Clinical pharmacology Flashcards
What is used when a patient has a heroin overdose?
naloxone
opiate receptor antagonist
Why is it important for those with a heroin overdose to stay in hospital until treatment is complete?
Naloxone has a very short half-life. A single naloxone dose can be cleared from the circulation (and its sites of action) before the opiate is cleared.
Recurrence of the overdose symptoms can happen
What are the sever symptoms of an opiate overdose?
unconscious and with a low respiratory rate
What is he affinity of a drug?
The affinity of a drug for its receptors is a measure of how well it binds a chemically sensitive site, or ‘receptor’. Drugs bind to receptors at a rate proportional to the drug concentration, but they unbind at a rate that depends only on the chemical properties of the drug-receptor complex.
There are 2 classes of drug antagonists, name them
competitive and non-competitive
What is the definition of affinity and efficacy and how do they relate?
Affinity - tendency of a molecule to bind to a receptor
Efficacy- how well an agonist achieves a response
Two drugs acting on the same target can have identical affinities but very different efficacies. Therefore, different drugs acting at the same receptors can be given at very different concentrations to achieve the same effect.
Important when switching between drugs of the same class
How does a non competitive antagonist, effect the efficacy and affinity of a drug?
agonist affinity is unaltered but efficacy is decreased.
Drug can still bind but its effect is reduced at a fixed concentration
How is the potency of a drug commonly described?
the concentration (or dose) that is able to elicit 50% of the maximal response (i.e. the individual effective concentration, EC50 or individual effective dose, ED50). A drug that has a higher potency achieves that size of response at a lower concentration.
What is a partial agonist?
a drug that has a lower maximal response resulting from lower efficacy
What are Allosteric Modulators?
Bind to proteins at sites other that the binding site for the principal agonist. When these allosteric modulators bind, they can either:
- Alter the affinity of the binding site for its agonists, or
- Change the efficacy of the response when the agonist binds
Allosteric Modulators can be positive or negative, what does this mean?
Positive (to increase the potency of the agonists) or
Negative (to decrease the potency of an agonist)
Give an example of a partial agonist drug type
Beta blockers
Give example of a positive Allosteric Modulator drug type? What is the advantage of this kind of drug?
cinacalcet, a positive allosteric modulator of Ca2+ sensing receptors. used for secondary hyperparathyroidism and parathyroid carcinoma.
Positive - they don’t directly activate (or inactivate) cell signalling, but rather they change the set-point for normal activity
How does desensitisations effect the potency of a drug? Describe how the long term use of a drug can alter its intended mode of action
Many drugs can lead to desensitisation of their receptor targets, also leading to reduced numbers of receptors. So the potency of the drug is reduced
Drugs can often have longer-term effects different from their initial action at receptors, which can result in altered levels of the drug or its target, thereby changing its potency.
Give an example of a drug which causes desensitisation?
Nicotine acts on neuronal nicotinic acetylcholine (ACh) receptors (nAChr).
A first cigarette can cause nausea of vomiting because activation of these receptors can cause tachycardia, increased blood pressure and alteration gastrointestinal motility
Tolerance to these effects develops quickly
Where are nicotine receptors located? How are they able to effect the gut?
Nicotinic receptors are found on skeletal (not smooth) muscle, autonomic neurons, and within the central nervous system (CNS).
For action on the gut, the most likely site of action is the large network of autonomic neurons within the gut wall - the enteric nervous system.
