Lecture 3. Pharmacodynamics Flashcards
(33 cards)
What are receptors?
Proteins inserted into the membrane which bind neurotransmitters, hormones etc and produce a cellular response
What are four different types of receptors?
- Ligand gated ion channels (ionotropic)
- G-protein coupled receptors (metabotropic)
- Kinase-linked receptors
- Receptors linked to gene transcription (nuclear receptors)
What responses caused by agonists can be measured experimentally?
Muscle contraction
Electrical current/change in membrane potential (electrophys)
Production of a second messenger (cAMP, IP3 etc) Inhibition of transmitter release change in heart rate, blood pressure etc
What do agonists do?
Agonists bind to receptors, creating an AR complex which then causes a response
What is the standard way of measuring agonists?
Using a log concentration graph
What does EC₅₀ mean?
The concentration of agonist that causes 50% of the maximum response
Why is there a maximum response?
- Finite number of receptors: all occupied (response = α[AR])
- Property of tissue/cell (for example maximum muscle contraction)
What is affinity?
How well a drug binds to the receptor
What is efficacy?
The measure of the response once a drug is bound to the receptor
What is potency?
The combination of both affinity and efficacy
What does Kd tell us?
The concentration of drug required to occupy 50% of the receptors
What does a lower Kd result in?
Higher affinity
How do you calculate the proportion (P) of receptors occupied?
P = [Drug]/(Kd+[D])
Why can’t ligand affinity be measured?
It involves a combination of affinity and efficacy
What occurs in a ligand bidning assay?
Displacement of radio-labelled ligand (³H, ¹⁴C or ¹²⁵I) by cold ligand
How can the concentration of bound ligand be calculated?
[bound] = Bmax Xa / (Xa + Kd)
Xa = concentration of ligand
Bmax = total number of binding sites in prep (pmol/mg protein)
What occurs in desensitisation/tachyphylaxis?
Loss of receptors (internalisation)
Exhaustion of mediators
Physiological adaptation (homeostatic response)
What is the difference between receptor desensitisation and tachyphylaxis?
Tachyphylaxis when response in muscles get smaller
What are clinical uses for agonists?
Adrenaline (heart: increase rate and force of contraction) also anaphylactic shock
Salbutamol (asthma)
Oxymetazoline (nasal congestion)
Dopamine (heart, increase rate and force of contraction)
Morphine (analgesic for severe pain) (opiate receptor agonist)
Do partial agonists have lower affinity than full agonists?
Partial agonists can have a higher affinity than full agonists, they’ll just have a much lower efficacy
In theory, what are the clinical uses of partial agonists?
Reduce over-activity but not block basal activity
What do inverse agonists reduce?
A receptor’s constitutive activity (activity that goes on without any agonist)
What are many antagonists?
Inverse agonists
What increases the opening of the GABA-A receptor?
Benzodiazepines (BZ)
