Drug metabolism Flashcards
Why would you want a drug to be lipophilic
So drugs can access tissues (therapeutic)
Why would you want a drug to be water soluble
Retained in the blood and delivered to excretion sites
What does the process of drug metabolism involve
Converting drugs that are usually lipid soluble to metabolites that are less lipid soluble and easier to excrete (usually done by the body)
What are the two kinds of biochemical reactions in drug metabolism
Phase 1 - introduce a reactive group to the drug to increase polarity
Phase 2 - add water soluble conjugate to the reactive group
What is the role of the functional group in phase II reactions and what is the relevance of redox and hydrolysis
Point of attachment, created by oxidation/reduction
Hydrolysis unmasks
What is the most common phase 1 metabolism reaction
oxidation (often starts with hydroxylation)
What are the 3 basic reactions that may occur in phase 1
Active parent -> inert metabolite
Active parent -> active metabolite (prolongs)
Inactive parent -> active metabolite (prodrug)
What is the most common phase 2 metabolism and give and example
Glucuronidation e.g. aspirin
what is glucuronidation, what does it use and what does it target
Low affinity and high capacity pathway so more likely to occur at high drug dosages
Uses UDP-glucuronic acid
Targets OH,COOH, NH2 and SH
What is sulfation , give an example and what does it target
High affinity and low capacity pathway so more likely to occur at low drug dosages e.g. paracetamol
Uses 3’-phosphoadenosine-5’-phosphosulphate
Targets OH and NH2
What is glutathione conjugation, what does it use and what is the requirement
phase 2 metabolism pathway using glutathione that requires the drug to be electrophilic
What is the importance of drug metabolism
Biological half-life of the chemical decreased and duration is reduced, avoiding accumulation of the compound
Potency/duration of the biological activity of the chemical can be altered
Pharmacology/toxicology of the drug can be governed by its metabolism
What are the main enzymes involved in phase 1 metabolism and how many types are there
Cytochrome P450 in the liver
57 subtypes
What are the types of phase 2 reactions
Glutathione conjugation Glucuronidation Acetylation Sulfation Methylation Amino acid conjugation
How is glutathione conjugation relevant to paracetamol overdoes
Glutathione stores are used up and the metabolite electrophile is very reactive and can cause major damage to the kidney and liver
