Week 3 Flashcards
What are the different types of drug receptors
Enzymes:
-cyclooxygenase; the aspirin receptor
Ion channels:
-Ca2+ channels blocked by nifedipine used to manage hypertension, angina, raynauds phenomenon
Transporters (pumps, transport proteins):
-noradrenaline transporter blocked by cocaine
‘Physiological’ receptors- receptors for hormones, neurotransmitters etc :
-acetylcholine, histamine, insulin etc
Nomenclature around drugs
In pharmacology distinct words used for drugs depending on the effect they have on a certain receptor
E.g. -100% efficacy= full inverse agonist
Ways of regulating cell function
Altered membrane potential
Altered enzyme activity
Altered gene expression
Most drugs affect cell function via physiological receptors
What is agonism
How drugs produce effects by binding to receptors- various ways in which effects are produced
What is antagonism and desensitization
How drugs block effects by binding to receptors- ways in which effects blocked or reduced
Why are partial agonists worse
Reduced frequency of open channels
What is a partial agonist
An agonist which is unable to induce maximal activation of a receptor population regardless of amount of drug applied
Lower efficacy than a full agonist
What is a inverse agonist
Is a ligand that binds to the same receptor-binding site as an agonist and not only antagonises the effects of an agonist but also exerts the opposite effect by suppressing spontaneous receptor signalling
Have negative efficacy
What is meant by allosteric effects on receptors
The allosteric modulation may result in slowing or inhibition of binding of ligands to the orthosteric binding site causing weakening of a signal or decreased activity
Super-agonists
Highly efficacious agonists
Can produce a maximal response from the cell without binding to all of the available receptors
Emax for these then >100%
Example of super-agonist
Goserelin (Zoladex) is a super agonist of the gonadotropin-releasing hormone receptor (GnRH-R).
It suppresses production of the sex hormones (testosterone and oestrogen) particularly in the treatment of breast and prostrate cancer
Example of partial agonist
Buprenorphine is an opioid used to treat opioid addiction, moderate acute pain and moderate chronic pain
What are competitive antagonists
Bind reversibly at the same site as the (natural) agonist doesn’t activate it, blocks action
Produce a parallel shift to the right of agonist dose/response curves
Need a higher concentration of agonists to get same effect
What are irreversible antagonists
Bind irreversibly at the same site as the agonist, forming a covalent bond or binding incredibly tight
Decrease maximal response to agonists
May produce an initial shift to the right of the dose/response curve with no decrease in max
Evidence for spare receptors
What are allosteric antagonists
Rare
Bind reversibly at a distinct site from agonist and decrease agonist affinity
Reduce likelihood of agonist binding
What are channel blockers
Bind inside the channel and prevent passage of ions
Binding of channel blockers tends to be enhanced by receptor activation
Use dependence
What are physiological antagonists
They antagonise the physiological effect of some agonists but via different mechanism. Opposite effect of agonist, will indirectly oppose action of agonist
Several substances that have anti-histaminergic action despite not being ligands for the histamine receptor are physiological antagonists to histamine
What are the classes of antagonists
Competitive antagonists
Irreversible antagonists
Allosteric antagonists
Channel blockers
“Physiological antagonists”
How are receptors classified
On the basis of the selective action of drugs
They’re named according to the transmitter or hormone with which they interact
What are the receptor super families
Integral ion channels e.g. Nicotinic receptor glycine receptor
Integral tyrosine kinases e.g. insulin receptor
Steroid receptors =nuclear receptors e.g. oestrogen receptor, androgen receptor
G protein coupled receptors e.g. muscarinic receptors, adrenoreceptors
Cytokine receptors e.g. prolactin receptor
Nuclear receptors
Act in the nucleus but most often located in the cytoplasm
Their ligand binding domain functions like a folding sensor. Without steroid ligand its unfolded and with steroid its folded
The DNA binding domain mediates binding of nuclear receptors to thousands of sites within genome
What can be a drug receptor
Anything that a drug binds to, to produce its pharmalogical effect
How does asparaginase act
As a medication, L-asparaginase is used to treat acute lymphoblastic leukaemia, acute myeloid leukaemia, and non-Hodgkin’s lymphoma. It’s given by injection into a vein, muscle or under skin
What is toxicology
The study of the unwanted or deleterious effects of drugs or chemicals on the body
What does the distribution of drugs into CNS usually depend on
Lipid diffusion
What can competition between two drugs for binding to plasma proteins result in
Change in concentration of free drug and potential drug toxicity
When considering absorption of drugs weakly basic drugs have a higher solubility at
Lower pH
At which stage of drug development can it first be proved that a drug is effective
Phase II trials
