Pharmacodynamics - Target Tissue Receptors Flashcards
affinity
- the amount of attraction between a drug and a receptor
- related to the drug amount that is required to bind to the unoccupied receptors
- drugs with a high affinity binds readily easily to open receptors even if the concentration of the drug is relatively low
What are the three kinds of surface receptors?
- ion channels
- enzymes (start chain of reaction)
- G proteins / regulatory proteins
What is an example of surface receptors that act as ion channels
- Acetylcholine (ACh) post synaptic membrane of neuromuscular junction
- GABA ion channel complex for neruonal membranes in the CNS
Whats an example of a surface receptor linked directly to an enzyme
- tyrosine kinase protein for insulin and other growth factors
Explain and give an example of surface receptors linked to regulatory proteins
- drug binds and links to G protien (activated by the binding of guanine nucleotides)
- called G-protien coupled receptors
- drug acts as a first messenger and intracellular pathway is second messenger
Ex; cAMP
What are common types of intracellular recptors/drugs for for these receptors
- receptors are specific for certain endogenous hormones and hormone-like drugs (steroids and thyroid compounds)
What factors impact drug-receptor interactions?
- drugs size and shape relative to binding site
- electrostatic attraction between drug and receptor
Allosteric modulators
- receptors may exit in variable affinity states depending on the influence of local regulators (allosteric modulators)
- these increase or decrease affinity for a drug by binding to another site on the receptor
What other factor besides allosteric modulators impact affinity
lipid membrane fluidity and organization
selective
drug that only affects one type of cell or tissue and produces a specific physiological response
drug selectivity is a relative term bc no drug produces only one effect
related closely to subtypes of receptors based on structural differences (so we can develop drugs that will affect only one receptor subtype and produce selevtive effects and limit side effects)
Describe the dose-response curve
- response is typically proportional to the number of receptors occupied by the drug,
- not a linear relationship bc threshold and ceiling effect
agonist vs antagonist
- agonist; agonist has both affinity and efficacy
- antagonist; has only affinity and it occupies the receptor to block the effect of another chemical
competitive vs noncompetitive
- competitive; whoever has the higher concnetration (antagonist or agonists) will win receptor spot
- noncompetitive; antagonist forms a permanent bond with receptor and the agonist can’t compete for that spot no matter how high the concentration (terminated only with normal protein turnover so the effect tends to remain long)
Partial Agonist
- drugs when they do not evoke a max response compared to a strong agonist
- does not completely activate the receptor after it binds
- but it is not due to decreased drug-receptor affinity
Mixed agonist-antagonist
agents that stimulate certain receptor subtypes while simultaneously blocking the effects of endogenous substances on other receptor subtypes
AKA acting as agonist on one tissue and antagonist on another tissue
promoting estrogen for bone but preventing growth on breast tissue (cancer) SERMs
Inverse agonist
- the opposite effect of an agonist on cellular function
- decreased activity where the receptor is too activated or overstimulated
Receptor Regulation
a prolonged increase in the stimulation of various receptors will lead to a decrease in receptor function
and decreased stimulation will lead to an increase in receptor numbers or sensitivity
desensitization
a fairly brief and transient decrease in responsiveness
associated with phosphorylation
brief response goes back to normal
decrease in respnse (may take longer once binded) whereas downregulation is decrease in actual number of receptors)
Receptor internalization
receptors are withdrawn from the cell membrane by endocytosis
brief response goes back to normal
Down regulation
more prolonged slower process
number of available receptors is diminished
possibly due to prolonged exposure of the aginost causing removal of receptors OR decreased receptor synthesis
What are receptor supersensitivity examples
a prolonged decrease in the stimulation of the postsynaptic receptors can result in a functional increase in receptor sensitivity
denervation supersensitivity - is when an area becomes overly sensitive after nerve damage, due to the body’s attempt to compensate for the loss of nerve function
