Name two common alpha-1-adrenoceptor antagonists, and their basic mechanism of action.
Prazosin (treats hypertension by reducing systemic vascular resistance)
Tamsulosin (treats BPH by relaxing prostate smooth muscle)
What is the major adverse effect of Prazosin, and therefore what must be checked routinely in any patient taking Prazosin to treat hypertension?
Orthostatic hypotension (it blocks peripheral vascular smooth muscle contraction). Orthostatic BP must be routinely checked.
Why does tamsulosin have relatively minor effects on BP?
Because it seems to have much greater affinity for the alpha-adrenoceptors of prostate smooth muscle rather than vascular smooth muscle.
Which type of ß-adrenoceptor (ß1 or ß2) do these drugs have a much greater affinity for? Metoprolol, Atenolol, Nebivolol.
ß1 >>> ß2
Which type of adrenoceptor does propanolol have greater affinity for : ß1 or ß2 ?
Affinity is equal between ß1 and ß2.
Give an example of a reversible α-adrenoceptor antagonist, and give an example of an irreversible one.
What happens to the pupils when an α-adrenoceptor agonist is given?
Contraction of the pupillary dilator muscle
--> dilation of pupils
On which adrenoceptors does labetalol exert its effect?
Both α and β
What do you know about irreversible β-adrenoceptor antagonists?
They are currently used only for experimental purposes. Clinically useful β-blockers are reversible antagonists.
Discuss the bioavailability of propranolol.
Propranolol undergoes extensive first-pass metabolism, and has a bioavailability of approximately 30%. However, increasing the oral dose will increase the bioavailability, suggesting that the hepatic extraction mechanisms become saturated.
The bioavailability of propranolol is approximately 30%. Name 4 other β-blockers that have a similar bioavailability. Name one that has a much higher bioavailability of 90%.
Atenolol, Carvedilol, Metoprolol, Labetalol.
Sotalol has a bioavailability of 90%. Bisoprolol has a bioavailability of 80%.
Name one β-antagonist that crosses the blood brain barrier.
Propranolol. It is lipophilic.
What is the approximate half-life of most β-antagonists?
Approx 5-10 hours.
In order to suppress renin release, which adrenoceptors should be antagonized?
Name four β1-selective antagonists.
Atenolol, Bisoprolol, Metoprolol, Nebivolol
Which β-antagonist has a very short half-life of 10 minutes?
Briefly explain how long-term use of β-antagonists such as propranolol and metoprolol can improve survival in patients with ischaemic heart disease.
These drugs reduce and stabilize heart rate, and reduce the force of contraction, which reduces cardiac oxygen demand.
Name three β-antagonists that have been shown to be effective in reducing mortality for patients with chronic heart failure. What does this appear to be due to?
Metoprolol, Bisoprolol, Carvedilol
Appears to be due to cardiac remodelling.
What is the most common adverse effect of β-antagonists?