PHARMA - Introduction to Chemotherapy of Infectious Diseases

Penicillins

Inhibit transpeptidase → prevent cross-linking of peptidoglycan in bacterial cell walls.

Bactericidal

Are penicillins bactericidal or bacteriostatic?

Gram-positive organisms

Which bacteria are most susceptible to penicillins?

B-lactams

Cephalosporins belong to which drug class?

Based on spectrum of activity

How are cephalosporins classified?

5th generation (Ceftaroline)

Which cephalosporin generation is effective against MRSA?

Carbapenems

Broad-spectrum β-lactams resistant to most β-lactamases.

Cilastatin (prevents renal degradation)

What is imipenem often combined with and why?

Gram-negative infections

What is the main clinical use of aztreonam (monobactam)?

Vancomycin

Binds D-Ala-D-Ala → inhibits cell wall synthesis.

MRSA, enterococci, and C. difficle

Against which bacteria is vancomycin especially important?

Red man syndrome, nephrotoxicity, ototoxicity

What toxicity is vancomycin known for?

Topically

How is bacitracin typically administered?

Resistant tuberculosis

What is cycloserine mainly used for?

Isoniazid (INH)

Inhibits mycolic acid synthesis in mycobacterial cell walls.

Vitamin B6 (pyridoxine) deficiency

Which vitamin deficiency can isoniazid cause?

Ethambutol

Inhibits arabinosyltransferase → blocks mycobacterial cell wall synthesis.

Optic neuritis (red-green color blindness)

What unique side effect is caused by ethambutol?

Aminoglycosides

Irreversibly bind 30S → inhibit initiation complex & cause misreading of mRNA.

Bactericidal

Are Aminoglycosides Bactericidal or bacteriostatic?

Aerobic gram-negative bacilli

Against which organisms are aminoglycosides effective?

Require O2 for uptake

Why are aminoglycosides ineffective against anaerobes?

Nephrotoxicity, ototoxicity, neuromuscular blockade

Major toxicities of aminoglycosides?

Streptomycin

Which aminoglycoside is used for TB?

Tetracyclines

Reversibly bind 30S → block attachment of aminoacyl-tRNA.

Bacteriostatic

Are tetracyclines Bacteriostatic or bactericidal?

Rickettsia, Chlamydia, Mycoplasma, Borrellia, acne

What are tetracyclines used for?

Calcium, Magnesium, Iron inhibit absorption

Why shouldn’t tetracyclines be taken with milk or antacids?

GI upset, photosensitivity, teeth discoloration, bone growth inhibition

Major side effects of tetracyclines?

Doxycycline

Which tetracycline is safe in renal failure?

Chloramphenicol

Inhibits peptidyl transferase activity of 50S ribosome.

Bacteriostatic

Are chloramphenicol Bacteriostatic or bactericidal?

Aplastic anema, gray baby syndrome

Main toxicities of chloramphenicol?

Macrolides

Bind 50S → block translocation.

Bacteriostatic

Are macrolides Bacteriostatic or bactericidal?

Atypical pneumonia, pertussis, respiratory infections

Common uses of macrolides?

GI upset, cholestatic hepatitis, prolonged QT interval

Major toxicities of macrolides?

Clindamycin

Binds 50S → inhibits peptide bond formation.

Anaerobic infections

What type of infections is clindamycin used for?

Pseudomembranous colitis

Major adverse effect of clindamycin?

Linezolid

Binds 50S → prevents initiation complex formation.

MRSA, VRE

What infections is linezolid used for?

Bone marrow suppression, serotonin syndrome, peripheral neuropathy

Major side effects of linezolid?

Streptogramins

Bind 50S → inhibit protein elongation.

VRE

What are streptogramins used for?

Rifampin

Inhibits bacterial DNA-dependent RNA polymerase.

Bactericidal

Is rifampin bacteriostatic or bactericidal?

TB, leprosy, prophylaxis for meningococcal & H. influenzae

Clinical uses of rifampin?

Orange-red discoloration of body fluids

What is the main adverse effect of rifampin?

Rifabutin

Which rifamycin is safer in HIV patients due to less CYP450 induction?

Fluoroquinolones

Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV.

Bactericidal

Are fluoroquinolones bacteriostatic or bactericidal?

Gram-negative bacili

Spectrum of activity for ciprofloxacin?

Respiratory pathogens

Spectrum of activity for levofloxacin/moxifloxacin?

Tendon rupture, QT prolongation, GI upset, contraindicated in pregnancy & children

Major adverse effects of fluoroquinolones?

Metronidazole

Forms toxic free radicals → DNA damage.

Bactericidal

Is metronidazole bacteriostatic or bactericidal?

Anaerobes, protozoa

What infections is metronidazole used for?

GET GAP

Clinical mnemonic for metronidazole?

Disulfiram-like reaction

Adverse effect of metronidazole with alcohol?

Polymyxins

Bind phospholipids of Gram-negative bacterial membranes → disrupt membrane integrity.

Bactericidal

Are polymyxins bacteriostatic or bactericidal?

Gram-negative infections

What are polymyxins used for?

Nephrotoxicitiy and neurotoxicity

Why are polymyxins not commonly used systemically?

Daptomycin

Inserts into Gram-positive bacterial membranes → depolarization → cell death.

MRSA, VRE

Clinical use of daptomycin?

Myopathy, elevated CPK

Main side effect of daptomycin?

Amphotericin B

Binds ergosterol in fungal membranes → forms pores → leakage of contents.

Severe systemic mycoses

Clinical use of amphotericin B?

Nephrotoxicity, fever/chils, hypokalemia, hypotension

Main toxicities of amphotericin B?

Nystatin

Same as amphotericin B → binds ergosterol, forms pores.

Topical or oral

How is nystatin administered?

Candida infections

Clinical use of nystatin?

Azoles

Inhibit fungal cytochrome P450 → block ergosterol synthesis.

Cryptococcal meningitis, candidiasis

Clinical use of fluconazole?

Histoplasma, Blastomyces, Sporothrix

Clinical use of itraconazole?

Hepatotoxicity, gynecomastia

Adverse effects of azoles?

Telavancin

Inhibits cell wall synthesis + disrupts cell membrane potential.

MRSA, complicated skin infections

Clinical use of telavancin?

Sulfonamides

Inhibit dihydropteroate synthase → block folic acid synthesis.

Bacteriostatic

Are sulfonamides bacteriostatic or bactericidal?

Broad spectrum

Spectrum of sulfonamides?

Hypersensitivity, hemolysis in G6PD deficiency, kernicterus, nephrotoxicity

Main adverse effects of sulfonamides?

Toxoplasmosis

Clinical uses of sulfadiazine + pyrimethamine?

Trimethoprim

Inhibits bacterial dihydrofolate reductase.

Bacteriostatic

Are trimethoprim Bacteriostatic or bactericidal?

UTIs, Shigella, Salmonella, Pneumocystis jirovecii prophylaxis

Clinical uses of trimethoprim?

Megaloblastic anemia, leukopenia, granulocytopenia

Adverse effects of trimethoprim?

Supplement with folic acid

How can TMP side effects be prevented?

Sequential blockade of folate synthesis (bactericidal synergy)

What is the advantage of TMP-SMX combination?

UTIs, Pneumocystis jirovecii pneumonia, MRSA, Shigella, Salmonella.

Clinical uses of TMP-SMX?

Dapsone

Inhibits dihydropteroate synthase (similar to sulfonamides).

Leprosy, Pneumocystis jirovecii prophylaxis

Clinical uses of dapsone?

Hemolysis in G6PD deficiency, methemoglobinemia

Adverse effects of dapsone?