Diseases affect drug metabolism Flashcards
What is Cirrhosis?
Parts of the liver is replaced by fibrous tissue + no. of functional hepatocytes is reduced
Drug metabolism is impaired
Phase 1 oxidative metabolism is affected
Glucuronidation is not affected
What are the theories to prove poor metabolism in cirrhosis?
Sick cell: blood flow through liver is normal but cells are deficient in drug-metabolising enzyme
Intact hepatocyte: cells are normal but do not receive normal blood flow (shunting of blood to get round fibrous tissue)
How does alcoholic liver disease occur?
Caused by chronic alcohol intake
Leads to a condition similar to cirrhosis with large portions of liver replaced by fibrous masses because of death of hepatocytes
How does alcohol intake affect drug metabolism?
How does viral hepatitis affect drug metabolism?
Decrease drug metabolism
Related to decrease in CYP2A6 activity
What is Hepatoma?
Cancerous growth from liver parenchymal cells
The drug metabolising capacity of tumour cells is less than normal cells (due to reduced amount of CYP450 enzymes)
The faster growing the tumour, the less capable for drug metabolism
Non-hepatic diseases include hormonal diseases + infectious diseases.
What are diseases are under hormonal?
How do infectious diseases affect drug metabolism.
Hormonal = hyperthyroidism, pituitary insufficiency, adrenal insufficiency, diabetes, thyroid tumours
Infectious diseases = bacterial + viral infections including malaria: drop in CYP450 content
How does age affect drug metabolism?
Newborns + elderly are more susceptible to drug action than adults
This is because of the reduced drug-metabolising activity in newborns and elderly (phase 1 + 2)
How does tobacco smoking affect drug metabolism?
Increases biotransformation of drugs (phase 1 + 2)
This is because of the ingestion of a pyrolysis product (from burning of the plant materials in tobacco) = A polycyclic hydrocarbon benzo(a)oyrene
Pyrolysis products are known inducers of CYP450 enzymes
Drug interactions that affect drug metabolism are _____
Phase 1 CYP450-related
Drugs with narrow therapeutic window
Due to inhibition/induction of an enzyme
Inhibition occurs quickly
Induction occurs over time
Inhibition can be reversible (most common) or irreversible
Reversible inhibition occurs when compounds quickly form _____ with the enzyme _____.
Reversible inhibition can be _____ or _____
Irreversible inhibition occurs with formation of a _____. This metabolite can covalently and irreversibly bind to the _____ and _____ the enzyme for subsequent reactions
Reversible inhibition occurs when compounds quickly form weak bonds with the enzyme without permanently disabling them.
Competitive or non-competitive
Reactive metabolite
Catalytic residue and permanently deactivate
Induction occurs gradually rather than rapidly and generally leads to compromised therapeutic goals rather than profound toxicity
Clinically significant induction results from a more than _____ in the number of ______ (due to increased synthesis of the enzyme or/and decreased degradation)
> 50-fold increase
Enzyme molecules
The oral bioavailability (F) of simvastatin is about 5% when taken with water. The low metabolism is mostly due to _____.
The oral bioavailability is increased 3.6-fold when simvastatin is given with _____.
_____ component (naringin) is a known inhibitor of _____.
To first-pass metabolism in the gut and liver
Grape fruit juice
CYP3A
Drug interactions that affect distribution
Affect protein binding Drugs bound to plasma proteins in bloodstream Acidic drugs bound to albumin Basic drugs bound to a-1-acid glycoprotein
Induction of alprenolol metabolism by pentobarbital pre-treatment (10 days) ______ the concentrations of alprenolol when it is given ______ but not when it is given _____.
Lack of changes after intravenous administration suggests that its ______ rather than _____-based metabolism is affected
Decreases
Orally
IV
Intestinal
Liver
