Interactions COPY 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?
- Amiodarone inhibits warfarin metabolism- enhanced anticoagulant effect
- Increased risk of bradycardia, AV block, myocardial depression with beta blockers
- Risk of ventricular arrhythmias with lithium
- Plasma concentration of digoxin increased by amiodarone
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?
- 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?
- Risk of lithium toxicity with ACEi (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
What are the common interactions with methotrexate?
- Increased risk of infection with vaccines
- PPIs at high doses reduce clearance of methotrexate increasing risk of toxicity
- Penicillins increases risk of methotrexate toxicity
- Trimethoprim- both folate antagonists, increased risk of side effects and nephrotoxicity
What are the common interactions with phenytoin?
- Effects of phenytoin enhanced by NSAIDs
- Amiodarone inhibits phenytoin metabolism
- Phenytoin accelerates metabolism of warfarin
- Cimeditine inhibits metabolism of phenytoin
- Plasma conc of phenytoin increased by fluoxetine
- St John’s Wort reduces plasma conc of phenytoin
- Ciprofloxacin affects the concentration of phenytoin
- Decreases efficacy of combined contraceptive pill
- Phenytoin decreases exposure to NOACS
What are the common interactions with theophylline?
- Increased risk of convulsions with quinolones e.g. ciprofloxacin
- Plasma conc of theophylline reduced by St John’s Wort
- Plasma conc of theophylline reduced by rifampicin
- Plasma conc of theophylline increased by cimetidine
- Plasma conc of theophylline increased by fluconazole
- Smoking can increase theophylline clearance and increased doses of theophylline are therefore required
What are the common interactions with warfarin?
- 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?
Increased sedative effect
What are the main interactions with combined oral contraceptives?
- Enzyme inducing drugs increase metabolism of contraceptives. Additional contraceptive precautions should be taken for 4-8 weeks after stopping treatment
- Some ABX may reduce efficacy of the pill 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
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?
- Orlistat reduces plasma conc of amiodarone
- Anticoagulants- monitor
- Acarbose for diabetes due to its GI effects
- Reduces absorption of ciclosporin
What is a pharmacokinetic interaction?
These occur when one drug alters the absorption, distribution, metabolism, or
excretion of another drug, thus increasing or reducing the amount of drug available
to produce its pharmacological effects.
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
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 slidenafil and yellow vision is a sign of digoxin toxicity alongside nausea and vomiting
Which SGLT is not licensed to be used with pioglitazone for triple therapy
Dapagflozin
What is drug interaction?
the modifications of effects of one drug by another drug (poly-pharmacy)
What is drug interaction? Pharmacodynamics (PD)
(“what the drug does to the body”)
related to the pharmacological activity of the interacting drugs leading to either:
synergistic effect, 1+1 > 2
or antagonistic effect, 1+1 < 2
What is drug interaction? Pharmacokinetic (PK)
(“what the body does to the drug”) related to the effect of a drug on another on physical disposition of the drug, i.e. movement of drug thru the body absorption distribution metabolism elimination
Effects of drug interaction
Increased effect: Additive or Synergistic
effect
BAD - Increased toxic effect GOOD - Increased therapeutic effect to produce synergistic therapeutic effects e.g. several antibiotic combinations Penicillin-Streptomycin
PD interactions arise when one drug changes the response of target or non-target tissues to another drug:
• Synergism
– Penicillin-Streptomycin
– Digoxin toxicity with diuretic induced potassium wasting
PD interactions arise when one drug changes the response of target or non-target tissues to another drug:
• Antagonism
– Beta adrenoceptor antagonist diminish the effectiveness of b-adrenoceptor agonists such as salbutamol
– Antidote: agents with a specific action against the activity or effect of drugs involved in poisoning cases
PK absorption eg. Altered pH; The non-ionized form of a drug is more lipid soluble and more readily absorbed from GIT than the
ionized form does.
-Ex1., antacids (aluminum or magnesium
hydroxide) Increase the pH and Reduce absorption of acidic drugs
digoxin (heart conditions), phenytoin (epilepsy), chlorpromazine (schizophrenia) isoniazid (tuberculosis) Therefore, these drugs must be separated by at least 2h in the time of administration of both.
PK absorption eg H2 antagonists increase the pH and Reduce absorption of acidic drugs:
digoxin (heart conditions), phenytoin (epilepsy), chlorpromazine (schizophrenia) isoniazid (tuberculosis) Therefore, these drugs must be separated by at least 2h in the time of administration of both.
Altered motility: Atropine (non-selective muscarinic blocker) Increase absorption of cyclosporine due to the increase of stomach emptying time and Increase the toxicity of cyclosporine example of - PD - PK absorption - PK excretion - PK metabolism - PK distribution
PK absorption
Chelation - Iron may chelate ciprofloxacin, resulting in decreased absorption example of - PD - PK absorption - PK excretion - PK metabolism - PK distribution
PK absorption
PK interactions (2): Distribution
• Drugs in bloodstream often bound to plasma proteins;
• Only unbound drugs can leave blood to affect target organs;
• Low albumin levels can increase availability of drugs and potentiate their effects;
• Competitive: drugs with higher affinity to albumin are capable to displace others, leading to increase concentration of free
drug (therefore yield more drug response):
Phenytoin (90%)
Tolbutamide (96%)
Warfarin (99%) –>
Aspirin
Sulfonamides
Phenylbutazone
PK interaction (3):Metabolism
the most drug-drug interactions are metabolism based (diagram)
Phase I metabolism: involves oxidative metabolism via the Cytochrome P450 (CYP) family of enzymes
Enzymatic induction
Inducer: Drug that will increase the synthesis of CYP450 enzymes
e.g. barbiturates, bzd, hydantoin antiepileptics, glucocorticoids, rifampicin, griseofulvin, St. John´s wort, smoking, grilled meat, chronic alcohol
intake – increase
SCRAP GPSS
-Decrease the effect of several drugs, e.g.
cardiotonics, steroid hormones, coumarin
anticoagulants
N.B enzyme induction involves protein synthesis. Therefore, it needs time up to 3 weeks to reach a maximal effect
Enzymatic inhibition
SICKFACES.COM
Inhibitor: Drug that will decrease the metabolism of a substrate
e.g. some macrolides, quinolones, sulfonamides, some antimycotics (e.g. ketoconazole, fluconazole), isoniazid, metronidazole, chloramphenicol,
amiodarone, verapamil, diltiazem, quinidine, SSRI, proton pump inhibitors, cimetidine, garlic, ginkgo, grapefruit juice
-Increase the effect of several drugs
Inhibition of the enzyme may be due to the competition on its binding sites , so the onset of action is short may be within 24h.
When an enzyme inducer (e.g.carbamazepine) is administered with an inhibitor (verapamil) -> the effect of the __________ will be predominant
inhibitor
Omeprazole Inhibits oxidative metabolism of A. aspirin B. diazepam C. sertraline D. clarithromycin
B. diazepam
Omeprazole has actual adverse influences on the pharmacokinetics of medications such as diazepam, carbamazepine, clozapine, indinavir, methotrexate, tacrolimus, mycophenolate mofetil, clopidogrel, digoxin, itraconazole, posaconazole, and oral iron supplementation.
PK interaction (4): Excretion
Drugs are eliminated from the body as an unchanged drug or metabolite
– Renal excretion is the major route of
elimination;
– affected by renal function and urinary pH
Drug-Food
interactions
Tetracycline interacts with Milk (Ca2+ ) -> Unabsorpable complex
Warfarin (diagram)
Vitamin K-containing foods
Drug-Disease interactions
HEART : b1 adrenergic receptors - Heart rate & Contractility
SMOOTH MUSCLE -airway & vasculature:
b2 adrenergic receptors -> Relaxation & dilation
Drug ADR: homologous targets
•Non-selective b antagonists, e.g. Propranolol, are contraindicated in patients with asthma
Drug-Disease interactions:
Contraindications of atropine
1- Patients with angle closure glaucoma
2- Patients with shallow anterior chamber
3- Senile hyperplasia of the prostate
4- Patients with gastric ulcer
(increase symptoms due to slowing gastric emptying)
Changes in absorption
Alteration -GI motility
Alteration/ action
GI motility - Increased GI motility caused by metoclopramide may decrease cefprozil absorption (2nd gen cephalosporin)
GI alkalinization by omeprazole may decrease absorption of A. amantadine B. dapsone C. metronidazole D. ketoconazole
D. ketoconazole
changes in absorption PK
GI flora - Decreased GI bacterial flora caused by an antibiotic admin could decrease bacterial production of vitamin K augmenting anticoagulant effect of
warfarin
Changes in absorption
Alteration -Drug metabolism in wall of intestine
Drug metabolism in wall of intestine -
certain antidepressants is that phenylephrine could potentiate a spike in blood pressure; TCAs and MAOI
MAO acts to break down neurotransmitters like norepinephrine (and dopamine and serotonin); thus, MAOIs act to increase the amount of these chemicals in our synapses. Monoamine oxidases (MAO) are in the wall of GI tract. NE = main neurotransmitter of SNS and works to immediately increase our BP. Thus, a sympathomimetic like phenylephrine + MAOI, which is also stimulating the sympathetic system, has the potential to elevate BP into a hypertensive crisis.
Incidentally, MOA is involved in other body processes including the breakdown of tyramine, an amino acid involved in BP regulation. Tyramine helps release more NE. Thus, to prevent hypertensive crises, patients who take MAOIs should stay away from..
foods rich in tyramine like strong/aged cheeses, cured meats, yeasts, beers and dried fruits.
Phase II metabolism
conjugates the previously oxidized molecule with a water soluble weak acid (glucouronic acid, tauric acid, etc) enhancing overall water solubility
How to do drug-drug interactions occur
Drug-drug interaction always due to interaction at phase I enzymes (i.e. cytochrome P450)
Passive tubular reabsorption example
Sodium bicarbonate. Increases lithium clearance and decreases its action
Antacids Increases salicylates clearance and decreases its action
What happens when pH increases
Ionisation doesn’t occur as it only occurs at acidic pH
PK interactions: Absorption a) b) c) d)
a) altered pH
b) altered motility
c) altered intestinal bacteria flora
d) chelation
which drugs have strong affinity to protein binding
Phenytoin (90%)
Tolbutamide (96%)
Warfarin (99%)
which drugs have weak affinity
Aspirin
Sufonamides
Phenylbutazone
