Clinical Pharmacology Flashcards
What 2 areas are drugs distributed?
Tissue reservoirs
Protein-bound drug
What is bioavailability?
Measure of drug absorption where it can be used (F) as compared to when given IV
What things can affect absorption of drugs?
Formulation
Age (luminal changes)
Food (chelation, gastric emptying)
Vomiting/ malabsorption (Crohn’s)
What areas are included in first pass metabolism?
Gut lumen, gut wall and liver
What factors affect distribution of medication throughout the body?
Blood flow/ capillary structure Lipophilicity/ hydrophilicity Acidic/ Basic drugs Protein binding - Albumin - acidic drugs Globulins - hormones Lipoproteins - basic drugs Glycoproteins - basic drugs Volume of distribution
What is the equation for volume of distribution?
Vd = Dose/ [Drug]plasma
How would you interpret a volume of distribution?
A lower Vd is indicative of more drug in the blood and less in the tissues
A higher Vd is indicative of less drug in the blood and more in the tissues
What is the units for volume of distribution?
mg/litre
How can dose be calculated from the volume of distribution and the drug concentration in the plasma?
Dose = Vd x [Drug]plasma
How many phases of metabolism are there?
2 phases
What happens in the phases of metabolism?
Phase 1- oxidation - dealkylation or reduction - hydrolysis
Phase 2- Glucuronidation, sulphation, glutathione added, N-cetyl added
What is another name for phase 1 enzymes?
Cytochrome P450 enzymes
What found in grapefruit juice is a cyp inhibitor?
Furanocoumarins irreversibly inhibit CYP 3A4 which is responsible for metabolising 50% of drugs.
What is the importance of CYP2D6 in caucasians and east africans?
Absent in 7% of caucasians
Hyperactive/ increased induction in ~30% of East Africans
Apart from the kidneys what are the other routes of drug elimination?
Sweat, tears, genital secretions, saliva, breast milk, faeces, hair, gases - volatile compounds
How can enterohepatic circulation affect drug elimination?
When the drug is absorbed and then metabolised by the liver it can then become conjugated with bilirubin and released into the GI system. This would then cause some of the conjugated drug and bilirubin to be reabsorbed with fats and so the drug would then potentially be reabsorbed distal to the common bile duct.
What is zero order kinetics for drug elimination?
The drug is eliminated at a constant rate over time
What is first order kinetics for drug elimination?
The drug elimination is exponentially decreasing. As time increases the elimination decreases. Log of the drug concentration produces a straight curve
How is half life related to kinetics?
Half life is related to first order kinetics
It is independent of concentration
1/time
Define the clearance of drugs?
Constant proportion not amount of drug that is cleared
Volume of blood cleared per unit time (mL/min)
How do you calculate clearance?
Rate of elimination from body / drug concentration in plasma
What is the relationship between drug concentration and clearance?
The higher the drug concentration the higher the elimination rate and more drug cleared
At therapeutic doses what type of kinetics do most drugs have?
First order kinetics therefore half life is constant
What effect does a high dose have on the kinetics?
As the enzymes become saturated at high doses the elimination can become zero order and so a set amount of the drug is eliminated at a constant rate