Antibiotics, Antivirals, Antifungals, and Parasite Drugs

Question 1

Penicillin

Answer 1

Penicillin G (IV form), penicillin V (oral). Prototype B-lactam antibiotics.
Mechanism: l. Bind penicillin-binding proteins 2. Block transpeptidase cross-linking of peptidoglycan 3. Activate autolytic enzymes
Use: Mostly used for gram-positive organisms (S. pneumoniae, S.pyogenes, Actinomyces) and syphilis. Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes. Not penicillinase resistant.
Tox: Hypersensitivity reactions, hemolytic anemia.
Resistance: B-lactamases cleave B-lactam ring.

Question 2

Oxacillin, nafcillin, dicloxacillin (penicillinase-resistant penicillin)

Answer 2

MOA: Same as penicillin. Narrow spectrum; penicillinase resistant because of bulkier R group.
USE: S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).
TOX: Hypersensitivity reactions; methicillin­
interstitial nephritis.
“use naf for staph”

Question 3

Ampicillin, amoxicillin (aminopenicillins)

Answer 3

MOA: Same as penicillin. Wider spectrum;
penicillinase sensitive. Also combine with
clavulanic acid to protect against B-lactamase.
AmOxicillin has greater Oral bioavailability than ampicillin.
AMinoPenicillins are AMPed-up penicillin
USE: Extended-spectrum penicillin- Haemophilus infiuenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci.
coverage: ampicillin/amoxicillin HELPSS kill enterococci
TOX: Hypersensitivity reactions; ampicillin rash; pseudomembranous colitis.
RESISTANCE: B-lactamases cleave B-lactam ring.

Question 4

Ticarcillin, piperacillin (antipseudomonals)

Answer 4

MOA: Same as penicillin. Extended spectrum.
USE: Pseudomonas spp. and gram-negative rods; susceptible to penicillinase; use with clavulanic acid.
TOX: Hypersensitivity reactions.

Question 5

B-lactamase inhibitors

Answer 5

CAST
Include Clavulanic Acid, Sulbactam, Tazobactam. Often added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase (penicillinase).

Question 6

Cephalosporins

Answer 6

MOA: �-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
USE: lst generation (cefazolin, cephalexin)-gram­ positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae.
2nd generation (cefoxitin, cefaclor, cefuroxime) -gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
3rd generation (ceftriaxone, cefotaxime, ceftazidime)-serious gram-negative infections resistant to other B-lactams.
4th generation (cefepime) -i activity against Pseudomonas and gram-positive organisms.
lst generation-PEcK.
2nd generation-HEN PEcKS.
Ceftriaxone-meningitis and gonorrhea. Ceftazidime-Pseudomonas.
Organisms not covered by cephalosporins
are LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci.
TOX: Hypersensitivity reactions, vitamin K deficiency.
Cross-hypersensitivity with penicillins occurs in 5-10% ofpatients. i nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (in cephalosporins with a methylthiotetrazole group, e.g., cefamandole) .

Question 7

Aztreonam

Answer 7

MOA: A monobactam resistant to �-lactamases. Inhibits cell wall synthesis (binds to PBP3). Synergistic with aminoglycosides. No cross-allergenicity with penicillins.
USE: Gram-negative rods only-No activity against gram-positives or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.
TOX: Usually nontoxic; occasional GI upset

Question 8

Imipenem/cilastatin, meropenem

Answer 8

MOA: Imipenem is a broad-spectrum, B-lactamase­ resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to .l. inactivation of drug in renal tubules.
USE: Gram-positive cocci, gram-negative rods, and anaerobes. Wide spectrum, but the significant side effects limit use to life-threatening infections, or after other drugs have failed. Meropenem, however, has a reduced risk of seizures and is stable to dihydropeptidase I.
With imipenem, “the kill is LASTIN’ with
ciLASTATIN.”
TOX: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
Newer carbapenems include ertapenem and dirpenem

Question 9

Vancomycin

Answer 9

MOA: Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors.
Bactericidal.
USE: Gram positive only-serious, multidrug-resistant organisms, including S. aureus, enterococci and Clostridium difficile (oral dose for pseudomembranous colitis).
TOX: Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing-“red man syndrome” (can largely prevent by pretreatment with antihistamines and slow infusion rate) . Well tolerated in general­ does NOT have many problems.
RESISTANCE: Occurs with amino acid change of D-ala D-ala to D-ala D-lac. “Pay back 2 0-alas (dollars) for vandalizing.”

Question 10

Aminoglycosides

Answer 10

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin.
“Mean” GNATS canNOT kill anaerobes. A “initiates” the alphabet.
MOA: Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA.
Require 02 for uptake; therefore ineffective against anaerobes.
USE: Severe gram-negative rod infections. Synergistic with B-lactam antibiotics.
Neomycin for bowel surgery.
TOX: N ephrotoxicity (especially when used with cephalosporins), Ototoxicity (especially when used with loop diuretics). Teratogen.
RESISTANCE: Transferase enzymes that inactivate the drug by acetylation, phosphorylation, or adenylation.

Question 11

Tetracyclines

Answer 11

Tetracycline, doxycycline, demeclocycline,
minocycline.
demeclocycline: ADH antagonist; acts as a diurectic in SIADH. Rarely used as an antibiotic
MOA: Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA; limited CNS penetration. Doxycycl ine is fecally eliminated and can be used in patients with renal failure. Must NOT take with milk, antacids, or iron­ containing preparations because divalent cations inhibit its absorption in the gut.
USE: Borrelia burgdorferi, M. pneumoniae. Drug’s ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia.
TOX: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
Contraindicated in pregnancy.
RESISTANCE: drop uptake into cells or up efflux out of cell by plasmid-encoded transport pumps.

Question 12

Macrolides

Answer 12

Erythromycin, azithromycin, clarithromycin.
MOA: Inhibit protein synthesis by blocking translocation (“macroSiides”); bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.
USE: Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), URis, STDs, gram-positive cocci (streptococcal infections in patients allergic to penicillin), and Neisseria.
TOX: Prolonged QT interval (especially erythromycin), GI discomfort (most common cause of noncompliance), acute cholestatic hepatitis, eosinophilia, skin rashes. Increases serum concentration of theophyllines, oral anticoagulants.
RESISTANCE: Methylation of 23S rRNA binding site.

Question 13

Chloramphenicol

Answer 13

MOA: Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic.
USE: Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae). Conservative use owing to toxicities but often still used in developing countries clue to low cost.
TOX: Anemia (close dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase).
RESISTANCE: Plasmid-encoded acetyltransferase that inactivates drug.

Question 14

Clindamycin

Answer 14

MOA: Blocks peptide bond formation at 50S ribosomal subunit. Bacteriostatic.
USE: Anaerobic infections (e.g., Bacteroides fragilis, Clostridium perfringens) in aspiration pneumonia or lung abscesses.
TOX: Pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea.
treats anaerobes above the diaphragm vs metronidazole (anaerobe infections below diaphragm)

Question 15

Sulfonamides

Answer 15

Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine.
MOA: PABA antimetabolites inhibit dihydropteroate synthetase. Bacteriostatic.
USE: Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.
TOX: Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis),
photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g., warfarin).
RESISTANCE: Altered enzyme (bacterial dihydropteroate synthetase), drop uptake, or up PABA synthesis.

Question 16

Trimethoprim

Answer 16

MOA: Inhibits bacterial dihydrofolate reductase.
Bacteriostatic.
USE: Used in combination with sulfonamides (trimethoprim-sulfamethoxazole [TMP­ SMX]), causing sequential block offolate synthesis. Combination used for UTis, Shigella, Salmonella, Pneumocystis iiroveci pneumonia.
TOX: Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid [leucovorin rescue] .)
Abbreviated TMP. TMP: Treats Marrow Poorly

Question 17

Fluoroquinolones

Answer 17

Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, enoxacin (fluoroquinolones), nalidixic acid (a quinolone).
MOA: InhibitDNAgyrase (topoisomerase II).
Bactericidal. Must not be taken with antacids.
USE: Gram-negative rods of urinary and Gl tracts (including Pseudomonas), Neisseria, some gram-positive organisms.
TOX: Gl upset, superinfections, skin rashes, headache, dizziness. Contraindicated in pregnant women and in children because animal studies show damage to cartilage. Tendonitis and tendon rupture in adults; leg cramps and myalgias in kids.
fluoroquinolones hurt attachments to your bones
RESISTANCE: Chromosome-encoded mutation in DNA gyrase.

Question 18

Metronidazole

Answer 18

MOA: Forms free radical toxic metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.
USE: Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. diffi.cile) . Used with bismuth and amoxicillin (or tetracycline) for “triple therapy” against H. Pylori.
GET GAP on the metro with metronidazole! Treats anaerobic infections below the diaphragm vs clindamycin (anaerobic infections above diaphragm)
TOX: Disulfiram-like reaction with alcohol; headache, metallic taste.

Question 19

Antimycobacterials

Answer 19

M. TB: prophylaxis with INH. Tx: rifampin, isoniazid, pyrazinamide, ethambutol (RIPE for tx)
MAIC: prophylaxis with azithromycin. Tx: azithromycin, rifampin, ethambutol, streptomycin
M leprae: no prophylaxis. Tx: long term tx with dapsone and rifampin for tuberculoid form. add clofazimine for lepromatous form

Question 20

Isoniazid

Answer 20

MOA: drop !. synthesis of mycolic acids. Bacteria catalase­ peroxidase (KatG) needed to convert INH to active metabolite.
USE: Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB.
Different INH half lives in fast v slow acetylators
TOX: Neurotoxicity, hepatotoxicity, lupus. Pyridoxine (vitamin B6) can prevent neurotoxicity, lupus.
INH injured neurons and hepatocytes

Question 21

Rifampin

Answer 21

MOA: Inhibits DNA-dependent RNA polymerase.
USE: Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus influenzae type B.
TOX: Minor hepatotoxicity and drug interactions (i P-450); orange body fluids (nonhazardous side effect).
4 Rs: RNA polymerase inhibitor, Revs up P450, Red/orange body fluids, rapid resistance if used alone

Question 22

Pyrazinamide

Answer 22

MOA: Inhibits mycolic acid production by blocking mycobacterial fatty acid synthase I; effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found.
USE: Mycobacterium tuberculosis.
TOX: Hyperuricemia, hepatotoxicity.

Question 23

Ethambutol

Answer 23

MOA: drop carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
USE: Mycobacterium tuberculosis.
TOX: Optic neuropathy (red-green color blindness).

Question 24

Prophylaxis Drugs

Answer 24

meningococcal infection: ciprofloxacin (drug of choice), rifampin for children
gonorrhea: ceftriaxone
syphilis: benzathine penicillin G
history or recurrent UTIs: TMP-SMX
endocarditis with surgical or dental procedures: Penicillins
prophylaxis of strep pharyngitis in child with prior rheumatic fever: oral penicillin
pregnant woman carrying group B strep: ampicillin
prevention of psotsurgical infection due to S aureus: cefazolin
prevention of gonococcal or chlamydial conjunctivitis in newborn: erythromycin ointment
CD4 <50: azithromycin for MAC
MRSA tx: vancomycin
VRE: linezolid and streptogramins (quinupristin/dalfopristin)

Question 25

Amphotericin B

Answer 25

MOA: Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes.
Amphotericin “tears” holes in the fungal membrane by forming pores
USE: Serious, systemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross blood-brain barrier. Supplement K and Mg because ofaltered renal tubule permeability.
TOX: Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity.

Question 26

Nystatin

Answer 26

MOA: Same as amphotericin B. Topical form because too toxic for systemic use.
USE: “Swish and swallow” for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.

Question 27

Azoles

Answer 27

Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole.
MOA: Inhibit fungal sterol (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to ergosterol.
USE: Local and less serious Systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients (because it can cross blood-brain barrier) and candidal infections ofall types. Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans; hypercortisolism. Clotrimazole and miconazole for topical fungal infections.
TOX: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450),

Question 28

Flucytosine

Answer 28

MOA: Inhibits DNA synthesis by conversion to 5-fluorouracil by cytosine deaminase.
USE: Used in systemic fungal infections (e.g., Cryptococcus) in combination with amphotericin B.
TOX: bone marrow suppression.

Question 29

Caspofungin, micafungin

Answer 29

MOA: Inhibits cell wall synthesis by inhibiting synthesis of B-glucan.
USE: Invasive aspergillosis, Candida.
TOX: GI upset, flushing (by histamine release)

Question 30

Terbinafine

Answer 30

MOA: inhibits the fungal enzyme squalene epoxidase
USE: Used to treat dermatophytoses (especially onychomycosis - fungal infection of finger or toe nails).
TOX: Abnormal LFT’s, visual disturbances.

Question 31

Griseofulvin

Answer 31

MOA: Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (e.g.,
nails).
USE: O r a l t r e a t m e n t o f s u p e r fi c i a l i n fe c t i o n s ; i n h i b i t s g r o w t h o f d e r m a t o p h y t e s ( t i n e a , r i n g w o r m ) .
TOX: Teratogenic, carcinogenic, confusion, headaches, i P-450 and warfarin metabolism.

Question 32

Antiprotozoan

Answer 32

Pyrimethamine (toxoplasmosis or Plasmodium falciparum), suramin and melarsoprol (Trypanosoma brucei), nifurtimox (T cruzi), sodium stibogluconate (leishmaniasis).

Question 33

Chloroquine

Answer 33

MOA: Blocks plasmodium heme polymerase.
USE: tx of plasmodial species other than P. falciparum 9frequency of resistance in too high). Resistance due to membrane pump that drops intracellular concentration of drug. Treat P. falciparum with artemether/lumifantrine or atovaquone/proguanil. For life-threatening malaria, use quinidine in US (quinine elsewhere) or artisunate.
TOX: Retinopathy, G6PD hemolysis.

Question 34

Antihelminthic

Answer 34

Mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel; immobilize helminths. Use praziquantel against flukes (trematodes) such as schistosoma

Question 35

Zanamivir, oseltamivir

Answer 35

MOA: Inhibit influenza neuraminidase, decreasing the release of progeny virus.
USE: Both influenza A and B.

Question 36

Ribavirin

Answer 36

MOA: Inhibits synthesis ofguanine nucleotides by competitively inhibiting IMP dehydrogenase.
USE: RSV, chronic hepatitis C.
TOX: Hemolytic anemia. Severe teratogen.

Question 37

Acyclovir

Answer 37

MOA: Monophosphorylated by HSV/VZV thymidine kinase. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination.
USE: HSV, VZV, EBV. Used for HSV-inducecl mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromisecl patients. No effect on latent forms of HSV and VZV. Valacyclovir, a prodrug ofacyclovir, has better oral bioavailability.
For herpes zoster, use a related agent, famciclovir.
TOX: Few serious adverse effects.
RESISTANCE: Lack of viral thymidine kinase.

Question 38

Amantadine

Answer 38

MOA: Blocks viral penetration/uncoating (M2 protein) . Also causes the release of dopamine from intact nerve terminals.
USE: Prophylaxis and treatment for influenza A only;
Parkinson’s disease.
TOX: Ataxia, dizziness, slurred speech.
RESISTANCE: Mutated MZ protein. 90% of all influenza A strains are resistant to amantadine, so not used.
“A Man 2 dine” takes offhis coat. Amantadine blocks influenza A and causes
problems with the cerebellA. Rimantidine is a derivative with fewer CNS side
effects. Does not cross the blood-brain barrier.

Question 39

Ganciclovir

Answer 39

MOA: 5’-monophosphate formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase.
USE: CMV, especially in immunocompromisecl patients. Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability.
TOX: Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovi r.
RESISTANCE: Mutated CMV DNA polymerase or lack of viral kinase.

Question 40

Foscarnet

Answer 40

MOA: Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme.
Does not require activation by viral kinase.
USE: CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir­ resistant HSV.
TOX: Nephrotoxicity.
RESISTANCE: Mutated DNA polymerase.

Question 41

Cidofovir

Answer 41

MOA: Preferentially inhibits viral DNA polymerase. Does NOT require phosphorylation by viral kinase.
USE: CMV retinitis in immunocompromised patients; acyclovir-resistant HSV. Long half-life.
TOX: Nephrotoxicity (coaclminister with probenecid).

Question 42

Protease Inhibitors

Answer 42

Lopinavir Atazanavir Darunavir Fosamprenavir Saquinavir Ritonavir
MOA: Assembly ofvirions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.
Ritonavir can “boost” other drug concentrations by inhibiting cytochrome P-450.
All protease inhibitors end in -navir. NAVIR (never) TEASE a proTEASE.
TOX: Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy.

Question 43

NRTIs

Answer 43

Tenofovir (TDF) Emtricitabine (FTC) Abacavir (ABC) Lamivudine (3TC) Zidovudine (ZDV, formerly AZT) Didanosine (deli) Staduvine (d4T)
MOA: Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’-0H group), Must be phosphorylated by thymidine kinase to be active.
ZDV is used for general prophylaxis
and during pregnancy to reduce risk of
fetal transmission.
Have you dined (vudine) with my nuclear (nucleosides) family?
TOX: Bone marrow suppression (can
be reversed with G-CSF and erythropoietin), peripheral neuropathy, lactic acidosis (nucleosides), rash (non­ nucleosides), megaloblastic anemia (ZDV).

Question 44

NNRTIs

Answer 44

NeVIRapine EfaVIRenz DelaVIRdine
MOA: Bind to reverse transcriptase at site different from NRTis. Do not require phosphorylation to be active or compete with nucleotides.
TOX: Same as NRTIs

Question 45

Integrace inhibitors

Answer 45

Raltegravir
MOA: Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase.
TOX: hypercholesterolemia

Question 46

Interferons

Answer 46

MOA: Glycoproteins synthesized by virus-infected cells block replication ofboth RNA and DNA viruses.
USE: IFN-a-chronic hepatitis B and C, Kaposi’s sarcoma. IFN-B-MS. IFN-y-NADPH oxidase deficiency
TOX: Neutropenia.

Question 47

Antibiotics in pregnancy

Answer 47

Clarithromycin-embryotoxic. 
Sulfonamides-kernicterus. 
Aminoglycosides-ototoxicity. 
Fluoroquinolones-cartilage damage. 
Tetracyclines-discolored teeth, inhibition of
bone growth.
Ribavirin (antiviral) -teratogenic. 
Griseofulvin (antifungal) -teratogenic. 
Chloramphenicol -"gray baby."