All Drugs- For Review

8/2/2019 All Drugs- For Review

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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


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)


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


prophylaxis,coronary

vasospasm,AV nodal

arrhythmias, arrhythmias

involving calcium-

dependent cardiac tissue


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


prophylaxis, AV nodal

arrhythmias, arrhythmias

involving calcium-dependent cardiac tissue




contractility; AV conductionvelocity

decreased --> increased PR interval,effectiverefractory period increased;

Constipation,edema,nausea,flushing, dizziness

Alsoused in

preterm laband Raynaud

Nimodipine Hemorrhagic stroke




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)



atopic dermatitis) Same as diphenhydramine Sedation Ineffective i

Terfenadine,

astemizole,

loratadine



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


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)


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


10/68


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



2; inhibitreleaseofmediatorsby mast

cells

Adrenalsuppression,oral

candidiasis (inhalers)

BeclomethasoneModerate to severeasthma, allergy



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


11/68


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


12/68


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


13/68


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


14/68


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)


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)


subunit) --> major stimulant of gonadal


15/68


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


16/68


17/68


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


18/68


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


19/68


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


20/68


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),


21/68


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


22/68


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


23/68


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


24/68


25/68


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


26/68


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;


27/68


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



28/68


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


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


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



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)



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


unresponsivetoother

agents

Inhibits dihydroorotate dehydrogenase

(enzymerequired by activated

lymphocytesforsynthesisofpyrimidines

needed for RNA synthesis) --> cell cycle

arrest

Teratogen, hepatotoxicity,

GI disturbance,skin

reactions

Infliximab,

etanercept


unresponsivetoother

Bind to and prevent actionofTNF-alpha

(plays a key role in chronic inflammation)

Infliximab:upper

respiratory infection;



29/68


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



30/68


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,



36/68

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


permeability by inhibiting synthesisof

ergosterol


hepatotoxicity Administere

Itraconazole

Drug ofchoice:systemic

infections dueto

blastomyces andsporothrix and for

subcutaneous

chromoblastomycosis



ergosterol


hepatotoxicity

Voriconazole

Widerspectrum than

itraconazole



ergosterol


hepatotoxicity


H d h t l


37/68

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


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


choice)


38/68

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


Nelfinavir HIV Similar to indinavir Diarrhea


39/68

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


Bacteroides, clostridia


40/68

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


Cinchonism (GI distress,


41/68

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


Rash, cough,nausea,


42/68

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)


Drug ofchoicefor


43/68

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


bilharziasis)


44/68

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)


bases --> cross-linking, abnormalbasepairing,strand breakage

GI distress,

myelosuppression,

alopecia,secondaryleukemia Nitrogen mu

Carmustine,

lomustine

Adjuncts intreatmentof

braintumors



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



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


reactions, secondary

l k i


45/68

leukemia

Busulfan CML


bases --> cross-linking, abnormalbasepairing,strand breakage

Adrenal insufficiency,bone

marrow suppression,

pulmonary fibrosis,skinpigmentation Alkylsulfona

Dacarbazine


ABVD)



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



ABVD) l h


46/68

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,

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