PHARM Pharmacokinetics Flashcards
What type of drug ionisation classification corresponds to the greatest solubility?
Unionised drugs have the greatest solubility.
pKa drug value means…
50% ionised, 50% unionised.
Discuss pro-drug metabolism. Benefits.
Pro-drugs require activation in first stage of metabolism (e.g., codeine -> morphine). Benefits: incease action & reduce risk of first pass metabolism.
Phase I Metabolism.
Catabolic/functionalisation/oxidation.
Introduction of a functional group - acid, amine, hydroxyl to enable conjugation -> increase polarity & increase water solubility.
Phase II Metabolism.
Synthetic/conjugation.
Body conjugates super soluble compounds to increase drug size & water solubility.
Zero order vs first order kinetics.
Zero order - rate of reaction is constant and independent of drug concentration.
First order - rate of reaction is proportional to drug concentration.
2 main types of drug elimination
Urinary - excretion = filtration (via glomerular) - reabsorption (plasma) + secretion (urine)
&
Hepatobiliary.
What is the role of the liver in drug metabolism?
Often recruited to make drugs more water-soluble so that they can be excreted via the kidneys.
Example of accessible drug which follows zero order elimination.
Alcohol/ethanol.
How many half lives are thought to be needed for removal of a drug?
4-5 t1/2
Vd. Expand & define.
Volume of distribution - relates the plasma concentration ot the total amount of drug in the body.
Factors influencing Vd
Factors influencing Vd:
• Lipophilicity – affinity of a drug to a lipid environment
• Ionisation – ionised = low lipid solubility, unionised = high lipid solubility
• Protein binding – high size reduces ability to move into vasculature
• Size – high molecular weight prevents passing of drugs into vasculature.
Vd equation
Vd = dose/[drug]plasma (L or L/kg body weight).
t1/2 equation. Define kinetic conditions.
t1/2 = (0.693 x Vd)/CL. Only for first order kinetics.`
Clearance Rate vs Rate of Elimination
The rate of elimination speaks to the amount of drug cleared from the blood per unit time (e.g., mg/min).
Clearance rate refers to the volume of blood that is cleared of drug per unit time (e.g., ml/min).
For many drugs, clearance is almost entirely carried out by the kidney and therefore clearance is often closely tied to renal function.
