Drug Metabolism Flashcards
Define pharmacodynamics
What a drug does to the body
Define pharmacokinetics
What the body does to the drug
What does pharmacokinetics essentially cover?
Absorption, Distribution, Metabolism and Elimination of a drug (ADME)
What usually occurs in phase I?
A reactive group is exposed or added to make them more unstable - reactive intermediate.
What are the most common chemical reactions in phase 1?
Redox and hydrolysis
What does phase I require?
Cytochrome P450 (CYP) system and NADPH
What occurs in phase II?
Intermediate from phase I is conjugated with a polar molecule to form a water-soluble molecule. (conjugation)
What is the most common conjugate of phase II?
Glucoronic acid. Can also be conjugated with sulphate ions and glutathione
What does phase II metabolism require?
Specific enzymes and uridine disphosphate glucuronic acid (UDGPA)
What is the first pass effect?
Substances absorbed from the ileum are extensively metabolised during the first pass through the liver
Why is CYP important?
Isoform CYP3 A4 is most important - accounting for ~55% of drug metabolism. NADPH is a cofactor for CYP
What is an actylator?
Someone who lacks the main enzyme for acetylation reaction in phase II
Give some examples of enzyme inducers
Ethanol, nicotine and barbiturates
How is paracetamol metabolised at a therapeutic level?
Conjugates with glucuronide or sulphate in phase II
What happens when someone overdoses on paracetamol?
Phase II becomes saturated and it undergoes phase I metabolism, forming NAPQI which is toxic.
What effect does NAPQI have?
Toxic to hepatocytes and also undergoes phase II conjugation with glutathione which is an important anti-oxidant
What is the major site of alcohol metabolism?
Liver
Write out the breakdown of alcohol
Alcohol —> acetaldehyde (alcohol dehydrogenase)
Acetaldehyde —> acetate (aldehyde dehydrogenase)
Complete oxidation requires NAD+ and forms NADH
How can excess alcohol lead to liver damage?
Aldehyde dehyd. has a low Km so keeps acetaldehyde to a minimum. Prolonged consumption can lead to a build of acetaldehyde which is toxic
What is NAD+ used for?
FA oxidation, conversion of lactate to pyruvate, metabolism of glycerol
What causes lactic acidosis?
Accumulation of lactate in the blood due to low NAD+
What are the effects of high actyl~CoA
Fatty acid synthesis increases however it cannot be moved thus causing fatty liver. Sometimes production of ketone bodies can lead to keto-acidosis
What can reduced liver function result in?
Jaundice, hyperammonaemia, serum albumin may produce oedema, increase in blood-clotting time, fatty liver
What are the indirect effects of alcohol?
Vitamin and mineral deficiencies. Inadequate protein and carbohydrate uptake
