Interactions Flashcards
Phenytoin and Amiodarone
Amiodarone increases phenytoin concentration
NB: Amiodarone is an enzyme inhibitor.
Due to amiodarones long half life: potential for interaction several months after discontinuation
Phenytoin and Warfarin
Phenytoin (p450 enzyme INDUCER) induces warfarins metabolism, decreases warfarin concentration, reduced anti-coagulation effect, decreases INR
Phenytoin and COC
Phenytoin (a p450 enzyme inducer) accelerates metabolism of Oestrogens, reducing their effectiveness
Patient should be changed to an IUD
Phenytoin and Fluoxetine
Fluoxetine increases phenytoin concentration
Phenytoin and Theophylline
Theophylline decreases phenytoin concentration
Phenytoin and St Johns Wort
St Johns Wort decreases phenytoin concentration
St Johns Wort is an enzyme inducer
Phenytoin and Fluconazole
Fluconazole increases phenytoin concentration (Fluconazole enzyme inhibitor part of SICKFACES)
Phenytoin and Cimetidine
Cimetidine increases phenytoin concentration (Cimetidine enzyme inhibitor part of SICKFACES)
Phenytoin and Diltiazem
Diltiazem increases phenytoin levels, and diltiazems own effects are decreased by phenytoin
Phenytoin and Rate limiting CCB’s
Phenytoin decreases effects of Verapamil and Diltiazem and also Felodipine
Amiodarone and Grapefruit Juice
Grapefruit Juice increases levels of Amiodarone
Grapefruit Juice is an enzyme inhibitor
Amiodarone and warfarin
Amiodarone increases warfarin levels
Enhances anti-coagulant effects, increased bleed risk
Amiodarone is an inhibitor of some of the CYP450 enzymes.
Amiodarone and Simvastatin
Increased risk of Myopathy
Max dose of Simvastatin: 20mg
This is not the same with Atorvastatin etc but still monitor for mypopathy
Amiodarone and beta blockers and Rate-limiting CCB’s diltiazem and verapamil
Increased risk of
Bradycardia
Myocardial depression
AV block
When given with beta blockers/ rate limiting CCB
Amiodarone and Lithium
Increased risk of Ventricular Arrhythmias
(poss associated with QT prolongation)
Also both effect THYROID function
Amiodarone and Digoxin
Amiodarone increases plasma level of Digoxin, leading to digoxin toxicity
Theophylline + enzyme inhibitors:
Cimetidine, Fluconazole, Ketoconazole, Ciprofloxcin, Erythromycin
Theophylline levels increased as it is metabolised by the CYP450 enzymes
Theophylline + enzyme Inducers:
Carbamazepine, Alcohol, Phenobarbital, Phenytoin, Rifampicin, St Johns Wort
(SCRAP GP’s)
Theophylline levels decreased
Theophylline and Quinolone antibiotics e.g. Ciprofloxaxin, Levofloxacin
Increased risk of SEIZURES
These BOTH lower seizure threshold
What do diltiazem and Verapamil (rate limiting CCBs) do to Theophyllines concentration?
Increase it
these are CYP3A4 enzyme inhibitors!
NSAIDs and warfarin/ phenindione
NSAIDs increase warfarin levels- increased anticoagulant effect
NSAIDs, like warfarin, have a high affinty for Albumin. They displace warfarin off the protein= more free warfarin
So remember the interaction is not because both drugs can increase bleed risk- NSAIDs actually increase the levels of warfarin
SSRI’s and TCA’s and warfarin
SSRI’s and TCA’s will increase warfarin levels- increased anticoagulant effect
Statins and warfarin
Only statin that interacts: Rosuvastatin
Increased effects of warfarin
Clopidogrel and warfarin
Anti-coagulant effect enhance (both thin blood)- increased risk of bleeds
Orlistat + Antiepileptics
Possible increased risk of convulsions- orlistat lowers seizure threshold
Methotrexate and Phenytoin
Do not use together- both deplete Folate
Methotrexate and Trimethoprim/ Co-trimoxazole (trimethoprim + Sulfamethoxazole)
Do not use together- both deplete folate- haematological blood toxicity risk
Sulfamethoxazole also increases methotrexate toxicity
Methotrexate and Ibuprofen
Methotrexate toxicity increased by NSAIDs due to decreased renal excretion
Methotrexate and Flucloxacillin
Methotrexate toxicity increased by all penicillins due to decreased renal excretion
Methotrexate and Clozapine
Neutropenia risk increased
PPI’s and Methotrexate
Increased risk of Methotrexate toxcity as excretion decreased
ALOT of antibiotics interact with Methotrexate. Can you think of any?
Trimethoprim/ co-trimoxazole (folate depletion)
The following increase methotrexate toxicity: Ciprfloxacin Doxycycline Tetracycline Sulfonamide (Sulfamethoxazole)
If in doubt, whats that ONE DRUG that seems to have interactions with everything?!
CICLOSPORIN
an immunosuppressant
Which OTC medication can possibly interact with ANTI-EPILEPTICS and increase the risk of CONVULSIONS?
ORLISTAT (Alli)
Carbamazepine is an enzyme inducer, but is itself metabolised by the CYP450 system. Which other enzyme inducers may reduce the concentration of carbamazepine?
Phenytoin (May also reduce phenytoins conc)
Rifabutin
St Johns Wort
What drugs, used in hypertension, can increase the risk of Myopathy?
Diltiazem
Verapamil
Amlodipine
Ranolazine
MAX SIMVASTATIN DOSE= 20mg for all of these!!
Drugs interacting with Gentamicin/ Vancomycin?
NEPHROTOXIC DRUGS:
Ciclosporin (immunosuppressant)
Tacrolimus (immunosuppressant)
Cephalosporins
OTOTOXICITY: Loop diuretics (furosemide)
What kind of OTC products should patients with high BP avoid?
SOLUBLE preparations e.g. effervescent
Due to high SODIUM content
Spironolactone + ACEi/ARB
Potassium sparing diuretic given with postassium elevating drugs: HYPERKALEAMIA
Spironolactone + Tacrolimus
Potassium sparing diuretic given with postassium elevating drug Tacrolimus: Hyperkaleamia
Furosemide + Vancomycin
Increased risk of Ototoxicity
Digoxin + Diuretics
Diuretics (thiazides and loops) can cause Hypokaleamia
Digoxin toxicity is precipitated by low potassium!!
Give potassium sparing diuretics/ potassium chloride to manage
Eplerenone (potassium sparing diuretic) is metabolised by the CYP450 enzyme system
Its concentration is increased by clarithromycin and itraconazole only
Its concentration is reduced by all the enzyme inducers
What drugs may cause hypoglyceamia and therefore reduce the amount of insulin a patient needs?
ACE inhibitors!
Other oral antidiabetics
NSAID + quinolone (ciprofloxacin, Levofloxacin)
Possible increased risk of seizures
NSAIDS are cautioned with other drugs increasing bleed risk. Can you think of any examples? (5)
SSRIs
Heparins
Dabigatran (NOAC)
Antiplatelets- clopidogrel, aspirin (itself is an NSAID)
NSAID + Diuretics
Increased risk of nephrotoxicity
NSAIDs will also antagonise the diuretic effects: Fluid retention! Can cause ankle swelling and high blood pressure with chronic use
NSAIDs + anti-hypertensives (beta-blockers, CCB’s, ACE inhibitors, alpha-blockers [tamsulosin, doxazosin] nitrates)
NSAIDs themselves can cause high BP
They antagonise the hypotensive effects of these drugs
Which opioid can enhance the anticoagulant effect of coumarins (warfarin)
Tramadol
Which antibiotic can reduce the effectiveness of most of the opioids, including fentanyl, morphine, codeine, methadone?
RIFAMPICIN!! (enzyme inducer)
Opioids can reduce BP (hypotensive)
Their hypotensive and sedative effects are increased by alcohol.
What happens if given with MAOIs?
Possible CNS excitation or depression
Hypotension or hypertension can occur
(remember MAOIs can cause hypotensive crisis)
Clopidogrel + enzyme inhibitors
Some of the enzyme inhibitors (erythromycin, cimetidine, ciprofloxacin, fluconazole, ketoconazole) actually REDUCE clopidogrels antiplatelet effect!- dont get confused in exam!
Clopidogrel + PPI’s
Antiplatelet effect REDUCED by omeprazole and esomeprazole
Pantoprazole safest PPI to use, or H2 antagonist
Sotalol + loop or thiazide diuretics
risk of ventricular arrhythmias caused by sotolol is increased by diuretics due to their hypokaleamia effect
Lithium + ACE inhibitors
ACE inhibitors will decrease the excretion of lithium!
Nothing to do with electrolyte disturbance
Lithium + Beta blockers
No interaction!
Lithium + Aminophylline/ Theophylline
These will increase the excretion of lithium, reducing its levels
NSAIDs + Lithium
Excretion of lithium reduced by NSAIDs so increased risk of Lithium Toxicity!
Lithium + SSRIs
Increased risk of CNS effects, lithium toxicity
think SSRI’s cause hyponatreamia- sodium levels effect lithium
Methotrexate and Aspirin
Methotrexate toxicity increased
As Aspirin and NSAIDs decrease methotrexate excretion
Doxycycline + Isotretinoin
Severe headache/ visual disturbance due to cranial (brain) hypertension
Atorvastatin and clarithromycin
increased risk of myopathy
Co-trimoxazole + Spironolactone
Increased risk of hyperkaleamia
Metronidazole + Mebendazole
severe skin reaction
Baclofen + ACE inhibitors
Baclofen enhances hypotensive effect
Baclofen + beta blockers
Baclofen enhances hypotensive effect
Alpha blockers (sildenafil) + nitrates (isosorbide mononitrate)
Enhanced hypotension effects
