Transcript Antimicrobial Agents (General considerations)

Antimicrobial Agents
(General considerations)
Prof. R. K. Dixit
Pharmacology and Therapeutics
K.G.M.U. Lucknow
[email protected]
Objectives….
– Important drug interactions related to antimicrobials
Important Drug Interactions of Antimicrobials
Pharmaceutical
•During manufacture, packaging, Storage
•During drug administration
•During Mixing and injecting drug
•Mixing in oral solutions
•Mixing in solvent,
• In bottle,
Pharmacokinetic
•No drug in
•Chlelation /(Antacids, Milk)- Tetracyclines
•Blood,
•Alteration of pH/ Ionization of drug- Penicillins
•Plasma and
•Alteration with Enterohepatic recirculation- (OCP)
•Electrolyte solutions
•Inducer (Barbiturates, Rifampicin, Griseofulvin,
Pharmacodynamic
Carbamazepine)
•Inhibitor (Cimetidine, Chlolramphenicol, Erythromycin,
•Synergism/Addition/
Quinolones)
•Antagonism
•Protein biding displacement of drug (Important with high
•Combinations of more than
protein binding drugs)- Sulphonamides
one antimicrobial
•Combination of antimicrobial
with other agents
(ADME)
Important Drug Interactions of Antimicrobials
Pharmaceutical
•During Manufacture, Packaging, Storage
•During drug administration
•During Mixing and injecting drug (If Coagulate Reject)
•Mixing in oral solutions (Not advisable)
•Mixing in solvent (According to instructions)
•No drug in
•Blood,
•Plasma and
•Electrolyte solutions
Important Drug Interactions of Antimicrobials
Pharmacodynamic
•Synergism/Addition(Cidal + Cidal, Static + Static)
•Antagonism (Cidal + Static) When more sensitive to Cidal
•Combination of antimicrobial with other agents
Important Drug Interactions of Antimicrobials
Pharmacokinetic (ADME)
•Chelation /(Antacids, Milk)•Tetracyclines
•Alteration of pH/ Ionization of drug•Penicillin G (not absorbed orally)
•Alteration with Enterohepatic recirculation•OCP with antimicrobials
•Inducers•Rifampicin, Griseofulvin,
•Inhibitors•Chlolramphenicol, Erythromycin, Quinolones (Grape fruit
(Furanocoumarins)
•Protein biding displacement of drug•Sulphonamides
List of Important Interactions Related to Antimicrobials
Sulphonamides
Oral
hypoglycaemics
(Especially
Sulphonylureas)
Increased
hypoglycemia
Oral
anticoagulants
Increased
anticoagulation
(Protein binding
displacement)
Methotrexate
Increased methotrexate
toxicity
(Folate deficiency)
(Inhibitor of
Dihydrofolate
Reducatase)
Fluoroquinolone
Antacids (Al,
Mg, Ca), Zinc,
Iron,
Sucralfate,
Milk
Reduced absorption of
Fluoroquinolone
Theophylline
Increased concentration
due to decreased
metabolism.
(Least with Lome, Levo,
Spar)
Warfarin (Oral
anti-coagulant)
Enhanced effect due to
decreased metabolism
(least with Levo, Spar)
Quinidine,
Procainamide,
Amidarone,
Erythromycin,
Cisapride,
Astemizole,
Terfenadine,
Enhance Q-T interval
leading to dangerous
arrhythmia
Ampicillin
(Penicillin),
Contraceptive
pills
(Cephalosporin)
Failure of contraception
(Inhibition of enterohepatic
recirculation)
Tetracycline,
Antagonism of bactericidal action
Chloramphenicol, (Cidal with Static)
Erythromycin
Aminoglycoside
in same syringe
Inactivation of both
(Pharmaceutical)
Hydrocortisone
Inactivation of penicillin
(Pharmaceutical)
Allopurinol
Increased incidence of non-urticarial
maculo-papular rashes
Probenecid
Decreases tubular secretion of
penicillin and increases action (Pk)
Clavulanic acid,
Sulbactam
Inhibition of Betalactamase leading to
better effect (Synergism)
Cephaloridine
Furosemide
Increased nephrotoxicity
Rifampicin
Warfarin and
OCP
Failure of anti-coagulation and
contraception
Griseofulvin
Cefoperazone,
Cefotetan,
Cefamandole
Metronidazole
Alcohol
Disulfiram like syndrome
(Aldehyde Syndrome)
(Good Chief Minister)
Ethyl Alcohol –
(Alcohol dehydrogenase or
Acetaldehyde synthetase)
Acetaldehyde(Acetaldehyde dehydrogenase)
(Blocked by Disulfiram)- Accumulation of Acetaldehyde
and precipitations of syndrome consisting of Headache,
Vomiting, Flushing etc.
Acetic AcidKreb’s cycle-
ATP + CO2+ H2O
Nalidixic acid
Oral
anticoagula
nts
Enhanced anticoagulation
Nitrofurantoin
Nalidixic
acid
Antagonises action of
nalidixic acid
Probenecid
Reduced tubular secretion
leading to decreased
concentration in urine
Digitalis
Amphotericin induced hypokalemia increases digitalis
toxicity
Amphotericin-B
Erythromycin
Linezolid
Theophylline,
Inhibition of metabolism
Carbamazepine (Inhibit CYP3A4)
Statins,
Warfarin,
Terfenadine,
Terfenadine
Q-T prolongation leading to life
threatening ventricular
arrhythmias
MAO inhibitors
Increased toxicity of MAO
inhibitors
(Linezolid is reversible inhibitor
of MAO and may lead to
cheese reaction with food
containing tyramine and can
precipitate Serotonin
syndrome
(confusion, hypertension,
seizures, tachycardia and
muscle rigidity)
Streptogramins
(Pristinamycin)
Calcium channel
blockers,
Cyclosporine,
Statins,
Diazepam,
Warfarin,
Terfenadine,
Cisapride
Reduce liver
metabolism of
these drugs
Aminoglycosides
Tetracyclines
Furosemide,
Ethacrynic acid
Increased Ototoxicity
Skeletal muscle
relaxants
(curare like
drugs)
Enhanced and
persistent
neuromuscular
blockade
Contraceptive
pills
Failure of
contraception
Antacids,
Iron
Milk ,
Food
Decreased absorption
due to Chelation
Chloramphenicol
Oral
hypoglycemic
Increased
hypoglycemic effect
(due to enzyme
inhibition by
Chloramphenicol)
Oral anticoagulant
Enhanced
anticoagulant
Ketoconazole
Griseofulvin
Cisapride,
Terfenadine,
Astemizole,
Quinidine,
Warfarin,
Cyclosporine
Tacrolimus
Statins
Ketoconazole inhibits
CYP3A4 leading to
decreased metabolism and
accumulation of other
drug
(Least with Fluconazole)
H2 blockers,
PPI,
Antacids
Decreased absorption of
Ketoconazole due to
decreased gastric acidity
Amphotericin B
Ketoconazole inhibits the
synthesis of ergosterol
and produces depletion of
membrane ergosterol
reducing the binding sites
for Amphotericin B
Other drug
Inducer of microsomal
Thanks