CPT2: Consolidating knowledge on drug classes Flashcards
(39 cards)
What is the mode of action of B-lactams such as penicilin?
Advantage of this mode?
Interferes with synthesis of bacterial cell wall peptidoglycan
via Inhibition of transpeptidation enzyme that cross links peptide chains attached to peptidoglycan
This results in weak cell wall and osmotic lysis
- Advantage of this mode of action – they do not kill any cells in the body
What are clinical uses of penicillins?
They are effective against gram positive and negative bacteria. Some have a more predominant Gram positve or negative affect depending on the indivual penicillin and specific chains
Clinical use:
- -septicaemia
- -pneumonia
- -meningitis
- -UTI
- -sinusitis
- -bone & joint infections
- -skin & soft tissue infections (e.g. cellulitis, “diabetic foot”)
Pharmacokinetics
Pharmacokinetics/routes of admin.
- Benzylpenicillin - not absorbed from gut - given im/iv
- Penicillin V – given orally
- Widely distributed into body fluids - breast milk, across placenta
- elimination mostly renal & occurs rapidly
Unwanted effects of penicillins
Unwanted effects:
- Relatively free from direct toxic effects due to selectivity of action on bacterial cells
- Main unwanted effect of penicillin = HYPERSENSITIVITY
- Skin rashes & fever common
- Acute anaphylactic shock
Penicilin:
- Cautions
- Contra-indications
- drug interactions
Cautions
- history of allergy, renal impairment
Contraindications
- penicillin hypersensitivity
Drug interactions
- very few
- broad spectrum penicillins may ↑INR if patient on warfarin
How does resitance to penicillins develop?
What can be used to avoid this?
Resistance developed due to:
- Production of betalactamases
- These are enzymes which breakdown B-lactam ring in penicillin structure
- Betalactamase inhibitor - Clavulanic acid (Augmentin®/Timentin®)
- Clavulanic acid contains a beta-lactam ring in its structure that binds in an irreversible fashion to beta-lactamases, preventing them from inactivating certain beta-lactam antibiotics, with efficacy in treating susceptible gram-positive and gram-negative infections.
- Betalactamase-resistant penicillin e.g. flucloxacillin
- Flucloxacillin has an acyl side chain attached to the β-lactam ring, which prevents access of β-lactamase to the ring and makes the drug resistant to inactivation by the enzyme.
- Betalactamase inhibitor - Clavulanic acid (Augmentin®/Timentin®)
- These are enzymes which breakdown B-lactam ring in penicillin structure
- A decrease in permeability of outer membrane occurs in G-ve organisms
Indications for cephalsporins?
Broad spectrum AB which are effective against Gram positive and Gram negative bacteria
Clinical uses:
- Septicaemia
- Pneumonia
- Meningitis
- Biliary-tract infections
- UTIs
- Peritonitis
Mechanism of action of cephalsporins
Attach to penicillin binding proteins/ transpeptidase enzyme, inhibiting cross-linking of peptide chains. This to interrupt cell wall biosynthesis, leading to weakened cell wall, osmotic lysis and cell death
Pharmacokinetics and routes of administration of cephalsporins
The pharmacology of the cephalosporins is similar to that of the penicillin’s.
- Mostly IV/ IM delivery, some oral
- All distribute well in body fluids e.g. breast milk and cross the placenta.
- Cephalosporins penetrate the cerebrospinal fluid poorly unless the meninges are inflamed; cefotaxime and ceftriaxone are suitable cephalosporins for infections of the CNS (e.g. meningitis).
- Excreted renally
Cephalsporin:
- Unwanted side effects
- Cautions
- Contraindications
Unwanted side effects
- Hypersensitivity
- Allergies
Cautions: Renal impairment, history of allergies to penicillin and cephalosporins
Contraindicated: Hypersensitivity to cephalosporins
Cephalsporin drug interactions
Drug interactions:
- Cephalosporins may increase the chance of bleeding if you’re taking blood-thinning medications (anticoagulants) such as heparin and warfarin.
- Aminoglycosides increase risk of nephrotoxicity
Aminoglycoside indications
Active against some Gram positive and many Gram-negative bacteria. Used for aerobic bacteria NOT anaerobic bacteria.
Mechanism of action
Mechanism:
- Inhibition of protein synthesis
- Binds to 30s ribosomal subunit and causes a misreading of genetic code
Streptomycin: Binding blocks formation of 30S initiation complex needed to start protein synthesis
Spectinomycin: Inhibits elongation phase. Inhibits normal translocation (movement) of ribosome along mRNA molecule.
Gentamycin, Tobramycin, neomycin: Elongation stopped by preventing binding of elongation factor (EF-G) to ribosome.
Route of administration and pharmacokinetics aminoglycosies
- Not absorbed from GUT so must be given via injections (IV/IM)
- Gentamycin most common choice
- Majority excreted by kidneys, small amount in bile
- MUST MONITOR GENTAMYCIN
Unwanted side effects of aminoglycosides
Unwanted side effects:
- Nephrotoxicity
- Ototoxicity
- Skin reactions
- Tinnitus
Aminoglycoside:
- Cautions
- Contraindications
Cautions
- Muscle weakness, renal impairment?
- Used with caution in premature infants because of their renal immaturity. Elderly, impaired renal function, diabetes, auditory vestibular dysfunctions, otitis media.
- history of otitis media, previous use of ototoxic drugs and a genetically determined high sensitivity to aminoglycoside induced ototoxicity, are other main factors which may pre-dispose the patient to toxicity.
Contra-indications
- Myasthenia Gravis
- Hypersensitivity to aminoglycoside
Drug interactions with aminoglycosides
(i) Antibacterials: increased risk of nephrotoxicity with cephalosporins notably cephalothin.
(ii) Gentamicin has been known to potentiate anticoagulants such as warfarin and phenindione.
(iii) Antifungals: increased risk of nephrotoxicity with amphotericin B.
(iv) Cholinergics: antagonism of effect of neostigmine and pyridostigmine.
(v) Cyclosporin, cisplatin: increased risk of nephrotoxicity.
(vi) Cytotoxics: increased risk of nephrotoxicity and possible risk of ototoxicity with cisplatin.
(vii) Diuretics: increased risk of ototoxicity with loop diuretics.
(viii) Muscle relaxants: effect of non-depolarising muscle relaxants such as tubocurarine enhanced. Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anesthesia.
Indications of macrolides
Used to treat Gram positive bacteria. Bactericidal e.g. erythromycin, clarithromycin
Can be alternative to penicillin
Clinical Indications:
- Campylobacter
- Enteritis
- Respiratory infections
- Legionella
- Chlamydial infection
- Non-gonococcal urethritis
1) Upper respiratory tract infections: laryngitis, pharyngitis, sinusitis, secondary infections in colds and influenza, tonsillitis, peritonsillar abscess.
2) Lower respiratory tract infections: acute and chronic bronchitis, tracheitis, pneumonia (lobar pneumonia, bronchopneumonia, primary atypical pneumonia), bronchiectasis, legionnaires disease.
3) Eye infections: blepharitis
4) Ear infections: otitis media and otitis externa, mastoiditis.
5) Oral infections: gingivitis, Vincent’s angina.
6) Skin and soft tissue infections: boils and carbuncles, abscesses, pustular acne, paronychia, impetigo, cellulitis, erysipelas.
7) Gastro-intestinal infections: staphylococcal enterocolitis, cholecytis
8) Other infections: gonorrhoea, syphilis, urethritis, osteomyelitis, lymphogranuloma venereum, diphtheria, prostatis, scarlet fever.
9) Prophylaxis: pre- and post-operative, burns, trauma, rheumatic fever.
Macrolide mechanism of action
Binds to specific site on 50S ribosomal subunit and binding stimulates premature dissociation of peptidyl tRNA from ribosomes during protein synthesis
Routes of action/ pharmacokinetics
- Excreted primarily in liver
- It is widely distributed throughout body tissues. Little metabolism occurs and only about 5% is excreted in the urine. It is excreted principally by the liver
- IV/ mouth
Macrolide unwanted reactions
- Skin reactions
- Allergic reactions
- Nausea, vomiting, diarrhoea
- Jaundice
- Hepatitis
Macrolide cautions
- Electrolyte disturbances (predisposition to QT interval), may aggravate myasthenia gravis, predisposition to QT interval prolongation
- Impaired hepatic impairment
Macrolide contraindications
- Hypersensitivity to macrolides
- Concomitant use with astemizole, terfenadine, cisapride or pimozide.
- Erythromycin is contraindicated with ergotamine and dihydroergotamine.
Drug interactions with macrolides
· Concomitant use of Erythromycin with terfenadine or astemizole is likely to result in an enhanced risk of cardiotoxicity with these drugs. The concomitant use of Erythromycin with either astemizole or terfenadine is therefore contraindicated.
· The metabolism of terfenadine and astemizole is significantly altered when either are taken concomitantly with erythromycin. Rare cases of serious cardiovascular events have been observed, including torsades de pointes, other ventricular arrhythmias and cardiac arrest. Death has been reported with the terfenadine / erythromycin combination.
· Elevated cisapride levels have been reported in patients receiving erythromycin and cisapride concomitantly. This may result in QT prolongation and cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation and Torsades de pointes.
· Similar effects have been observed with concomitant administration of pimozide and clarithromycin, another macrolide antibiotic.
· Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterised by the rapid development of severe peripheral vasospasm and dysaesthesia.
· Increases in serum concentrations of the following drugs metabolised by the cytochrome P450 system may occur when administered concurrently with erythromycin: alfentanil, astemizole, bromocriptine, carbamazepine, cyclosporin, digoxin, dihydroergotamine, disopyramide, ergotamine, hexobarbitone, midazolam, phenytoin, quinidine, tacrolimus, terfenadine, theophylline, triazolam, valproate, and warfarin. Appropriate monitoring should be undertaken and dosage should be adjusted as necessary.