Drug-Drug interactions Flashcards by Chloe Lee

Definition of drug interaction

Modification of a drugs effect by prior or concomitant administration of another drug, herb, foodstuff, drink

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What can interact with drugs?

Drugs, Herbs, food, drink and pharmacogenetic

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What is the object drugs?

Drug whose activity is effected

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What is the precipitant?

Agents which effects a drugs interaction

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What factors modify drug action?

Smoking, food, alcohol and herbs

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What can drug interaction treat?

Hypertension and Parkinsonism with carbidopa and levadopa

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What is the risk of a patient seeing multiple doctors?

Dangerous as the different doctors prescribe different drugs

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Name drugs involved with serious interactions

Lithium
Digoxin
Warfarin
Theophylline
Cylosporin
Macrolides

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Importance of therapeutic drug monitoring

Drugs involved in serious reactions have a narrow therapeutic index - therefore small change in blood levels can induce toxicity

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Name foods that interact with Warfarin

Vegetables: broccoli, brussellese sprouts, cabbage, onion, spinach

Herbals: green tea, tonic beans, woodruff

Miscellaneous: avocado, fish oils, liver, soybeans

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Name the susceptible patents

Elderly
Young
Critically ill
Patients undergoing complicated surgical procedures

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Conditions that can make patients more susceptible

Liver disease
Renal disease
Diabetes mellitus
Epilepsy
Asthma

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Name the mechanisms of drug interactions

Pharmacodynamic

- Pharmacokinetic - ADME

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What is ADME of drug pharmacokinetics

One drug can alter a drugs:
Absorption
Distribution 
Metabolism 
Elimination

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Describ pharmocodynamic drug interactions

Antagonistic or additive/synergistic
Due to to changes in drug transport
Due to fluid ad electrolyte disturbances

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How can a drug alter ADME?

There is marked inter-individual variation in these process - so predict potential interaction but not able to predict who will have interaction

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Possible absorption interaction outcomes

Formation of insoluble complexes
Altered pH
Altered bacterial flora
Altered GIT motility

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Describe interaction of drugs in the GI tract and how can it be avoided?

Result in change of absorption rate rather than the extent of absorption - this is bad if drug has short half life when high plasma levels rapidly

Delayed absorption can be avoided if 2-4hrs are left between administration

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What drugs bind in the GI tract?

Tetracycine and erythromycin complex with Fe, Ca, Mg

Cholestyramin resin binds cholesterol and also drugs (warfarin, digoxin)

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How does changes in pH affect absorption?

Alters degree of ionisation - H2 antagonists, proton pump blockers and antacids reduce H+ and so increase the pH

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What drugs alter pH?

H2 antagonist, proton pump blockers and antacids

They reduce H+ so increase pH

Describe cause and effect of changes in GI bacterial flora

Broad spectrum antibiotics destroy normal gut flora and lead to failure of oral contraceptive or digoxin toxicity (nausea, vomiting)

What is the rate limiting step in GI motility?

Gastric emptying

What drugs delay gastric emptying?

Anticholinergics, tricyclic anti-depressants, opiates

What drugs increase gastric emptying?

Domperidone and metoclopramide

What is protein-binding displacement?

Occurs when there is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug

What is the effect of protein-binding displacement?

Increases bioavailability of the displaced drug as only unbound drug is pharmacologically active

Two important plasma proteins

Albumin and alpha1-glycoprotein

Problem and solution of protein-binding displacement

1% displacement doubles the free plasma levels but patients are protected by increase in metabolism and excretion

Examples of displacing drug

Indomethacin and warfarin

How do drugs alter drug metabolism

One drug can induces or inhibits the metabolism of another - commonly occurs in the liver via the cytochrome P450 system

What drugs inhibit the cytochrome P450 system in metabolism?

Macrolides, cimetidine, ketoconazole, omeprazole, CCBs (diltiazem)

What drug inhibits metabolism of warfarin and diazepam by the cytochrome P450 system?

Cimetidine

What drug inhibits metabolism of warfarin and alcohol by the cytochrome P450 system?

Metronidazole

What drug inhibits metabolism of warfarin and phenytoin by the cytochrome P450 system?

Omeprazole

What drugs induce cytochrome P450?

Barbiturates, carbamazepine, phenytoin, rifapacin and tobacco smoke

What does enzyme induction (i.e. cytochrome P450) depend on?

Age, disease, genetic and concurrent drug therapies

What drugs do phenytoin induce the metabolism of by cytochrome P450?

Warfarin, steroids and OC

What drugs do rifampacin induce the metabolism of by cytochrome P450?

Warfarin, OC

What drug does rifampacin increase the metabolism of by CYP 3A4?

Ciclosporin

What drug does St John's Wort increase the metabolism of by CYP 3A4?

Ciclosporin

What are drugs excreted in?

Urine or bile

How do drugs effect elimination/excretion?

- Change GFR or tubular secretion | - Dogoxin and lithium are toxic agents eliminated by the kidney - problem could lead to their build up in blood

What drugs inhibit excretion?

CCBs - verapamil, diltiazem

What drugs increase tubular reabsorption in kidneys?

Loop diuretics and lithium

When do pharmacodynamic interactions occur?

When pharmacodynamic actions of a drug are changed due to presence of another drug either acting directly on the same receptor or indirectly on different receptors

What are the types of pharmacodynamic interaction?

Direct Indirect Antagonistic Synergistic/Agonistic

Describe direct antagonism of Pharmacodynamic interactions

Beta-blockers (atenolol) block the actions of agonists i.e. bronchodilators such as salbutamol

Describe synergistic interactions of pharmacodynamic interactions

When two drugs with the same pharmacological effect acting on the same receptor are given together

Name drugs with indirect agonist effect and what the effect is

- Warfarin (anti-coagulant) and NSAIDs (indomethacin) - bleeding becomes increased - Bendodiazepines (sedative) and tricyclics (anti-depressants) or alcohol - relax muscles and cause CNS depression - Atenolol and verapamil

Drugs involved in indirect antagonistic interactions?

NSAIDS and antihypertensive medication or with treatment for heart failure

How do you deal with an interaction?

If altering dose timing or an alternative drug does not solve the issue ADJUST drug dosage and monitor drug level (TDM) and physiological functions