Individual Variability in Response to Drugs

Question 1

What are the internal and external factors influencing variability in response?

Answer 1

INTERNAL - disease, age and genetics
EXTERNAL - drug interactions, lifestyle

Question 2

Describe the effect of disease on pharmacokinetics. PART 1

Answer 2

• HEART DISEASE - Reduced blood flow Reduced clearance and transport to liver for metabolism.
• THYROID DISEASE - metabolism reduced in hypothyroidisim

Question 3

Describe the effect of disease on pharmacokinetics. PART 2

Answer 3

• LIVER DISEASE - reduced first pass metabolism. High bioavailability so reduced dose required.
• RENAL DISEASE - Altered renal elimination rate - drug is not inactivated by metabolism and excreted unchanged.

Question 4

How does old age alter pharmacokinetics?

Answer 4

• Decline in metabolic activity with age
• Age related decrease in liver mass and hepatic blood flow
• Variability in half life of drugs
• Increased risk of drug-drug interactions due to more frequent taking of medication

Question 5

How can pharmacokinetics be affected in neonates?

Answer 5

• Low activity of cytochrome P450
• Reduced conjugating activity

Question 6

How are distribution and renal excretion affected during aging?

Answer 6

• DISTRIBUTION - decreased Vd of hydrophilic drugs. Due to increase in body fat.
• EXCRETION - reduced due to reduced GFR and tubular secretion

Question 7

How can antacids influence absorption?

Answer 7

• Altered pH
• Altered percentage of drug in neutral format

Question 8

How can plasma protein binding affect distribution?

Answer 8

• Less binding = greater efficacy and diffusion across membrane
• Greater binding = more confined to plasma
• Only unbound are pharmacologically active
• Reduced plasma protein counts in infants and elderly. More of drug is bioavailable so reduced dose required.

Question 9

Describe enzyme induction.

Answer 9

• Increased effectiveness of enzyme
• Faster metabolism and shorter duration of action.
• Reduction in plasma half-life and efficacy.
• HIGHER DOSE REQUIRED

Question 10

Describe enzyme inhibition.

Answer 10

• Prolonged metabolism of drugs
• Longer duration of action
• Increased efficacy
• EXAMPLE - grapefruit juice interfres with statins

Question 11

Explain how pharmacogenetic variation can influence responses to drugs.

Answer 11

• Cytochrome P450 enzymes display polymorphic expression
• Alters enzyme activity and levels of metabolism
• Higher drug concentrations following dosage = slow metabolisers
• Duration of drug action varies amongst individuals

Question 12

What is Asian Flush?

Answer 12

• Altered form of aldehyde dehydrogenase in 30-50% of people particularly in Asians
• Causes flushed skin, SOB, blurred vision, vomiting

Question 13

What are the two types of pharmacodynamic interactions?

Answer 13

• ADDITIVE - drugs with similar effects
• Competing effects of drugs with opposite actions

Question 14

What does tolerance mean?

Answer 14

Reduction in response to a drug after repeated administration

Question 15

What does desensitisation refer to?

Answer 15

• Receptors continually change conformation over time
• Receptor downregulation
• Decreased activity of intracellular signalling pathways