Pharmacology

Question 1

Why is it important to polarise drugs for excretion?

Answer 1

Allows it to be absorbed in water (excreted in urine)

If not, will be reabsorbed in nephron DCT.

Question 2

What is the aim of drug metabolism?

Answer 2

Aim is to facilitate drug excretion

Primarily achieved by making substance more water soluble, → more amenable to excretion in urine

Question 3

What are the two phases of drug metabolism?

Answer 3

Phase 1 - insert/expose functional groups
- Cytochrome P450 enzymes (aka CYP enzymes)
- Either make molecule more polar or provide a site for further metabolism in a phase 2 reaction
- Catalyse oxidation, reduction & hydrolysis reactions

Phase 2
- Conjugation of molecule with a polar ligand, e.g. glucuronate
- Involves various enzymes
- Glucoronidation, sulfation, acetylation, methylation, AA conjugation, glutathione conjugation

Question 4

Define elimination and excretion

Answer 4

Eliminationis theloss of the parent drug moleculefrom the body. This can occur because it ismetabolisedinto another molecule, orexcretedfrom the body.

Excretionis theexpulsion of drug material(parent molecule and/ormetabolites) from the body in liquid, solid or gaseous ‘waste’

Question 5

Describe first order kinetics of drugs

Answer 5

Rate of metabolism proportional to concentration
- Concentration falls exponentially
- So has a constant halving time (half life)
- Drugs with 1st order kinetics will be more than 95% eliminated after 5 half lives have elapsed.
Half life also determines steady state
- With a regular drug dosing, steady state will be achieved in ~5 half lives (drug with 1st order kinetics)

Question 6

What is the steady state of drugs?

Answer 6

Steady state is the state in which, under conditions of regular drug dosing, rate of drug administration = rate of drug elimination (so plasma concentration stable)

Question 7

What are Zero order kinetics

Answer 7

When metabolising enzymes are limiting factor
- Rate of metabolising constant - will not increase with concentration
- Linear fall in drug concentration - falls by constant amount per unit time
- Half life is variable
- Only applies once concentration is at or above full saturation of enzymes, so switches from first to zero order at this point. Same can happen in reverse

Question 8

What are some C-P450 inducers & inhibitors?

Answer 8

SCRAP GIVER

Inducers:
St Johns Wart
Carbamazipine
Rifampicin
Alcohol (chronic)
Phenytoin

Inhibitors:
Grapefruit juice
Isoniazid
Valproate
Erythromycin
Ritonavir