1

Class

Drug

Penicillins

Disease

Gram (+) cocci

Gram (-) cocci
(meningococci)

Gram (+) rods

(Anthrax, Diphtheria)

Gram (-) rods

(Bacteriodes)
Penicillin G

Syphilis (prophylaxis
& treatment)

Prophylax recurrent

Biological Target /
Mechanism
inhibits
transpepdidation that
results in crosslinking of cell wall;
activates autolytic
enzymes cell lysis
(bactericidal)

Route of
Admin.

Side Effects

IV
(acid labile)
oral for
newborns &
elderly

procaine
syndrome, if
given IV instead
of IM

convulsions
with massive
doses

H. flu
enterococcal
endocarditis

Leptospirosis
[same as Pen G]

Amoxicillin
(+ clavulanic acid =
augmentin)

Hemophilus
Gonorrhea

oral
oral (acid
stable)

Gram (+) rods

Ampicillin

(Listeria)

Gram (-) rods

oral (acid
stable)

(H. pylori)
Ticarcillin

Gram (-) rods, esp.

pseudomonas

Drug Resistance

allergy &
hypersensitivity

inactivated by
*-lactamases

MRSA:

rheumatic fever

Penicillin V

Contraindications

no oral
absorpion

Nausea
Vomiting
Diarrhea
Nausea
Vomiting
Diarrhea
skin rashes

mutation of
penicillinbinding protein

2
Nafcillin
*-lactamase
Inhibitors

Clavulanic Acid

IV (acid
labile)

staph
Use with amoxicillin
= augmentin

Sulbactam
Tazobactam

Antibiotics

penicillinaseresistant

3
Antibiotics cont.

Class

Drug

Diseases

Biological Target /
Mechanism

Route of
Admin.

Side Effects

Contraindications

form of

UTIs (crystalluria not

likely)

Nocordia infections (sulfa

+ minocycline)
Sulfamethoxazole

Drug-resistant malaria &

toxoplasmosis (sulfa +
pyrimethamine)

oral route
preferred
competes with PABA
for enzyme
dihydropteroate
synthetase and blocks
folate synthesis

Prevent recurrence of
rheumatic fever if Pen G
cannont be given

slow IV
preferable
to IM
(irritates
muscle
tissue)

Toxicity:

bone marrow
depression

crystalluria
agranulocytosis
& aplastic
anemia in highrisk pts.

Kernicterus in
neonates

Sulfonamides
and
Trimethoprim

Trimethoprim

acute UTI

inhibits folate
reduction (inhibits
DHFR)

(Quinolones are DOC)

Co-Trimoxazole
(Sulfamethoxazole
+ Trimethoprim)

due to H. flu or strep

Gonococcal urethritis
Oralpharyngeal gonorrhea

oral route
preferred

Pregnancy
Increases
anticoagulant
effect of oral
anticoagulants
(displaces them
from albumin)

Synergistic effect
with sulfonyl
urea
hypoglycemia

Stevens-Johnson G6DP-deficient
syndrome

pts.: causes acute

hemolytic anemia

Combination
reduces individual
side effects

Pneumocystic carinii
Shigella & Salmonella
UTI
Otitis media in children
Respiratory tract infection

Drug Resistance

In AIDS pts.:
synergistic effect

Fever
Rash
Leukoplakia
Folate
deficiency

Hepatitis

pregnancy

dihydropteroate
with low affinity
for sulfonamides

increased PABA
production to
overcome sulfa
drugs

alternate
pathways for
nucleic acid
synthesis
bacteriostatic
agents negated by
pus, which
contains
thymidine &
purines, so no
need for folate

4
Antibiotics cont.
Class

Drug
Cefalexin

1st gen

Cefazolin

Cefuroxime
2nd gen

Cephalosporins

Cefotetan

Ceftriaxone
3rd gen

Cefotaxime

(longest
duration)
Ceftazidime

4th gen
(more
resistant to *lactamases)

Cefepime

Diseases

Gram (+) cocci

Gram (+) cocci
E. coli
Klebsiella
Proteus
Gram (-)
Meningitis
Gram (-)
B. fragillis
Huge Gram (-) coverage
Meningitis
Haemophilus
Neisseria
Huge Gram (-) coverage
Meningitis
Pseudomonas
P. aeruginosa
Enterobacteri a
S. aureus
S. pneumoniae
Haemophilus
Neisseria

Biological Target / Mechanism

Route of
Admin.

Side Effects

Drug Resistance

oral

inhibits transpepdidation that

results in cross-linking (same as
penicillins)
inactive against MRSA &
enterococci (Strep Group D)

same as penicillin

inactivated by *lactamases (same

as penicillins)

5
Antibiotics cont.

Class

Drug

Diseases

Biological Target /
Mechanism

Route
of
Admin.

Side Effects

Contraindications

Drug
Resistance

NO renal toxicity
(unlike aminoglycosides)

Penicillin allergic
pts. CAN tolerate
this drug

resistant to *lactamases

allergy to
penicillin

resistant to
most *lactamases but
not metallo-*lactamases

Substitute for aminoglycosides

DO2ndC:
Aztreonam

Klebsiella
P. aeruginosa
Serratia

binds to PBP & inhibits cell

wall synthesis;
synergistic with
aminoglycosides

IM /
IV

Nausea
Vomiting
Diarrhea
Skin rash

DOC:
Penems &
Monobactams

Enterobacter
DO2ndC:
Imipenem

Staph infection
B. fragillis
P. aeruginosa

Toxicity:

Seizures in pts. with

renal failure

Tetracyclines,
Chloramphenicol
and
Aminoglycosides

Cilastatin

use with imipenem

Tetracycline

Rickettsia
Chlamydia
Vibrio cholera
Plague
Lyme disease
Protozoa
Prophylax meningococcal

NOT an antibiotic;
inhibits renal
dihydropeptidase I and thus
prevents penem degredation
binds to 30S subunit and
blocks binding of tRNA to A
site on ribosome;
bacteriostatic;
bacteria have TC-uptake
system and can concentrate
TCs

oral
(not
with
food)

Very Toxic:

Retard bone growth in

children (damage
teeth, bone, nails)

Suprainfection (treat
with vancomycin)

Hepatic dysfunction
(preggers)

Renal toxicity

pregnancy (bone
deformity, growth
inhibition of
fetus)

efflux of
tetracyclines
out of
bacteria

plasmidmediated
resistance

resistance is
wide-spread

meningitis

prophylaxis for travelers

diarrhea
Doxycycline

prostate infections
prophylax malaria in
Chloroquine-resistant areas

photo-sensitization

7
Antibiotics cont.

Class

Drug

Biological Target /
Mechanism

Diseases

Route of
Admin.

Side Effects

Contraindications

Drug Resistance

Severe infections only

Endocarditis caused by

Tetracyclines,
Chloramphenicol
and
Aminoglycosides
cont.

[aerobic Gram (-) only]Aminoglycosides

Streptomycin

enterococci or viridans
group

TB
Severe infections only
Neomycin

Gram (-) enteric

In combo with *lactams synergism,
expands spectrum to
Gram (+)

Gentamicin

Pseudomonas
(antipseudomonal
penicillin)

Tobramycin

Chronic UTI
E. coil or Klebsiella

Nephrotoxic
1)

binds to P12
receptor protein on
30S subunit
2)
blocks
formation of
[mRNA+formyl
methionine+tRNA]
complex
3)
mRNA is
misread
4)
wrong aa
inserted
bactericidal

(with ampicillin,
cephalosporin)
DO2ndC:

Chloramphenicol

Meningitis
TC diseases
Typhoid
Brain abscess caused
by anaerobes

Eye infections

usually IM,
rarely oral
or IV (no
adverse
effects with
oral, but
only affect
GI
microbes)

Deletion of P12

Neuromuscular
blockade

gene
(chromosomal
resistance)

Serious
Ototoxicity:

Hearing loss

PlasmidMyasthenia Gravis

to fetus /
newborn

Vertigo
Loss of

dependent
production of
destructive
enzymes

Mutant porins
Mutant 30S

vestibular
organ

ribosome

Very Toxic:
binds to 50S ribosome
and inhibits
transpeptidation
(peptidyl transferase)

pancytopenia
bone marrow
disturbances

Gray Baby
syndrome

death

G6PD-deficient pts.
(hemolytic anemia),
same as sulfa drugs

chloramphenicol
acetyl transferase
(from a plasmid
gene) inactivates
drug

8
Antibiotics cont.

Class

Drug

Diseases

Biological Target /
Mechanism

Route of
Admin.

Misc.

Vancomycin

Quinolones

Bacitracin

Only Gram (+)

Meningitis caused by staph
MRSA
C. diff suprainfection
Gram (+) cocci
Eye & skin infection
UTIs caused by multidrug-

Ciprofloxacin

Norfloxacin

Ofloxacin

resistant bacteria

Pseudomonas
Shigella
Salonella
E. coli
Helicobacter
Infections of soft tissue,
bones, joints (not routine)

Intraabdominal &
respiratory tract infections
(not routine)

Gonococcal infections
Chlamydia
Prophylax travelers

Side Effects

Contraindications

Nephrotoxicity
Ototoxicity
Thrombophlebitis
Diffuse flushing

prevents peptidoglycan
construction (inhibits
cell wall mucopeptide
formation)

(red man
syndrome)
interferes with
regeneration of lipid
carrier in peptidoglycan
synthesis by blocking its
dephosphorylation
inhibits DNA gyrase

oral

GI disturbances
Suprainfection
with streptococci
& candida

pts. <18 yrs (cartilage

damage)

Drug
Resistance

9
diarrhea

10
Antibiotics cont.
Class

Drug

Diseases

Biological Target /
Mechanism

Route of
Admin

Side Effects

Drug Resistance

Use in penicillin-allergic pts.

(same spectrum as penicillin)

Macrolides

Erythromycin

Misc.
cont.

Mycoplasma pneumonia
Chlamydia
Legionella
Helicobacter
Listeria
Neisseria
Bordetella pertussis
Treponema
Campylobacter
Gram (+)

binds to 50S ribosome;

inhibits aminoacyl
translocation

plasmid-mediated gene
encodes alternate protein
on 50S ribosome

QID dosing
Azithromycin

Chlamydia
H. flu
SID dosing

Clarithromycin

H. pylori
H. flu
BID dosing

Clindamycin

B. fragilis

inhibits protein synthesis

Metronidazole

Bacteriodes
Clostridia
Pseudomembranous colitis

inhibits DNA synthesis;

bactericidal

Polymyxins

Topical for eye & ear (with

bacitracin or neomycin)

oral, IV
available

Suprainfection by C. diff
Hepatotoxicity
Minor GI disturbances
Minor CNS symptoms
Interferes with alcohol
metabolism

binds to phosphotidyl
ethanolamine, disrupts
transport; detergent-like
action

11

Anti-Virals

12
Disease

Drug

Clinical Uses

Biological Target /
Mechanism

Route
of
Admin.

reduces incidence of
oppotunistic infections

Zidovudine
(azidothymidine:
AZT)

stabilizes weight
reduces HIV-associated
dementia

delays onset of AIDS in

analogue of pyrimidine,
thymidine; inhibits reverse
transcriptase

IV &
oral

HIV+ pts.

Reduces risk of
transplacental transmission

AIDS

NRTI

used in combination with AZT

Anemia
Neutropenia
GI disturbances
Skin rash
Paresthesia
Fever, headache
Abnormalities of liver

Drug Resistance

point mutation in reverse

transcriptase leads to
reduced drug sensitivity

response wanes with longterm use

function

Prophylaxis after exposure

Zalcitabine
(dideoxycystidine:
ddC)

Side Effects

inhibits reverse
transcriptase; activated in T
cells by different
phosphorylation pathway
than AZT

oral

myopathy
dose-related neuropathy
GI disturbances
Headache
Mouth ulcers
Nail changes
Edema of lower limbs
General malaise

a dideoxynucleoside
Lamivudine
(3TC)

used in combination with AZT

terminates synthesis of
proviral DNA chain

oral

pancreatitis in peds

resistance to AZT develops

more slowly when given in
combo. With 3TC

inhibits reverse transcriptase

Didanosine
(dideoxyinosine: ddI)

switching to ddI after AZT

therapy shown to be beneficial

chain terminator
oral
inhibits reverse transcriptase

peripheral neuropathy
pancreatitis
headache
GI disturbances
Skin rash
Bone marrow depression
Alteration of liver
function

resistance with long-term

use, but less so than with
AZT

13
Anti-Virals cont.

Disease

NtRTI

Drug

Tenofovir

Clinical Uses
used in
combination with
other antiretrovirals
(except ddI
increases conc.)

Treatment of
Nevirapine

AIDS & related

symptoms

prevention of

does not require

phosphorylation or other
modification for activation
inhibit reverse transcriptase

do not require
phosphorylation for
activation

Delavirdine

bind to lipophilc pocket of

reverse transcriptase
distinct from substrate
binding site

Efavirenz

inhibit P-450 system, so

decrease metabolism of
protease inhibitors (except
nevirapine)

transplacental
transmission
NNRTI

Biological Target /
Mechanism

act synergistically with

NRTIs

AIDS
cont.

Side Effects

Renal failure
Faconi syndrome
Proteinuria
Tubular necrosis
rash
fever, headache
fatigue
nausea
rash (not as severe as nevirapine)
CNS effects: dizziness, drowsiness, insomnia,
Teratogenic in monkeys
Induces metabolic enzyme, CYP3ZA4, which
reduces plasma methodone and serum levels of
other antivirals including protease inhibitors

Nelfinavir
Protease
Inhibitors
Ritonavir

inhibition of HIV-1
protease (cleaves precursor
protein to generate viral
proteins essential for final
stage of viral formation)

increase bilirubin without hepatic abnormalities

nephrolithiasis
diarrhea
asthenia
headache
moderate hypertension
GI disturbances
Elevated hepatic aminotransferase &

rapid resistance at sub-optimal

dose:
must administer at highest
tolerable dose & in combo.
with RTIs

triglyceride levels inhibit CYP3A4, leading to

decreased metabolism of other drugs

Saquinavir

Mild diarrhea, abdominal discomfort, nausea

Low bioavailability & metabolized by P-450,
and combo. with rifamycin or cabamazepine
further decreases concentration

14

rapid resistance if given alone;

decreased when combined
with NRTI

headache, confusion, amnesia, agitation,

depression, nightmares

crystallization of drug in urine leads to

Indinavir

Drug Resistance

resistance after ~1 year due to

single amino acid mutation

15
Anti-Virals cont.
Disease

AIDS
cont.

Drug

Protease
Inhibitors
cont.

Lopinavir
100 /
Ritonavir
400

Fusion
Inhibitors

Enfuvirtide

Acyclovir

Clinical Uses

Biological Target / Mechanism

sub-therapeutic dose of
ritonavir inhibits CYP3Amediated metabolism,
thereby inreasing lopinavir
concentrations
pts. with persistant HIV-1
replication despire tx. with
other anti-viral drugs

inhibition of HIV-1 protease

(cleaves precursor protein to
generate viral proteins essential
for final stage of viral
formation)
mimics HR2 region of gp41
viral glycoprotein and binds to
gp41, blocking entry into cell

Shingles
Chicken pox
Herpes simplex

converted 1st to a
monophosphate by viral
thymidine kinase, then to a
triphosphate by mammalian
kinase: acyclovir-triphosphate
inhibits viral DNA polymerase

[same as acyclovir]

an L-valyl ester of acyclovir

Route of
Admin.

Side Effects

Drug Resistance
combination results
in low resistance
resistance does
occur, but no crossresistance found

Local inflammation at IV
site
oral or IV

Renal dysfunction if given

too rapidly IV

Nausea & headache

mutations in viral
genes for
thymidine kinase or
DNA polymerase
lead to resistance

similar to acyclovir
Valacyclovir
Herpes Simplex
Virus

almost completely metabolized

to acyclovir, but higher
bioavailability

Herpes simplex in neonates

Herpes-associated
Vidarabine

encephalitis

Varicella-zoster in AIDS

oral
generally well tolerated

phosphorylated to triphosphate,
which inhibits DNA
polymerase

slow IV or
topical

phosphorylated by cellular
kinases and incorporated into
both viral and host DNA

topically
dissolved
in dimethysulfoxide

pts.

2 line drug after acyclovir

Herpes simplex &
nd

Idoxuridine

varicella-zoster infections
of the eye

Life- or sight-threatening
Ganciclovir
Cytomegalovirus

CMV

Prophylaxis in transplant
pts.

nd

Foscarnet

line for CMV eye

infection

GI disturbances
Neurotoxicity late in therapy
with high doses (reversible)

Bone marrow disturbances

Can be carcinogenic
Irritation / contact dermatitis
(due to DMSO)

Bone marrow suppression

Severe myelosuppression if

guanosine analogue;
phosphorylated 1st by viral
protein kinase, then by host
kinase to form triphosphate,
which competes with guanosine
triphosphate for incorporation
into viral DNA

IV

pyrophosphate analogue;
binds to pyrophosphate binding
site and inhibits viral DNA
polymerase

IV

given with AZT (both cause

granulocytopenia)

Potentially carcinogenic and

teratogenic

Serious nephrotoxicity
(reversible with dialysis)

some resistance
reported

16
Anti-Virals cont.
Disease

Drug

Clinical Uses

Biological Target / Mechanism

Early stages of
Lassa Fever

Ribavirin

Lassa Fever

Respiratory

adenosine/guanosine analogue;
alters viral DNA and mRNA synthesis

Syncytial Virus

Route of
Admin.

Side Effecs

IV for Lassa
fever;
oral, aerosol
for RSV

Teratogenic
Embryotoxic
Oncogenic
Anemia (dose-related & reversible)

Drug
Resistance

Common

interferon 2b

Fever, headache
Lassitude
Myalgia

HBV
Kaposi sarcoma
Hairy cell
leukoplakia

Hepatitis B
&
Hepatitis C

Other
induce host enzymes that inhibit
translation of viral mRNA

Bone marrow suppression

CV changes
Rashes & alopecia
Altered thyroid & renal function
Exacerbate autoimmune diseases

IFN receptors (gangliosides) inhibit viral

replication
interferon 2b
& Ribavirin

HCV

(e.g. thyroiditis)

Acute, reversible hearing loss or

tinnitus
Influenza

Oseltamivir

Tx. and prevention

of flu

inhibition of viral neuraminidase

alteration of virus particle aggregation and
release

Zanamivir

Anti-Fungals

oral

Renal impairment

associated
with changes
in aa
sequence

17

Drug

Disease

Biological Target / Mechanism

Route of
Admin.

Side Effects

Contraindications

Drug
Resistance

subcutaneous & systemic

Amphotericin B

*fungal meningitis*
blastomyces
coccidioides
histoplasma
candida
cryptococcus

VERY TOXIC

fever, chills, headache

nausea, vomiting,
binds to fungal membrane
ergosterol, and alters selective
prermeability; cidal

intrathecal
injection

neoformans

aspergillis
mucor

Griseofulvin

Nystatin

superficial

Candida (intestinal)

subcutaneous & systemic

Flucytosine

Candida
Cryptococcus

anorexia
renal hypokalemia
thrombocytopenia,
leukopenia, anemia

superficial

ringworm
microsporum
trichophyton
epidermophyton

abdominal pain

binds to fungal microtubules;

interferes with spindle
formation and inhibits cell
division; static

binds to fungal membrane

ergosterol, and alters selective
prermeability; cidal
converted to 5-flurouracil,
which inhibits thymidylate
synthetase, which inhibits DNA
& RNA synthesis
never used alone: use with
Amphotericin B for synergism

oral

GI distress
Hepatotoxicity
Rashes
(hypersensitivity)

Leukopenia
Albuminuria
oral,
topical

Epigastric distress
Hematologic problems
oral

(reduced by admin. of
uracil)

Bone marrow
depression

Stevens-Johnson
syndrome in AIDS pts.

Phenobarbital decreases
levels of GF by interfering
with absorption

Anticoagulants GF
diminishes activity of
coumarins by increasing rate
of metabolism

Pregnancy: teratogenic
Lupus relapse

resistance via
decrease in
drug uptake

18
Anti-Fungals cont.
Drug

Diseases

Route of
Admin.

Biological Target / Mechanism

Side Effects

subcutaneous & systemic AND superficial

Ketoconazole

Candida vaginitis
Cutaneous Dermatophyte infection alternative
inhibits synthesis of ergosterol; increases
permeability of membrane; static

superficial
Clotrimazole

Miconazole
Tolnaftate

oral

Dermatophytic tinea
candida
subcutaneous & systemic AND superficial

topical

topical

athletes foot (OTC)

athletes foot (OTC)

unknown

severe GI disturbances (oral only)

topical

Anti-Mycobacterial
Disease

Drug

Biological Target / Mechanism

Route of
Admin.

Side Effects

Contraindications

Drug Resistance

Hemolysis of RBCs
(no anemia)
Dapsone

inhibition of folate synthesis

Rifampin

[see TB]

Clofazimine

Lepromatous leprosy only

Binds DNA, may interfere with DNA

oral

Leprosy

replication

Alternative to dapsone

Methemoglobinemia
Anorexia, nausea, vomiting
Allergic dermatitis
Fever

resistance increasing,
so combination
therapy used

Skin discoloration
oral

(red-brown to black)

GI intolerance

Expensive!

19
Anti-Mycobacterial cont.
Disease

Drug

Biological Target / Mechanism

Route of
Admin.

Tuberculosis

Isoniazid

Bacteriostatic against resting bacteria

Bacteriocidal against dividing bacteria
Effective on intracellular bacteria
Pro-drug activated by catalase-

oral or
parental
injection

peroxidase enzyme; inhibits mycolic acid

Side Effects

Drug-induced hepatitis
Allergic skin eruptions
Fever
Hepatotoxicity
Arthritic symptoms
Pyroxidine deficiency vit.

Contraindications

Drug Resistance

decreased penetration
Decreases
metabolism of
antiepileptic
drugs

into infected cell

mutations leading to
overexpression of
inhA or ahpC

mutation in KatG

B6 deficiency

inhibits DNA-dependent RNA

polymerase in prokaryotic cells
Rifampin

Effective on intracellular, Gram (+), and

Gram (-) bacteria

oral

Good penetration into tissue and

macrophages

Ethambutol

Pyrazinamide

inhibits synthesis of arabinogalactin (cell

wall component)

active at acid pH only

effective against intracellular bacteria in

oral

oral or
injection

macrophages
Streptomycin

irreversibly binds to 30S ribosome

extracellular bacteria only
used for life-threatening TB + meningitis

IV

Orange saliva, tears, sweat

Pts. on warfarin,
Fever
glucocorticoids,
narcotic
GI disturbances
analgesics, or
Skin eruption
estrogen (oral
contraceptives)
Induces hepatic enzymes
Optic neuritis, if renal function
decreased:
Red-green color blindness
Decreased visual acuity

GI upset
Malaise
Fever
hepatotoxicity
nausea, vomiting
fever
hyperuricemia
vertigo & hearing loss
8th nerve toxicity
disequilibrium & deafness

mutation in DNAdependent RNA

polymerase reduced
affinity of drug binding

resistance occurs
rapidly if given alone
mutations leading to
overexpression of emb
gene

rapidly developed

Enzymatic
deactivation of
aminoglycoside

Change in

20
permeability

Mutation of 30S
ribosome

Anti-Protozoals
Disease

Drug

Malaria
prevention
only

Doxycycline

Clinical Uses

prophylax in
Chloroquineresistant areas

Biological Target / Mechanism

inhibits protein synthesis

prophylax travel to inhibits parasite hydrolysis of

N. Africa,
Chloroquine

Carribean,
temperate S.
America, most of
Central America,
part of Middle East

tx. of erythrocytic
stage

prevention
OR
treatment

hemoglobin, leading to
accumulation of toxic heme
by-products and lysis of cell
membrane

binds to DNA
fragments parasite RNA

DOC for tx. and

Mefloquine

prevention of
Chloroquineresistant strains

similar to Chloroquine

may be taken by
preggers & kids

Atovaquone and
proguanil
treatment
only

Primaquine

Active against
erythrocytic AND
exoerythrocytic
stages

prevent relapse
tx. of hepatic stages

Side Effects

photosensitivity
GI disturbances
Vaginities
GI upset
Visual disturbances
Headache
CV chances
Ototoxicity
Renal impairment
Skin eruptions

Tx. of erythrocytic

with antacids or
oral iron

Caused by:

Increased
efflux

Decreased
uptake

toxicity

Increased
metabolism

teratogenic

Atovaquone inhibits parasite

mitochondrial transport;
Proguanil metabolizes to a
dihydrofolate reductase
inhibitor, which disrupts
deoxythymidylate synthesis

Headaches
GI disturbances
Mouth ulcers
G6PD-deficient
pts: causes
hemolytic anemia

generation of active oxidation

products
inhibit folate pathway
inhibition of DNA synthesis

Skin rash

Drug
Resistance

not to be taken

Hx. of epilepsy
GI disturbances
or psychiatric dx
Dysphoria, dizziness
Hypersensitivity
CNS signs
Pregnancy
Visual & auditory disturbance may be

(not P. falciparum)
Pyrimethamine

Contrainidcations

21
PyrimethamineSulfadoxine
(Fansidar)

Quinine

stage

used only for

Chloroquine-resistant
and multidrugresistant P.
falciparum

2 drugs inhibit different steps in

folate pathway synergistic
inhibition of DNA synthesis

similar to Chloroquine, but

more toxic & less effective

Anti-Protozoals cont.

Megaloblastic anemia
Severe-fatal cutaneous rxn.
cinchonism
Disturbed vision
Dysrhythmias
Hypotension
Hypoglycemia

wide-spread
resistance d/t
overuse

Hypersensitivity

Drug

Parasite / Disease

Biological Target / Mechanism

Route of
Admin

Side Effects
VERY TOXIC

Melarsopol

African
Trypanosomiasis, with
CNS involvement

Local rxn.s
Fever, encephalopathy
HTN & myocardial damage
Vomiting & abdominal colic

arsenic compound;
binds to sulfhydryl groups on proteins,
inactivating enzymes

IV, d/t rapid decrease in BP:

African
Pentamidine
isethionate

Trypanosomiasis, w/o
CNS involvement
(combo. w/ suramin)

2 line for Leishmania

P. carinii
nd

inhibition of adenosine uptake

IM or IV
DNA binding and topoisomerase inhibition

Breathlessness
Tachycardia
Dizziness
Headache
Vomiting
IM:

Hyper- or hypoglycemia & IDD

Skin rashes
Nephrotoxicity (reversible)
Thrombocytopenia, anemia, thrombophlebitis, neutropenia
Elevated liver enzymes
Immediate

Suramin

African
Trypanosomiasis, w/o
CNS involvement

Nifurtimox

Acute T. cruzi

Benznidazole

2nd line for T. cruzi

infections

Nausea, vomiting
Shock
Loss of consciousness
inhibits parasite energy production

converted to free radicals

free radical formation, like metronidazole

Delayed

Optic atrophy
Adrenal insufficiency
Skin rash
Hemolytic anemia
GI disturbances & weight loss
Peripheral neuropathy
CNS excitability
Suppression of cell-mediated immune rxn.s
similar to metronidazole

22

23
Anti-Protozoals cont.
Drug

Parasite / Disease

Amebiasis (with

Diloxanide
furoate

metronidazole)

Biological Target / Mechanism

luminal amebicide active only against intestinal
form of amoeba

Amebiasis
mixed amebicide active against amebas in both GI
Trichomonas vaginalis lumen and systemic tissues
selective toxicity for anaerobic and microaerophilic
E. histolytica
microorg.s
Giardia
accepts electrons from flavoproteins, creating free
[see also antibiotics]
radicals

Metronidazole

Paromomycin

Amebiasis

Iodoquinol

Amebiasis

luminal amebicide;
an aminoglycoside; binds 30S ribosome & inhibits
protein synthesis

Quinacrine

Giardia

Nebupent

[aerosol form of
Pentamidine isethionate]

Pyrimethaminesulfadoxine
TrimethoprimSulfamethoxazole

intercalates into DNA; flavoenzyme inhibition

Side Effects

Contraindications

pregnancy

well tolerated

headache
nausea
Concomitant CNS dx.
dry mouth and metallic taste
Safe at therapeutic doses in
disulfirum-like rxn.s (interferes pregnancy
with ethanol metabolism)

CNS & peripheral effects

GI upset & diarrhea
Otherwise well tolerated
Headache, dizziness
Vomiting
Exacerbates psoriasis
Yellow skin, black & blue nails
Toxic psychosis at high doses

Toxoplasmosis
[see also malaria]
P. carinii
[see antibiotics]

Anti-Helminthic
Class

Drug

Roundworms
(Nematodes)

Mebendazole

Helminth

Ascaris
Intestinal
capillariasis

Biological Target / Mechanism

bind selectively to worm *-tubulin and

inhibit microtubule polymerization

uncouple oxidative phosphorylation

Route of
Admin.
oral

Side Effects

Contraindications

24

Enterobiasis
Trichuria
Hookworms
GI nematodes, esp.
Albendazole

Pyrantel
Pamoate

Ascaris
Trichuria
Hookworms
Ascaris
Enteribiasis
Ancylostoma
N. americanus
Trichostongylus
2 line for
nd

Piperazine

roundworms &
pinworms

Pregnancy teratogenic &

embryotoxic in animals

selectively active against GI parasites

activates nicotinic receptors and inhibits
cholinesterases

depolarizing neuromuscular blocker

parasite spasm and paralysis
paralysis of parasite skeletal muscle;
parasites expelled alive

oral
(lethal if
given
parenteral)

GI upset
Headache, fever
Rash
dizziness
lethal at high doses
usually well tolerated

Ivermectin

Flatworms
(Cestodes)

Flukes
(Trematodes)

Niclosamide

Praziquantel

Onchocerciasis
Nematodes
Tapeworms
Schistosomiasis
Liver flukes
Other cestodes &
flukes

induces tonic paralysis of musculature

activates invertebrate GABA or glutamategates Cl- channels

Inhibition of oxidative phosphorylation

Stimulation of ATPase
Leads to depletion of ATP
causes increased muscular activity
followed by contraction & spastic paralysis
by increasing Ca2+ permeability

high doses cause tegumental damage which

activates host immune system

fever, headache
rash
muscle, joint pain

Children <5 yrs.

Pregnancy
Meningitis pts.

mild

GI upset
Headache
Muscle, joint pain

Children <4 yrs.

Pregnancy
Ocular cysticercosis