in
patients with wasting
Androgensenter cells and bind to
cytosolic receptors; hormone-receptor
complexentersnucleus and modulates
expressionofcertain genes:normal
developmentofmalefetus and infant,
male changes at puberty,secondary sex
characteristics, male-patternbaldness;
Virilization in females;
feminization in men with
excessive doses due to
feedback inhibition of
pituitary and conversion to
estrogens (decreased
spermatogenesis, sexual
Others: oxa
nandrolone
increased lib
sebaceous g
secretion (a
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syndromes anabolic actions (increased muscle size
and strength, increased RBC production,
maintain bone density)
dysfunction); behavioral
effects (hostility, aggression
["roid rage"]); cholestatic
jaundice, elevation of liver
enzymes, possiblyhepatocellular carcinoma
Antiandrogens
Flutamide Prostate carcinoma
Nonsteroidal competitive antagonists at
androgen receptors; decrease action of
endogenous hormones in prostate
carcinoma
Gynecomastia, hotflushes,
hepatic dysfunction
Cyproterone Hirsutism
Act as competitive antagonists at
androgen receptors; decrease actionof
endogenous hormones in prostate
carcinoma; also has progestational
activity that providesnegativefeedback
tothe pituitary
Spironolactone Hirsutism
Discussed above; potassium-sparing
diuretic; also inhibits androgen receptors
Leuprolide Discussed above
Finasteride
Benign prostatic
hyperplasia, prevent hair
loss in men (lower dose)
5-alpha-reductase inhibitor --> inhibits
conversion of testosterone to
dihydrotestosterone
Combined oral
contraceptives Hirsutism
Estrogen in contraceptive acts inliverto
increase productionofsex hormone
binding globulin --> reduces
concentrationoffree androgen inblood
Ketoconazole Discussed above
Insulin
Insulin
Diabetes mellitus,
diabetic ketoacidosis
Activation of insulin receptor (tyrosine
kinase) --> autophosphorylation and
phosphorylationofa variety of
intracellular proteins; liver: increases
glycogen, GLUT 2 glucosetransport
insertion in cell walls,synthesisof
pyruvate kinase, PFK, glucokinase,
decreases protein catabolism; muscle:
Hypoglycemia from
excessive insulin effect;
immunologic toxic effects
from developmentof
antibodies
Ultra rapid a
short action
rapid onset
action (regu
intermediat
action (NPH
onset and lo
(ultralente),
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glycogen and proteinsynthesis, insertion
ofGLUT 4transporters; adipose: plasma
lipoproteinlipase activation,triglyceride
storage, GLUT 4,reduces intracellular
lipolysis
acting (glarg
Insulin
secretagogues
(sulfonylureas)
Glyburide, glipizide,
glimepride Type 2 diabetes mellitus
Stimulate release of endogenous insulin;
sulfonylureas close K+ channels -->
depolarization --> insulin release
Relatively uncommon:
hypoglycemia,rash
(occasionally), allergy,
transient leukopenia
(agranulocytosis), SIADH
(chlorpropamide)
Noteffective
wholack fun
cells; others
tolbutamide
chlorpropam
acetohexam
tolazamide
Insulin
secretagogues
(meglitinides)Repaglinide
Type 2 diabetes mellitus
(takenbefore mealsfor
postprandial glucose
control)
Also promotes insulinreleaseby binding
to K+ channels in pancreatic B cell
membranes
Rapid onset
durationofa
compared to
sulfonylurea
Biguanides
Metformin Type 2 diabetes mellitus
Act by an unknown mechanism to reduce
postprandial and fasting glucose levels in
patients with type 2 diabetes (mayincrease glucose uptake by muscle and
adipose tissue and decrease hepatic
gluconeogenesis and glucose output)
GI distress (nausea,diarrhea),lactic acidosis,
inhibitsvitamin B12
absorption
Effects dono
onfunctiona
Thiazolidinediones
Rosiglitazone,
pioglitazone Type 2 diabetes mellitus
Stimulate peroxisome proliferator-
activated receptor-gamma nuclear
receptor --> transcriptionofgenes
involved in carbohydrate and lipid
metabolism --> increasetargettissuesensitivity to insulin, inhibit hepatic
gluconeogenesis Edema, mild anemia
Alpha-glucosidase
inhibitors
Acarbose, miglitol
Postprandial
hyperglycemia intype 2
diabetes mellitus
Carbohydrate analogsthat act withinthe
intestineto inhibit alpha-glucosidase, an
enzymenecessary forthe conversionof
complexstarches,oligosaccharides, and
disaccharidesto monosaccharidesthat
canbe absorbed
Flatulence, diarrhea, and
abdominal pain
Treatmento
hypoglycem
glucose (dex
sucrose
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Hyperglycemic drugs
Glucagon
Severe hypoglycemia in
diabetics; x-ray studiesof
bowelor abdomen when
reductionofmotility isnecessary; management
of severe beta blocker
overdose
Acts on G-protein coupled receptors
located in heart,smooth muscle, and
liver --> stimulate adenylyl cyclase -->
increases intracellular cAMP --> increases
heartrate, contraction,hepaticglycogenolysis and gluconeogenesis,
lipolysis, and relaxationofsmooth muscle
(gut)
Decrease in
glucose stim
release
Drugs affecting bone
mineral homeostasis
Parathyroid
hormone
Postmenopausal
osteoporosis (using low
doses of a PTH analog)
Actson membrane G protein-coupled
receptors --> increase cAMP inbone and
therenaltubule --> increase resorption of
bone, increase renal reabsorption of
calcium,excretionofphosphate -->increasesblood calcium and decreases
phosphate; increases active vitamin D
formation; increase net bone formation
at low doses (physiologic levels)
Vitamin D
Treatmentofdeficiency
states: chronic renal
failure, intestinal
osteodystrophy,nutritionalrickets,
postmenopausal
osteoporosis
Increased intestinal calcium and
phosphorus absorption, decreased renalexcretion, and net increase inblood
levels; increases bone resorption of
calcium
Calcitonin
Paget's disease,hypercalcemia,
osteoporosis
Decreases bone resorption and serum
calcium and phosphate by osteoclast
inhibition; increases renal reabsorption
of calcium; boneformationnot impaired
initially,butultimately reduced;contained in parafollicular cells (C cells)
of thyroid
Salmon calc
oftenused blonger half-l
greater pote
Estrogens and
SERMs
Postmenopausalbone
loss
May involve inhibitionofPTH-stimulated
boneresorption
Bisphosphonates
Osteoporosis
(postmenopausal,
glucocorticoid-induced),
Reduce both the resorption and the
formation of boneby an actiononthe
basic hydroxyapatite crystalstructure Esophagealulceration
Alendronate
pamidronat
risedronate
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Paget's disease
Fluoride Dental caries
Appropriate concentrations in drinking
water and as a dentifrice have a well-
documented ability toreduce dental
caries; chronic exposure,especially in
high concentrations, may increasenew
bonesynthesis
Acutetoxicity (usually
caused by ingestionofrat
poison): GI and neurologic
symptoms; chronic toxicity
(fluorosis):ectopic bone
formation,exostoses,
chalky deposits on teeth
Plicamycin
(mithramycin)
Paget's disease,testicular
cancer, serious
hypercalcemia (short-
term treatment)
Antibiotic used toreduceserum calcium
and boneresorption
Serioustoxicity:
thrombocytopenia,
hemorrhage, hepatic and
renal damage Notused co
Drugs with important actions on blood, inflammation, and gout
Drugs used in
anemias
Iron Iron deficiency anemia
Essential metallic componentofheme; an
importantfraction isbound totransferrin
(transport protein) and ferritin (storage
protein)
Most common in children
dueto ingestionof
supplements:necrotizing
gastroenteritis,shock,
metabolic acidosis, coma,
death; chronic toxicity with
frequenttransfusions,
hemochromatosis, inherited
abnormality in absorption
Should notb
hemolytic an
because iron
elevated; tre
acute iron in
deferoxami
treatmento
toxicity: phle
Vitamin B12
Pernicious anemia and
anemia caused by gastric
resection
Absorbed from GI tract inthe presenceof
intrinsic factor --> cofactor intransferof
one-carbonunits (necessary for DNA
synthesis) --> stored inliver (enough to
last5 years) --> deficiency manifestsfirst
as anemia; also, developmentof
neurologic defects Nosignificanttoxicity
Essentialfor
reactions: co
methylmalo
succinyl-CoA
conversiono
homocystein
methionine
Folic acid
Anemia duetofolic acid
deficiency; anemia in
vitamin B12 deficiency
(butnotneurologic
defects)
Absorbed from GI tract --> only modest
amounts stored in body --> decreased
intakefollowed by anemia in a few
months (folic acid necessary fornormal
DNA synthesis) None
Folic acid -->
tetrahydrofo
dihydrofolat
important in
cycle
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disulfiram); crosses
placenta --> birth defects
Antiplatelet drugs
Aspirin and other
NSAIDs
Preventfurther infarcts in
those with previous MI;
may reduce incidence of
first MI; prevent
transient ischemic
attacks, ischemic stroke,
and otherthrombotic
events
Discussed below; inhibit thromboxane
synthesis by blocking cyclooxygenase;
thromboxane A2 is a potent stimulator
of platelet aggregation; irreversible
inhibition with aspirin (several days) GI and CNS effects Increase ble
Dipyridamole
Increases cAMP by inhibiting cyclic
nucleotide phosphodiesterase --> inhibits
thromboxane A2 production in platelets -
-> inhibits platelet aggregation
InhibitorsofADP
receptors(ticlopidine,
clopidogrel)
Prevent transient
ischemic attacks,
ischemic strokes, MI,
preventthrombosis inthose with recent
coronary artery stent
Irreversible inhibition of the ADP-
receptor --> inhibition of ADP-mediatedpathway involved in binding of platelets
to fibrinogen and to each other
Ticlopidine:bleeding,leukopenia,
agranulocytosis Increaseble
Glycoprotein IIb/IIIa
receptor inhibitors
(abciximab,
tirofiban,
eptifibatide)
Preventrestenosis after
coronary angioplasty,
used in acute coronary
syndromes
Reversibly inhibitsthebinding offibrin
and otherligandstothe IIb/IIIa receptor
(involved in platelet cross-linking)
Bleeding,
thrombocytopenia (chronic
use) Increaseble
Thrombolytic agentsAlteplase,reteplase
Emergency treatment ofcoronary artery
thrombosis, ischemic
stroke, multiple
pulmonary emboli
Directly converts fibrin-bound
plasminogen to plasmin; not allergenic
(compared to streptokinase) Bleeding
Mustruleou
hemorrhage
Urokinase
Emergency treatmentof
coronary artery
thrombosis, multiple Directly converts plasminogento plasmin Bleeding
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pulmonary emboli
Streptokinase
Emergency treatment of
coronary artery
thrombosis, multiple
pulmonary emboli,deep
vein thrombosis
Forms a complex with endogenous
plasminogen --> complex catalyzes rapid
conversion of plasminogen to plasmin Bleeding, allergic reactions
Anistreplase
Emergency treatmentof
coronary artery
thrombosis, multiple
pulmonary emboli
Anisoylated plasminogen-streptokinase
activator complex is a prodrug; as anisoyl
group is hydrolyzed invivo,streptokinase-
activated plasminogen isreleased -->
convertsendogenous plasminogento
plasmin Bleeding
Drugs used in
bleeding disorders
Vitamin K
Deficiency ofvitamin K
(common innewborns
and older individuals with
abnormalities infat
absorption); reverse
warfarin
Aids in posttranslational modification of
clotting factors in the liver (factors II, VII,
IX, and X)
Clotting factors
Hemophilia (factors VIII
and IX) Clotting factors
Infection and immunologic
reactions
Antiplasmin agents
(aminocaproic acid)
Acutebleeding episodes
in hemophiliacs and
others with bleeding
disorders
Inhibit fibrinolysis by inhibiting
plasminogen activation
Resins
Cholestyramine,
colestipol
Hypercholesterolemia;
used toreduce pruritus in
patients with cholestasis
and bilesalt
accumulation
Bile acid-binding resins prevent
absorption of dietary cholesterol and
reduce reabsorption of bile acids
secreted by liver --> divert hepatic
cholesterol to synthesis of new bile acids
--> reduces available cholesterol -->
modest reduction of LDL
Bloating,constipation,
unpleasant gritty taste;
impaired absorptionof
vitamins, drugs
Interfere wit
absorptiono
reductase in
HMG-CoA reductase
inhibitorsLovastatin,
simvastatin,
atorvastatin Hypercholesterolemia
Competitively inhibit mevalonate
synthesis by HMG-CoA reductase
(essential for cholesterol biosynthesis in
liver) --> liver compensatesby increasing
Mild elevations of serum
aminotransferases;
increase in creatine kinase,
severe muscle pain,
Others: prav
cerivastatin,
metabolized
teratogenic;
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LDL receptors --> increased clearance of
IDL and LDL from the blood
rhabdomyolysis myopathy w
coadministe
niacin, gemf
Niacin
Niacin (nicotinic
acid)
Familial
hypercholesterolemia,
hypercholesterolemia
Directly reduces the secretion of VLDL
from the liver and inhibits hepatic
synthesis of apolipoproteins or
cholesterol --> decreased LDL; increased
clearance of VLDL by lipoprotein lipase in
the periphery --> decreased triglycerides;
may increase HDL
Cutaneous flushing, dose-dependentnausea and
abdominal discomfort,
pruritus and otherskin
conditions,elevation of
liver enzymes,
hepatotoxicity may occur,
hyperuricemia
Fibric acid
derivativesGemfibrozil,
fenofibrate,
clofibrate Hypertriglyceridemia
Ligandsfor PPAR-alpha protein (regulatestranscriptionofgenes involved inlipid
metabolism) --> increased activity of
lipoprotein lipase and enhanced
clearance of triglyceride-rich lipoproteins
(VLDL); may be small decrease in LDL and
small increase in HDL
Nausea,skinrashes
(gemfibrozil), increased risk
for cholesterol gallstones
NSAIDsAspirin
Antiplatelet effects (low
dose),antipyretic and
analgesic effects
(intermediate dose),
antiinflammatory effect
(high dose)
Irreversibly inhibit COX-1 and COX-2 -->
decrease prostaglandin and
thromboxane synthesis
Gastric upset, ulceration,
bleeding; renal effects(acute failure; interstitial
nephritis; reduced renin -->
reduced aldosterone -->
hyperkalemia; inhibit uric
acid excretion -->
hyperuricemia)
Reye's synd
children wit
infections; z
elimination
concentratio
Others (ibuprofen,
indomethacin,
naproxen,etc.)
Mild to moderate pain,
especially pain ofinflammation
(rheumatoid arthritis,
gout); dysmenorrhea
(naproxen, ibuprofen);
patent ductus arteriosus
(indomethacin)
Reversibly inhibit COX-1 and COX-2 -->
decrease prostaglandin and
thromboxane synthesis
GI disturbance,renal
damage,bone marrow
depression (indomethacin)
Phenylbutaz
aplastic ane
agranulocyt
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Celecoxib,rofecoxib Inflammatory disorders
Selectively inhibitCOX-2 (expressed in
inflammatory cells)
Reduced gastric effects,
hypersensitivity (celecoxib
is a sulfonamide)
Ketorolac
Short-term management
of postoperative pain
NSAID with antiinflammatory and
analgesic properties
Disease-modifying,
slow-actingantirheumatic drugs
Methotrexate
Rheumatoid arthritis
unresponsivetoother
agents, anticancer
Discussed below; probably actsby
reducing thenumbersofimmune cells
availableto maintainthe inflammatory
response
Nausea, mucosalulcers,
hematotoxicity,
teratogenicity
May develo
deficiency b
dihydrofola
(converts di
back into ac
tetrahydrof
Sulfasalazine
Rheumatoid arthritis
unresponsivetootheragents, inflammatory
bowel disease
Notfully understood; main metabolites:
5-aminosalicylic acid (active in IBD),sulfapyridine (active inrheumatoid
arthritis)
Rash, GI disturbance,dizziness, headache,
leukopenia
Hydroxychloroquine
Rheumatoid arthritis
unresponsive to other
agents, antimalarial
May interfere with activity ofT
lymphocytes, decreaseleukocyte
chemotaxis,stabilizelysosomal
membranes, interfere with DNA and RNA
synthesis, and trap freeradicals
Rash, GI disturbance,
ototoxicity, myopathy,
peripheralneuropathy
Penicillamine
Rheumatoid arthritis
unresponsive to other
agents,chelating agent
(lead, copper, mercury)
Anti-inflammatory effectssimilarto
hydroxychloroquine; chelating agent
Many adverseeffects:proteinuria, dermatitis, GI
disturbance, hematologic
abnormalities (aplastic
anemia)
Organic gold
compounds
(auranofin)
Rheumatoid arthritis
unresponsive to other
agents
Alter activity of macrophages and
suppress leukocyte activity (lysosomal
enzymes, phagocytosis, mediator
release)
Many adverseeffects:
diarrhea,dermatitis,
hematologic abnormalities
(aplastic anemia)
Gold poison
with dimerc
Leflunomide
Rheumatoid arthritis
unresponsivetoother
agents
Inhibits dihydroorotate dehydrogenase
(enzymerequired by activated
lymphocytesforsynthesisofpyrimidines
needed for RNA synthesis) --> cell cycle
arrest
Teratogen, hepatotoxicity,
GI disturbance,skin
reactions
Infliximab,
etanercept
Rheumatoid arthritis
unresponsivetoother
Bind to and prevent actionofTNF-alpha
(plays a key role in chronic inflammation)
Infliximab:upper
respiratory infection;
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agents,Crohn's disease
(infliximab)
etanercept: injectionsite
reactions
Acetaminophen
Acetaminophen
Same indications as
intermediate-dose
aspirin (substitute inchildren with viral
infections, aspirin
hypersensitivity)
Unclear; weak COX inhibitor in peripheral
tissues; may be a moreeffective inhibitor
ofprostaglandinsynthesis intheCNS -->
analgesic,antipyretic
Very dangeroushepatotoxin when taken in
overdose; renal tubular cell
injury
Overdose tr
N-acetylcyst
Drugs used in gout
Indomethacin Discussed above
Colchicine
Acute gout attacks (and
also prophylaxis),
Mediterraneanfever
Selective inhibitor of microtubule
assembly, reduces leukocyte migration
and phagocytosis
Severeliver and kidney
damage, GI disutrbance
(diarrhea)
Uricosuric agents
(probenecid,
sulfinpyrazone)
Chronic gout (withheld 1-
2 weeks after an acute
episode)
Weak acids that compete with uric acid
for reabsorption by weak acid transport
mechanism in proximal tubule
May precipitate acute
attack ofgouty arthritis,
allergenicity (sulfonamide)
Atlow dose
compete wit
forsecretion
tubule --> m
serum uric a
Allopurinol
Chronic gout (withheld 1-
2 weeks after an acute
episode), cancer
chemotherapy
Converted to oxipurinol (alloxanthine) by
xanthine oxidase (enzyme that converts
hypoxanthine to xanthine to uric acid);
allopurinol and oxipurinol are
irreversible suicide inhibitors of this
enzyme
May precipitate acute
attack ofgouty arthritis, GI
upset,granulomatous
hepatitis, rash, fever
Inhibits met
mercaptopu
azathioprine
xanthineoxi
elimination)
Chemotherapeutic drugs
PenicillinsPenicillin G (IM)
Common strep,
meningococci, gram-
positive bacilli,
spirochetes
Bactericidal; inhibit cell wall synthesis:
bind to penicillin-binding proteins in
bacterial cytoplasmic membrane -->
inhibittranspeptidaseenzymes (crosslink
cell wall) --> activate autolytic enzymes --
> causelesions in cell wall
Allergy (urticaria,severe
pruritus,fever, joint
swelling, hemolytic anemia,
nephritis, anaphylaxis),
hypersensitivity vasculitis
syndrome Pregnancy O
Penicillin V (oral)
Oropharyngeal
infections,
pneumococcal
pneumonia Same as penicillin G Nausea, diarrhea, allergy Pregnancy O
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Methicillin,nafcillin,
oxacillin,
dicloxacillin
Knownorsuspected
staphylococcal infections
Same as penicillin G; penicillinase
resistant
Nephritis (methicillin),
neutropenia (nafcillin),
allergy Pregnancy O
Ampicillin,amoxicillin
Similar to penicillin G,
plus infections dueto
enterococci, Listeria
monocytogenes,E. coli,
P. mirabilis, H.
influenzae, Moraxellacatarrhalis Same as penicillin G
Allergy; ampicillin:
maculopapularskinrash,
nausea, diarrhea,pseudomembranous colitis
Whenused
combinationinhibitorsof
(clavulanic a
antibacteria
enhanced; p
OK; bacteria
endocarditis
in dental su
patients witdisease
Piperacillin,
ticarcillin,
carbenicillin P. aeruginosa Same as penicillin G Hypersensitivity reactions Pregnancy O
Cephalosporins
First-generation
(cefazolin
[parenteral],cephalexin [oral])
Gram-positive cocci, P.
mirabilis, E. coli, K.pneumoniae
Bactericidal; bind to PBPsonbacterial cell
membranesto inhibitbacterial cell wall
synthesisby mechanismssimilarto
penicillins; lesssusceptibletopenicillinases
Allergy (skinrashesto
anaphylactic shock) isoniazid
to 12 month
P450
Rifampin
Tuberculosis,leprosy, TB
prophylaxis; drug of
choice for chronic
carriers of N.
meningitidis, S. aureus,
and H. influenzae
Bactericidal; inhibits DNA-dependent RNA
polymerase in M. tuberculosis and many
other microorganisms
Light chain proteinuria,skin
rashes,thrombocytopenia,
nephritis,liver dysfunction,
induces cytochrome P450
enzymes
Activates P4
enhancesel
thefollowin
anticonvulsa
contraceptiv
cyclosporine
ketoconazol
methadone,
Ethambutol Tuberculosis
Inhibits arabinosyltransferases involved
insynthesisofarabinogalactan
(componentofmycobacterial cell wall)
Dose-dependent visual
disturbances (decreased
visual acuity,red-green
colorblindness,optic
neuritis)
Pyrazinamide Tuberculosis Bacteriostatic; mechanism not known
Nongouty polyarthralgia,
hyperuricemia,hepatitis
Streptomycin
Life-threatening
tuberculous disease
Bactericidal; penetrate cellenvelope
(ox
ygen
-de
pen
dent
tr
ans
port
) -->b
in
dto
30S subunit --> inhibit proteinsynthesis
(block formationofinitiation complex,
cause misreading ofcodeon mRNA
template, inhibittranslocation)
Ototoxicity, nephrotoxicity,
neuromuscularblockade
(rare),skinreactions Others:kana
Drugs for leprosy
Sulfones (dapsone) Leprosy
May involve inhibitionoffolic acid
synthesis
GI irritation,fever,skin
rashes,
methemoglobinemia,
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hemolytic anemia
Drugs for systemic
fungal infections
Amphotericin B
Systemic mycoses(aspergillus,C. albicans,
cryptococcus,
histoplasma, mucor)
Fungicidal; bind to ergosterol (specific to
fungal cell membranes) --> cause
formation of artificial pores
Infusion-related:fever,
chills, musclespasms,
vomiting,shock-likefall inBP; dose-limiting:
decreased GFR, renal
tubular acidosis Administere
Flucytosine
Antifungal treatment in
combination with
amphotericin B:
Cryptococcus
neoformans,systemiccandidal infections
Accumulated infungal cellsby membrane
permease and converted by cytosine
deaminaseto5-FU (inhibitorofthymidylatesynthase)
Reversiblebone marrow
depression, alopecia, andliver dysfunction
Ketoconazole
Backup drug forsystemic
infections caused by
certainblastomyces,
coccidioides,
histoplasma
Interfere with fungal cell membrane
permeability by inhibiting synthesis of
ergosterol
Vomiting, diarrhea,rash,
hepatotoxicity
Inhibits P45
increase pla
of anticoagu
cyclosporine
hypoglycem
phenytoin
Fluconazole
Drug ofchoice:esophageal and
oropharyngeal
candidiasis and most
infectionsofcoccidioides;
cryptococcal meningitis
Interfere with fungal cell membrane
permeability by inhibiting synthesisof
ergosterol
Vomiting, diarrhea,rash,
hepatotoxicity Administere
Itraconazole
Drug ofchoice:systemic
infections dueto
blastomyces andsporothrix and for
subcutaneous
chromoblastomycosis
Interfere with fungal cell membrane
permeability by inhibiting synthesisof
ergosterol
Vomiting, diarrhea,rash,
hepatotoxicity
Voriconazole
Widerspectrum than
itraconazole
Interfere with fungal cell membrane
permeability by inhibiting synthesisof
ergosterol
Vomiting, diarrhea,rash,
hepatotoxicity
PHARMACOLOGY REVIEWER
H d h t l
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Systemic drugs for
superficial fungal
infections
Griseofulvin
Severe dermatophytoses
oftheskin, hair, and nails
Interferes with microtubulefunction in
dermatophytes; may also inhibitsynthesis
and polymerizationofnucleic acids
Headaches, mental
confusion, GI irritation,
photosensitivity, changes in
liverfunction
Terbinafine Onychomycosis
Fungicidal; inhibits a fungalenzyme,
squaleneepoxidase --> accumulationof
toxic levelsofsqualene --> interferes with
ergosterolsynthesis
GI upsets,rash, headache,
taste disturbances
Azoles Dermatophytes Discussed above
Topical drugs for
superficial fungalinfections
Nystatin
Local candida infections,
GI fungi
Disrupts fungal membranes by binding to
ergosterol
Miconazole,clotrimazole Topical antifungal agents
Interfere with fungal cell membrane
permeability by inhibiting synthesisofergosterol Azole compo
Haloprogin,
tolnaftate,
undecylenic acid
Topical antifungal agents
(dermatophyte
infections) Nonazole co
Antiherpes drugs
Acyclovir
Drug of choice:
mucocutaneous and
genital herpes lesions,
prophylaxis inimmunocompromised,
varicella-zoster virus
Guanosine analog --> activated toform
acyclovirtriphosphate (competitive
substratefor DNA polymerase) -->incorporation intoviral DNA --> chain
termination GI distress, headache
Famciclovir
Orally in genital herpes
and for herpes zoster
Prodrug converted to penciclovirby first-
pass metabolism intheliver --> activation
by viralthymidine kinase --> inhibits DNA
polymerase (no chain termination) Welltolerated
Foscarnet
Prophylaxis andtreatmentof
cytomegalovirus
infections, herpes
Inhibitsviral RNA polymerase, DNA
polymerase, and HIV reverse
transcriptase
Nephrotoxicity
(hypocalcemia),genitourinary ulceration,
CNS effects (headache,
hallucinations,seizures)
Ganciclovir
Prophylaxis and
treatment of
cytomegalovirus
infections (drug of
Guanosine analog --> triphosphorylated --
> inhibits DNA polymerasesofCMV and
HSV (no chaintermination)
Leukopenia,neutropenia,
thrombocytopenia,renal
toxicity
PHARMACOLOGY REVIEWER
choice)
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choice)
Cidofovir
CMV retinitis,
mucocutaneous HSV
infections, genital warts
Inhibits DNA polymerasesofHSV,CMV,
adenovirus, and papillomavirus Nephrotoxicity
Nucleoside reversetranscriptase
inhibitors
Zidovudine (ZDV;
formerly AZT)
HIV (most frequently
used NRTI in HAART),
HIV prophylaxis
Phosphorylationby host cell kinases -->
thymidine analog --> inhibits reverse
transcriptase of HIV-1 and HIV-2 and
causes chain termination in viral DNA
Bone marrow suppression -
-> anemia, neutropenia,
thrombocytopenia
Didanosine (ddI) HIV (used in HAART) Similarto ZDV
Pancreatitis (more
frequently in alcoholics and
those with
hypertriglyceridemia),sensorimotor neuropathy
Zalcitabine (ddC) HIV (used in HAART) Similarto ZDV Sensorimotor neuropathy
Lamivudine (3TC)
HIV (used in HAART), HBV
(used with interferon
alpha) Similarto ZDV
Usually mild (GI distress,
headache, insomnia,
fatigue)
Stavudine (d4T) HIV (used in HAART) Similarto ZDV Peripheralneuropathy
Abacavir
HIV (used in
combinations with ZDV
and 3TC) Similarto ZDV
Severe hypersensitivity
reactions
Nonnucleoside
reverse transcriptase
inhibitors
Nevirapine
HIV, preventionofHIV
verticaltransmission
Bind to a siteonreversetranscriptase
differentfrom NRTI binding site
Hypersensitivity reactions
(Stevens-Johnson
syndrome,toxic epidermal
necrolysis)
Efavirenz
HIV (showntobe
effective whenused with
twoNRTIs)
Bind to a siteonreversetranscriptase
differentfrom NRTI binding site
CNS dysfunction,skinrash,
elevationsofplasma
cholesterol
Protease inhibitors Indinavir
HIV (used mostoften
with twoNRTIs)
Inhibits HIV-1 protease (cleavesviral
precursor proteins, criticalto production
ofmature infectiousvirions)
Nausea, diarrhea,
thrombocytopenia,
hyperbilirubinemia, and
nephrolithiasis
Ritonavir HIV Similarto indinavir GI irritation,bittertaste
Saquinavir HIV Similarto indinavir
GI distress, headache,
neutropenia
PHARMACOLOGY REVIEWER
Nelfinavir HIV Similar to indinavir Diarrhea
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Nelfinavir HIV Similarto indinavir Diarrhea
Amprenavir
HIV (effective whenused
with twoNRTIs) Similarto indinavir
Skinrash, insome cases
leading to Stevens-Johnson
syndrome
Miscellaneous
antiviral agents
Amantadine
Influenza A virus
infection and prophylaxis
Inhibitthefirststeps inreplicationofthe
influenza A and rubella viruses (viral
adsorption, penetration,uncapping); also
bindsto protein insurface coatofvirusto
preventfusion
CNS effects: dizziness,
ataxia,slurred speech,
insomnia,nervousness
Use catiousl
with epileps
psychosis
Rimantadine
Influenza A virus
infection and prophylaxis
Inhibitthefirststeps inreplicationofthe
influenza A and rubella viruses (viral
adsorption, penetration,uncapping)
Less CNS effects than
amantadine
Oseltamivir,
zanamivir
De
cre
ase
the
tim
eto
alleviationofinfluenza
symptoms
Inhibitorsofneuraminidase produced by
influenza A and B --> impedeviralspread
Interferons
Chronic hepatitis A and B
infections, Kaposi's
sarcoma, papillomatosis,
genital warts (topical)
Glycoproteins produced in human
leukocytes (alpha),fibroblasts (beta), and
immune cells (gamma) --> affectviral RNA
and DNA synthesis,block peptide chain
initiation, degradeterminalnucleotidesof
tRNA, activate Rnase
Neutropenia, GI irritation,
fatigue, myalgia, mental
confusion,reversible
cardiomyopathy
Ribavirin
Respiratory syncytial
virus bronchiolitis
(aerosol),wide range of
RNA and DNA viruses:
Lassa fever and other
viral hemorrhagic fevers
(IV), hepatitisC
Not known; inhibits guanosine
triphosphateformation --> prevents
capping ofviral mRNA; canblock RNA-
dependent RNA polymerases
Aerosol: conjunctivalor
bronchial irritation;
systemic: myelosuppression Teratogen
Idoxuridine,cytarabine,
trifluorothymidine
Herpes simplex eye
infections Trifluorothymidine: thymidine analog
Marked systemic toxicity(bone marrow, hepatic,
renal) --> topicaluse Topical drug
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Bacteroides, clostridia
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Miscellaneous
antimicrobial agents Metronidazole
Bacteroides, clostridia
(drug of choice for
pseudomembranous
colitis due to C. difficile),
anaerobic or mixed
intra-abdominal
infections,brain abscess,
Gardnerella vaginalis,
component of H. pylori
therapy,trichomoniasis
and giardiasis (drug of
choice), intestinal
amebiasis, amebic
hepatic abscess
Undergoes a reductivebioactivationofits
nitro group by ferredoxin (present in
anaerobic parasites) toform reactive
cytotoxic productsthat interfere with
nucleic acid synthesis
GI irritation (diarrhea),
headache, dizziness, rash,
dark colorationofurine
Mupirocin
Impetigo caused by
staphylococci, beta-
hemolytic streptococci
(topical)
Actson gram-positive cocci and inhibits
proteinsynthesisby specifically binding to
isoleucyl-tRNA synthetase Local itching and burning
Polymyxins
Topicaltherapy of
resistant gram-negative
infections (including
enterobacter,
pseudomonas)
Bactericidal against gram-negative
bacteria; interact with a specific
lipopolysaccharide componentofthe
outer cell membrane --> distorts
membranelipid structure --> increased
permeability to polar molecules -->
marked changes in cell metabolism
Neurotoxicity, acuterenal
tubularnecrosis
Urinary antiseptics
Nitrofurantoin
Many urinary tract
pathogens (not proteus
or pseudomonas)
Rapidly excreted intheurine and acts
theretosuppressbacteriuria
GI irritation,skinrashes,
phototoxicity,neuropathies,
hemolysis in patients with
glucose-6-phosphate
dehydrogenase deficiency,
pulmonary fibrosis
Drugs for malaria
Chloroquine
Acute attacksof
nonfalciparum and
sensitivefalciparum
malaria
Prevent polymerizationofheme into
hemozoin (accumulationofheme is
toxic); selectivetoxicity duetoenergy-
dependent carrier mechanism in
parasitized cells
GI irritation,skinrash,
headaches
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Cinchonism (GI distress,
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Quinine
P. falciparum resistantto
chloroquine
Complexes with dsDNA to preventstrand
separation --> block DNA replication and
transcription
C c o s (G d st ess,
headache,vertigo,blurred
vision,tinnitus), Blackwater
fever (rare; intravascular
hemolysis)
Mefloquine
P. falciparum, P. vivax
prophylaxis and
treatment (drug of
choice)
Chemically related to quinine; mechanism
not known
Lesstoxic than quinine; GI
distress,skinrash,
headache, dizziness
Primaquine
Eradicate liver stages of
P. vivax and P. ovale
Forms quinoline-quinone metabolites -->
electron-transferring redox compounds
that act as cellular oxidants
Welltolerated; GI distress,
pruritus, headaches,
methemoglobinemia,
hemolytic anemia
Antifolate drugs Discussed above
Drugs for amebiasis
Diloxanidefuroate
Asymptomatic amebiasis,
mild intestinal disease
Converted in gutto diloxanidefreebase
form (active amebicide) GI symptoms
Emetines
Backup drugsforsevere
intestinalor hepatic
amebiasis in hospitalized
patients
Inhibit proteinsynthesisby blocking
ribosomal movement along mRNA
GI distress, muscle
weakness, cardiovascular
(arrhythmias,CHF)
Iodoquinol
Alternative drug for mild-to-severe intestinal
infections Luminal amebicide GI effects
Metronidazole Discussed above
Paromomycin
Second-lineluminal
amebicide,
cryptosporidiosis GI effects
Drugs for
pneumocystis and
toxoplasmosis Pentamidine
Pneumocystis in HIV
patient allergic orresistant to
trimethoprim-
sulfamethoxazole,
trypanosomiasis
Unknown; may involve inhibitionof
glycolysisor interference with nucleic acid
metabolism ofprotozoans and fungi
Respiratory stimulation
followed by depression,hypotension (peripheral
vasodilation), hypoglycemia,
anemia,neutropenia,
hepatitis, pancreatitis
Trimethoprim-
sulfamethoxazole Discussed above
Antifolate drugs Discussed above
PHARMACOLOGY REVIEWER
Rash, cough,nausea,
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Atovaquone
Mild to moderate
pneumocystis pneumonia
Inhibits mitochondrialelectrontransport
and probably folate metabolism
g
vomiting, diarrhea,fever,
abnormal LFTs
Drugs for
trypanosomiasis
Pentamidine Discussed above
Melarsoprol
Drug ofchoice in African
sleeping sickness Inhibitsenzymesulfhydryl groups Reactiveencephalopathy
Nifurtimox
Drug ofchoice in
American
trypanosomiasis,
mucocutaneous
leishmaniasis
Inhibits parasite-uniqueenzyme
trypanothionereductase
Allergies, GI irritation,CNS
effects
Suramin
Drug ofchoiceforearly
hemolymphatic stagesof
Africantrypanosomiasis
Skinrashes, GI distress,
neurologic complications
Drugs for
leishmaniasis
Sodium
stibogluconate Leishmania
Inhibitionofglycolysisoreffectson
nucleic acid metabolism --> kills parasite
Drugs that act
against nematodes
Albendazole
Alternativeforlarva
migrans, ascariasis,
infections caused by
roundworms,
whipworms, hookworms,pinworms,threadworms;
Microsporidia (drug of
choice)
Unclear; blocks glucoseuptake inboth
larval and adult parasites --> decreased
ATP --> parasite immobilization
Few during short courseof
therapy
Diethylcarbamazine
Drug ofchoicefor
filariasis; alternativeforonchocerciasis (used with
suramin)
Immobilizes microfilariaeby anunknownmechanism --> susceptibleto host
defenses
Headache, malaise,
weakness, anorexia;
reactionto proteins
released by dying filariae
(fever,rash,ocular damage,joint and muscle pain,
lymphangitis)
Mazzotti rea
onchocercia
(described a
effects pluspyrexia,resp
distress, pro
Ivermectin
Drug ofchoicefor
onchocerciasis,
strongyloidiasis
Intensifies GABA-mediated
neurotransmission innematodes (does
not crossblood-brainbarrier --> selective
toxicity) --> immobilizationofparasites -->
removalby reticuloendothelialsystem
Mazzotti reactions (fever,
headache, dizziness,rashes,
pruritus,tachycardia,
hypotension, pain in joints,
muscles,lymph glands)
PHARMACOLOGY REVIEWER
Drug ofchoicefor
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Mebendazole
pinworm and whipworm
infections,roundworm
(with pyrantel pamoate),
combined infections with
ascarids and hookworm;
trichinosis
Selectively inhibiting microtubule
synthesis and glucoseuptake in
nematodes GI irritation
Piperazine
Alternative drug for
ascariasis
Paralyzes ascarisby acting as an agonist at
GABA receptors --> expelled by normal
peristalsis
Mild GI irritation (most
common)
Contraindica
patients wit
disorders
Pyrantel pamoate
One of two drugs of
choice (with
mebendazole) for
infectionsdue to
hookworm,pinworm,
roundworm
Stimulatenicotinic receptors present at
neuromuscular junctionsofnematodes --
> muscle contraction --> depolarization-
induced paralysis
Minor (GI distress,
headache, weakness)
Levamisole
Adjunctive therapy with
5-FU in colorectal cancer
Stimulates maturation and proliferation
of T cells in patients with impaired
immune function; also antiparasitic (same
mechanism as pyrantel pamoate)
Thiabendazole
Drug ofchoicefor
visceralformsoflarva
migrans; strongyloidiasis,
cutaneouslarva migrans,
threadworm Similar action as mebendazole
GI irritation, headache,
dizziness,leukopenia,
hematuria, allergic
reactions (intrahepatic
cholestasis)
Drugs that act
against trematodes
Praziquantel
Drug of choice in
schistosomiasis,
clonorchiasis,
paragonimiasis, flukes,
cestodes, cysticercosis
Increases membrane permeability to
calcium --> marked contraction initially -->
paralysisoftremeatode muscles -->
vacuolization and parasite death
Headache, dizziness,
malaise
Bithionol
Drug ofchoicefor
fascioliasis (sheep liver
fluke) Unknown
Nausea and vomiting,
diarrhea and abdominal
cramps, dizziness,
headache, phototoxicity
Metrifonate
Schistosoma
haematobium (causeof
Converted inthebody tothe
cholinesterase inhibitor dichlorvos
Excess cholinergic
stimulation
PHARMACOLOGY REVIEWER
bilharziasis)
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Oxamniquine Schistosoma mansoni Dizziness
Drugs that act
against cestodes(tapeworms)Niclosamide
Oneoftwo drugsof
choice (with
praziquantel) forcestodes
Uncouplesoxidative phosphorylationorby activating ATPases
GI distress, headache,rash,fever
Noteffective
cysticercosis
disease causEchinococcu
Alkylating agents
Chlorambucil
Chronic lymphocytic
leukemia
Slow-acting; alkylate nucleophilic groups
on DNA bases --> cross-linking, abnormal
base pairing,strand breakage Myelosuppression Nitrogen mu
Cyclophosphamide
Non-Hodgkin's
lymphoma (in COP),
multiple myeloma,
lymphoblasticleukemias, breast (in
CMF), ovarian, lung, and
cervical cancers, mycosis
fungoides, and
neuroblastoma
Alkylate nucleophilic groups on DNA
bases --> cross-linking, abnormalbase
pairing,strand breakage --> inhibit
proliferation of lymphocytes (B cells > T
cells)
GI distress,myelosuppression,
alopecia,secondary
leukemia,transitional cell
carcinoma,hemorrhagic
cystitis Nitrogen mu
MechlorethamineHodgkin's disease (inMOPP)
Alkylate nucleophilic groups on DNA
bases --> cross-linking, abnormalbasepairing,strand breakage
GI distress,
myelosuppression,
alopecia,secondaryleukemia Nitrogen mu
Carmustine,
lomustine
Adjuncts intreatmentof
braintumors
Alkylate nucleophilic groups on DNA
bases --> cross-linking, abnormalbase
pairing,strand breakage; high lipophilicity
facilitatesCNS entry
GI distress,
myelosuppression,CNS
dysfunction Nitrosureas
Cisplatin (Platinol),
carboplatin
Testicular carcinoma (in
PVB and PEB), and
cancers of bladder, lung,
and ovary
Alkylate nucleophilic groups on DNA
bases --> cross-linking, abnormalbase
pairing,strand breakage
GI distress, mild
hematotoxicity,neurotoxic
(peripheralneuritis),
ototoxicity (acoustic nerve
damage), hypomagnesemia
--> hypocalcemia,
nephrotoxic
Procarbazine
Hodgkin's disease (in
MOPP)
Reactive agentthatforms hydrogen
peroxide --> generatesfreeradicalsthat
cause DNA strand scission
Myelosuppressant, GI
irritation,CNS dysfunction,
peripheralneuropathy,skin
PHARMACOLOGY REVIEWER
reactions, secondary
l k i
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leukemia
Busulfan CML
Alkylate nucleophilic groups on DNA
bases --> cross-linking, abnormalbasepairing,strand breakage
Adrenal insufficiency,bone
marrow suppression,
pulmonary fibrosis,skinpigmentation Alkylsulfona
Dacarbazine
Hodgkin's disease (in
ABVD)
Alkylate nucleophilic groups on DNA
bases --> cross-linking, abnormalbase
pairing,strand breakage
Alopecia,skinrash, GI
distress,myelosuppression,
phototoxicity,flu-like
syndrome
Antimetabolites
Methotrexate
Choriocarcinoma,acute
leukemias,non-
Hodgkin's and cutaneousT celllymphomas,breast
cancer (inCMF)
Substrate for and inhibitor of
dihydrofolate reductase --> decreasedsynthesisofthymidylate, purine
nucleotides, and amino acids
Bone marrow suppression,
toxic effectsonskin and GI
mucosa (mucositis),folatedeficiency, liver disease
(fatty change, fibrosis)
"Leucovorin
reducetoxicadministrati
acid (leucov
Mercaptopurine (6-
MP),thioguanine
(6-TG)
Acute leukemias
(maintenance),CML
Purine antimetabolites activated by
hypoxanthine-guanine
phosphoribosyltransferases (HGPRTases) -
-> toxic nucleotidesthat inhibitseveral
enzymes involved in purine metabolism Bone marrow suppression
Cytarabine (Ara-C) Acuteleukemias
Pyrimidine antimetabolite activated bykinases to AraCTP --> inhibits DNA
polymerases; specific for S phase
GI irritation,
myelosuppression
Fluorouracil (5-FU)
Bladder, breast (in CMF),
colon, head and neck,
liver, and ovarian
cancers; skin cancers
(topically)
Biotransformed to5-fluoro-2'-
deoxyuridine-5'-monophosphate (5-
FdUMP) --> inhibitsthymidylatesynthase
--> "thymineless death"
GI distress,
myelosuppression,
alopecia, dermatitis,
stomatitis
Plant alkaloids
Vincristine
(Oncovin)
Hodgkin's disease (inMOPP), lymphomas (in
COP), used in acute
leukemias, Wilms'
tumor, CNS tumors,
sarcomas,
choriocarcinoma
Spindle poisons --> prevent assembly of
tubulin dimers into microtubules; act
primarily in M phase Neurotoxicity
Vinca alkalo
chemothera
not associat
developmen
marrow sup
PHARMACOLOGY REVIEWER
Hodgkin's disease (in
ABVD) l h
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Vinblastine
ABVD), lymphomas,
neuroblastoma,
testicular carcinoma (in
PVB), Kaposi's sarcoma
Spindle poisons --> prevent assembly of
tubulin dimers into microtubules; act
primarily in M phase
GI distress, alopecia,bone
marrow suppression Vinca alkalo
Etoposide,
teniposide
Used in combination
regimens for lung (small
cell), prostate,and
testicular carcinoma (in
PEB)
Increases degradation of DNA, possibly
via interaction with topoisomerase II,
and also inhibits mitochondrialelectron
transport; most active inlate S and early
G2 phase
GI irritants, alopecia,bone
marrow suppression,
stomatitis, erythema Podophyllot
Paclitaxel,
Recommended