Module 32 Flashcards
A patient with asthma developed hypertension and was started on an antihypertensive drug. About 1 hour later the patient developed a severe case of asthma. What class of drug could lead to such a worsening of asthma? How would you treat the asthma?
This is a classic story of an asthmatic treated with a ß-blocker. It has resulted in deaths. Even the selective ß-blockers are not completely selective. ß-blockers are competitive inhibitors, so in principle it should be possible to overcome the blockade by using very high doses of a ß-agonist such as salbutamol.
Some of the side-effects of propranolol involve the CNS. They include fatigue, depression, and nightmares. From the structure of propranolol and nadolol, which would you expect to have the greater CNS side-effects? What is the evidence that your expectation is correct?
This was mostly a marketing ploy. Although nadolol is a bit more polar, there is no reason that it cannot get into the CNS, and the clinical data do not support a clear difference. However, marketing nadolol in this way helped to gain market share.
How would you treat someone who has just taken a large overdose of propranolol?
- In most cases nothing needs to be done. Propranolol is a competitive inhibitor. At a therapeutic dose the % ß-blockade is on the order of 90%, and increasing the dose beyond that has little effect. Therefore, in a healthy person an overdose does not result in serious consequences, and no treatment is required. It can cause problems in someone with heart disease or diabetes, and then the treatment should fit the problem that the patient develops, e.g. hypotension, hypoglycemia etc.
AC is a 70 year old gentleman with benign prostatic hyperplasia. The severity of his symptoms now warrants pharmacologic intervention. He is otherwise well with his only other medical condition being hypertension for which he receives ramipril (an ACE inhibitor). Would you consider a change in his anti-hypertensive regimen in light of the new need to treat benign prostatic hypertrophy? Why?
- A major class of drugs used to treat benign prostatic hypertrophy are alpha-1-adrenergic blockers. The smooth muscle in the urethra is innervated by alpha-1-adrenergic receptors, and the blockers lead to muscle relaxation and increased urine flow. Examples of alpha-blockers are prazosin, terazosin. and doxazosin.
- However, these drugs also decrease blood pressure. In fact, prazosin was developed for the treatment of hypertension, but it is associated with postural hypotension, and it is rarely used for that indication. Therefore, you need to be careful with the combination of ramipril and an alpha-blocker because postural hypotension could lead to a fall, broken hip, etc. It would be best to decrease or stop the ramipril, titrate the alpha-blocker, and then add back the appropriate amount of ACE inhibitor
Phenoxybenzamine is an alpha-1-adrenergic blocker used before surgery on pheochromocytomas to prevent a severe hypertensive crisis that can be caused by the release of norepinephrine during surgery. It is an irreversible inhibitor. Why?
- Notice that phenoxybenzamine is a nitrogen mustard. It forms a very reactive aziridinium ion that irreversibly binds to the a-adrenergic receptor and is very effective. However, unlike the nitrogen mustards used to treat cancer, it is monofunctional and cannot crosslink DNA; therefore, it is not as toxic. However, I would not want to take it for a long period of time.
