Drug Metabolism By The Liver Flashcards
First pass metabolism
Drug metabolised usually liver, before reaching systemic circulation.
resulting in a lower concentration of the active substance when it reaches its site of action or systemic circulation
= reduces bioavailability
Role of phase 1
Make drug more water soluble
Can easily be excreted via kidneys
Catabolism
What happens when you e digest food and the molecules break down in the body for use as energy
Cytochrome p450 cycle allows for?
Recyuing of cytochrome p450 and the generation of an oxidised derivative of the drug
Most common isoform the cytochrome p450 family
CYP3A4/5
Omeprazale is what type of inhibitor?
Proton pump inhibitor used for treating gastric ulcers, ALS inhibitor of CYP2C19
Furanocoumarins
In grapefruit nice = mediators grapefruit juice-drug interaction
Phase 2 reaction involve?
Conjugation of a reactive group
What happens in glucuronidation?
Phase 2 reaction
UDP glucuronide, attaches to N, O or S atoms
Increases water solubility which facilitates excretion
Liver receives oxygenated blood-via?
The hepatic artery from the systemic circulation
75% of the blood supply to liver is from?
25% is from?
75% = portal vein
25% = hepatic artery
Majority of drugs administered orally are absorbed in?
Small intestine which is entirely drained by the portal vein (so contains nutrients and absorbed drugs)
Bioavailability
Fraction of a drug dose that reaches the systemic circulation
Concentration- time graph: for bioavailability
Area under the curve represents?
How much of the drug has been absorbed in systemic circulation
How to calculate f fromconcentration-time graph?
F= AUC oral/ AUC intravenous
Significant first pass metabolism increases or reduces bioavailability?
Reduces
Bigger doses need to be given orally than IV
First pass metabolism can be avoided by what route of drug administration?
Buccal, sublingual and rectal (to some extent)
Enterohepatic circulation
recirculation of bile salts, drugs and their metabolites via biliary excretion and reabsorption in the intestine that can maintain drug plasma concentration
Bill is released in small intestine to?
Aid lipid digestion, and can also be used as a means to eliminate waste products
Enterohepatic recycling
Process by which biliary excreted drug is reabsorbed in the intestine instead of being removed from the body
May delay elimination
Features of enterohepatic recycling
May increase half-life
The therapeutic or toxic effects may be prolonged
Kinetics is
The rate of the reaction
Enzyme kinetics for first order
Doubling concentration of the drug doubles the reaction rate
Enzyme kinetics for zero order
Reaction rate is always the same irrespective of drag concentration
Plateau line
Enzyme kinetics for non-linear
Reaction rate increases with drug concentration until enzymessaturated and rate reaches constant
For zero order on enzyme kinetics drug elimination half life (graph) is
Constant, so drug is eliminated per unit time
For first order on enzyme kinetics drug elimination half life (graph) is
Constant proportion of drug iseliminated per unit time
Graph curves down
Enzyme induction has what effects on enzyme activity and substrate drugs?
Increased enzyme activity and metabolism of substrate drugs
= lower plasma concentrations and less efficacy/toxicity
Enzyme inhibition has what effects on enzyme activity and substrate drugs?
Decreased enzyme activity and metabolism of substrate drugs
= higher plasma concentrations and more efficacy/toxicity
What is warfarin?
Anticoagulant
Higher prothrombin time means?
Longer it takes for blood to clot
Enzyme inhibition on prothrombin time
Prothrombin time stays higher for longer, patient is more likely to bled
Some factor affecting drug metabolising enzymes
Age, smoking, alcohol, food, drugs, liver and kidney disease, genetics, pregnancy
Define Therapeutic range
Dosage range or plasma concentration usually expected to achieve the desired tuerapectie effect
What is TD 50?
Dose at which you see 50% toxicity
What is ED 50?
Dose at which you see 50% effectiveness
Theophylline is used for?
Severe forms of COPD
Digoxin used in?
Cardiac arrhythmias
Lithium is used in?
Bipolar disorder and good disorders
Aminoglycosides are?
Antibiotics
Cyclosporin prevents?
The body from rejecting transplanted organs
