Polypharmacy

Question 1

What is polypharmacy

Answer 1

concurrent use of multiple medication items in one individual

Question 2

What levels can drug-drug interactions occur?

Answer 2

Pharmaceutical
Interaction prior to administration
Pharmacokinetic
Tissue/plasma levels of one drug altered by another one
Pharmacodynamic
Action of one drug is altered by another one

Question 3

What are the outcomes of drug-drug interactions?

Answer 3

Enhanced effect
Inhibited effect
Completely new effects
No change

Question 4

Summation meaning

Answer 4

Combined effect of two drugs that equals the sum of individual effects of each agent
1+1=2

Question 5

Summation example

Answer 5

Midazolam lowers the dose of propofol needed for anaesthesia

Question 6

Potentiation meaning

Answer 6

When a drug on its own does not have an effect but may affect or be affected in combination with another drug
0+1=2

Question 7

Potentiation example

Answer 7

Probenecid reduces penicillin excretion in urine and increases effectiveness of penicillin

Question 8

Synergism meaning

Answer 8

Drug combinations produce a therapeutic or toxic effect greater than sum of each drug’s action
1+1=3

Question 9

Synergism example

Answer 9

Sulphonamide-trimethoprim (enhanced effects)
Aminoglycosides and furosemide (toxicity)

Question 10

Pharmaceutical mechanisms of interactions

Answer 10

Interactions prior to administration
Physical or chemical

Question 11

Physical pharmaceutical mechanisms

Answer 11

Incompatibility reaction
Binding to plastic
E.g. diazepam
Insolubility in certain solutions
E.g. amphotericin B precipitates in electrolyte solutions

Question 12

Chemical pharmaceutical mechanisms

Answer 12

Stability of drugs often pH dependent - activated or inactivated
* E.g. penicillin G is inactivated by alkaline sulphonamide
Oxidation/reduction reactions
* E.g. tetracyclines are oxidised by riboflavin
Complex formation
* E.g. chelation of drugs
Inactivated by certain vehicles
* E.g. Fluoroquinolones can be inactivated in calcium-containing solutions

Question 13

Pharmacokinetic mechanisms of interaction

Answer 13

Tissue/plasma levels of one drug altered by another one
Absorption
Distribution
Metabolism
Excretion

Question 14

Absorption examples

Answer 14

Change in gastric pH and bacterial flora
Chelation of drug in stomach
Altered gastric emptying – can increase or decrease absorption
Interference with intestinal efflux protein (P-glycoprotein)

Question 15

Distribution examples

Answer 15

Competition plasma protein binding
E.g. warfarin and phenylbutazone
Some drugs reduce circulation and blood flow to tissue, leading to:
Reduced absorption from intra-muscular or sub-cutaneous administration
□ I.e. injectable and inhalant anaesthetics
Reduced clearance

Question 16

Metabolism examples

Answer 16

Inhibition/induction of liver enzymes (CYP P450)

Question 17

Metabolism inhibition examples

Answer 17

Chloramphenicol
Fluoroquinolones
Cimetidine
Azole anti-fungals
Calcium channel blocker
Omeprazole
Propofol

Inhibit metabolism of other drugs

Question 18

Metabolism Induction examples

Answer 18

Barbiturates
E.g. phenobartibal, primidone
Cyclosporin
Carbamazepine

Induce metabolism of other drugs

Question 19

Excretion examples

Answer 19

Urinary pH will alter clearance of renally excreted drugs
I.e. sodium bicarbonate makes urine more alkaline
Increases excretion of weak acids

Question 20

Pharmacodynamic mechanisms of action

Answer 20

Additive - could be beneficial or detrimental
Synergistic - combination leads to greater than the sum of each drug’s action
Negation - opposing action leading to reduced effect

Question 21

Additive mechanism

Answer 21

Could enable reduced doses to be administered
E.g. Barbiturates and benzodiazepines in producing sedation/hypnosis
E.g. combinations of opioids and NSAIDs for analgesia
Could lead to increased toxicity
E.g. NSAIDs with steroids lead to increased risk of GI ulceration
E.g. NSAIDs with aminoglycosides increase chance of nephrotoxicity

Question 22

Synergistic mechanism

Answer 22

Produce an enhanced therapeutic effect or increased toxicity
Common examples:
Sulphonamide-trimethoprim or β-lactam antibiotics and aminoglycosides (enhanced)
Aminoglycosides and furosemide (toxicity)

Question 23

Negation mechanism

Answer 23

The basis of antidote / reversal agents:
Atipamezole & medetomidine
The basis of antidote / reversal agents:
Opioids & naloxone

Question 24

Adverse Events

Answer 24

Unintended or noxious response to a drug that occurs within a reasonable time frame following administration