Pharmacology workshop Flashcards
What is the bioavailability of a drug?
How much of the dose given will end up in circulation
Describe the bioavailability of oral drugs
Oral drugs need to be small, lipophilic molecules to cross the gut
After absorption they will enter the hepatic poral vein and travel to the liver (first pass metabolism) before entering circulation - this causes oral medicine to have a lower bioavailability than other routes
Describe bioavailability of IV drugs
100% - goes directly into the blood stream
Why is oral medication never given to ruminants?
Rumen breaks down drugs very efficiently (fermentation chamber) so bioavailability of oral medicines in ruminants is very low
Compare the apparent Vd for phenobarbital of 0.75L/kg with that for propofol (5L/kg) and warfarin (0.1L/kg) What does this tell you about the potential movement of these drugs within the body?
Warfarin:
- tightly bound to plasma protein so cannot cross plasma membrane
- high water solubility
- higher concentration in plasma (lower Vd)
Phenobarbital:
- bound to plasma and can distribute to other tissues
- slightly higher Vd
Propofol:
- small, lipophilic molecule
- distributed to other tissues more readily
- high Vd
Why would obese animals need a higher dose of medication?
Obese animals – more fat for lipophilic drugs to leave plasma => lower plasma concentration
What factors contribute to the half-life of a drug?
Clearance (higher rate of clearance => shorter half life)
Vd (lower Vd => shorter half life)
What is a loading dose and how is it determined?
A larger dose given at the start of a course of medication to establish a therapeutic level
Vd x C (Desired conc)
How is half-life calculated?
Half life = (0.693xVd)/Cl
What is the clearance of a drug?
The volume of plasma/blood irreversibly cleared of a drug during a specified time period (ml/h)
A measure of the efficiency of drug elimination
Clearance does not change
How is clearance calculated?
How is elimination rate calculated?
What is the difference between clearance and elimination rate?
Clearance does not change as plasma conc changes
Elimination rate decreases as plasma conc decreases
What biological factors can influence the clearance of drugs by the liver?
Liver disease
water solubility (high water solubility => lower clearance as it cannot cross plasma membrane of hepatocyte to be metabolised, water soluble would be cleared quickly by kidney)
CYP enzymes
Liver blood flow
High plasma protein binding => not available to be absorbed => low clearance
What could happen to plasma concentrations of phenobarbital in a patient with hepatic failure? (phenobarbital is metabolised by the liver)
Drug plasma conc increases as it is not metabolised => toxicity
Could give a lower dose or give less frequently - or find a different drug
What factors are used to determine a dosage regimen?
What is the effect of increasing dosage frequency?
Increasing frequency decreases peaks, increases troughs to achieve the most similar levels to IV infusion
What are normal drug kinetics?
Dosage and plasma conc are directly proportional
Doubling dosage => doubling plasma conc
Drugs with high therapeutic indexes
What are saturating drug kinetics?
Drugs with larger, disproportional increases in plasma concentration in relation to dosage
Need to be careful with dosages
