PROTEIN INHIBITORS * BROAD-SPECTRUM ANTIBIOTIC

1. TETRACYCLINE -general: bacteriostatic but bactericidal at high [] -moa: inhibit bact protein synthesis (30S) -uses: resistant to almost ALL gram +/- COCCI except for N.gonorrhea but sensitive to bacilli -class: i. Tetracycline (6-10 hrs) - short ii. Democlocycline (12-13 hrs) intermediate iii. Doxycycline (18-20 hrs) long-acting -pk: i. oral especially wf doxycycline (IV if required) coz food x TC absorption ii. x wf dairy products iii. x in csf iv. liverurine but doxycycline in bile -a/e: epigastric pain + discoloration of teeth + hepatotoxic + nephrotoxic

2. CHLORAMPHENICOL -general: bacteriostatic, from Streptomyces venezuelae -moa: inhibit bact protein synthesis (50S), - 70S causes host toxicity -pk: i. oral ii. distributed in csf iii. liverurine -a/e: bone marrow suppression + Gray Baby syndrome

3. MACROLIDES

-general: bacteriostatic but bactericidal at high [] -class: i. natural- erythromycin ii. semisynthetic- azithromycin -moa: inhibit bact protein synthesis (50S) at ALKALINE pH -pk: i. x in csf ii. liverbile -a/e: severe epigastric pain (motilin receptor agonist) -d/i: cytochrome enzyme inhibitor (not azithromycin)

4. CLINDAMYCIN -general: clindamycin + lincomycin = lincosamide -uses: serious infection of staph and strept (anaerobes) -a/e: pseudomembranous colitis + NMJ block (IV)

5. LINEZOLID -general: synthetic,bacteriostatic -moa: inhibit bact protein synthesis (50S) -uses: ONLY gram + (MRSA including vancomycin-resistant strains)

6. KETOLIDES -general: struc related to macrolides -uses: RT infection caused by macrolide-resistant bacteria

7. STREPTOGRAMINS -moa: inhibit bact protein synthesis (50S and 70S)

-uses: MRSA infection

Lect 2 CELL WALL INHIBITORS * FOSFOMYCIN inhibit biosynthetic enzyme * BACITRACIN combined wf carrier molecules * VANCOMYCIN combined wf cell wall substrates * BETA LACTAMS inhibit attachment of new peptidoglycan into cell wall * BROAD-SPECTRUM ANTIBIOTICS * BACTERICIDAL

BETA-LACTAMS * ALL r resistant to MRSA 1. PENICILLINS -class: i. natural- penicillin V + G (short) and procain benzylpenicillin (long) ii. semisynthetica. AMPICILLIN (sulbactam) b. anti-pseudomonal : TICARCILLIN (clavulanate) + PIPERACILLIN (tazobactam) c. anti-staph : METHICILLIN - penicillinase resistant d. beta-lactamase inhibitor : *in bold -a/e: allergy, git discomfort

2. CEPHALOSPORINS

-class: i. 1st generation: more against gram + ( ), low against gram and less resistant to beta-lactamase ii. 2nd iii. 3rd iv. 4th generation: more against gram ( ), more resistant to betalactamase -a/e: same wf penicillin

3. CARBAPENEM -progrug: imipenem -pk: only iv -a/e: some wf others but ++ cns (seizure) + cvs (hypotension)

4. MONOBACTAM -prodrug: aztreonam -uses: high gram -ve -only iv + highly protein-bound

Lect 3 AMINOGLYCOSIDES -prodrugs: i. streptomycin ii. gentamycin iii. amikacin iv. neomycin v. kanamycin topical use -moa: inhibit bact protein synthesis (30S)

- BACTERICIDAL -uses: GRAM - ONLY -pk: i. iv for systemic infection, oral if want topical effect on gut ii. x in csf iii. NOT metabolised, excreted unchanged by kidney iv. NARROW therapeutic window -a/e: reversible nephrotoxicity + irreversible hearing impairment + reversible balance disturbance

Lect 4 SPECTINOMYCIN -general: derived from Streptomyces spectabilis -uses: GRAM + AND -moa: inhibit protein synthesis (30S) - bacteriostatic -a/e: hypersensitivity

Lect 5 SYNTHETIC ANTIMICROBIALS (ANTI-FOLATES) 1. SULPHONAMIDES -general: more soluble at ALKALINE pH -moa: have structural similarity wf PABA hence can compete for dihydropteroate sythase -class: i. oral a. sulfadiazine short

b. sulfamethoxazole intermediate acting c. sulfadoxine long ii. orally x absorbed:- sulfasalazine w is used in ulcerative colitis iii. topical:- sulfacetamide -uses: GRAM ONLY -pk: i. NEVER given iv or im ii. cross BBB iii. liverurine -a/e: crystalluria + renal toxic + hypersensitivity rxn + haemolytic anemia

2. TRIMETHOPRIM -moa: competitively dihydrofolate reductase -uses: GRAM AND + -pk: i. oral ii. distributed in csf iii. renal excretion (adjustment wf renal insufficiency)

3. SULFAMETHOXAZOLE + TRIMETHOPRIM = COTRIMOXAZOLE -general: in ratio of 5:1 -iv or oral -can produce SEQUENTIAL BLOCKADE