Page 183 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 10 Adrenoceptor Antagonist Drugs 169

activity may enhance skeletal muscle tremor, it is not surprising and feet in winter. CNS effects include mild sedation, vivid dreams,
that β antagonists have been found to reduce certain tremors (see and rarely, depression. Discontinuing the use of β blockers in any
Chapter 28). The somatic manifestations of anxiety may respond patient who develops psychiatric depression should be seriously
dramatically to low doses of propranolol, particularly when taken considered if clinically feasible. It has been claimed that β-receptor
prophylactically. For example, benefit has been found in musicians antagonist drugs with low lipid solubility are associated with a lower
with performance anxiety (“stage fright”). Propranolol may incidence of CNS adverse effects than compounds with higher lipid
contribute to the symptomatic treatment of alcohol withdrawal solubility (Table 10–2). Further studies designed to compare the
in some patients. CNS adverse effects of various drugs are required before specific
recommendations can be made, although it seems reasonable to try
Miscellaneous the hydrophilic drugs nadolol or atenolol in a patient who experi-
ences unpleasant CNS effects with other β blockers.
Beta-receptor antagonists have been found to diminish portal
vein pressure in patients with cirrhosis. There is evidence that The major adverse effects of β-receptor antagonist drugs relate
both propranolol and nadolol decrease the incidence of the first to the predictable consequences of β blockade. Beta -receptor
2
episode of bleeding from esophageal varices and decrease the blockade associated with the use of nonselective agents com-
mortality rate associated with bleeding in patients with cirrhosis. monly causes worsening of preexisting asthma and other forms of
Nadolol in combination with isosorbide mononitrate appears to airway obstruction without having these consequences in normal
be more efficacious than sclerotherapy in preventing rebleeding individuals. Indeed, relatively trivial asthma may become severe
in patients who have previously bled from esophageal varices. after β blockade. However, because of their lifesaving potential
Variceal band ligation in combination with a β antagonist may be in cardiovascular disease, strong consideration should be given
more efficacious. to individualized therapeutic trials in some classes of patients,
In the current era of repurposing established drugs that are well eg, those with chronic obstructive pulmonary disease who have
1
tolerated, unexpected benefits can emerge. Infantile hemangio- appropriate indications for β blockers. While β -selective drugs
mas are the most common vascular tumors of infancy, which can may have less effect on airways than nonselective β antagonists,
disfigure or impair vital functions. Propranolol at 2 mg/kg/d has they must be used very cautiously in patients with reactive airway
1
been found to reduce the volume, color, and elevation of infantile disease. Beta -selective antagonists are generally well tolerated in
hemangioma in infants younger than 6 months and children up patients with mild to moderate peripheral vascular disease, but
to 5 years of age, perhaps displacing more toxic drugs such as caution is required in patients with severe peripheral vascular
systemic glucocorticoids, vincristine, and interferon-alfa. disease or vasospastic disorders.
Beta-receptor blockade depresses myocardial contractility and
excitability. In patients with abnormal myocardial function,
CHOICE OF A BETA-ADRENOCEPTOR cardiac output may be dependent on sympathetic drive. If this
ANTAGONIST DRUG stimulus is removed by β blockade, cardiac decompensation may
ensue. Thus, caution must be exercised in starting a β-receptor
Propranolol is the standard against which newer β antagonists antagonist in patients with compensated heart failure even though
for systemic use have been compared. In many years of very wide long-term use of these drugs in these patients may prolong life.
use, propranolol has been found to be a safe and effective drug A life-threatening adverse cardiac effect of a β antagonist may be
for many indications. Since it is possible that some actions of a overcome directly with isoproterenol or with glucagon (glucagon
β-receptor antagonist may relate to some other effect of the drug, stimulates the heart via glucagon receptors, which are not blocked
these drugs should not be considered interchangeable for all appli- by β antagonists), but neither of these methods is without hazard.
cations. For example, only β antagonists known to be effective in A very small dose of a β antagonist (eg, 10 mg of propranolol)
stable heart failure or in prophylactic therapy after myocardial may provoke severe cardiac failure in a susceptible individual.
infarction should be used for those indications. It is possible that Beta blockers may interact with the calcium antagonist vera-
the beneficial effects of one drug in these settings might not be pamil; severe hypotension, bradycardia, heart failure, and cardiac
shared by another drug in the same class. The possible advantages conduction abnormalities have all been described. These adverse
and disadvantages of β-receptor partial agonists have not been effects may even arise in susceptible patients taking a topical
clearly defined in clinical settings, although current evidence sug- (ophthalmic) β blocker and oral verapamil.
gests that they are probably less efficacious in secondary preven- Patients with ischemic heart disease or renovascular hyperten-
tion after a myocardial infarction compared with pure antagonists. sion may be at increased risk if β blockade is suddenly interrupted.
The mechanism of this effect might involve up-regulation of the
number of β receptors. Until better evidence is available regard-
CLINICAL TOXICITY OF THE BETA- ing the magnitude of the risk, prudence dictates the gradual
RECEPTOR ANTAGONIST DRUGS tapering rather than abrupt cessation of dosage when these drugs
are discontinued, especially drugs with short half-lives, such as
Many adverse effects have been reported for propranolol but most propranolol and metoprolol.
are minor. Bradycardia is the most common adverse cardiac effect The incidence of hypoglycemic episodes exacerbated by β-blocking
of β-blocking drugs. Sometimes patients note coolness of hands agents in diabetics is unknown. Nevertheless, it is inadvisable to use