S2 L1 part 1 Pharmacokinetics and Pharmacodynamics

Question 1

What is pharmacokinetics and pharmacodynamics?

Answer 1

- Pharmacokinetics: what the body does to the drug

- Pharmacodynamics: what the drug does to the body

Question 2

What are some of the pharmacokinetic facts we need to know about a drug before it can be approved for use?

Answer 2

Question 3

What are some factors that can affect the pharmacokinetics/Vd of a drug?

Answer 3

Question 4

What is bioavailabilty and what is it affected by?

Answer 4

Amount of drug that gets to the systemic circulation unchanged!

Affected by: formulation, age, food (chelation), vomiting, malabsorption (Crohn’s)
Also: First pass metabolism (metabolism before reaching systemic ciruclation e.g. in gut lumen, gut wall)

100% in IV

Question 5

Why is metformin available in different preparations?

Answer 5

• Modified slow release only needs to be taken once a day, less likely to have GI side effects
• More expensive to have extended release but patients more likely to adhere if less side effects
• Most of the time different preparations are just branding, e.g nurofen period pain

Question 6

What are some factors that affect the distribution of a drug?

Answer 6

• Blood flow
• Lipophilicity
• Hydrophilicty
• Protein binding (difficult to distribute when bound)
• Vd
• Pregnancy
• Hypoalbuminaemia
• Renal failure
• Other drugs displacing the original drug from protein binding

Question 7

What is the multicompartment model of drug distribution?

Answer 7

Question 8

When prescribing a patient a second drug, when should you be really careful with the first drug interactions?

Answer 8

• Second drug may displace first so more first drug that can elicit a response
• Be careful if first drug is highly protein bound, has a narrow therapeutic index, low Vd

Question 9

How do you work out the volume of distribution?

Answer 9

• Larger Vd than body water means it is absorbed by the adipose tissue
• Larger weight, more adipose so larger Vd so need higher dose

Question 10

What are the two phases of drug metabolism?

Answer 10

Question 11

What CYP’s are affected by smoking and alcohol, and what else can they be affected by?

Answer 11

• Age
• Hepatic disease
• Blood flow to liver
• Alcohol and Cigarette smoking (CYP450 inhibited in acute, induced in chronic)

Question 12

What changes can CYP450 enzymes make to a drug?

Answer 12

• Can inactivate active drugs
• Can activate inactive drugs, e.g Levodopa
• Can covert active drug into another one e.g codeine to morphine

Question 13

What is the most common CYP that metabolises drugs and what CYP is an example of genetic variations?

Answer 13

• CYP3A4
• CYP2D6 absent in some caucasians and over expressed in 30% of Africans. Has substrates like beta blockers and SSRIs

Question 14

When dosing two different patients for a drug, what should you think about in terms of the metabolism of the drug?

Answer 14

• Race
• Sex (women slower ethanol metaboliser)
• Self induced metabolism with drugs e.g Carbamazepine
• If they are taking St John’s Wort (inducer of CYP3A4)
• Weight
• Smoking and drinking status
• Age

Question 15

What routes can drugs be eliminated from the body?

Answer 15

• Mainly through the kidney
• Faeces
• Hair
• Sweat
• Tears
• Saliva
• Breast milk
• Genital secretions

Question 16

What type of drug molecules are excreted renally?

Answer 16

• Low weight polar molecules
• Clearance mainly affected by GFR

Question 17

What type of drug molecules are excreted hepatically and therefore into the faeces?

Answer 17

Usually high molecular weight molecules, conjugated with glucaronic acid

Question 18

How can cardiac disease affect the elimination of a drug?

Answer 18

• Reduces perfusion to the organs, like liver and kidney so less clearance