Pharmacokinetics 2 Flashcards
What is the blood brain barrier
A group of endothelial cells lining the blood vessels in the CNS forming tight junctions impermeable to water soluble molecules - lipid soluble molecules such as caffeine and ethanol can cross easily
What happens to tight junctions during inflammation
They become leaky - in meningitis this allows antiobiotics through the blood brain barrier more readily aiding in treatment
What is the chemoreceptor trigger zone
Found in the medulla oblongata and its stimulation induces the nausea and vomiting reflex - triggered by certain molecules - Dopaminergic antagonist prevent this response
How does albumin effect distribution of a drug
Albumin is a plasma protein that binds many acidic drugs - it carries a charge so prevents the diffusion of the drug across the lipid membrane
How does body fact interact with lipid soluble drugs
Act as a store - anaesthetics are highly lipid soluble - individuals with high body fat require increased concentrations to reach the correct amount in neurons
How do bones and teeth affect tetracycline
Bind with a high affinity for calcium, should not be used in children for this reason
What processes outline the phase 1 reactions in the liver
Catabolic reactions (oxidation, reduction, hydrolysis) often forming a more reactive compound than the initial drug - usually due to the addition of a hydroxyl group - this is necessary as it becomes the target point for the phase two reaction
Give an example drug that has a toxic intermediate compound
Paracetamol - under normal dosage, not very much produced.
What processes outline phase 2 reactions in the ;liver
Anabolic reaction (synthesis) involving conjugation to produce an inactive product - large groups added to prevent their reabsorption
What are pro-drugs
Drugs that become active only after being metabolised - therefore have a slower induction effect - useful for sedative and the controlling of seizures
How is aspirin eliminated from the body
Phase 1 - methyl ester group replaced by a hydroxyl group - Phase 2 - hydroxyl group reacts with a sugar group to form glucuronide. This increases the molecular weight so it is unable to cross the plasma membrane or act on its receptors
How many genes are present for P450 enzymes
57
What are P450 enzymes
Microsomal enzymes found intracellularly that act upon the uncharged drug once it has crossed the plasma membrane
How are P450 enzymes influenced by other drugs and environmental factors
Expression is influenced - Brussel sprouts induce P450 expression - increasing alcohol metabolism
Grapefruit juice inhibits P450 expression
How is penicillin excreted
Almost completely removed by proximal tubule secretion - and is therefore rapidly eliminated
