Drug interactions & metabolism Flashcards
Name 5 main types of drug interactions
- Absorption reactions
- Distribution reactions
- Metabolism reactions
- Excretion reactions
- Pharmacodynamic reactions
Give 2 examples of drugs that react with metal ions eg Ca, Mg, Fe
Ciprofloxacin
Tetracyclines (eg Doxycycline)
Cholestyramine does what with other drugs in the GIT
Absorbs them so dropping their effectiveness
How can you minimised the problem of absorption reactions between diff substances
Give at diff times to avoid interaction
How does metclopramide influence the uptake of paracetamol in the drug Paramax
It incr gut motility so incr absorption of paracetamol
How do PPIs influence the uptake of acid drugs e.g. Ketoconazole (anti fungal)
By reducing stomach acidity - reduces absorption of weak acids
How does rifampicin interact with the transporter P-glycoprotein and what affect does this have on Digoxin absorption
P-glycoprotein reduces Digoxin absorption in gut.
Rifampicin INDUCES P-glycoprotein so will reduce level of Digoxin absorbed even more.
What effect does clarithromycin have on CYP450 enzymes. How might this influence the metabolism of statins and what might be the consequence
It is an INHIBITOR - will prevent CYP450 from metabolizing free drug.
Will increase free statin in blood - lead to neuropathy.
What effect does rifampicin have on CYP450 enzymes. How might this influence the metabolism of statins and what might be the consequence
It is an INDUCER - will speed up metabolism of free drug.
Will have less statin free in blood (but not clinically shown to be an issue)
What drugs reduce kidney perfusion.
How does this affect the levels of renally excreted drugs e.g. methotrexate.
NSAIDs e.g. aspirin, ibuprofen reduce kidney perfusion.
This reduces renal excretion so will get incr in methotrexate = toxicity
How do antidiuretics influence the excretion of lithium
Antidiuretics retain Na - Lithium v similar molecule so is also retained. = Lithium toxicity
How does urine alkilinisation help in OD of aspirin
Increases the excretion of weak acids e.g. aspirin, methotrexate.
Additive pharmacodynamic effects:
What is the possible consequence of adding Beta2 agonist (eg ventolin) and diuretics.
Hypokalaemia
Additive pharmacodynamic effects:
What is the possible consequence of adding Alcohol and anti-histamines
Drowsiness
Additive pharmacodynamic effects:
What is the possible consequence of adding aminoglycosides & ciclosporin
Renal toxicity
Opposing effects:
Why should patients on antihypertensives (eg ACE inhibitors) avoid NSAIDs
NSAIDs cause increased BP
Why should patients on warfarin avoid too much green veg
Green veg = vit K, which acts as warfarin antagonist
Why should patients taking anti-diabetic drugs be cautious of using corticosteroids
Corticosteroids increase blood glucose
Name 7 drugs with a narrow therapeutic window and so are at high risk of drug interactions
- Warfarin (anti coag)
- Gentamicin (aminoglycoside antibiotic)
- Tacrolimus (immuno suppressant - transplants)
- Lithium - (psych sedation)
- Digoxin - (slow HR - used in congestive hrt fail)
- Phenytoin (anti-epileptic)
- Carbamazepine (anti-epileptic)
What does a black dot in the BNF indicate
A significant interaction
Name 7 common CYP450 INDUCERS
- Rifampicin
- Green veg / broccoli etc. (Vit K)
- Alchohol
- Smoking
- St John’s wort
- Phenytoin
- Carbamazepine
Name7 common CYP450 inhibitors
- Grapefruit juice
- Clarithromycin / erythromycin
- Metronidazole
- Cimetidine
- Miconazole
- Verapamil
- Amiodarone
What are the main 2 aims of drug metabolism
- Make drug more hydrophillic - easier to excrete in urine
2. Inactivate drug - reduce free amount in system
Main 2 sites & enzymes of drug metabolism
- Liver - CYP450
2. Gut - Monoamine Oxidase (MAO)
