Drug-Drug interactions

Question 1

5 Rs of prescribing

Answer 1

• Right patient
• Right drug
• Right route
• Right time
• Right dose

Question 2

High risk patients of drug-drug interaction

Answer 2

• Increases exponentially with the number of medicaments
• Elderly
• Young
• Critically ill
• Patients undergoing complicated surgical procedures
• Diseases: liver, renal, diabetes, epilepsy, asthma
• Interactions which are minor in normal patients can be really severe in other patients

Question 3

Drug-drug interaction definition

Answer 3

• Modification of a drug’s effect by prior or concomitant administration

Question 4

Types of drug interactions

Answer 4

• Drug-drug
• Herbal-drug
• Food-drug
• Pharmacogenetic interactions

Question 5

Characteristics of drugs likely to have a drug-drug interaction

Answer 5

• All these drugs are potent with a narrow therapeutic index: small change in blood levels can induce profound toxicity.
• Why it is necessary to have therapeutic drug monitoring

Question 6

Mechanisms of drug-drug interaction: Absorption

Answer 6

• Formation of insoluble complexes
• Altered pH
• Altered bacterial flora
• Altered GI motility

Question 7

How altered pH affected drug-drug interactions

Answer 7

• Absorption dependent on pH

- H2 antagonists, proton pump blockers (omeprazole) and antacid reduce H+ and increase the pH

Question 8

How altered bacterial flora affected drug-drug interactions

Answer 8

• Usually found in the large bowel
• Broad spectrum antibiotics destroy normal gut flora
• May lead to failure of OCP or digoxin toxicity

Question 9

How altered GI motility affected drug-drug interactions

Answer 9

• Complex
• Most of these interactions change absorption rate, not extent of absorption -> affects half life
• Some drugs bind to each other in GI tract: tetracycline and erythromycin complex with iron, calcium and magnesium
• Most oral medicines are absorbed in the small intestine
• Gastric emptying is rate limiting step.

Question 10

Drugs that affect gastric emptying

Answer 10

• Delay emptying: anticholinergics, tricyclic, anti-depressants, opiates
• Increase gastric emptying and accelerate absorption of paracetamol: domeperidone, metoclopramide

Question 11

Mechanisms of drug-drug interaction: Distribution

Answer 11

• Protein-protein placement

- Protein-binding displacement

Question 12

How altered protein-binding displacement affected drug-drug interactions

Answer 12

• reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
• Results in increased bioavailability of displaced drug
• Type of interaction is common but patients are protected by increased metabolism and excretion

Question 13

Examples of protein-binding displacement drugs

Answer 13

• Indomethacin and warfarin
• 95% of drugs have protein binding: amitripyline, furosemide, ibuprofen
• Lithium, as an antiepileptic has the same symptoms as the disease

Question 14

Mechanisms of drug-drug interaction: Metabolism

Answer 14

• Occur when one drug induces or inhibits the metabolism of another
• Through Cytochrome P450

Question 15

Examples of drugs that inhibit cytochrome system

Answer 15

• Clarithromycin
• Erythromycin
• Omeprazole

Question 16

Examples of drugs that inhibit cytochrome inducers, increase metabolism

Answer 16

• Carbamazepine
• Phenytoin (w/warfarin, steroids, OCP)
• Rifampicin (ciclosporin, warfarin, OCP)
• Tobacco smoke

Question 17

Elimination

Answer 17

• Most drugs excreted in urine or bile
• If patient gets dehydrated, they get renal damage due to nephrotoxicity of drug, stop drinking and this changes the GFR or tubular secretion
• Have to monitor bloods and fluid intake
• Loop diuretic increase tubular reabsorption e.g. furosemide

Question 18

Examples of toxic agents eliminated by kidney

Answer 18

Digoxin and lithium are examples of toxic agents eliminated by kidney

Question 19

Pharmacodynamic drug-drug interactions

Answer 19

• 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

Question 20

Synergistic or additive drugs

Answer 20

• Two drugs with the same pharmacological effect acting on the same receptor are given concurrently, effect can be additive or multiplicative

Question 21

Indirect agonism

Answer 21

• Central nervous system depression: Benzodiazepines and tricyclics or alcohol
• Warfarin and NSAIDs (Indomethacin)
• Atenolol and verapamil

Question 22

Antagonistic

Answer 22

• Direct antagonism: beta-blockers such as atenolol will block the actions of antagonists
• Indirect antagonism: NSAIDS raise blood pressure and antihypertensives lower BP

Question 23

Examples of pharmacodynamic drug interactions

Answer 23

• Synergistic or additive
• Antagonistic
• Interactions due to changes in drug transport
• Interactions due to fldui and electrolyte disturbances
• Indirect pharmacodynamic interactions

Question 24

Object drug

Answer 24

Drug whose activity is affected by such an interaction

Question 25

Precipitant

Answer 25

• Agent which precipitates such an interaction

Question 26

Examples of drug interactions which are not always detrimental

Answer 26

• Treatment of hypertension

- Treatment of Parkinsonism with carbidopa and levidopa. Carbidopa prevents the side effects of levodopa

Question 27

How to deal with an interaction

Answer 27

• Is the interaction detrimental or desired?
• Is the interaction clinically important
• Will altering the dose timing solve the interaction?
• Will using an alternative solve the interaction

If altering the timing or no alternative solve the issues then adjust the drug dosage and monitor drug level (TDM) and physiological functions