Drug Metabolism and Elimination Flashcards
1
Q
What is drug metabolism?
How is it achieved?
What is drug excretion?
How is it achieved?
What are both drug metabolism and excretion important for determining?
A
- Removal of lipid-soluble drug molecules to prevent reabsorption in kidneys
- By converting drugs into water-soluble molecules, mostly in Liver
- Removal of drug and its metabolites
- Mostly through Urine, as well as Bile/Faeces, Sweat, Tears, Saliva, Breastmilk
- Dosage and steady state achievement, as well as safety issues due to the presence of active metabolites
2
Q
Drug Metabolism:
What is it called if a drug only becomes activated by metabolism?
What does metabolism do to the drug? How?
What is Phase I of metabolism?
What occurs in Phase I?
What is Phase II of metabolism?
What occurs in Phase II?
Why is Paracetamol overdose Hepatoxic?
A
- Prodrug
- Causes reduction of biological activity by increasing polarity/decreased receptor affinity
- Oxidation
- • Adds chemically reactive groups; main process is oxidation In liver
• Addition of oxygen; carried out by Cytochrome P450 in liver
• Other reactions - hydrolysis and hydration - Conjugation
- • Increases water solubility of drug for excretion
• Conjugates Phase I product with an endogenous substance with covalent bonds - Paracetamol undergoes Phase II metabolism, and only does Phase I if saturated; phase I products are hepatoxic
3
Q
Kidney excretion:
How does it relate to Glomerular Filtration?
How does it relate to Reabsorption?
How does it relate to Tubular Secretion?
Renal Clearance:
What is it?
What’s the link between renal clearance and half-life?
A
- Excretion rate depends on levels of drug bound to plasma proteins
- As molecules pass through tubules, they become concentrated as water is drawn out; increases the gradient for reabsorption to occur
- Acid/base molecule carriers transport molecules into tubular fluid; secretion of drug leads to less bound [drug]
- Volume of plasma cleared of drug in one pass through kidney
- ↓Renal elimination = ↑Half-life
4
Q
What factors affect drug metabolism and excretion?
A
- • Age; Cytochrome P450 and GFR is reduced in neonates/elderly, ↑fat content
• Genetics
• Drug-metabolising enzymes; induced or inhibited by drugs or lifestyle
• Disease; Liver disease impairs drug metabolism, Renal disease alters pharmacokinetics (ADME)
