12 - Pharmacokinetics Drug Out Flashcards
How are drugs eliminated from the body?
Excretion - mainly renal
Metabolism - mainly hepatic, made more soluble so can be removed by kidney
How are drugs metabolised?
Mainly in the liver
Why do you want to make drugs hydrophilic when metabolising them?
Because if they were lipophilic they would just diffuse out of renal tubules back to plasma
What happens during phase I?
- Cytochrome P450 enzymes
- Catalyse redox, diacylation and hydroxylation reactions
- Products have increased ionic charge
- Eliminate directly (kidney) or enter phase II or prodrug activated
What is the properties of cytochrome P450 drugs?
- Low specificity, high affinity for lipophilic drugs
- >50 drugs located on cytoplasmic face of ER
- Three superfamilies
- Six isoforms metabolise
- Inducible/Inhibitable
What drugs are enzyme inducers and what do enzyme inducers do?
These drugs increase the expression of CYP450 drugs so drugs eliminated faster
What drugs are enzyme inhibitors?
They reduce expression of CYP450 so drug not eliminated as much
What is an example of phase I activation?
Codeine to morphine
Dangerous because morphine has a much higher affinity than codeine for U-opioid
What happens during phase II?
- Hepatic cytosolic enzymes
- Broad specificity (more rapid kinetics than CYP450)
- Conjugation
- Increase hydrophilicity so renal elimination can occur
What is first order kinetics and what do the graphs look like?
- Rate of elimination is proportional to drug level
- Half life (t1/2) can be defined
- Not massive issue if overdose
What is zero order kinetics of elimination and what do the graphs look like?
- Constant unit of drug eliminated in unit time
- Due to enzymes being at Vmax
- Starts first order at low dose, increase dose then zero order
- e.g VODKA, PROBLEM WITH ODing
What do the dose-effect graphs look like for zero and first order drug elimination?
What is drug clearance?
Rate of elimination of active drug from body
Total = Hepatic + Renal + Other Routes
How do you work out half life and why is this important?
- Designing dosing schedules
- Minimising adverse drug reactions
What is repeated dosing?
- Steady state achieved in 5 half states
- Long half life means long time to reach steady concentration
What do you do if a drug has a long half-life but patient has emergency? e.g heparin and digoxin
- Bolus loading dose to get to therapeutic effect
How are drugs excreted and reabsorbed through the kidneys?
What does passive reabsorption of a drug in the kidney depend on?
pH of urine
What is aspirin poisoning and how do you treat it?
When you overdose on aspirin it is a weak acid so normally protonated in the blood so reabsorbed.
Give patient bicarbonate to make urine alkaline, will become deprotonated so aspirin not reabsorbed
