Pharmacokinetics and Pharmacodynamics Flashcards
Define pharamcodynamics
What the drug does to the body
What are the four main types of receptors?
ReceptorsEnzymesCarrier/transportersIon Channels
Define agonist
Bind to and stabilise receptor sites in the active state
Define antagonist
Bind to and stabilise the receptor site in the inactive state
Define partial agonist/antagonist
When drugs act as a mixture of both agonists and antagonists. the overall action of the rugs depends on the proportion of each receptor type activated
Define affinity
The ability of a drug to bind at a receptor site
Define Efficacy
The maximal effect of a drug when it is bound to a receptor
Define Kd
The concentration at which half available agonist receptors are bound
Define Ki
The concentration at which half available antagonist receptors are bound
Define efficacy
The maximal effect of a drug when bound to a receptor
Define potency for an agonist
Concentration that produces 50% of a maximal response
Define potency for an antagonist
Concentration that reduces the maximum activation by 50%
Define competitive antagonism
The antagonist competes for the active site with the agonist. It can be overcome by increasing the agonist concentration
Define non-competitive antagonism
The antagonist binds to a site other than the actives site OR is bound to the active site but removal is very slow. You cannot overcome this antagonism by adding more of an agonist. The maximal effect is decreased in proportion to the degree of antagonist binding.
What actions does metoclopramide have?
Is a dopamine antagonist- antiemetic- gastroprokineticTherefore it increases the rate of gastric emptying and therefore increase the rate of uptake via the small intestine. This can potential increase the absorption of some drugs.
How can the distribution phase be affected by drug:drug interactions?
- Competition at protein/ lipid binding sitesCan have serious issues if the drug has non-linear kinetics and has a narrow therapeutic window so the concentration of the drug builds up.
How can drug/drug interactions affect metabolism?
They can cause induction or inhibition of certain CYP enzymes
What are the main mechanisms which affect drug excretion?
- Protein binding- decreased binding increases amount of unbound drug, which increases its rate of removal2. Tubular secretion- inhibiting tubular secretion will increase the plasma levels of a drug3. Urinary pH- this has an effect on acidic/basic drugs being able to diffuse back into the blood
Describe a specfic drug-drug interaction
Propanolo (non-selective beta antagonist) reduces the effects of salbutamol (Beta2 receptor agonist). Therefore, betablockers should not be administrated to asthmatics or should be done with caution.
Give some anticonvulsants which commonly give rise to drug-drug interactions
PhenytoinCarbamezepine
Give an anticoagulant which commonly gives rise to drug-drug interactions
Warfarin
Give an antidepressant which commonly gives rise to drug-drug interactions
Monoamine oxidases
Give some antibiotics which commonly give rise to drug-drug interactions
RifampicinMacrolidesQuinolones
Give an antiarrhthymic which commonly gives rise to drug-drug interactions
Amiodarone
What are the mechanisms by which induction takes place in CYP450 enzymes?
Increased transcriptionIncreased translationSlower degradation
What does induction of CYP450 enzymes do?
Increases the rate of elimination
What happens when CYP450 enzymes are inhibited?
Drug half-lives increaseDrug clearance decreases
Why do drug interactions occur when hepatic disease is present?
- Decreased clearance of hepatic metabolised drugs- Reduced CYP450 activity- Hypoalbuminaemia due to malnutrition and nephrotic syndromeleads to less albumin for drugs to bind to so the free plasma drug levels are higher
Why do drug interactions occur with renal disease?
- Falling GFR (acute or chronic)- Reduced clearance of renally excreted drugs (Digoxin, aminoglycosides)- Electrolyte disturbances may predispose to toxicity - NephrotoxinsE.g. Aminoglycosides are nephrotoxic, and can further enhance their own and other drug toxicities by reducing GFR
Why do drug interactions occur with cardiac disease?
- Decreased organ perfusion- Excessive response to hypotensive agents
What interactions can occur with certain types of food?
Grapefruit and cranberry juice inhibit CYP450 enzymes. They will reduced the clearance of a number of drugs including warfarin and statins.
Define on-target adverse drug reactions
These are due to:- an exaggerated therapeutic effect of a drug, usually due to increased dosing. e.g. hypertension treatment leading to hypotension- The same effect, but occurring in different tissuese.g. antihistamine receptors acting on immune system receptors as well as H1 receptors in the heart, causing drowsiness.
Define off-target adverse drug reactions
These are interactions with other receptor subtypes which occur secondarily to the one intended for therapeutic effect. This is very common in most drugs.
Give some groups of people who are prone to adverse effects
Pregnant women- teratogenicity- thalidomideBreast feeding womenElderly - polypharmacy- reduced renal clearance- nervous system is more sensitive to drugsPatients with genetic enzyme defects- G6PD deficiency, haemolysis occurs is an oxidant drug is taken
When are drug interaction likely to occur?
With polypharmacy- the more drugs you are taking, the greater the risk of a drug-drug interaction occuring
