Metabolism Flashcards
What is phase 1 of metabolism?
most frequently oxidisation, but also reduction
What is phase 2 of metabolism?
conjugative or synthetic addition of a large polar molecule that renders the drug water soluable
Which organ is the primary organ for metabolism?
Liver
What are the main enzymes involved with metabolism in the liver called?
C-450
What happens when CYP450 enzymes are increased?
metabolism increases
What do the enzymes in the liver do to prodrugs?
convert prodrugs to metabolites
What do enzymes in the liver do to active drugs?
convert active drugs to inactive forms
What is a metabolite?
byproduct of the body breaking down, or “metabolizing,” a drug into a different substance
What happens to lipid (fat) soluble drugs in the kidney?
passively reabsorbed as urine concentrates
What are foreign compounds also known as?
xenobiotics
CYP450 stand for?
Cytochrome P450
What are CYP450 enzymes essential for?
- metabolism
- cholesterol
- Steroids
What happens when CYP450 enzymes are not as able to break down drugs?
The effects of the drug and side effects increase
What is an effect of CYP450 inhibitors?
May result in drug levels rising in the body
What is an effect of inducers of CYP450?
may result in a decrease of the drug levels (and therapeutic value)
What does hydrophillic mean?
Attracted to/easily bound to water
What does ionisation mean?
Adding or removal of electrons, changing/applying and electrical charge
What is a catalyst?
enables a chemical reaction
What is conjugation?
the attachment of a chemical group
What is oxidisation?
the gain of oxygen, the loss of a hydrogen, or the loss (or partial loss) of electrons
What is reduction?
The opposite chemical reaction of oxidisation (the gain of oxygen, the loss of a hydrogen, or the loss (or partial loss) of electrons
endogenous
substance that arises from within the body
what is metabolism?
the chemical alteration of a substance within the body. lipid (fat) soluable, non-polar compounds into water soluble, polar compounds to enable excretion
what is first pass metabolism?
Goes to the liver first
what are two consequences of first pass metabolism?
larger dose needed, individual variation and so unpredictability of reactions
What are the reactions that usually occur in phase 1 of metabolism?
- hydrolysis
- oxidisation
- reduction
What are the outcomes of phase 1 metabolic reactions?
- Inactivation of the drug
- activation from a pro-drug to the active form
- Modification of activity
- Formation of toxic metabolites
What is an example of a pro-drug?
ACE-inhibitors e.g benazepril
What is the most common phase 2 reaction in metabolism?
Glucuronidation
What phase 2 metabolism reactions are deficient in companion animals?
Glucuronidation and some glucuronyl transferases (cats) and acetylation (dogs).
Which species has a poorly developed phase 2 metabolism process?
cats
What factors effect drug metabolism?
- Hepatic impairment
- Renal impairment
- Endocrine (hormone) disease e.g. thyroid
- Drug interactions
- Species
- Age
- weight
