Elimination And Metabolism II Flashcards
What is phase 1 reactions for
Increasing reactivity and polarity for excretion in kidney
What is phase 2 conjugate for
Increase polarity and water solubility
Explain aspirin metabolism
Aspirin to salicylate via aspirin esterase
Phase 2 adds a glucoronide / glucoronic acid for water solubility
What is phase 1 introduction called
Functionalisation
How do cytochrome p450 work in oxidation with the drug in phase 1
Bind to the drug to form a complex
Use NADPH reductase and NADPH and O2 to oxidate the drug to form water soluble product
Donate electrons
Most reactions occur via CYP, name and explain one which is independent and also occurs in liver
Alcohol dehydrogenase
Converts ethanol to acetal aldehyde via NAD reduction
Alcohol metabolism can also use which type of CYP to form acetal aldehyde from NADPH oxidation
CYP 2E1
Name 3 groups attached in phase II
Glucoronyl, sulphate, acetyl
Which enzyme is involved in glucoronidation eg of aspirin
UDP glucoronyl transferase
Which groups are added in penecillin phase 2 metabolism
Glucoronic acid and sulphate
Other than the glucoronidation of paracetamol and addition of sulphate , what other pathway is there which produces toxic product
CYP 2E1 which metabolised it to NAPQI (toxic)
Which enzyme detoxifies NAPQI from paracetamol metabolism
Glutathione s transferase
Why does overdose in paracetamol cause build up of NAPQI
Because too little glucoronyl and sulphate left to convert it
Name 3 internal factors affecting drug metabolism
Age
Genetics
Disease
Why does genetics affect drug metabolism
genetics will determine if someone has fast metabolism or slow metabolism
If someone has a fast metabolism, they have a normal therapeutic response and Cp level to the drug, what happens if someone has low rate
High Cp build up causing toxic effects
They have an excess therapeutic response to a small dose
Why do both children and elderly have low metabolic rate
Low levels of cytochrome p450 and other conjugating enzymes such as udp glucoronyl transferase
Elderly also have dysfunctional liver etc
Name some exogenous factors affecting metabolism and why they affect it
Drugs, smoking, alcohol
They either induce or inhibit metabolic enzymes
Why does induction of metabolic enzymes mean someone needs to take more of the drug
Faster metabolic rate meaning lower therapeutic effect
Why is ethanol toxic when taken with paracetamol
Induces CYP 2E1 which causes NAPQI production
What does inhibition by factors such as drugs mean
Reduced rate of metabolism
(Lower effect of CYP or others)
Causes too high therapeutic response to a small dose
Which exogenous factor is both an inducer and inhibitor
Ethanol / alcohol
