Pharmacodynamics II Flashcards
Understand the difference between pharmacokinetic and pharmacodynamic tolerance.
Pharmacokinetic tolerance is due to induction of drug metabolizing enzymes, it is also called metabolic tolerance whereas pharmacodynamic tolerance is due to cellular tolerance, this can be due to changes in the number of receptors or changes in receptor function.
Understand the difference between physiological and competitive antagonism
Physiological antagonism:
* Two agents have opposing physiological effects
* Histamine causes vasodilation and norepinephrine causes vasoconstriction
* When administered together these agents tend to counteract each other
Competitive antagonism (blocks at the binding site ofreceptor)
* Naloxone blocks effects of morphine
* Atropine blocks effects of AChat muscarinic receptors
* Propranolol blocks effects of isoproterenol at beta-adrenergic receptors
Understand the mechanisms of supersensitivity
Enhancedresponse due to increased number of receptors, caused by absence of agonist or presence of antagonist.
Know the four processes that comprise pharmacokinetics
AbsorptionDistributionMetabolismExcretion
Explain the mechanism of signaling of Guanylyl Cyclase receptors.
NO is synthesized in endothelial cells, this diffuses into the vascular smooth muscles where it activates Guanylyl Cyclase, it converts GTP to cGMP.cGMP activates protein kinase G. This leads to multiple steps leading to vasodilation.
Explain how ligand activated ion channels work.
Ligand binds to a receptor resulting in conformational change, leading to opening an ion channelIt is important to know that ligand activated ion channels exhibit their full effect in a matter of micro seconds, whereas nuclear receptors exhibit their effect in a matter of hours to days
How does G protein coupled receptors work?
When bound to a ligand, it promotes the release of GDP and binding of GTP to the nucleotide binding site, this leads to G protein regulating an enzyme or an ion channel for intracellular signaling.Signal is terminated by hydrolysis of GTP.
How can an agonist binding to a receptor lead to desensitization?
Agonist binding to a receptor activates the receptor, prolong activation promotes phosphorylation and then internalization of the receptor. This receptor may then be degraded.This is common for beta adrenergic receptors, and this process is called the beta Arrestin pathway
Understand physiological synergism.
Enhanced receptor response that can occur with 2 drugs that produce the same effect through different mechanisms.
