Drug interactions Flashcards
What is a drug interaction
Clinically meaningful alteration in effect of one drug as a result of co-administration of another drug, food or chemical (precipitant)
What types of durug interactions increase effect
Summative
Synergistic
When are drug interactions only clinically relevant often
When narrow therapeutic index
How common are drug interactions
15-65% potnetial
Actually around 6%
hospital admission 4-8%
Reduced efficacy 8%
How does polypharmacy increase DDI
2 drugs - 13%
4 drugs - 38%
>7 drugs - 82%
What is a pharmacodynamic interaction
Drugs act on same target site of clinical effect
What are pharmacokinetic DDIs
Altered drug concentration at target site of clinical effect eg ADME
What is pharmacodynamic DDI causes resp depression
opiates and benzos
What pharmacokinetic DDI causes COCP failure
Antibiotics
How can synergistic DDIs be beneficial
Increase effect eg antimicrobial efect of rifampacin and isoniazid at mycobacterim TB
What effect does alcohol and benzos have
Increased action at GABA - sedative effect on CNS
What drug antagonises salbutamol
atenolol - bronchoconstrictor - beta adrenoreceptors
How does naloxone work
Antagonist at opioid receptor (which morphine is endogenous agonist) - reverses sedative effect of morphine
What is danger os sildenail and isosorbide mononitrate
Markedly increased hypotnesion = can be extermely dangerous esp if cardiac problems/IHD
Mechanisms which can alter rate and extent of absorption
pH
Gastric emptying and intestinal motility
Physio-chemical interaction
What happens to absorption when pH lowered eg antacid
Reduced absorption - more ionisation, can’t cross membrane of cell
What happens to drug absorption if pH of stomach increased
eg alcohol
Less ionisation and faster absorption
What drugs delay gastric emptrying
opiate analgesics - morphine, pethidine
Antimuscarinics eg atropine, propantheline
TCAs eg impiramine - side effect
What drugs increase rate of gastric emptying
Metoclopramide
Muscarinic agents eg bethanechol
What is the clinical significance of decreased gastric emptying
Lower peak concentration
BUT prolonged duration
What drugs do antacids make insoluble therefore reduce absorption
Tetracyclines
Quinolones
Iron
Bisphosphonates
What drug can be used to reduce absorption of acidic drugs in overdose
Cholestyramine
Examples of acidic drugs that overdoses can be treated with cholestyramine if uick
Digoxin, warfarin
How does activated charcoal stop absorption
Adsorbs toxins to surface, not absorbed by digestive system so excreted in faeces
What are distribution interactions
Displacement of plasma protein bound drugs by another drug - increased free drug conversion
Danger is from toxicity
What drugs have high protein binding
Warfarin, statins, amiodarone, diazepam, NSAIDs, heparin, furosemide tolbutamide, phenytoin, sulphonamides
When does distribution DDI become significant
normally minor - compensation increase in metabolism and excretion free drug
IF 2nd mechanism eg drug also inhibits metabolism of old drug
Produces toxicitiy
What drug interacts with phenytoin in distribution interaction
Valproate
Also inhibits metabolism
What two cardiac drugs can interact distibutionally causing toxicity
Digoixin and quinidine/verapamil/amiodarone
mechanism of digoxin toxicity when given with quindien
Quinidine displaces digoxin from cardiac receptors
Increase plasma concentration of digoxin -> toxiciity
ALSO decreases excretion of digoxin
Effect of CYP450 inducers vs inhibitors on effect of drugs
Inducers increase metabolism -> reduce effect of drug
INhibitors slow metabolism -> enhanced effect
Why does induction OF cyp450 take days to weeks?
Need an increase in actual enzymes - liver grows and blood flow increases, increased clearance of everything
Why is inhibition immediate of CYP450
Blocking exisitng CYP450s - dont need more time
Examples of CYP450 inducers
CRAPGP
Phenytoin
Carbamazepine
Barbituatesn(phenobarbitone)
Rifampicin
Alcohol - chronic
St johns wort
Grisefolun
Exmaples of CYP450 inhibitors
Cimetidine
Erythromycin/clarithromycin
Ciprofloxacin
Sulphonamides
Isoniazids
Verapamil
Metronidazole
Omeprazole
Grapefruit juice
Alcohol - acutely
Amiodarone
Antifungals
What drug can baribituates induce
Warfarin (reduced effect)
What drug can rifampacin induce (reduce effect)
Theophylline
What drug can phenytoin induce
COCP
What need to watch for when stopping medication
If its a CYP450 inducer - may increase effect of other drug
How can wtihdrawal of carbamazepine affect warfarin
Higher dose of warfarin due to inductino by carbamazepine (normal blood levels as increased clearnace)
If carbamazepine stopped acutely + reaplced by valproate (inhibitor) warfarin clearance falls, blood levels above therapeutic index -> haemorrhage
What drugs will st johns wort interfere with
CYP450 inducer - makes below less effective
Warfarin
COCP
SSRI - serotonin syndrome
Ciclosporin - transplant failure
Theophylline
Digoxin
Carbamazepine
Phenytoin
What enzyme do grapefruit and cranberry juice block
CYP3A4 in gut wall and liver
What drugs do grapefruit and cranberry juice interact with
Drugs metbaolised by CYP3A4
CCBs
Benzos
Simastatin - myopathy
Why can COCP be less effective with antibiotics
Enterohepatic recycling - oestrogen from liver -> gut in bile -> free oestrogen by bacteria
Antibiotics reduce bacteria and therefore amount of free oestrogen released from the gut
Precautions with COCP and antibiotics
None if antibiotic not inducer and no N/V - short course
Long course - gut recolonised
What drug can inhibit active tubular secretion of acidic drugs
Penicillin, methotrexate
What drugs inhibit tubular secretion about digoxin
Quinidine and verapamil
What does interaction between lithium and thiazide diuretics?
Lithium retained in tubules -> increased and potnetial toxicity
What can NaCl and spirinolactone cause
Hyperkalaemia
Potassium sparing and adding potassium
What effect do some antibiotics (ciprofloxacin, clarith/erythromycin) have on theophylline
CYP450 inducers -> theophylline toxicity
Theophylline toxicity symptoms
Dizziness, hypotension
Seizures, cardiac arrhtyhmias, death
What enzyme causes interaction between methotrexate and trimethoprim and what do they cause
Dihydrofolate reductase enzyme inhibitors folate deficiency (bone marrow supression)
Steps when DDI
Understand pharmacolgoy
Avoid combination - alternative
Adjust dose
Monitor therapy - clinical (signs), therapeutic eg drug conc, measure marker for interaction eg U+Es
Continue medication
What antibiotics increase effect of warfarin and shld be avoided
Erythromycin
Metronidazole
What drugs that increase bleeding risk (GI) avoid with warfarin
Aspirin or NSAIDs
PPI cover
What antibiotics increase effect of CBZ and what do when given
Erythromycin, clarithromycin, fluconazole
What do you do when NSAID/diuretic is prescribed with lithium and why
Decrease lithium dose by 50% They increase Li levels in blood (confuse with sodium in tubules and retain)
What drugs avoid with COCP as makes ineffective
Carbamazepine
Rifampacin
Can increase dose of
What drugs can interact with SSRIs and cause serotonin syndrome or hypertensive crisis
St Johns Wort
Triptans
MAOI
