Pharmacokinetics: Drug Metabolism Flashcards
What does the metabolism of a drug mean?
- process where a drug is chemically altered
- alteration can activate action of drug
- alteration can enhances its elimination from the body
What are the 4 different things that can happen to a drug once it has been metabolised?
1 - inactive
2 - less active
3 - active (therapeutic/toxic)
4 - activated (pro drug)
What are the 5 main sites in the body where drug metabolism occurs?
1 - LIVER (MAIN SITE)
2 - kidney
3 - GIT
4 - lungs
5 - skin
Are there any specific enzymes for the biotransformation (transformation of a molecule from one compound to another, usually to reduce toxicity) of drugs?
- no
- same enzymes involved in the synthesis and biotransformation of other endogenous and exogenous compounds in the body
What is oxidation and reduction?
- oxidation = loss of electrons (NADH to NAD+)
- reduction = additions of electrons (NAD+ to NADH)
In drug metabolism enzymes involved in their metabolism are grouped into phase 1 or phase 2 reactions. What are phase 1 reactions?
- also called oxidation/reduction enzymes (losing electrons)
- cytochrome P450 enzymes
What is oxidation and reduction?
- oxdiation = loss of electrons and H+
- reduction = addition of electrons and H+
What is phase II reactions, also called conjugation/hydrolysis?
- hydrolysis = breaking molecule with H2O
- conjugation = adding of molecules (adding electrons)
- multiple enzyme types
What family of enzymes is responsible for 75% metabolism of all drugs?
- cytochrome P450
What are some functional factors of people that can affect metabolism?
- age (enzymes can increase and decrease wih age)
- gender
- pathophysiology (liver/renal disease)
In drug metabolism, if we inhibit or induct a drug what will happen to the drug metabolism?
- inhibit = slow metabolism (less enzymes or activity)
- induct = increase metabolism (more enzymes or activity)
In drug metabolism, if we can inhibit (slow metabolism (less enzymes or activity) or induct (increase metabolism (more enzymes or activity). What do both of these do to the drug concentration in the body?
- inhibit = higher drug concentration in plasma for longer
- induct = lower drug concentration in plasma
In the figure below, the what does the bottom of each peak denote?
- time point of drug administration
In the figure below, out of numbers 1 and 2, which denotes the inhibitor and which is the inducer?
- 1 = inducer, faster metabolism and plasma concentration is lower
- 2 = inhibitor, slower metabolism and plasma concentration is higher
In the figure below what does the black line denote?
- the effects of a drug we would expect
- no inhibitor or inducer
The therapeutic window describes what?
- minimum dose required for therapeutic effect
- maximum dose before drug is toxic
Out of inducers and inhibitors, which is more likley to cause sub-therapeutics (drug doesnt have enough of an effect) and which is more likley to become toxic?
- inhibitors = toxicity (drug stays in plasma for longer)
- inducers = sub-therapeutic (drug removed from plasma quickly)
Why do we need to be cautious with drugs that are metabolised by cytochrome P450 (CP450)?
- can reduce the therapeutic window
- warfarin is a good example of this
Drugs that are metabolised by cytochrome P450 (CP450) can drastically alter their therapeutic window which can be very dangerous. Using Warfarin as an example, which is metabolised by CP450, what could happen if an inducer or inhibitor was added alongside the drug?
- inducer = reduced metabolism, meaning warfarin would not stop coagulation and you could develop thrombosis
- inhibitor = increased metabolism, meaning warfarin levels could become toxic in the plasma
If we induce or inhibit a drug what happens to the bioavailability (how much of drug is effective at the site) of that drug in the body?
- induce = decreased bioavailability (remove drug quicker)
- inhibit = increased bioavailabilty (keep drug for longer)
If we induce or inhibit a drug what happens to the therapeutic effect of that drug in the body?
- induce = decreased therapeutic effect (remove drug quicker)
- inhibit = increased therapeutic effect (keep drug for longer)
If we induce or inhibit a drug what happens to the toxic effect of that drug in the body?
- induce = decreased toxic effect (remove drug quicker)
- inhibit = increased toxic effect (keep drug for longer)
If we induce or inhibit a drug what happens to the first pass metabolism of that drug in the body?
- induce = increased (more of drug metabolised by liver)
- inhibit = decreased (less of drug metabolised by liver)
If we induce or inhibit a drug what happens to the metabolism of that drug in the body?
- induce = increased (remove drug quicker)
- inhibit = decreased (keep drug for longer)
