Page 180 - Basic _ Clinical Pharmacology ( PDFDrive )

166 SECTION II Autonomic Drugs

TABLE 10–3 Drugs used in open-angle glaucoma.

Drugs Mechanism Methods of Administration
Cholinomimetics
Pilocarpine, carbachol, physostigmine, Ciliary muscle contraction, opening of Topical drops or gel; plastic film
echothiophate, demecarium trabecular meshwork; increased outflow slow-release insert
Alpha agonists
Nonselective Increased outflow Topical drops
Epinephrine, dipivefrin
Alpha 2 -selective Decreased aqueous secretion
Apraclonidine Topical, postlaser only
Brimonidine Topical
Beta blockers
Timolol, betaxolol, carteolol, levobunolol, Decreased aqueous secretion from the Topical drops
metipranolol ciliary epithelium
Carbonic anhydrase inhibitors
Dorzolamide, brinzolamide Decreased aqueous secretion due to Topical
−
lack of HCO 3
Acetazolamide, dichlorphenamide, Oral
methazolamide
Prostaglandins
Latanoprost, bimatoprost, travoprost, Increased outflow Topical
unoprostone

β receptors are probably important in liver (recovery from hypo- antidepressant medications. Acebutolol is also a β -selective
2
1
glycemia) and blood vessels (vasodilation). antagonist.
Nebivolol is the most highly selective β -adrenergic receptor Celiprolol is a β -selective antagonist with a modest capac-
1
1
blocker, although some of its metabolites do not have this level of ity to activate β receptors. There is limited evidence suggesting
2
specificity. Nebivolol has the additional quality of eliciting vaso- that celiprolol may have less adverse bronchoconstrictor effect in
dilation. This is due to an action of the drug on endothelial nitric asthma and may even promote bronchodilation.
oxide production. Nebivolol may increase insulin sensitivity and Labetalol is a reversible adrenoceptor antagonist available as a
does not adversely affect lipid profile. Agents of this type are some- racemic mixture of two pairs of chiral isomers (the molecule has
times referred to as third-generation β-blocking drugs because two centers of asymmetry). The (S,S)- and (R,S)-isomers are nearly
they activate nitric oxide synthase. In patients with metabolic inactive, the (S,R)-isomer is a potent α blocker, and the (R,R)-
syndrome, for an equivalent reduction of blood pressure and heart isomer is a potent β blocker. Labetalol’s affinity for α receptors
rate, metoprolol, but not nebivolol, decreased insulin sensitivity is less than that of phentolamine, but labetalol is α -selective. Its
1
and increased oxidative stress. β-blocking potency is somewhat lower than that of propranolol.
Timolol is a nonselective agent with no local anesthetic activity. Hypotension induced by labetalol is accompanied by less tachycar-
It has excellent ocular hypotensive effects when administered topi- dia than occurs with phentolamine and similar α blockers.
*
*
cally in the eye. Nadolol is noteworthy for its very long duration of Carvedilol, medroxalol, and bucindolol are nonselective
action; its spectrum of action is similar to that of timolol. Levobu- β-receptor antagonists with some capacity to block α -adrenergic
1
nolol (nonselective) and betaxolol (β -selective) are also used for receptors. Carvedilol antagonizes the actions of catecholamines
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topical ophthalmic application in glaucoma; the latter drug may be more potently at β receptors than at α receptors. The drug has a
1
less likely to induce bronchoconstriction than nonselective antago- half-life of 6–8 hours. It is extensively metabolized in the liver, and
nists. Carteolol is a nonselective β-receptor antagonist. stereoselective metabolism of its two isomers is observed. Since
*
*
Pindolol, acebutolol, carteolol, bopindolol, oxprenolol, metabolism of (R)-carvedilol is influenced by polymorphisms in
*
celiprolol, and penbutolol are of interest because they have CYP2D6 activity and by drugs that inhibit this enzyme’s activity
partial β-agonist activity. They are effective in the major cardio- (such as quinidine and fluoxetine, see Chapter 4), drug interac-
vascular applications of the β-blocking group (hypertension and tions may occur. Carvedilol also appears to attenuate oxygen free
angina). Although these partial agonists may be less likely to cause radical–initiated lipid peroxidation and to inhibit vascular smooth
bradycardia and abnormalities in plasma lipids than are antago- muscle mitogenesis independently of adrenoceptor blockade.
nists, the overall clinical significance of intrinsic sympathomimetic
activity remains uncertain. Pindolol, perhaps as a result of actions
on serotonin signaling, may potentiate the action of traditional * Not available in the USA.