Pharmacology 2: Pharmacokinetics and dynamics, drug interactions and toxicology Flashcards
4 principle classes of receptor type?
receptors, enzymes, carriers or transporters, ion channels
RICE
what is the response of a drug generally proportional to?
the number of receptor sites bound by the drug
how does EC50 differ between use of competitive and non-competitive antagonists?
competitive: changes as increasing concentration of agonist is required to overcome antagonism, but maximal effect value for agonist stays the same
non-competitive: EC50 stays the same as agonist not competing to occupy binding site, but maximal effect will be depressed proportional to degree of antagonist binding to receptor.
define therapeutic window
concentration range of a drug over which it exerts a clinically useful effect without significant toxic effects
where do ACEIs act primarily in the body?
pulmonary and coronary arterial endothelial surfaces
which drug groups commonly contribute to drug-drug interactions?
anticonvulsants e.g. phenytoin and carbamazepine
anticoagulants e.g. warfarin
antiarrhythmics e.g. amiodarone
antidepressants e.g. mono-amine oxidases
antibiotics e.g. quinolones, macrolides and rifampicin
why might circulating albumin levels be low?
hepatic failure
nephrotic syndrome
malnutrition
why must lidocaine, a Na+ channel blocker used in arrhythmias, be given parenterally?
extensively metabolised by the liver if given orally, so has a very small bioavailability
what is the primary mechanism by which CYP 450 induction takes places?
increased transcription to increase enzyme expression
but increased translation, and reduced degradation can play a role
a drug that induces the CYP 450 system can increase metabolism of a drug so that it is no longer therapeutically effective, and can increase the metabolism of itself e.g. carbamazepine, but why else can it be problematic?
can result in production of toxic levels of reactive drug metabolites, resulting in tissue damage.
importance of a pharmacodynamic drug-drug interaction in DVT prophylaxis?
e.g. after hip replacement surgery, pateints given prophylactic warfarin for no. wks but therapeutic level in plasma may not be reached for several days so heparin may be give aswell. both together can produce supratherapeutic levels of anticoagulation, so patient may experience significant bleeding.
what does the clinical effectiveness of a drug, after it is stopped, depend on?
therapeutic window
minimal plasma conc of drug which is effective
why does penicillin have few SEs in terms of its selectivity? and what transporter is used for its secretion at the PCT of the kidney nephron?
inhibits transpeptidase enzyme involved in bacterial cell wall synthesis, and mammalian cells do not have a cell wall.
organic anion transporter
difference between drug selectivity and drug specificity?
selectivity: how selective is a drug in binding to its target. High selectivity= lower chance it will interact with different targets to produce SEs
specificity: high specificity= drug interacts only with 1 specific receptor subtype so has less action on other organs.
why is cranberry juice used therapeutically in the treatment of UTIs? why if on warfarin should patient be advised not to drink this?
inhibits bacterial adherence to urothelium
enzyme inhibitor- warfarin therefore has reduced clearance so there is increased risk of haemorrhage
when is there high risk of adverse drug reactions?
drugs with narrow therapeutic indexes
polypharmacy
patients with multiple conditions
patients at extremes of age- altered PK profile, and co-morbidities
ignorant, inappropriate or reckless prescribing
drugs being used near their minimum effective conc- increased risk of tment failure if increased drug metabolism
problem with using plasma creatinine level as a measure of renal function in elderly patients when determing drug doses?
elderly= less muscle mass, so plasma creatinine may be in normal range despite mild to moderate renal failure, so dose which you administer based on presumption that normal renal function is present can result in serioud drug OD producing toxicity as renal clearance will be reduced in renal failure.
equation for oral bioavailability?
AUC oral/AUC iv
what factors relating to a drug can affect its apparent volume of distribution?
formulation- slow or fast release e..g. particular coating
lipophilicity/hydrophobicity
charge
ability to bind to proteins
which drugs are likely to distribute to the blood plasma?
highly plasma protein-bound e.g. warfarin, very large, very charged
e.g. heparin
which drugs are likely to distribute to AT?
highly lipophilic e.g. diazepam
examples of drugs with very large volumes of distribution and hence may require higher initial does to achieve plasma concentrations which are therapeutically effective?
digoxin- reduces HR
azithromycin- used in chlamydia tment
amiodarone- K+ channel blocker, prolongs QT interval