pharmacokinetics Flashcards
in order to induce anaesthesia quickly what characteristics should the drug have in terms of its protein binding?
Protein binding lowers the free concentration of a drug
Therefore high protein binding results in a low plasma concentration of free drug
Ideally want the drug to have low protein binding to enable a high initial plasma concentration
in order to induce anaesthesia quickly what characteristics should the drug have in terms of its lipid solubility?
drug should have a high lipid solubility in order for it to readily cross the blood brain barrier and reach its site of action
High lipid solubility leads to fast absorption and distribution
an anaesthetic (thiopentone) is given intravenously.
Explain in terms of the drug distribution of the intravenous drug why an additional volatile drug needs to be given as soon as the patient is asleep. What would happen if it were not given?
anaesthetic is administered IV therefore has 100% bioavailability
will be taken up by well perfused areas (ie. the brain) very quickly, leading to high initial brain concentrations, sending the patient to sleep
however this is short lives as other less perfused areas continuously take up the drug eg. the muscles
leaving less drug available for the brain
if no additional drug is given, patient will have muscle paralysis but brain would wake up
define agonist
a ligand that binds to a receptor to activate it and form a chemical-receptor complex
can be full or partial or inverse
define a partial agonist
drugs that bind to and activate a given receptor, but have lower efficacy than a full agonist.
It produces sub-maximal activation even when occupying the total receptor population, therefore cannot produce the maximal response, irrespective of the concentration applied.
give an example of an agonist and name its receptors
Adrenaline is an agonist at beta adrenoceptors
Opioids are agonists for opioid receptors in the brain
define an antagonist
a ligand that binds to a receptor to for a chemical-receptor complex. it does not activate the receptor, instead it reduces the effect of an agonist
(by preventing the agonist from binding to a receptor).
give an example if an a antagonist
propranolol, a β-adrenoceptor antagonist, binds to β-adrenoceptors in the heart and prevents catecholamine-induced tachycardia (for example in response to exercise).
define a competitive antagonist
directly competes with the agonist by binding to the same site and blocking its action. It inhibits, does not activate the receptor
define a non-competitive antagonist
Binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor.
It does not completely block the effect of the agonist
are competitive antagonists reversible?
are they surmountable?
they are reversible and surmountable
ie. if you increase dose of agonist you can overcome (surmount) the antagonist
give an example of a competitive antagonist
naloxone (reverses effects)
= the Opioid antidote
give an example of a non-competitive antagonist
Ketamine at the NDMA-glutamate receptor,
memantine ( used to slow the progression of Alzheimer’s)
In addition to ‘receptors’ what three other drug targets are there?
receptors
enzymes
transporters
ion channels
give an example of a drug that targets and acts on receptors and explain how it produces its desired effect.
Muscle relaxants target receptors
These are competitive antagonists of ACh at the postsynaptic nicotinic receptor
They block the receptor, preventing ACh from, binding and causing muscle contraction
give an example of a drug that targets and acts on enzymes and explain how it produces its desired effect.
ACE inhibitors (example of enzyme inhibition) eg. ramipril
Blocks the conversion of angiotensin I to angiotensin II
Causes vasodilation, reduces BP
give an example of a drug that targets and acts on Transporters and explain how it produces its desired effect.
Proton pump inhibitors eg. lansoprazole
Prevent production of stomach acid by the proton pump
Proton pump produces H+ in the parietal cells
give an example of a drug that targets and acts on Ion channels
and explain how it produces its desired effect.
Calcium channel blockers
Eg. verapamil
These target the calcium ion channels which lead to atrial vasodilation
define bioavailability
the amount of drug that reaches the systemic circulation unaltered.
compare the bioavailability of IV, IM and oral
IV = 100%
IM = also very high
oral = much less (around 50%)
why is oral bioavailability lower than IM and IV?
IV and IM are high because they are absorbed directly into blood
Oral is lower because undergoes first pass metabolism in the gut before they can enter systemic circulation
define first pass metabolism
rapid uptake and metabolism of an agent into inactive compounds by the liver, immediately after enteric absorption and before it reaches the systemic circulation
concentration of the drug is greatly reduced before it reaches systemic circulation.
(leading to lower bioavailiabity)
the oral dose of morphine is twice the intramuscular morphine e.g. IM dose is 5mg
and oral dose is 10mg.
because IM morphine is absorbed directly into blood
oral morphine undergoes first pass metabolism : It is metabolised/extracted by the intestine and metabolised by the liver before entering the systemic circulation
therefore you need more oral morphine to produce same affect as IV/IM
why would a Dr prescribe a patient with renal impairment a lower dose of morphine, given at longer intervals?
Morphine is metabolised in the liver to morphine 6 glucuronide which is more potent than morphine.
morphine 6 glucuronide is then excreted by the kidneys
therefore if a patient has renal failure it will not be as readily excreted, the toxic compound will build up leading to an opioid overdose
