Combinations

Possitive interaction: summation 1+1=2 potentiation 1+1=3 Negative interaction: decreased effect

5R

• • • • •

Right drug

– drug for the diagnosis

Right dose

– estimated therapeutic dose

Right time

effectivity – drugs at developped disease loose

Right form

- drugs as insulin must be administered as s.c. injection, if administered perorally, they dissolve in GIT

Right patient

– is the one who needs the drug and we know his risk profile

Factors Increasing Risk of Drug Interactions

• • • • • • • • • Polypharmacy Polymorbidity Treatment lasting long time Chronic disease Combination of drugs with similar effect Low therapeutic index Simultaneous ordination of more drugs by different physicians Abuses Self-treatment

Drugs with High Risk

• • • • • • • Peroral antidiabetics Peroral anticoagulants Heart glykosides Antiepileptic drugs Antimanic drugs NSA Antibiotics

Division

• according to the level at which they arise:

pharmaceutic incompatibility – physical and chemical

•

pharmacocinetic

– absorption distribution biotransformation excretion •

pharmacodynamic

Absorption

• pH in GIT – antacids • motility of GIT – prokinetics antidiarrhoea drugs drugs causing obstipation

Distribution

• Insufficiency of plasmatic proteins – hepatopathy • Binding to plasmatic proteins • • Benzodiazepine site Warfarin site

Biotransformation

• Enzyme system CYP 450 • Inductors – E.g. barbiturates, hydantoin antiepileptics ...

– Also cigarette smoke • Inhibitors – E.g. azol antimycotics, diltiazem ...

– Also grapefruit juice

Pharmacodynamic Interactions

• Most often potentiation of sedative effect on CNS (benzodiasepines and alcohol) • Also potentiation of bradycardia (verapamil a betablockers) • Dangerous simultaneous administration of warfarin and aspirin