Alpha, agonists effects

RESPONSE 1 have tended to think that things do not have affinity unless we see low nanomolar affinity. I think the EEG studies are fairly revealing in that regard. The fact that we see this increase in alpha-1 power in the striatum is a characteristic of 5-HT2 agonists. And we are clearly seeing EEG effects at doses that are not increasing that power in the alpha-1 frequency. 1 tend to think that 5-HT2 agonist effects are not that important in the action of these compounds. 

In the eye, the radial pupillary dilator muscle of the iris contains oo receptors activation by drugs such as phenylephrine causes mydriasis (see Figure 6-9). Alpha stimulants also have important effects on intraocular pressure. Alpha agonists increase the outflow of aqueous humor from the eye and can be used clinically to reduce intraocular pressure. In contrast, agonists have little effect, but antagonists decrease the production of aqueous humor. These effects are important in the treatment of glaucoma (see Chapter 10), a leading cause of blindness. 

Arnsten AF, Goldman-Rakic PS. 1990. Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys. Neurobiol Aging 11 583-590. 

The authors suggested that the alpha-blocking effect of olanzapine was involved and that an alpha-adrenoceptor agonist (such as ephedrine) would reduce urinary incontinence in such cases. 

BETA-BLOCKERS COCAINE Risk of hypertensive crisis Cocaine produces both alpha- and beta-adrenergic agonist effects selective beta-blockade leads to unopposed alpha-agonism (vasoconstriction) Avoid concurrent use... 

These are used in treatment of migraine and in obstetrics (to control late uterine bleeding - postpartum haemorrhage). Their predominant action involves vasoconstriction (partial agonist effects at alpha-adrenergic receptors and 5-HT receptor-mediated effects). They are metabolized mainly via CYP3A4. 

Lofexidine is an alpha-agonist that is used to reduce the sympathetic autonomic effects of acute opioid withdrawal symptoms,... 

Roden DM, Nadeau JH, Primm RK. Electrophysiologic and hemodynamic effects of chronic oral therapy with the alpha-agonists clonidine and tiamenidine in hypertensive volunteers. Clin Pharmacol Ther 1988 43(6) 648-54. 

Noradrenaline is a catecholamine with agonist effects mainly at alpha-adrenoceptors. It is still occasionally used to maintain blood pressure in acute emergencies. 

The major dired-ading adrenoceptor agonist drugs are described. The alpha agonist phenylephrine increases mean BP, has no effed on pulse pressure, and elicits a reflex bradycardia. Isoproterenol, a beta agonist, decreases mean BP, increases pulse pressure, and causes marked tachycardia. Cardiovascular effects of norepinephrine (NE) are similar to phenylephrine, but it is also a cardiac (i, adrenoceptor j activator. The cardiovascular effects of epinephrine (E) are betalike at low doses and alphalike at high j doses. 

Answer A. Mydriasis and fixed far vision can be due to either muscarinic receptor antagonists or ganglionic blockade. Because no M blockers are listed, the correct answer is mecamylamine. Alpha agonists (phenylephrine) have no effects on the focus of the eye. The cholinesterase inhibitor (neostigmine) and alpha blocker (phentolamine) cause miosis. Ocular effects of the beta blocker (timolol) are restricted to decreased formation of aqueous humor by the ciliary epithelium. 

Drug X decreases TPR and BP, eliciting a reflex sympathetic discharge (note delay in response), resulting in increased CO. There is no direct effect on CO (choices A, B, C, and E are ruled out). Drugs X and Y are terbutaline and phenylephrine. Note that the alpha agonist does not antagonize the decrease in respiratory resistance (a P2 response). 

Describe the major organ system effects of a pure alpha agonist, a pure beta agonist, and a mixed alpha and beta agonist. Give examples of each type of drug. 

Selective alpha agonist, beta agonist Drugs that have relatively greater effects on alpha or beta adrenoceptors none are absolutely selective... 

Drug Y caused a marked increase in diastoUc pressure, suggesting strong alpha vasoconstrictor effects. It also caused a moderate increase in pulse pressure, suggesting some beta-agonist action. The drug that best matches this description in norepinephrine. The answer is (E). 

A pure alpha agonist will cause reflex bradycardia in a subject with intact cardiac innervation, but no change in hean rate if this innervation is severed, eg, in a heart transplant patient. The other drugs listed have direct beta agonist effects and will increase heart rate in the denervated heart. The answer is (D). 

Figure 10-2. The effects of an alpha-blocker, eg, phentolamine, on the blood pressure responses to epinephrine and phenylephrine. The epinephrine response exhibits reversal of the mean blood pressure change from a net increase (the alpha response) to a net decrease (the beta response). The response to phenylephrine is suppressed but not reversed, because phenylephrine is a pure" alpha agonist without beta action.

Phenylephrine is a sympathomimetic, and as such may carry some risk of potentiating arrhythmias if it is used with inhalational anaesthetics such as halothane -see Anaesthetics, general + Inotropes and Vasopressors , p.99. However, it is considered that it is much less likely than adrenaline (epinephrine) to have this effect, since it has primarily alpha-agonist activity. ... 

Treatment with injections into the corpus caver-nosum of alpha adrenergic receptor agonists after aspiration would be the next therapy after terbutaline. Phenylephrine, 10 cc, which corresponds to a dose of 200 ig, is injected into the penis after aspiration. Frequent blood pressure measurements and preferably ECG monitoring are required throughout, and failure to respond may require a second injection of 200 ig and a final dose of 500 pg. Alternatively, epinephrine can be injected in 1-3-cc boluses up to 10 cc (O Brien et al. 1989). Methylene blue has been shown to be useful as an alternative to alpha agonists, with a mechanism felt to be related to inhibition of cyclic GMP, which in turn inhibits smooth muscle relaxation (Steers and Selby 1991). Intracavernosal injection with 50 mg of methylene blue is followed by aspiration and penile compression for 5 min. Transient penile burning and blue discoloration lasting for about 3 days were the reported side effects (Martinez Portillo et al. 2001). 

---