Pharmacology

Question 1

What are the organs of drug metabolism?

Answer 1

Liver - main
Gi tract
Lungs
Plasma

Question 2

Describe drug metabolism

Answer 2

1. Converts parent drugs into polar metabolites that are not readily absorbed by the kidney, facilitating excretion
2. Convert drugs o metabolites that are pharmacologically less active than their original compound

Question 3

What are the 2 phases of drug metabolism?

Answer 3

1. Make drug more polar so that it can be excreted more easily
2. Add endogenous compound to increase polarity (eg. glucuronyl, sulphate)

Question 4

Describe the monooxygenase P450 cycle

Answer 4

1. drug enters cycle as drug substrate (RH)
2. Oxygen (O2) provides 2 oxygen atoms
3. Oxygen added to drug to make ROH + H2O

Question 5

Where does phase 2 reactions of drug metabolism occur

Answer 5

Mainly in liver

Question 6

Describe the link between paracetamol and the liver

Answer 6

• Paracetamol usually safe but hepatotoxic in overdose
• Toxicity occurs due to altered metabolism of paracetamol
• Normal doses of Paracetamol are metabolised to glucuonate and sulphate (Phase 2)
• In overdose processes are saturated and produces toxic metabolite (NAPBQI)

Question 7

Treatment of paracetamol poisoning

Answer 7

• Within 1 hr - administer activated charcoal orally
• If 4+ hrs since ingestion - look at plasma concentration of paracetamol and assess liver damage
• Antidote = N - acetylcysteine by infusion

Question 8

MOA of N - acetylcysteine

Answer 8

increases synthesis of GSH permitting increased conjugation and elimination of NAPBQI

Question 9

Are products of phase 1 and 2 metabolism cleared faster or slower than parent compound

Answer 9

faster

Question 10

what are the 3 process of renal drug excretion

Answer 10

1. Glomerular filtration
2. active tubular secretion
3. Passive reabsorption by diffusion across tubular epithelium

Question 11

Describe glomerular filtration of drugs

Answer 11

About 20% of renal flow filtered through glomerulus

Drugs unbound to protein can be filtered those bound to a protein complex cannot

Question 12

what is the most effective method of drug elimination by the kidney?

Answer 12

Elimination by tubular secretion

Which involves the remaining 80% of plasma delivered to proximal tubule

Question 13

what are the 2 transporter systems of the epithelial cells of proximal tubule and what do they do?

Answer 13

Role - actively secrete drugs into lumen of nephron

1. Organic anion transporters - handle acidic drugs (penicillin’s, uric acid)
2. Organic cation transporters - handle basic drugs (morphine)

Question 14

How does tubular secretion of drugs differ from glomerular filtration

Answer 14

Tubular secretion can secrete drugs that are highly protein bound

Question 15

where is water filtered and where is water reabsorbed?

Answer 15

filtered - Glomerulus

Reabsorbed - tubule

Question 16

factors influencing reabsorption

Answer 16

Lipid solubility
Polarity
Urinary flow rate
Urinary pH 
 - alkaline - increases excretion of acids, acidic pH increases excretion of bases

Question 17

What 2 mechanisms of adverse drug interactions are there?

Answer 17

1. Pharmacodynamic - drug A modifies the pharmacological effect of drug B without altering its concentration in tissue fluid
2. Pharmacokinetic - drug A modifies concentration for drug B that reaches its site of action

Question 18

Altered responses to drugs in liver disease

Answer 18

1. Reduced synthesis of plasma proteins in severe disease - causes increased toxicity of highly bound protein bound drugs
2. Reduced synthesis of clotting factors
3. Impaired excretion of drugs eliminated by the bile
4. Altered pharmacodynamics
5. hepatic encephalopathy
6. Ascites - worsened by drugs that cause fluid retention

Question 19

why are elderly people more vunerable to adverse affects of drugs

Answer 19

• Impaired renal elimination
• Increased sensitivity of target organs to drugs
• Polypharmacy

Question 20

what is pharmacokinetics

Answer 20

analysis of drug disposition factors (absorption, distribution, metabolism and excretion