Agonism Flashcards
Explain the difference between Pharmacokinetics and Pharmacodynamics.
Pharmackinetics: what the body does to the drug. (relationship b/t dose and concentration acheived at site of action; duration etc)
Pharmacodynamics: what the drug does to the body (relationship b/t the concentration at site of action and outcomes)
Explain the dose-response mechanism and the concept of therapeutic windows.
Usually a larger dose gives a larger effect, but not always. The slope of the curve determines sensible dose increments. Drugs often have a ceiling dose beyond which response does not increase.
“The Right Dose”:
If there is an identical therapeutic and toxic mechanism such as digitalis or phentoin (anti-epileptic drug)
If there are different therapeutic and toxic mechanisms such as paracetamol. (perhaps activates cannabanoid receptors in the brain to relieve pain but it can also damage the liver due to its metabolism. )
The right dose for drugs is not really ‘all or none’.
The usable dose of a drug is often constrained by unwanted actions.
Therapeutic Window: The dosage at which therapy is useful but not yet dangerous. It is narrow in drugs in which have the same therapeutic and toxic mechanisms. The therapeutic window can be very different for different individuals and so it is not always an appropriate drug for every individual.
What are Dose-limiting side effects?
The side effects that stop delivery of increased dose of a drug that has a therapeutic effect.
What is Potency?
measure of drug activity expressed in terms of the amount required to produce an effect of given intensity.
What is EC50?
Effective concentration to effect 50% of the population
What is ED50?
Effective dose to effect 50% of the population
What is efficacy?
capacity for beneficial change (or therapeutic effect) of a given intervention.
That is, The ability of the drug to do the right thing/therapeutic effect.
What is a partial agonist?
Partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist.
What are some examples of partial agonists?
- Salbutamol: Beta2 adrenoceptors that is used as a treatment for asthma
- Sumatriptan: migraine attack treatment that vasoconstricts brain blood vessels. (the 5- HT1 receptors that it acts on are also in the heart which could stop the heart)
- Buprenorphin: opiate receptors
- Prenalterol: maximum response of 70% and is 30-fold less potent that the full agonist counterpart Isoprenaline.
What are some properties of drugs and receptors that effect the agonist efficacy of the drug interaction?
- concentration of the drug
- number of receptors
- Drug/receptor affinity
- Intrinsic efficacy (the number of responses per unit times)
What is the difference between pharmacological efficacy and clinical efficacy?
- Pharmacological efficacy refers to the strength of the receptor activation (full: high efficacy; partial: low efficacy)
- Clinical efficacy refers to the strength of the beneficial effect (full/partial both have benefits and disadvantages)
In relation to acute and chronic heart failure, explain the effects of isoprenaline and prenalterol.
Two drugs are used for heart failure:
- Isoprenaline - Positive inotropic effects in acute and chronic heart failure
- Prenalterol - Positive inotropic effects in acute heart failure & Negative inotropic effects in chronic heart failure
In Chronic heart failure, the normal mechanisms that attempt to overcome heart failure allow the heart to recover for a period of time however slowly, cardiac output decreases.
(Acute heart failure refers to the initial components of heart failure. )
The chronic over-activation of beta-adrenoceptors causes reduced sensitivity to those receptor agonists
Isoprenaline therefore only needed some of the receptors to elicit a response (they have a receptor reserve); whereas prenalterol required all the receptors to gain the therapeutic effect and so when the adrenoceptors are desensitised, there aren’t enough receptors to have a positive inotropic effect on the heart.
Because prenalterol is a partial agonist it binds well but its ability to activate is limited by the number of receptors available.
During heart failure, the receptors are downregulated and this inhibits prenalterol’s ability to activate. Due to the high sympathetic tone that is found during heart failure, there is alot of noradrenaline and adrenaline at the site of the receptors and therefore it results in prenalterol’s behaviour as an antagonist.
