Interactions Flashcards
Name the enzyme inhibitors (SICKFACES.COM)
Sodium valproate Isoniazid / itraconazole Cimetidine Ketoconazole Fluconazole / fluoxetine Alcohol (acute, binge) / Amiodarone Chloramphenicol Erythromycin + clarithromycin Sulphonamides (co-trimoxazole) Ciprofloxacin Omeprazole Metronidazole
Also:
Grapefruit juice
Name the enzyme inducers (SCRAP GPSS)
Sulphonylureas Carbamazepine Rifampicin Alcohol (chronic) Phenytoin
Griseofulvin
Phenobarbital
St John’s Wort
Smoking
What are the main interactions with amiodarone? WARFARIN BETA BLOCKERS LITHIUM DIGOXIN
- Amiodarone inhibits warfarin metabolism- enhanced anticoagulant effect
- Increased risk of bradycardia, AV block, myocardial depression with beta blockers
- Risk of ventricular arrhythmias with lithium; both prolong QT
- Plasma concentration of digoxin increased by amiodarone. half dose of digoxin if used concurrently.
Amiodarone has a very long half life so there is potential for drug interactions to occur weeks/months after stopping treatment.
What are the common interactions with digoxin? Amiodarone Erythromycin Rifampicin St John's wort Loop/Thiazide diuretics CCBs
- Plasma conc of digoxin increased by amiodarone (enzyme inhibitor)
- Plasma conc of digoxin increased by erythromycin (enzyme inhibitor)
- Plasma conc of digoxin reduced by rifampicin (enzyme inducer)
- Plasma conc of digoxin reduced by St John’s Worst (enzyme inducer)
- Increased toxicity of digoxin if hypokalaemia occurs with loop and thiazide diuretics
- Plasma conc of digoxin increased by CCBs
What are the common interactions with lithium? ACEi NSAIDs Loop/Thiazide diuretics Amiodarone
- Risk of lithium toxicity with ACEi (kidney excretion reduced)
- Risk of lithium toxicity with NSAIDs (excretion reduced)
- Sodium depletion with loop and thiazide diuretics (excretion of lithium reduced)
- Risk of ventricular arrhythmias with amiodarone; prolong QT interval
Therapeutic dose: 0.4 - 1 mmol/L measured 12 hrs after dose. tests BMI, eGFT, TFTs, U&Es done every 6 months.
brand specific
overdose; n+v, diarrhoea, polyuria, fine tremor
What are the common interactions with methotrexate? Vaccines PPIs Penicillins Trimethoprim NSAIDs alcohol + doxycycline carbamazepine + clozapine
- ^risk of infection with vaccines
- PPIs at ^doses reduce clearance of MTX = increasing risk of toxicity
- Penicillins increases risk of MTX toxicity
- Trimethoprim- both folate antagonists, increased risk of side effects and nephrotoxicity
- NSAIDs; inhibit renal excretion = ^MTX
- alcohol = hepatotoxicity
- doxycycline = hepatotoxicity
- carbamazepine = myelosuppression
- clozapine = myelosuppresion
What are the common interactions with phenytoin? NSAIDs Amiodarone Warfarin Fluoxetine Cimetidine St John's wort Ciprofloxacin Contraceptive pill NOACs
- NSAIDs enhance phenytoin
- Amiodarone = ^ phenytoin SE
- Phenytoin = accelerates metabolism of warfarin
- Cimetidine = inhibitor ^ phenytoin
- Fluoxetine = inhibitor ^ phenytoin
- St John’s Wort = inducer low phenytoin
- Ciprofloxacin =inducer low phenytoin
- Decreases efficacy of COC pill
- Phenytoin decreases exposure to NOACS
Enzyme inducers: CRAPGPSS Carbamazepine Rifampicin Alcohol Phenobarbitol Griseofulvin Phenytoin St Johns Wort Sulphonylureas
Enzyme inhibitors: SICKFACES.COM Sodium valproate Itraconazole + Isoniazid Cimetidine Fluconazole + Fluoxetine Alcohol, Amiodarone Ciprofloxacin Erythromycin Sulphonamides . Grapefruit juice Chloramphenicol Omeprazole Metronidazole
What are the common interactions with theophylline? Quinolones St Johns Wort Rifampicin Cimetidine Fluconazole Smoking St John's Wort
- Increased !! CONVULSIONS !! with quinolones e.g. ciprofloxacin
- Plasma [theophylline] reduced by St John’s Wort (inducer)
- Plasma [theophylline] reduced by rifampicin (inducer)
- Plasma [theophylline] increased by cimetidine (inhibitor)
- Plasma [theophylline] increased by fluconazole (inhibitor)
- Smoking can increase theophylline clearance and increased doses of theophylline are therefore required
What are the common interactions with warfarin? ▪︎NSAIDs ▪︎fluconazole ▪︎statins ▪︎ciprofloxacin erythromycin metronidazole ▪︎griseofulvin ▪︎alcohol ▪︎vitamin K ▪︎cranberry juice ▪︎antiepileptics
- Anticoagulant effect increased by NSAIDs
- Anticoagulant effect increased by fluconazole
- Anticoagulant effect increased by statins
- Anticoagulant effect increased by ciprofloxacin, erythromycin, metronidazole
- Anticoagulant effect reduced by griseofulvin
- Anticoagulant effect reduced by antiepileptics
- Alcohol effects anticoagulant control
- Anticoagulant effect antagonised by Vitamin K
- Anticoagulant effect enhanced by cranberry juice
What is the risk of consuming tyramine based food and drink e.g. cheese if on MAOIs?
Hypertensive crisis
How does alcohol interact with TCAs and mirtazapine?
Alcohol x TCAs / Mirtazepine
Alcohol x Metrondiazole / chloramphenicol
Increased sedative effect - TCAs / mirtazepine
A disulfiram-like drug is a drug that causes an ADR to alcohol = n+v, flushing, dizziness, throbbing headache, chest and abdominal discomfort, and general hangover-like symptoms among others.
What are the main interactions with combined oral contraceptives?
- Enzyme inducing drugs ^ metabolism of COC. Additional contraceptive precautions should be taken for 4-8 weeks after stopping treatment.
- Some antibiotics may reduce efficacy by impairing bacterial flora responsible for recycling ethinylestradiol e.g. ampicillin, amoxicillin, doxycycline. Additional precautions are required for duration of treatment and for 7 days after stopping
What are the main interactions with progesterone only contraceptives?
Efficacy reduced by enzyme inducers
SCRAPGPSS
Additional protection is needed for duration of treatment and 4 weeks after
What are the main interactions with sympathomimetics e.g. pseudoephedrine?
- MAOI- hypertensive crisis
- Beta blockers- hypertension risk
What are the main interactions with Orlistat? Amiodarone Anticoagulants Acarbose Ciclosporin
- Orlistat reduces plasma conc of amiodarone
- Anticoagulants- monitor as bleeding more easily, reduce absorption fat soluble vit (K)
- Acarbose for DB due to its GI effects
- Reduces absorption of ciclosporin
Orlistat might affect the absorption of concurrently administered drugs—consider separating administration. Particular care should be taken with AED, antiretrovirals, and narrow therapeutic index drhgs.
What is a pharmacokinetic interaction?
When drug alters the absorption, distribution, metabolism, or excretion (ADME) of another drug, thus increasing or reducing the amount of drug available to produce its pharmacological effects.
- Sickfaces.com inhibitors
- Scrapgpss inducers
What is a pharmacodynamic interaction?
This is where effects of one drug are changed by the presence of another drug at its pharmacological site of action.
e.g. electrolyte imbalance, combined toxicity, antagonising effects
What PPI does clopidogrel interact with and what would be an alternative?
Omeprazole and esomeprazole = reduces the inhibition of platelet aggregation, whether the two medicines are given simultaneously or 12 hours apart.
Lansoprazole would be an alternative
What drug can cause blue vision and which drug can cause yellow vision in overdose
Blue vision can be cause by sildenafil and yellow vision is a sign of digoxin toxicity alongside n+v
Which SGLT is not licensed to be used with pioglitazone for triple therapy
Dapagflozin
10 interactions you should know
- Fluoxetine and Phenelzine
- Digoxin and Quinidine
- Sildenafil and Isosorbide Mononitrate
- Potassium Chloride and Spironolactone
- Clonidine and Propranolol
- Warfarin and Diflunisal
- Theophylline and Ciprofloxacin
- Pimozide and Ketoconazole
- Methotrexate and Probenecid
- Bromocriptine and Pseudoephedrine
- Fluoxetine + Phenelzine:
- serotonin syndrome: mental changes, agitation, sweating, tachycardia, death.
- SS = any MAOI (tranylcypromine) + any drug that ^serotonin lvls, e.g. dextromethorphan, meperidine, other SSRIs.
- Stop Fluox. 5 weeks b4 MAOI.
- Stop MAOI 2 weeks b4 SSRI. - Digoxin + Quinidine:
- dec. VoD => dig tox <24 hrs.
- dec. renal/nonrenal excretion dig
- Avg ^x2; n+v - death.
- Digoxin half dose. - Sildenafil + ISMN:
- ^ hypotensive effects of ISMN. PDE5 inhibitors + nitrates can cause intense ^ cGMP & BP drop.
- Pts taking ISMN/nitrate, incl. nitroglycerin, should not take sildenafil. - KCl + Spironolactone:
- Hyperkalaemia => cardiac failure/death.
- Renal impairment pt at risk.
- Spiron. = comp. antag. of mineral corticoids (aldosterone) in distal portion of nephron => excretion of Na+ while saving K+ ions. Pts with K-depleting diuretics eg amiloride or triamterene, may also hv this interaction. Severe hyperK is dangerous: monitor serum [K+] - Clonidine + Propranolol:
- HTN unrelated to individual pharmacology.
- sudden withdrawal of clonidine from combo therapy => fatal rebound HTN.
- Clonidine = a-2 agonist: suppresses sympathetic NS from the brain = decrease in NE in the synaptic cleft => Alpha-1 rec become ^sensitized. When clonidine is suddenly withdrawn = sudden ^NE => sensitized a-1 rec stimulated => exaggerated vasoconstriction. The body cannot compensate because the b-2 rec are blocked by propranolol. 24 to 72 hours = dramatic rebound hypertension - Warfarin + Diflunisal:
- NSAID (diflunisal) ^risk GI bleeding & anticoagulant response
- In most patients, indomethacin has little effect on hypothrombinemic response.
- Paracetamol is alternative of choice but if NSAID; nonacetylated salicylates e.g. Mg salicylate are safer: min effects on platelets and gastric mucosa. - Theophylline + Ciprofloxacin;
- Ciproflox CYP1A2 enz inhibitor
- Alt; levofloxacin/ofloxacin
- Signs of theophylline toxicity: headache, dizziness, hypotension, hallucinations, tachycardia, and seizures - Pimozide + Ketoconazole:
- Pimozide alone = prolong QT interval, and linked with ventricular arrhythmias (TdP).
- Pimozide = CYP3A4 substrate, ketoconazole = potent CYP3A4 inhibitor
- Other: itraconazole, clarithromycin, erythromycin, diltiazem, and nefazodone = also potent CYP3A4 inhibitors.
- Fluconazole weaker but inhibits in larger doses. Terbinafine safer choice - does not affect CYP3A4. - MTX and Probenecid:
- 2 to 3-fold ^MTX = diarrhoea, n+v, diaphoresis, renal failure, death.
- Probenecid acts as active tubular secretion inhibitor and prevents MTX excretion.
- Also with penicillins and salicylates.
- low-dose MTX (arthritis) is lower risk; in fact, NSAIDs in combo with low-dose MTX are often prescribed purposely.
- Alt: paracetamol, Celecoxib does not affect MTX pharmacokinetics. However, rofecoxib produces some ^ in [MTX] - Bromocriptine and Pseudoephedrine;
- severe peripheral vasoconstriction, ventricular tachycardia, seizures, death
- Bromocriptine = ergot-derived dopamine agonist [antiparkinsonian therapy].
- SE: thickening of bronchial secretions and nasal congestion. Sig as pt on bromocriptine likely to self medicate OTC decongestant such as pseudoephedrine.
- Patients receiving bromocriptine should be advised to avoid all sympathomime-tics.
Clarithromycin X Amitryptyline
Prolong QT interval
- amitryptyline [TCA]
- amiodarone [class III anitarrhythmic]
- amisulpride [antipsychotic]
- chlorpromazine [schizophrenic drug]
- haloperidol [antipsychotic, 3A4 inhibitor]
- olanzapine [atypical antipsychotic]
- quetiapine [atypical antipsychotic]
Isocarboxid x Amitriptyline
MAOI x TCA
Amitriptyline increases risk of severe toxic rxn with isocarboxazid. Wait 2 weeks after discontinuing MAOIs before starting SSRIs.
Examples of MAOIs - rasagiline (Azilect), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate).
Simvastatin x amlodipine
Amlodipine => ^ blood levels ofsimvastatin.
In practice, effect is x2 that compared to uninhibitedsimvastatin.
- patients onamlo10mg + simvastatin20mg, = effect of having simvastatin40mg alone. Limit to 20mg.