Pharmacology

Question 1

What proportion of ADRs are preventable?

Answer 1

Approximately half

Question 2

What is the therapeutic index?

Answer 2

The relationship between the concentration causing adverse effects and concentrations causing desired effect

Question 3

Through what mechanism does trimethoprim cause renal tubular acidosis/hyperkalaemia?

Answer 3

Blocks epithelial sodium channels

Question 4

What is pharmacovigilence?

Answer 4

Post marketing surveillence of a drug in the real world population

Question 5

What pharmacokinetic changes occur with old age?

Answer 5

• Absorption: Increased Tmax, decreased Cmax
• Distribution: decreased VD hydrophilic, increased VD lipophilic
• Metabolism: Decreased phase I, decreased phase II in frailty
  -Excretion: decreased CrCl

Question 6

What pharmacodynamic changes occur with old age?

Answer 6

• beta receptors are less sensitive to agonists and antagonists
• More sensitive to sedation with GABA and opioids
• More sensitive to anticholinergic effects from muscarinics
• reduced physiological reserves makes more sensitive to most drug effects

Question 7

In drugs with low hepatic extraction (< 0.3) what influences elimination and clearance?

Answer 7

Enzyme activity

Question 8

In drugs with high hepatic extraction (>0.7) what influences elimination and clearance?

Answer 8

Changes in blood flow

Question 9

What pharmacokinetic changes are seen in liver disease?

Answer 9

• Elimination and metabolism: impaired intrinsic hepatic elimination capacity, impaired biliary excretion, decreased hepatic blood flow
  -Distribution: alter body composition, increased unbound fraction (low Alb)
  -Absorption: increased bioavailability due to reduced first pass extraction, reduced bioavailability due to reduced bile secretion

Question 10

What is the role of HLA-B*15:02 screening when starting carbamazepine?

Answer 10

Indicated in Oceanian, East Asian and South Asians to prevent carbamazepine induced SJS/TEN

Question 11

What transporter is associated with increased risk of statin myopathy?

Answer 11

OATP1B1 on sinusoidal membrane of hepatocytes

Question 12

What are features of the anticholinergic toxidrome?

Answer 12

MAD = altered mental state
BLIND = mydriasis (dilated pupil)
RED = vasodilation
HOT = hyperthermia
DRY = dry mouth, urine retention

Question 13

When should activated charcoal be used for overdose?

Answer 13

For most medicines within 1-2 hours of ingestion

Not useful for acids, alkali, alcohols, ions/metals

Question 14

When should whole bowel irrigation be used for overdose?

Answer 14

Useful for acids, alkali, alcohols, ions/metals
Large overdose
SR preparation

Question 15

What are methods of enhanced elimination for overdose and their mechanism of action?

Answer 15

• Multi-dose activated charcoal: interrupts enterohepatic circulation
  -Urinary alkalisation: increases excretion in urine (salicylates, methotrexate)
• extracorporeal blood purification (Dialysis)

Question 16

What is pharmacokinetics?

Answer 16

How much drug you are exposed to when you take a medicine

Question 17

What is drug exposure?

Answer 17

The systemic concentration over time of the active moiety of an administered drug

Question 18

What are the 4 principles of pharmacokinetics?

Answer 18

ABCD

A- administration (route, adherence)
B - bioavailability (absorption, first pass metabolism, activation)
C - clearance (metabolism, excretion)
D - distribution (diffusion, transport)

Question 19

What are the two physiological parameters that dictate half life?

Answer 19

• size (bigger person has bigger volume of distribution)
• Elimination (faster clearance results in less drug, metabolism)

Question 20

What are the two factors that determine bioavailability?

Answer 20

1. Extent: the proportion of oral medicine reaching systemic circulation, often expressed as F = IV to oral conversion
   High F = low variability in proportion reaching circulation
2. Rate