Neuropharmacology - 1 Flashcards
what is Site of action
drug in the systemic circulation
Routes of Administration of drug
intravenous injection , The Oral Route
what are most drugs?
weak ACIDS or BASES
in what form is the drug best absorbed?
unionised form
what is the term used for a drug to break down into smaller particles so that it can be absorbed into the systemic circulation?
dissolution
Rate of absorption also dependent on?
Gut motility –>
Gastric emptying modulated by:
meal size
meal composition (fat)
drugs (opioids, anticholinergics)
physiological state (position) - stressed then sower + also lying doen slows down
Migraine (gastric stasis)
what is meant by Splanchnic blood flow
and how can it be effected?
blood supply to the gastrointestinal tract, liver, spleen, and pancreas.
- meal size
what is first pass metabolism and how is it a negative?
metabolism that occurs before drug enters in system
- means drugs have to be administered another way
what is the reason for failure of drugs designed for the brain?
blood brain barrier
why is oral root preferred for drug administration?
Safest, most convenient and economical route
–> needs patient cooperation and not always bioavailable
Large blood flow in muscles of upper arm
Route is reliable
Volume: 1-5 ml into muscle bed
Quick uptake into body (within ~ 20 minutes)
Suitable for irritant drugs
Good for depot preparations (long lasting) - oral contraceptives too
Absorption is perfusion limited (increased with exercise)
No self administration
Can be painful
Example drugs: vaccines, antipsychotic drugs, contraceptives
what is tachyfelaxis?
intrinsic sympathetic activity?
What is an agonist ?
agonist (A) binds to receptors (R) → AR complex → (conformational change of receptor - AR* ) → Response
for a Log concentration responce sure what do we use? dose or concentration? why?
dose –> we dont know the concentration only how much we gave
so why is there a maxin=mum to the dose responce curve - 2 possible reasons?
becuase receptors are all filled up ==> respnce is directly proportional to the concentration of the agonist receptor complex
or
it can only contract to a certain degree. It can’t keep contracting because it can’t get any smaller.
So we may reach the top of the curve simply because the tissue is at its maximum = gut
why is knowing the Kd of a drug helpful?
experimental desing - knowing what quantity of drug/agonist to use
why cant we measure the responce of a curve and determine the ligand affinity?
becyase the responc eis both the affinity and efficacy
what is tachyphylaxis? and what is the difference between tachyphylaxis and desensitization?
= response in that tissue gets smaller
“Tachyphylaxis typically involves rapid changes in receptor sensitivity or downstream signaling pathways in response to repeated drug exposure”
The term tachyphylaxis is used to describe desensitization that occurs
what is an partial agonist and an inverse agonist?
cannot produce a full response.
So a full agonist produces a full response. - clinic use no uphoria and stops full agonist from causing euphoria
produces the opposite responce of an agonit –> reducing the response by removing the constitutive activity of the receptor.
Do partial agonists have lower affinity?
no - not necessarily –> just lower EFFICACY
whats an example of an inverse agonist?
the GABA receptor - gaba always preent - agonist = act like gaba = open channel more
inverse agonist = it binds to that site
and it decreases the actions of Gaba
PAMs, AgoPAMs , NAMS?
positive steric modulator increases the coupling to the G protein.
Nans = do the opposite. They bind, but they reduce the effectiveness of the G protein
AgoPAMs = bind, but they also activate the receptor.
By modifying ongoing receptor activity, NAMs can fine-tune the signaling pathway and maintain the temporal pattern of receptor activation while reducing its overall intensity.
how do we measure antagonist potency?
pA2 value = negative log of the molar concentration of antagonist
that reduces the effect of a known concentration of agonist
to that of half the concentration.
what is another use of non compatitive antagonists?
measure amount of spare receptors. - 80% active 20% spare - eg.
lecture 4 –>
Anatomy of the synaptic nervous system
singe nerone - body in the ventral horn
axon - runs alog
neuromuscular junction (NMJ) –> synapse (uses acetylcholine)
–> there can be more branching of axon to connect eith more muscle fibres
what is the diference between the Anatomy of the synaptic nervous system and the anatomy of the autonomic nervous system?
there are preganglionic and postganglionc neurons + uses ACh (acetylcoline) + but does not synpse with SKELETAL MUSCLE
