Pharmacokinetics Flashcards
What is the equation for bioavailability? And what does it show?
Oral AUC/ IV AUC
- This is the feaction of the administered (oral) dose of a drug that reaches the systemic circulation
What is first pass (pre-systemic) metabolism?
This refers to metabolism of the drug prior to reaching systemic circulation
- how much is metabolised/extracted in the liver?
- this can reduce the bioavailability of the drug if the first pass effect is large
What is Drug Distribution ?
- Process by which the drug is transferred reversible from the systemic circulation into tissues
- this occurs as conc. of the drug in the blood increases
- movement of the drug from the tissue to the blood when the circulatory conc. decreases during elimination
Vascular > interstitial > intracellular compartments
How does a drug exert its effect?
The unbound or free fraction is the drug that can be excreted or exert it’s intended
- drugs bound to albumin or other plasma proteins can not be metabolized or excreted
Give examples ot highly protein bound drugs
Warfarin Phenytoin Aspirin Thyroxine Ibuprofen Heparin Furosemide
What factors are important to consider when looking at drug Distribution when administering drugs?
- Drug physio chemical properties: lipid or water solubility
- Drug particle size
- Drug protein binding
- The environment: blood flow, pH
What is the volume of distribution?
Vd = dose mg/ plasma conc. mg/L
- a high Vd is usually fat soluble so distributes quickly into the tissue, however there is a low amount circulating
- therefore a loading dose is needed to equilibrate the dose levels across all body fluid compartments, so there is enough of the drug circulating to the other areas where it is needed
What are the two main phases of drug metabolism?
- Phase 1: products undergo oxidation, reduction and hydrolysis reactions. ( Cytochrome P450)
- can produce a Pro-drug, Inactive form or a Toxic product
- Phase 2: undergo conjugation reactions to make them more water soluble
What is the Therapeutic Index?
= the ratio of concentration associated with toxicity (MTC) vs concentration associated with efficacy (MEC)
- the margin of drug concentration between the drug toxicity and the drug being at sub therapeutic levels
- wide margin or a narrow margin
What precautions need to be considered when prescribing codeine?
- a CYP2D6 polymorphism with ultra ultrarapid metaboliser effect causes opiate toxicity even at a low dose, causing an exaggerated codeine
- younger children can also have ultrarapid metaboliser effect ( age 12-18)
- a CYP2D6 polymorphism with poor metaboliser effect causes inadequate pain relief by codeine in some individuals
How can Phase II reactions in drug metabolism be impacted by genetics?
N-acetyltransferase can be fast or slow
- those who have fast acetylators are at an increased risk of ionized hepatotoxicity
- those with slow acetylators are at an increased risk of ionized neuropathy
- slow acetylators also at an increased risk of drug induced lupus with hydralazine
What drugs are zero-order kinetics ( undergo saturable metabolism)?
What does this mean?
The rate of drug metabolism is independent of drug concentration
- Phenytoun
- Alcohol
- Aspirin
- Methotrexate
- Fluoxetine
- Verapamil
What are causes of low drug clearance?
Normal variation Renal impairment Liver impairment Enzyme inhibition Genetic poor metaboliser Neonate/ old age
What are causes of high drug clearance?
Normal variation
Increased renal blood flow ( pregnancy)
Genetic hypermetabolism
Enzyme induction
How many half life does it take for the plasma conc. of a drug to be eliminated?
- 5 half lives for the effects to be negligible
- 7 for the drug to be almost or completely gone
