Skip to main content
UploadLanguage (EN)Support
BusinessMobileSocial MediaMarketingTechnologyArt & PhotosCareerDesignEducationPresentations & Public SpeakingGovernment & NonprofitHealthcareInternetLawLeadership & ManagementAutomotiveEngineeringSoftwareRecruiting & HRRetailSalesServicesScienceSmall Business & EntrepreneurshipFoodEnvironmentEconomy & FinanceData & AnalyticsInvestor RelationsSportsSpiritualNews & PoliticsTravelSelf ImprovementReal EstateEntertainment & HumorHealth & MedicineDevices & HardwareLifestyle
Naser Tadvi, profile picture
Uploaded byNaser Tadvi
PPTX, PDF28,658 views

Penicillins

The document discusses beta-lactam antibiotics, particularly penicillins, including their history, mechanism of action, and various classifications and therapeutic uses. It details the pharmacokinetics, bacterial resistance mechanisms, adverse effects, and precautions associated with penicillins. Additionally, it covers semisynthetic penicillins, antipseudomonal penicillins, and β-lactamase inhibitors, outlining their spectrum of activity and clinical applications.

Health & Medicine◦
Downloaded 171 times
Beta Lactam antibiotics-1 (Penicillins) Dr Naser Ashraf Tadvi Associate Professor Department of Pharmacology Ayaan Institute of Medical Sciences
Beta Lactum antibiotics • Penicillins • Cephalosporins • Monobactum: – Aztreonam • Carbapenems: – Imipenem, merpenem, ertapenem, doripenem
History of penicillins • 1928 - Alexander Fleming – Bread mold (Penicillium notatum) growing on petri dish • 1939 - Florey, Chain, and Associates – Began work on isolating and synthesizing large amounts of Penicillin. • 1944 - Used in WWII to treat infections • Late 1940’s - available for general use in US
Site of penicillinase action. Breakage of the  lactam ring. STRUCTURE OF PENICILLIN C NH CH CH C O O C N CH CH3 CH3 COOH S AB
Mechanism of action
Mechanism of action
Cross-linking of peptidoglycan
Mechanism of action Penicillins Bind & inactivate PBP on cell wall of susceptible bacteria Inhibit transpeptidase Autolysis & cell death Prevent peptidoglycan synthesis Cell wall deficient forms
Mechanism of bacterial resistance • Beta lactamases hydrolyse & inactivate β-lactum ring • Altered PBP • ↓ penetration of drug to its site of action • Activation of efflux mechanisms
Classification Narrow spectrum penicillins Extended spectrum penicillins β- Lactamase sensitive β- Lactamase resistant All are sensitive to β- Lactamase
Narrow spectrum penicillins β- Lactamase sensitive β- Lactamase resistant Oral • Cloxacillin • Dicloxacillin • Flucloxacillin Parenteral •Methicillin • Nafcillin •Penicillin G •Procaine penicillin G •Benzathine penicillin G •Penicillin V (Oral)
Extended spectrum penicillins Oral Parenteral Carboxy penicillins •Carbenicillin •Ticarcillin Ureidopenicillins •Mezlocillin •Azlocillin •Piperacillin Amino penicillins • Ampicillin •Bacampicillin •Talampicillin • Amoxycillin
Benzyl penicillin G • Antibacterial activity: – Gm(+) Cocci: Streptococci – Gm(-) Cocci : Gonococci, meningococci – Gm(+) Bacilli: Corynebacterium diptheriae , clostridium, bacteroides , listeria – Spirochaetes, treponema pallidum – Actinomyces • No significant activity against Gm negative rods
Why Gm(+) mainly
Pharmacokinetics • Acid labile hence given IM/IV • Duration of action:4-6 hrs, Elimination t½ = 30 min • Excreted 80 -85% tubular secretion & 10-15% glomerular filtration • Always prepare fresh solution • Renal failure prolongs half life of penicillins • Nafcillin,cloxacillin, dicloxacillin excreted by biliary route
Repository preparations of Penicillin G • Procaine penicillin G: – DOA = 12-24 hrs – Moderate plasma concentration – Used in mild to moderate infections – Less painful injection • Benzathine penicillin G: – DOA= 3-4 weeks – Slow onset but longest DOA – Used in syphilis , rheumatic fever prophylaxis
Therapeutic uses of Penicillin G • Streptococcal infections – Pharyngitis, sinusitis, otitis, rheumatic fever – Procaine penicillin G : 6 lac units IM OD • Pneumococcal infections – Pneumococcal pneumonia, meningitis • Meningococcal meningitis: – IV penicillin G, Not for prophylaxis
Therapeutic uses of Penicillin G • Gonococcal infections: Unreliable now • Syphilis • Leptospirosis • Diptheria • Clostridial infections: Tetanus & gas gangrene • Anthrax: Benzyl penicillin DOC 8-10 days • listeria, trench mouth • Actinomycosis:
Prophylactic uses • Rheumatic fever – Benzathine penicillin 1.2 million units IM every 4 weeks • Bacterial endocarditis – Valvular lesion patients before surgery – Should be given 1 hr before the surgery
Adverse effects of Penicillins • Local irritation and direct toxicity – IV penicillin G : thrombophlebitis – Procaine penicillin G: anxiety seizures – Intrathecal penicillin G: arachidonitis, convulsions • Hypersensitivity reactions • Jarisch herxheimer reaction
Precautions with penicillin • Always take history of allergies & drug therapy • Perform skin sensitivity test before administering penicillin G & its preparations – 0.02 ml of penicillin G – Drop of 10000 units on skin – 0.05 ml penicilloyl polylysine • Keep adrenaline ready in emergency tray
Semisynthetic penicillins Penicillin Use Penicillin V: Mild streptococcal & pneumococcal infections Oxacillin Cloxacillin Staph aureus, staph epidermidis Ampicillin Amoxicillin Spectrum extended to Gm(-) bacilli Carbenicillin UTI by pseudomonas Mezlocillin piperacillin Pseudomonas , klebsiella infections
Penicillin V • Acid stable, oral absorption is better • Used only for mild to moderate infections – Streptococcal pharyngitis, sinusitis, otitis media – Prophylaxis of rheumatic fever – Less serious pneumococcal infections, trench mouth • Dose: 250 to 500 mg 6 hrly
Penicillinase resistant penicillins • Resistant to staphylococcal penicillinase • Their only indication is infections caused by penicillinase producing staphylococci (DOC) • These drugs are not resistant to Gm (-) β-lactamases • Methicillin: not used now – Hematuria, albuminuria, reversible interstitial nephritis • These drugs are not effective in MRSA infection
Cloxacillin • Highly penicillinase as well as acid resistant • Incomplete but dependable absorption from oral route • > 90% protein bound • Eliminated by kidneys also partly by liver • Dose: 250 – 500 mg QID , in severe infections can be given IM /IV
Aminopenicillins • Extended spectrum penicillins • Spectrum of action: – Like penicillin G in addition some Gm(-) bacilli like H.influenzae, E.coli, Shigella, salmonella, proteus – More active for streptococcus viridans & enterococci
Ampicillin & Amoxycillin Ampicillin Amoxycillin Incompletely absorbed from GIT Completely absorbed Diarrhoea more common Less common Food ↓ absorption No effect Enterohepatic circulation No Effective against shigella and H. Influenza Less effective Dose = 250-500 mg QID 250 -500 mg TDS
Uses of aminopenicillins • Upper respiratory tract infections: • Urinary tract infections: • Meningococcal Meningitis • Shigellosis: Ampicillin • Subacute bacterial endocarditis: • Ampicillin 2 gm IV 6 Hrly in place of penicillin G • Typhoid fever • Cholecystitis: Ampicillin
Antipseudomonal penicillins • Carbenicillin: – Higher doses can cause fluid retention, CCF & can interfere with platelet function • Piperacillin – 8 times more active than carbenicillin – Good activity against klebsiella – Uses: • Neutropenic, immunocompromised patients having serious Gm(-) infections and burns, septicemia
Reverse spectrum penicillins • Mecillinam , pivmecillinam • More stable to β-lactamases degeneration than ampicillin • Acid stable but poorly absorbed • Act by inhibiting PBP-2, prevent cell elongation causing spherical forms • Reverse spectrum? – Mainly effective against Gm(-) bacilli- E.coli. Enterobacter, salmonella, klebsiella
β-lactamase inhibitors • Clavulanic Acid • Sulbactum • Tazobactum Also called as suicide inhibitors
Clavulinic acid • Isolated from Streptomyces clavuligerus • Inhibits β lactamases produced by variety of Gm(+) & Gm(-) bacteria • Rapid oral absorption, 60 % bioavailable • Elimination half life & tissue distribution matches with amoxycillin • Use: infections caused by β lactamase producing strains of S.aureus, E.coli, H.influenzae, proteus
Sulbactum • Semisynthetic β-lactamase inhibitor • 2-3 times less potent than clavulanic acid • Oral absorption inconsistent • Uses: – PPNG gonorrhoea – Mixed aerobic-anaerobic infections • Combined with ampicillin for IV/IM administration
Tazobactum • More potent than sulbactum • Pharmacokinetics matches with piperacillin • Available in combination with piperacillin • Uses: – Severe infection like peritonitis, , pelvic, urinary, respiratory infections caused by β-lactamase producing bacteria