PMCOL 233 FINAL

almost done

gram negative bacteria

two membranes with cell wall within

gram positive bacteria

thick cell wall no outer membrane

two types of antibiotics that target folate synthesis

sulfonamides, folic acid antagonists

sulfonamides examples

sulfanilamide, sulfamethoxazole, sulfasalazine, sulfadiazine, sulfadoxine

sulfonamide mechanism

PABA analogs to inhibit dihydropteroate synthetase

sulfonamide PK

metabolized by liver

sulfonamide adverse effects

hepatitis, hypersensitivity reactions (steven’s johnsons), bone marrow depression, acute renal failure, cyanosis, nausea, vomiting, headache, depression

folic acid antagonists examples

trimethoprim, pyrimethamine

folic acid antagonist examples

resemble pteridine moiety thereby inhibiting bacterial dihydrofolate reductase (combined with sulfonamide)

folic acid antagonist adverse effects

folate deficiency, megaloblastic anemia, nausea, vomiting, dyscrasia, rashes

B-lactam antibiotics

target peptidoglycan synthesis

B- lactam mechanism

irreversible inhibitor of enzymes that develop peptidoglycan

B-lactamase

B lactam resistance

B- lactam antibiotics examples

penicillins, cephalosporins, carbapenems, monobactams

penicillins

different spectrums of action

penicillin G

poor oral availability - sensitive - prototype

penicillin V

better oral availability - sensitive - prototype

methicilin

poor oral availability - resistant - narrow spectrum

oxacillin, cloxacillin, dicloxacillin

good oral availability - resistant - narrow spetrum

ampicillin

good oral availability - sensitive - broad spectrum

amoxicillin

better oral availability - sensitive - broad spectrum

carbenicillin

poor oral availability - sensitive - extended spectrum

B lactamase inhibitors examples

clavulanic acid , sulbactam

penicillins PK

eliminated via renal tubular secretion

penicillins adverse effects

hypersensitivity, skin rashes, fever, anaphylaxis, GI distburances, proconvulsant effect

cephalosporins

b lactam antibiotics

cephalosporins mehcanism

irreversibl einhibition of penicillin binding proteins

cephalosporin adverse effects

hypersensitivity, nephrotoxicity, drug induced alcohol intolerance, bone marrow suppression, diarrhea

carbapenems

B lactam antibiotics

carbapenems examples

imipenem, meropenem, ertapenem

cephalosporins examples

cephalexin, cefazolin, cefaclor, cefuroxime, cefotaxime, cefexim, cefepim, ceftarolin

imipenem PK

inactivated by renal dipeptidases

carbapenems adverse effects

nausea, vomiting, neurotoxicity

imipenem adverse effect

seizures

monobactams example

aztreonam

monobactam mechanism

irreversible inhibitor of PBP 3 (only gram negative)

carbapenems mechanism

binds differently to PBPs

monobactams adverse effects

well tolerated! infrequent side effects

glycopeptides and lipopeptides examples

vancomycin, teicoplanin, daptomycin

glycopeptides and lipopeptides mechanism

bacterial cell wall biosynthesis inhibitors ; inhibit transglycosylase and transpeptidase so prevents cross links bw NAG and NAM

glycopeptides and lipopeptides adverse effects

fever, rashes, phlebitis, ototoxicity, nephrotoxicity, flushing, neutropenia, hypersensitivity

polymixin antibiotics examples

polymixin, colistimethate (polymixin E)

polymixin antibiotics mehcanism

binds PO4 group of membrane and disrupts for gram negative bacilli

polymixin antibiotics adverse effects

neurotoxicity and nephrotoxicity (serious)

fosfomycin

inhibits peptidoglycan synthesis by inactivity MurA (inhibits NAM and NAG)

inhibit protein synthesis

tetracyclines, aminoglycosides, macrolides, chloramphenicol, oxazolidinones, fusidic acid, streptogramins

tetracyclines examples

tetracycline, oxytetracycline, demeclocycline, doxycyline, minocycline, tigecycline

tetracyclines use

broad spectrum (positive and negative)

tetracycline mechanism

taken up by active transport, bind reversibly to 30S subunit, inhibit translation

tetracyclines adverse effects

Gi disturbances, staining of teeth and dental hypoplasia, bone deformities, hepatotoxicity, phototoxicity, vestibular disturbances, anti anabolic, bone marrow depression

tetracyclines contraindications

pregnant women, nursing mothers, and children

aminoglycosides examples

gentamicin, streptomycin, amikacin, tobramycin, neomycin

aminoglycosides mechanism

irreversibly bind to 30S and inhibit protein synthesis and cause leakage

aminoglycoside adverse effects

ototoxicity, nephrotoxicity, paralysis via NMJ blockage

macrolides examples

erythromycin, clarithromycin, azithromycin, telithromycin

macrolides mechanims

bind to 50S subuit and inhibit peptidyl transferase to inhibit amino acid linking

macrolides adverse effects

GI disturbances, hypersensitivity, transient hearing disturbances, cholestatic jaundice with long term use

chloramphenicol

bacteriostatic

chloramphenicol mechanism

bind to 50S subunit and inhibit peptidyl transferase to block amino linking

chloramphenicol adverse effects

severe depression of bone marrow causing pancytopenia, grey baby syndrome (CANT USE IN BABIES)

oxazolidinone mechanism

inhibit bacterial protein synthesis by binding to 70S ribosome - prevents translation

oxazolidenedione adverse effects

diarrhea, nausea, rash, dizziness, thrombocytopenia, serotonin syndrome, hyperlactatemia

fusidic acid mechanism

inhibits bacterial protein synthesis by interfering with translation - no steroid activity

fusidic acid adverse effects

GI disturbances , jaundice

streptogramins mechanism

bind to 50S subunit to inhibit protein synthesis

streptogramins adverse effects

nausea, vomiting, diarrhea, inflammation (arthralgia, myalgia)

clindamycin mechanism

bind 50S ribosomal subunit and inhibit peptidyl transferase

clindamycin adverse effects

GI disturbances, potentially lethal pseudomembranous colitis

quinolones examples

nalidixic acid, ciprofloxacin, levofloxacin, ofloxacin, norfloxacin, moxifloxacin

quinolones mechanism

inhibit topoisomerase II and IV ( prevent negative supercoiling by DNA gyrase, prevents replication

quinolones adverse effects

GI disturbances, hypersensitivity, arthropathy, headache, dizziness, convulsions

2 types of helminths

nemathelminths, platyhelminthes

benzimidazoles examples

mebendazole, tiabendazole, albendazole

benzimidazole mechanism

inhbits polymerization of helminth B tubulin and interfering w MT dependent functions

benzimidazole indications

pinworm, whipworm, roundworm, hookworm

benzimidazole adverse effects

GI disturbances

nitazoxanide mehcanism

inhibit pyruvate:ferredoxin oxidoreductase enzyme dependent electron trasnfer - stops anaerobic energy metabolism

praziquantel mechanism

binds protein kinase C and induces Ca influx resulting in paralysis and death of worm

praziquantel adverse effects

minimal. dizziness, headache, nausea, abdominal distress

piperazine mechanism

GABA receptor agonist, nerve ending hyperpolarization and induces paralysis

piperazine adverse effets

GI disturbances, urticaria, bronchospasm, seizures

pyrvinium mechanism

PIN WORMS ONLY, inhibits mitochondrial respiration complex 1 and suppression ; interferes with glucose uptake

pyrvinium adverse effects

Gi disturbances

diethylcarbamazine

derivative of piperazine

diethylcarbamazine mechanism

unknown

diethylcarbamazine adverse effects

GI disturbances, joint pain, headache, weakness, allergic side effects

niclosamide

for tapeworms

niclosamide mechanism

diminishes potential of inner mitochondrial membrane - inhibits ox phos

niclosamide adverse effects

nausea, vomiting, pruritis, light headed

levamisole mechanism

nicotine like action stimulates and blocks NMJ to paralyze

levamisole adverse effects

CNS and GI disturbances, agranulocytosis

ivermectin adverse effects

skin rash, itching, encephalopathy

ivermectin mechanism

open glutamate gated chloride channels and increase Cl conductance - motor paralysis

TB therapy initial phase

isoniazid, rifampicin, pyrazinamide, maybe ethambutol

TB therapy continuation phase

isoniazid and rifampicin

paucili leprosy treated

dapsone and rifampicin

multi leprosy treated

dapsone, rifampicin, clofazimine

TB first line agents

isoniazid, rifampicin, ethambutol, pyrazinamide

TB second line agents

capreomycin, cycloserine, streptomycin

isoniazid

prodrug activated by kaTG