Drug and drug disease interactions

Question 1

What does drug variability lead to?

Answer 1

Loss of efficacy

Unexpected side effects or toxicity

Question 2

What are the three different types of drug variability?

Answer 2

Pharmacokinetic
Pharmacodynamic
Idiosyncratic

Question 3

What is pharmacokinetic variability?

Answer 3

Different concentrations of the drug reaching the site of action.

‘What the body does to the drug that varies the amount’

Question 4

What is pharmacodynamic variability?

Answer 4

Different degree of response to the same drug concentration.

‘What the drug does to the body - changes to receptors etc’

Question 5

What is idiosyncratic variability?

Answer 5

Different unpredictable response.

‘Differences in response but we don’t really understand why’

Question 6

How does age affect drug metabolism?

Answer 6

Drug metabolism is slower in young children and older people as young children have immature organ function eg liver, and older people have failing organ function.

Question 7

How does age affect renal excretion?

Answer 7

Renal excretion is less efficient in young children and older people

Question 8

What is pharmacogenetics?

Answer 8

How different individual genotypes relate to different drug responses

Question 9

What is pharmacogenomics?

Answer 9

This is pharmacogenetics applied to the whole genome

Question 10

What are the group of oxidases that affect breakdown of metabolites called? Polymorphisms in these can lead to differences in drug metabolism and adverse recations.

Answer 10

Cytochrome P450 (CYP450)

Question 11

Which groups of patients are at high risk for harmful drug interactions?

Answer 11

Elderly
Those with hepatic and renal disease
Multiple drug prescriptions (polypharmacy)
Patients taking drugs with narrow therapeutic ranges eg phenytoin

Question 12

What are the 4 levels at which drug interactions can occur?

Answer 12

A- absorption. At the pharmaceutical level: due to chemical interactions when drugs are mixed eg solubility.

D - distribution. At the pharmacokinetic level 1: Drugs might interfere with each other’s absorption or alter their distribution.

M - metabolism. At the pharmacokinetic level 2: Drugs may affect the metabolism or excretion of other drugs.

E - excretion. At the pharmacodynamic level: Drugs may interfere with others at the site of action - receptors, enzymes etc.

Question 13

Name 4 types of pharmacodynamic interactions

Answer 13

Agonism at receptor. Occurs with 2 drugs of the same/ similar class eg multiple opioids

Antagonism at receptor. Occurs in giving drugs of opposing classes eg opiate analgesics and naloxone or beta blockers and beta 2 agonist such as salbutamol

Non selective drug nature. Drugs are capable of binding similar receptors elsewhere in the body, where therapeutic action is not required. eg antidepressants interact with many receptor subtypes (anti-muscarinics)

Enhanced effect by other means. eg increased digoxin toxicity by hypokalaemia caused by loop diuretic eg furosemide.
(Furosemide makes you pass out more Na+ and K+, digoxin is sensitive to K+ levels.)

Question 14

How does the pharmacodynamic interaction ‘agonism at receptor’ occur?

Answer 14

Occurs with 2 drugs of the same/ similar class eg multiple opioids

Question 15

How does the pharmacodynamic interaction ‘antagonism at receptor’ occur?

Answer 15

Occurs in giving drugs of opposing classes eg opiate analgesics and naloxone or beta blockers and beta 2 agonist such as salbutamol

Question 16

How does the pharmacodynamic interaction ‘non selective drug nature’ occur?

Answer 16

Drugs are capable of binding similar receptors elsewhere in the body, where therapeutic action is not required. eg antidepressants interact with many receptor subtypes (anti-muscarinics)

Question 17

How does the pharmacodynamic interaction ‘enhanced effect by other means’ occur?

Answer 17

Enhanced effect by other means. eg increased digoxin toxicity by hypokalaemia caused by loop diuretic eg furosemide.
(Furosemide makes you pass out more Na+ and K+, digoxin is sensitive to K+ levels.)

Question 18

What 3 factors alter drug absorbtion?

Answer 18

Changes in gut motility

Interference with absorption and enterohepatic circulation

Altered P-Glycoprotein Activity

Question 19

Which drugs can alter gut motility?

Answer 19

Opiates and atropine slow gut down

Metoclopramide speeds gut up

Question 20

Which drugs interfere with absorption and enterohepatic circulation?

Answer 20

Calcium salts bind tetracyclines in gut
Cholestyramine binds warfarin and digoxin
Use of activated charcoal to bind drugs in gut after overdose