Pulm drugs

Question 1

Gentamycin

Answer 1

Aminoglycoside. Bactericidal; irreversible inhibition of initiation complex thru binding of the 30S subunit. Ineffective against anaerobes. Used against severe gram negative rod infections. Synergistic with beta lactams. AEs include nephrotoxicity, neuromuscular blockade, ototoxicity, teratogenic.

Question 2

Tenofovir

Answer 2

HIV anti-viral. Competitively inhibits nucleotide binding to reverse transcriptase; chain terminator (lacks 3’-OH group)/ AEs: bone marrow suppression, peripheral neuropathy.

Question 3

Penicillin G

Answer 3

Beta lactam prototype. D-Ala-D-Ala structure analog. Binds penicillin binding protein (PBP) and blocks transpeptidase cross-linking of peptidoglycan in cell wall (last step of cell wall synthesis). Used primarily for gram + organisms (S. pneumo, S. progenies, actinomyces), gram neg cocci (N meningitidis), and spirochetes (T pallidum). Bacteria that create beta lactmases = resistant.

Question 4

Amoxicillin

Answer 4

Penicillinase-sensitive penicillin. D-Ala-D-Ala structure analog, block transpeptidase cross linking/last step of cell wall synthesis. Effective against extended spectrum including H influenzae, H pylori, E coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci. MOR = penicilinase (beta lactamase) that cleaves the beta lactam ring.

Question 5

Piperacillin

Answer 5

Antipseduomonal penicillin. D-Ala-D-Ala analog. Blocks transpeptidase cross-linking of petidoglycan in cell wall. Used a/g pseudomonas and gram neg rods; susceptible to penicillinases; often in combo with tazobactam (beta lactamase inhibitor)

Question 6

Ceftriaxone

Answer 6

3rd generation cephalosporin. beta lactam drug that inhibits cell wall synthesis but less susceptible to penicillinases. Used for serious gram negative infections resistant to other beta lactams. Effective for meningitis, gonorrhea, disseminated Lyme disease.

Question 7

Cefepime

Answer 7

4th generation cephalosporin. beta lactam drug that inhibits cell wall synthesis but less susceptible to penicillinases. Effective against gram neg organisms w/ increased activity against gram positive organisms and pseudomonas.

Question 8

Imipenam

Answer 8

Carbapenam. Differs from penicillin by substitution of sulfur w/ a carbon and addition of a double bond to 5-member ring. Stable to most beta lactamases. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of the drug in the renal tubules. Effective against gram + cocci, gram - rods, and anaerobes. wide spectrum. AEs include GI distress, rash, CNS toxicity (seizures) at high plasma levels.

Question 9

Vancomycin

Answer 9

Cell wall inhibitor. Inhibits cell wall peptidoglycan formation by binding D-Ala-D-ala portion of cell wall precursors. Not susceptible to beta lactamases. GRAM + bugs only. Effective against serious multi drug resistant organisms including MRSA, S. epidermis, sensitive Enterococcus species, and C. diff (oral). AEs: Nephrotoxicity, ototoxicity, thrombophlebitis, red man syndrome.

Mech of resistance: AA modification of D-ala-D-ala to D-ala-D-lac.

Question 10

Daptomycin

Answer 10

Lipopeptide that disrupts the cell membrane of gram + cocci.

Used for staph aureus skin infections (esp MRSA), bacteremia, endocarditis, VRE.

AEs = myopathy, rhabdomyolysis

Question 11

Ciprofloxacin

Answer 11

Fluoroquinolone. Inhibits prokaryotic topoisomerase II (DNA gyrase) & topoisomerase IV. Bactericidal. Can’t take with antacids. Used a/g gram - rods of urinary & GI tracts INCLUDING pseudomonas, Neisseria, some gram + organisms. Prolonged QT interval, tendonitis/tendon rupture = AEs.

Question 12

Levofloxacin

Answer 12

Fluoroquinolone. Inhibits prokaryotic topoisomerase II (DNA gyrase) & topoisomerase IV. Bactericidal. Can’t take with antacids. Used a/g gram - rods of urinary tract; GI tracts INCLUDING pseudomonas, Neisseria, some gram + organisms. Prolonged QT interval, tendonitis/tendon rupture = AEs.

Question 13

Erythromycin

Answer 13

Macrolide. Inhibits protein synthesis by blocking translocation- bind to 23S rRNA of 50S subunit. Bacteriostatic. Used for atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram + cocci (strep infections if allergic to penicillin) and pertussis.

AEs: GI motility, Arrhythmia due to prolonged QT intervals, acute cholestatic hepatitis, rash, esosinophilia. Increases concentration in serum of anticoagulants (oral). Inhibits cytochrome P450.

Question 14

Azithromycin

Answer 14

Better macrolide. Inhibits protein synthesis by blocking translocation- bind to 23S rRNA of 50S subunit. Bacteriostatic. Used for atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STIs (Chlamydia), gram + cocci (strep infections if allergic to penicillin) and pertussis. No P450 inhibition.

Question 15

Linezolid

Answer 15

Oxazolindinone. Inhibits protein synthesis by binding to 50S subunit and preventing initiation complex formation. Effective against gram + species including MRSA and VRE. AEs include bone marrow suppression, peripheral neuropathy, serotonin syndrome.

Question 16

Doxycycline

Answer 16

Tetracycline. Bacteriostatic. Binds 30S subunit and prevents attachment of aminoacyl-tRNA. Limited CNS penetration. Fecally eliminated- safe for kidney failure. Avoid with milk/antacids/iron containing preparations (inhibit gut absorption). Used against M. pneumoniae & borrelia bugdorferi, Chlamydia and Rickettsia.

AEs: GI distress, teeth discoloration (children), inhibition of bone growth (children), photosensitivity, contraindicated in pregnancy.

Question 17

Isoniazid

Answer 17

Anti-mycobacterial. Decreases synthesis of mycolic acids. Bacterial catalase peroxidase (encoded by KatG) necessary to convert INH to active metabolite. Used for TB. Only agent used for solo prophylaxis against TB or mono therapy for latent TB.

AEs: hepatotoxicity, P450 inhibition, drug-induced SLE, B6 deficiency. Administered w/ B6. Resistance mechanism = mutations leading to under expression of KatG.

Question 18

Rifampin

Answer 18

Rifamycin. Antimycobacterial. Inhibits DNA-dependent RNA polymerase. Used for TB.

AEs: minor hepatotoxicity; drug interactions (induces P450). Orange/red body fluids/urine.
[Can use Ribabutin instead for less drug-drug interactions]

Mech of resistance: mutations reduce drug binding to RNA polymerase. Monotherapy rapidly leads to resistance.

Question 19

Pyrazinamide

Answer 19

Anti-mycobacterial. MOA unknown. Prodrug converted to active compound pyrazonic acid. Works best in acidic pH (aka phagolysosomes of host). Used for TB.

AEs= hyperuricemia (sometimes progressing to gout), hepatotoxicity

Question 20

Ethambutol

Answer 20

Anti-mycobacterial. Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase. Used for TB.

AEs: OPTIC NEUROPATHY.

Question 21

Moxifloxacin

Answer 21

Fluoroquinolone. Inhibits prokaryotic topoisomerase II (DNA gyrase) & topoisomerase IV. Bactericidal. Can’t take with antacids. Used a/g gram - rods of urinary & GI tracts INCLUDING pseudomonas, Neisseria, some gram + organisms. Prolonged QT interval, tendonitis/tendon rupture = AEs.

Question 22

Oseltamivir

Answer 22

Antiviral. Neuraminidase inhibitor. Decreases release of progeny virus. Used to treat/prevent influenza A and B.

Question 23

Ribavirin

Answer 23

Antiviral. Guanine nucleotide synthesis? For RSV, HCV. Usually only in really bad infection or immunocompromised because really bad side effects.

Question 24

Palivizumab

Answer 24

Passive immunization (prophylaxis) for RSV in high-risk infants (such a premature infants or those with chronic lung disease)

Question 25

Trimethoprim-Sulfamethoxazol

Answer 25

Aka Bactrim. Antibiotic. SMX is a sulfonamide- inhibits dihydropteroate synthase/ inhibits folate synthesis. Used for pneumocystis jirovecii pneumonia treatment and prophylaxis.

AEs: megaloblastic anemia, leukopenia, granulocytopenia

Question 26

Capsofungin

Answer 26

Echinocandin. Antifungal. Inhibits cell wall synthesis by inhibiting synthesis of beta glucan. Used for invasive aspergillosis, **candida, pneumocystis. Fungicidal in YEAST, fungistatic in filamentous fungi. Don’t penetrate CNS or eye. Concentration-dependent. IV only. Relatively low toxicity.

AEs: GI upset, flushing

Question 27

Amphotericin B

Answer 27

Polyene antimycotic. IV only. Fungicidal. Binds ergosterol and forms membrane pores that allow electrolyte leakage. Used for serious, systemic mycoses- broader spectrum than most antifungals. Cryptococcus, blastomyces, coccidioides, histoplasma, candida. Can use intrathecally for fungal meningitis.

AEs: fever, chills, hypotension, NEPHROTOXICITY, arrhythmias, anemia, IV phlebitis, SEVERE INFUSION REACTIONS (can premedicate to prevent)

Liposomal Amphotericin B (AmBisome) is the best tolerated

Question 28

Nystatin

Answer 28

Antifungal. Same MOA as amphotericin B. Oral/Topical only. Used for oral candidiasis, topical for diaper rash or vaginal candidiasis.

No systemic absorption

Question 29

Fluconazole

Answer 29

Antifungal, azole. Inhibit ergosterol synthesis by inhibiting cytochrome P450 enzyme that converts lanosterol to ergosterol. IV or PO. Good CNS penetration. Used for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types.

Treatment of choice for “the 3 C’s”: candida, crypto, coccy.

AEs: liver dysfunction (inhibits P450) but it’s the least potent azole P450 inhibitor.

Question 30

Itraconazole

Answer 30

Antifungal, azole. Inhibit ergosterol synthesis by inhibiting cytochrome P450 enzyme that converts lanosterol to ergosterol. Must take pills with acids (like orange juice) or liquid on empty stomach. Poor CNS/eye penetration. Used for blastomyces, coccidiodes, histoplasma, spore, onchycho (used for the dimorphics)

AEs: liver dysfunction (inhibits P450)

Question 31

Voriconazole

Answer 31

Antifungal, azole. Inhibit ergosterol synthesis by inhibiting cytochrome P450 enzyme that converts lanosterol to ergosterol. Treatment of choice for aspergillosis.

AEs: liver dysfunction (inhibits P450). Also causes visual symptoms and renal toxicity.

Question 32

Terbinafine

Answer 32

Allyamine anti fungal. Inhibits the fungal enzyme squalene 2,3 epoxidase. Used for dermatophytoses (finger/toe fungus particularly). Don’t drink alcohol with this; it compounds liver toxicity.

AEs: GI upset, HA, hepatotoxicity, taste disturbance

Question 33

Flucytosine

Answer 33

Antifungal. Inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase (not a human enzyme). Used for systemic fungal infections (particularly meningitis caused by cryptococcus) in combo with amphotericin B.

AEs: bone marrow suppression. Excreted by kidneys, must keep an eye on the kidneys.