Interactions Flashcards by Olivia Watkins

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

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Phenytoin and Warfarin

Phenytoin (p450 enzyme INDUCER) induces warfarins metabolism, decreases warfarin concentration, reduced anti-coagulation effect, decreases INR

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Phenytoin and COC

Phenytoin (a p450 enzyme inducer) accelerates metabolism of Oestrogens, reducing their effectiveness

Patient should be changed to an IUD

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Phenytoin and Fluoxetine

Fluoxetine increases phenytoin concentration

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Phenytoin and Theophylline

Theophylline decreases phenytoin concentration

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Phenytoin and St Johns Wort

St Johns Wort decreases phenytoin concentration

St Johns Wort is an enzyme inducer

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Phenytoin and Fluconazole

Fluconazole increases phenytoin concentration (Fluconazole enzyme inhibitor part of SICKFACES)

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Phenytoin and Cimetidine

Cimetidine increases phenytoin concentration (Cimetidine enzyme inhibitor part of SICKFACES)

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Phenytoin and Diltiazem

Diltiazem increases phenytoin levels, and diltiazems own effects are decreased by phenytoin

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Phenytoin and Rate limiting CCB’s

Phenytoin decreases effects of Verapamil and Diltiazem and also Felodipine

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Amiodarone and Grapefruit Juice

Grapefruit Juice increases levels of Amiodarone

Grapefruit Juice is an enzyme inhibitor

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Amiodarone and warfarin

Amiodarone increases warfarin levels
Enhances anti-coagulant effects, increased bleed risk

Amiodarone is an inhibitor of some of the CYP450 enzymes.

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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

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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

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Amiodarone and Lithium

Increased risk of Ventricular Arrhythmias
(poss associated with QT prolongation)

Also both effect THYROID function

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Amiodarone and Digoxin

Amiodarone increases plasma level of Digoxin, leading to digoxin toxicity

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Theophylline + enzyme inhibitors:

Cimetidine, Fluconazole, Ketoconazole, Ciprofloxcin, Erythromycin

Theophylline levels increased as it is metabolised by the CYP450 enzymes

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Theophylline + enzyme Inducers:
Carbamazepine, Alcohol, Phenobarbital, Phenytoin, Rifampicin, St Johns Wort
(SCRAP GP’s)

Theophylline levels decreased

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Theophylline and Quinolone antibiotics e.g. Ciprofloxaxin, Levofloxacin

Increased risk of SEIZURES

These BOTH lower seizure threshold

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What do diltiazem and Verapamil (rate limiting CCBs) do to Theophyllines concentration?

Increase it

these are CYP3A4 enzyme inhibitors!

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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

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SSRI’s and TCA’s and warfarin

SSRI’s and TCA’s will increase warfarin levels- increased anticoagulant effect

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Statins and warfarin

Only statin that interacts: Rosuvastatin

Increased effects of warfarin

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Clopidogrel and warfarin

Anti-coagulant effect enhance (both thin blood)- increased risk of bleeds

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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