Drug Interactions and Therapeutic Drug Monitoring Flashcards
What is the medical importance of drug interactions in terms of morbidity and mortality
Costs to healthcare is high due to increased hospitalisation and administration of drugs to resolve it
Factors that may predispose a patient to a drug interactions
The number of medications Elderly Young Critically ill Patients undergoing complicated surgery Patients with chronic conditions: Liver disease Kidney impairment Diabetes mellitus Epilepsy Asthma
Classification of Drug-Drug interactions
Pharmacodynamic: Direct antagonism, synergistic, indirect agonist, indirect antagonism
Pharmacokinetic: Absorption, Distribution, Metabolism and Elimination
Importance of Therapeutic drug monitoring
Drugs have small therapeutic index
Precipitant
The agent which precipitates out in such an interaction
Drugs involved with serious interactions and why?
Warfarin Gentamicin Erythromycin Linezolid These drugs have a narrow therapeutic index which means that a small change in blood plasma levels can induce prodounf toxicity
Food that interact with Warfarin
Vegetables like: Asparagus, Broccoli, Cabbage, Kale, Lettuce, Onions, Spinach, Watercress
Herbals like: Ginseng, Green tea
Miscellaneous: Avocado, Fish oils, Liver, Soya beans
Food that interact with Warfarin
Vegetables like: Asparagus, Broccoli, Cabbage, Kale, Lettuce, Onions, Spinach, Watercress
Herbals like: Ginseng, Green tea
Miscellaneous: Avocado, Fish oils, Liver, Soya beans
Direct Antagonism
beta-blockers will block actions of agonists
Synergistic Interaction
Two drugs with the same pharmacological effect acting on the same receptor given concurrently
Indirect Agonism
Warfarin and NSAIDs, Atenolol and Verapamil
Indirect Antagonism
NSAIDs and anti-hypertensiive medication and NSAIDs and treatment for heart failure
Drug-drug interactions in Absorption
Formation of insoluble complexes
Altered PH
Altered bacterial flora
Altered GI motility
Drug-drug interactions in Distribution
Protein binding displacement
Drug-drug interactions in Metabolism
Occurs when one drug induces or inhibits the metabolism of another
Drug-drug interactions in Elimination
Inhibit secretion
Increase tubular reabsorption
Tetracyclin and erythromycin complex with _________ to form insoluble complexes
Magnesium, iron and calcium
__________ reduce H+ and increase____
H2 antagonist, proton pump blockers and antacids and PH
__________ destroy normal gut flora leading to
Broad spectrum antibiotics and failure of oral contraceptive or digoxin toxicity
Oral medicines are mostly absorbed in the ______ and ______ is the limiting step and increase leads to_______
small intestine and gastric emptying and increased absorption
Anticholinergics delays_____
Gastric emptying
If a drug is 99% bound displacement of 1% leads to______
Doubling of free plasma levels
2 most important proteins are_____
Albumin and alpha-1 glycoprotein
Drugs with 99% protein binding
Ibruprofen, naproxen, Warfarin, Valproic acid, Phenytoin
Drug-Drug interactions that affect metabolism normally occur in the _____
Liver via the cytochrome P450
Drugs that inhibit the metabolism of drugs metabolised by the P450 system
Cimetidine (warfarin, diazepam), Metronidazole (Warfarin, alcohol), Omeprazole (phenytoin, warfarin)
Drugs that induce cytochrome P450
Barbiturates, Carbamazepine, Phenytoin (warfarin, steroid, OC), Rifampacin (warfarin, OC) and tobacco smoke
How long does enzyme induction take
2-3 weeks
Rifampicin___
Increases metabolism of ciclosporin by inducing CYP 3A4
St John’s Wort_____
Increases metabolism of ciclosporin by inducing CYP 3A4
Verapamil/diltiazem and digoxin____
Inhibit secretion
Loop diuretic and lithium
Increase tubular reabsorption
