pharmacokinetics - drug metabolism Flashcards
(48 cards)
drug metabolism/biotransformation definition
chemical reactions responsible for the conversion of drugs into other products within body before + after they reach site of action
how do metabolic reactions take place?
via enzyme catalysis - therefore they exhibit the general characteristics of enzyme controlled processes
what are the 2 types of process involved in drug metabolism?
phase 1 - asynthetic
phase 2 - synthetic
- these labels are unrelated to chronology
what effect to metabolic reactions usually have on drugs?
they are usually made more water soluble - makes it more easily excretable
are products of drug metabolism usually pharmacologically active or inactive?
can be both - some drugs take advantage of this and are administered in inactive forms then converted to the active form in body, lasts longer
what is a disadvantage of drug metabolites still being pharmacologically active?
means metabolites can interact with other receptors/targets around the body causing side effects
first pass metabolism definition
rapid breakdown of drugs by liver/gut wall before reaching systemic circulation - first big hurdle for a drug to pass, especially oral drugs
when is a drug considered bioavailable?
when its passed first pass metabolism and is flowing around the body in the blood - from now the drugs bioavailability can be considered
what 2 types of enzyme are involved in metabolism of drugs?
specific and non-specific enzymes
why does the body contain non-specific enzymes?
part of its defense against unwanted xenobiotics
give 4 biological factors that affect metabolism
age
gender
genetics
diseases
how can diseases affect drug metabolism?
diseases affecting liver + kidneys affect metabolic + excretory processes which slow down metabolism and excretion of drugs
how can genetics affect drug metabolism?
changes in genes encoding enzymes can alter how people metabolise drugs / enzyme affectiveness
polymorphism definition
when there is more than 1 allele for a gene within a population, and at least 1% of the population has this gene
how can gender affect drug metabolism - specifically ADME ?
- adsorption - differences in gastric enzyme levels affect first pass metabolism and gastric acid levels + gut motility change mean transit time between men and women
- distribution - women have lower plasma/water content than men so drugs linger in body for longer, as plasma proteins bind drugs
- metabolism - women have higher activity of some enzymes, men have higher metabolic rates overall
- elimination - renal clearance is generally higher in males
how can gender affect drug metabolism - other ways?
- oestrogen/progesterone levels affect hepatic enzyme/liver activity
- women tend to be more sensitive to some drugs and are much more likely to show an adverse drug reaction
give one potential reason why women are more likely to have adverse drug reactions?
men are more likely to be chosen for clinical trials, as women complicates things as menstrual cycle can be a factor to look out for
- this means drug profiles of safety/effectiveness are based on men
how can environment affect drug metabolism?
poor diet, drinking, smoking, drug abuse/self medication can all impact ability to metabolise a drug
how is drug metabolism a large cause of toxic action?
drug metabolites can activate alternative receptors or act as precursors for other toxic compounds, causing further toxic effects
- this is why dosage is so important, even OTC drugs like paracetamol can have these effects if too much is taken
detoxification process definition
a reaction which produces pharmalogically inactive metabolites - as metabolites have no effect other than being the result of drug breakdown, this slows drug action
how do phase 1 metabolic reactions affect drugs?
usually increase water solubility by introducing polar water soluble groups
e.g. OH, COOH, SO3H
or unmasking polar groups
e.g. ester hydrolysis -> OH + COOH
what are the 3 main types of reaction in phase 1 metabolism
oxidation, reduction, hydrolysis
how do phase 1 oxidative processes take place?
via mixed-function oxidases or monooxygenases, found in liver mostly
- CYP450 = oxidative enzyme that works by inserting an O atom into a C-H bond
give 4 functional groups that are often reduced in phase 1 metabolism reactions
aldehydes, ketones, alkenes, nitro groups
