Pharmacology Third Year

1. Aminoglycosides

2. Aminoglycosides
For Local action: Kanamycin, Neomycin
For Systemic action: Streptomycin, Gentamicin,
Tobramycin, Amikacin.
For Both routes; Gentamicin, Tobramycin

3. Aminoglycosides
Common Properties
• Poor absorption from GIT
• Synergistic action if combined with β lactam antibiotics
• Show Concentration dependent killing
• Post antibiotic effect –Persistent killing of bacteria even
below MIC, greater effect with single large dose than
small multiple doses
• Narrow margin of safety
• Exhibit Ototoxicity, Nephrotoxicity, & Neurotoxicity
• Unchanged excretion by kidneys, dosage adjustment or
discontinuance in renal impairment

4. Aminoglycosides
Mechanism of Action
• Bind to 30 S subunit of ribosomes, inhibit initiation
complex=> misreading of mRNA, non functioning
monosomes
Adverse effects:
• Ototoxicity ( irreversible)
• Nephrotoxicity ( reversible) > 5 days of therapy
• Neuro Muscular blockade
• Teratogenicity=> Neonatal deafness.
Contraindications - Pregnancy

5. Aminoglycosides
Uses:
Streptomycin - Tuberculosis, Brucellosis, Plague & enterococcal
endocarditis.
Gentamicin
• ( Along with β lactams) – Sepsis, Pneumonia, & Enterococcal
endocarditis
• Topical: Conjunctivitis, Wounds, Burns
Neomycin - Topically-infective wounds,
Amikacin ( Resistant to many inactivating enzyme)
• Multi Drug resistant Tuberculosis.

6. Macrolides

7. Macrolides
• Erythromycin, Clarithromycin & Azithromycin
Mechanism of action:
• Bind 50 S ribosomal RNA, inhibits protein synthesis by
blocking aminoacyl translocation & initiation complex
(bacteriostatic)
Resistance
• Efflux pump mechanism & ribosomal protection by methylase
• Drug metabolising esterases ( Enterobacteria)

8. Macrolides
Erythromycin
• Effective against Mycoplasma, Chlamydia, Legionella,
Campylobacter, Gm+ve & some Gm-ve organisms
Pharmacokinetics:
• Food interferes with the absorption
• Erythromycin stereate & esters are acid resistant hence better
absorbed, erythromycin estolate is best absorbed.
Uses
• Community acquired pneumonia (Mycoplasma pneumoniae)
• Diphtheria, ( Corynebacterium Diphtheriae)
• Infections due to Chlamydia, Legionella & Campylobacter
• Prophylaxis against endocarditis during dental procedures in
patients with valvular heart disease.

9. Macrolides
Adverse effects:
• Vomiting & Diarrhea
• Acute Cholestatic hepatitis (Erythromycin estolate)
• Skin rashes
Drug Interactions:
• Inhibition of CYP 450 enzymes: ↑serum concentration of
theophylline, oral anticoagulant, cyclosporine etc.

10. Clarithromycin
• Same antibacterial spectrum & uses as erythromycin.
• Less GI upset & less frequent dosing i.e. administered
twice daily
Uses
• Eradication of H pylori in the treatment of peptic ulcer.
• Prophylaxis & treatment of M avium complex,
toxoplasmosis

11. Azithromycin
• Similar antibacterial spectrum, but is more active against H
influenza, Moraxella catarrhalis, & Neisseria
• Because of its long half-life, a single dose is effective (once
daily) and reduce the duration of treatment
• Does not inhibit CYP 450 enzymes, hence free from drug
interactions
Uses
• Community acquired pneumonia,
• Urogenital infections caused by Chlamydiae trachomatis

12. Antitubercular drugs

13. Tuberculosis
Tuberculosis is a chronic granulomatous disease caused by
mycobacterium tuberculosis bacteria affecting lungs
causing pulmonary tuberculosis.
It may infect many other organs of the body, GIT, lymph
nodes, CNS, skin, bones etc

14. Anti-TB drugs
First line drugs
1. Isoniazid (INH)
2. Rifampicin
3. Pyrazinamide
4. Ethambutol
5. Streptomycin
All are bactericidal except
Ethambutol (bacteriostatic)
Second line drugs
1. Ethionamide
2. Para amino salicylic acid
3. Cycloserine
4. Clarithromycin
5. Capreomycin
All are bacteriostatic except
Capreomycin (bactericidal)

15. Anti-TB drugs
INH
Mech of action:
• Inhibits synthesis of mycolic acids, an essential component of
mycobacterial cell walls.
Adv effects:
• Peripheral neuritis (prevented by Pyridoxine (B6) )
• Hepatotoxicity
• Hemolysis in G6PD deficiency patient
RIFAMPICIN
Mech of action: Inhibits DNA-dependent RNA polymerase, thereby
blocking production of RNA.
Adv effects:
• Orange discoloration of urine and other body fluids
• Flu like syndrome,
• Hepatitis

16. Anti-TB drugs
PYRAZINAMIDE
• More active at acidic pH effective only against intracellular
bacilli (macrophages)
Adv effects:
• Hyperuricemia (precipitates gouty arthritis)
• Teratogenicity -Spina bifida (contraindicated in pregnancy)
ETHAMBUTOL
• Inhibits Arabinosyl transferase involved in polymerization of
Arabinoglycan ( Myco cell wall)
Adv effects; Retrobulbar Optic neuritis=>loss of visual acuity &
Colour blindness hence contraindicated in children <8 yrs

17. Anti-TB drugs
STREPTOMYCIN
Mech of action;
• Binds S 12 subunit of ribosomal proteins & inhibits bacterial
protein synthesis
• Effective against extracelluar organisms
• Given IM
Adv effects:
• Ototoxicity ( Vertigo & Deafness), nephrotoxicity, &
neurotoxicity
Neonatal deafness (contraindicated during pregnancy)

18. Treatment of Tuberculosis
SHORT COURSE CHEMOTHERAPY
Combination therapy:
• Rapid killing of the organisms, ↓ resistance & ↓ duration of
therapy
Initial intensive phase (rapid killing) 2-3 months
Continuation phase (elimination of remaining bacilli) 4-6 months
• Initial Phase Continuation Phase Total duration (months)
• 2 HRZE (S) 4 HR 6
• 3 HRZE (S) 6 HR 9
H=INH, R=Rifampicin, Z=Pyrazinamide, E=Ethambutol, &
S=Streptomycin