pharmacokinetics Flashcards
what is the volume of distribution?
The volume of distribution (Vd) is defined as the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.
how do we calculate the volume of distribution?
It is calculated by the amount of the drug in the body divided by the plasma concentration
what does the volume of distribution reflect about a drug in terms of how tissue bound it is?
reflects the extent to which the drug is present in extravascular tissues but not in plasma
As such, drugs that are extensively tissue bound (e.g., digoxin) have a large Vd; (small plasma conc/denominator)
drugs that are primarily restricted to the intravascular space (in vessels) (e.g., phenytoin) have a small Vd (large concentration in plasma)
why might the Volume of distribution of drugs differ?
Drugs made up of larger molecules are more difficult to diffuse out of the circulatory system, so a higher concentration remains in the plasma, reducing the Vd
Drugs made up of highly lipid soluble molecules are likely to leave the bloodstream due to its low fat content, and thus are likely to have a lower plasma concentration and greater Vd
Highly water-soluble drugs may have a hard time penetrating the lipid bilayer and so remain in the plasma/extracellular fluid, increasing their concentration and reducing their Vd
what is plasma clearance?
Plasma clearance is a volume per time thus it is a flow.
Clearance specifically is a measurement of the volume of plasma from which a substance is completely removed per unit time.
Like Vd, clearance is a theoretical value
how do we calculate clearance?
Usually, clearance is measured in L/h or mL/min. It is calculated by dividing the rate of drug elimination by plasma concentration.
Plasma clearance is a totally theoretical volume of blood which is cleared of the drug per every unit of time, a measure which has nothing to do with the drug dose or concentration.
what’s is drug half life?
Drug Half-life (t1/2) is defined as the amount of time required for the drug concentration to be reduced to exactly half its initial concentration or amount in the blood.
what factors effect half life?
Drug specific (as well as individual specific) variables can affect half-life.
Whether the drug accumulates in fats or other tissues
Whether it binds to proteins or not, and if so how readily
The properties (charge, size…)
The volume distribution of the drug
give 3 examples of non-depolarising neuromuscular blocking drugs
Gallamine
d-tubocurarine
atracurium
give an example of a polarising neuromuscular blocking agent
Suxamethonium is a depolarizing neuromuscular-blocking drug that consists of two acetylcholine molecules joined together
how do polarising neuromuscular blocking agents work?
When two molecules of suxamethonium bind to the nicotinic N2 receptor it acts as an agonist and depolarises the motor endplate.
However, suxamethonium is not hydrolysed by AChE and therefore produces more prolonged depolarisation than ACh.
The voltage-gated Na+channels are kept in their inactive state, producing depolarising block
how do non-depolarising neuromuscular blocking agents work?
They act as competitive antagonists at nicotinic acetylcholine receptors on the motor end plate of the neuromuscular junction and cause relaxation of skeletal muscle.
Essentially, they compete with acetylcholine (ACh) molecules and bind to nicotinic acetylcholine receptors on the post-synaptic membrane of the motor endplate. Because they block the action of ACh, this prevents activation of the muscle contraction process.
They can also act on nicotinic presynaptic acetylcholine receptors which inhibits the release of ACh.
they an also act on muscarinic receptors (cardiac and smooth muscle)
compare the 3 drugs
d-Tubocurarine and atracurium act on the NMJ. d-tubocurarine compete with at least an equal affinity to acetylcholine, and at the same position on nicotinic receptors. Hence it does not affect cardiac muscle or smooth muscle
In comparison, gallamine blocks the cardiac vagus and may cause sinus tachycardia, hypertension and increased cardiac output as it binds to the muscarinic ACh receptors. Gallamine also works at the NMJ too.
how are the 3 drugs used clinically?
Tubocurarine is used mainly in anaesthesiology causing prolonged muscle relaxation during an operation. Small doses cause temporary relaxation of skeletal muscle without any vital change of primary body functions
Gallamine is used as adjuncts to anaesthesia to induce skeletal muscle relaxation and to facilitate the management of patients undergoing mechanical ventilation
Atracurium is also for use, as an adjunct to general anaesthesia, to provide skeletal muscle relaxation during surgery or mechanical ventilation
what are the adverse effects of these drugs?
Atracurium and d-tubocurarine have histamine-releasing properties and may cause flushing/rash on the skin, hypotension and tachycardia.
Gallamine may also cause tachycardia, but unlike d-tubocurarine and atracurium, it may cause hypertension instead of hypotension.
ALL 3 CAUSE TACHYCARDIA
