Clinical Sports Medicine Collection. Davis AT Collection. Davis PT Collection. Murtagh Collection. About Search. Enable Autosuggest. You have successfully created a MyAccess Profile for alertsuccessName. Previous Chapter. Next Chapter. AMA Citation Chapter Butterworth J. John F. Butterworth, IV, et al. McGraw Hill; Accessed November 14, APA Citation Chapter McGraw Hill. MLA Citation "Chapter Download citation file: RIS Zotero. Reference Manager. Furthermore epinephrine, like several other direct-acting hyperalgesic agents, caused a potentiation of tetrodotoxin-resistant sodium current, an effect that was abolished by Rp-adenosine 3',5'-cyclic monophosphate and significantly attenuated by bisindolylmaleimide.
Isoproterenol also potentiated tetrodotoxin-resistant sodium current. In conclusion, epinephrine produces cutaneous mechanical hyperalgesia and sensitizes cultured dorsal root ganglion neurons in the absence of nerve injury via an action at a beta-adrenergic receptor.
These effects of epinephrine are mediated by both the protein kinase A and protein kinase C second-messenger pathways. Abstract Hyperalgesic and nociceptor sensitizing effects mediated by the beta-adrenergic receptor were evaluated in the rat. Methyldopa is a prodrug which must first be taken up into the nerve terminal and converted to " -methylnorepinephrine.
This is the same synthetic pathway that converts dopa to norepinephrine. Clonidine is the most widely used drug of this class. It can be given orally or in patch form. Side effects include drowsiness. This is a common occurrence for drugs that work in the CNS. Another prominent side effect of clonidine is presistent dry mouth. Clonidine has many other uses including opiate withdrawal, nicotine withdrawal, vascular headaches, diabetic diarrhea, glaucoma, ulcerative colitis and Tourette's syndrome.
The other drugs are second-line agents used in the treatment of hypertension. Methyldopa has the particularly troublesome side effect of inducing hemolytic anemia. Prazosin and analogs doxazosin, terazosin, trimazosin - Selective, competitive antagonists. Phentolamine-Nonselective, competitive antagonist. Effects of Prazosin and Analogs on the Cardiovascular System:.
Prazosin and its analogs are selective alpha1-receptor blockers used to treat hypertension. These agents have similar cardiovascular actions, differing only in pharmacokinetic parameters. Doxazosin, trimazosin and terazosin are more widely used than prazosin.
These agent relax the smooth muscle associated with arteries and veins. This results in a decrease in systemic arterial blood pressure due to a decrease in peripheral vascular resistance and venous return. The reduction in arterial blood pressure does not result in a significant increase in heart rate. Treatment with these drugs can result in fluid retention as a response to the lowering of blood pressure. Thus the drugs can be prescribed with a diuretic in the treatment of hypertension.
Prazosin and related analogs also relax the smooth muscle associated with the bladder neck and prostate. Tamsulosin has a similar action and is also used to treat BPH. Tamsulosin is an example of a drug that is selective for one of the subtypes of the alpha1-adrenergic receptors.
This ligand selectively blocks the alpha1A-receptor. The alpha1A-receptor is involved in regulating the smooth muscle tone associated with the prostate. Therefore, tamsulosin selectively antagonizes the receptor subtype involved in regulating prostate function.
Tamsulosin is less likely than the prazosin analogs to cause hypotension. Postural hypotension and first dose syncope, which occur with greater frequency with the prazosin analogs than with tamsulosin.
Nonselective competitive " 1 and " 2 blocker. Used to treat pheochromocytoma. Irreversible " 1 and " 2 receptor antagonist. These drugs are competitive antagonists of the beta adrenergic receptor The beta blockers used in clinical therapeutics are either selective for the beta 1 receptor or nonselective beta 1 and beta 2 antagonists. Cardiovascular Effects of the Beta Blockers. The beta1-adrenergic receptor associated with the heart increases the force and rate of myocardial contraction.
Beta antagonists block the ability of the sympathetic nervous system to increase the contractile force and the rate of contraction. The release of renin from the kidney is also regulated by the beta1-receptor. By blocking renin secretion beta1 blockers reduce the formation and hence the biological activity of angiotensin II. Beta1-receptor antagonists decrease blood pressure. While the mechanisms underlying this effect are not completely understood, they certainly involve a decrease in cardiac output and heart rate as well as decreasing angiotensin II levels.
This reduction in blood pressure makes the beta blockers useful in the treatment of hypertension. Beta blockers are also useful in treating ischemic heart disease. This is because two major determinants of myocardial oxygen consumption are the force and rate of myocardial contraction which are diminished by this class of drugs.
Beta blockers are also given following a myocardial infarction to prevent reinfarction. As will be discussed in the lectures on heart failure, certain beta blockers, specifically, metoprolol, bisoprolol and carvedilol, can be used to treat congestive heart failure.
Certain arrhythmias are due to excess stimulation of the beta1-receptors. Thus beta blockers are useful in treating supraventricular tachyarrhythmias.
There are many indications for beta blockers unrelated to cardiovascular therapeutics. A major disadvantage of nonselective beta blockers is the fact that they will block beta 2 receptors associated with airway or vascular smooth muscle.
To overcome this disadvantage, "selective" beta 1 blockers have been developed. These agents have the ability to preferentially block beta 1 receptors. However, this selectivity is only relative and in higher doses selective antagonists will also block beta 2 receptors. Certain beta blockers actually have a modest degree of agonist activity. In other words these agents are partial agonists with low intrinsic activity. This is referred to as intrinsic sympathomimetic activity or ISA.
These drugs may have a lesser effect on resting heart rate or cardiac output than compounds without ISA. This refers to the ability of some of the beta blockers to also block sodium channels. As a result nerve cells become less excitable, hence the term "membrane stabilizing. However, you will often find this term used to describe the beta blockers. Beta blockers should be used with caution in patients with diabetes. In fact, nonselective beta blockers are contraindicated in diabetic patients.
This is because catecholamines utilize the beta 2 receptor to promote glycogenolysis and mobilize glucose. This effect would be blocked by non-selective beta blockers. In addition all beta blockers mask the tachycardia associated with hypoglycemia. As a result the diabetic patient is deprived of one of the earliest physiologic responses to hypoglycemia.
The beta blockers have a variety of side effects. These include sedation, fatigue, and impairment of mental function. Hypotension and bradycardia can occur. These agents increase triglycerides and decrease HDL cholesterol. The effects on glucose metabolism has been discussed above. Nonselective beta blockers exacerbate peripheral vascular disease and airway dysfunction. These ligands block alpha 1 receptors as well as beta 1 and beta 2 receptors. Labetalol is used to treat hypertension.
The side effect profile is what would be expected of a drug that blocks both alpha 1 and beta receptors. These include orthostatic hypotension, sedation, fatigue and other affects attributed to the blockade of beta receptors. In addition to treating hypertension, several recent clinical trials have shown carvedilol to be very effective in treating congestive heart failure. There are several proposed mechanisms underlying this effectiveness. Blockade of the beta 1 receptor appears to be more relevant than alpha 1 receptor blockade.
This results in an improvement in left ventricular function. One pathophysiology of heart failure is that the heart increases dimensions. These increases result in a hypertrophied heart with decreased contractile performance. Carvedilol reverses these changes. Furthermore, carvedilol as antioxidant and antiproliferative activity. The extent to which these actions contribute to therapeutic efficacy in not clear.
Depletes catecholamines from nerve endings in CNS and periphery. Interferes with the vesicular storage of norepinephrine and other neurotransmitters This results in an inhibition of both alpha and beta receptor dependent events. Reserpine produces hypotension due to decreased peripheral vascular resistance and cardiac output.
This drug can produce a variety of unpleasant CNS side effects such as insomnia, sedation and depression. Long term use of Guanethidine depletes catecholamines from nerve terminals. Does not interfere with central neurotransmitter storage or function. Produces hypotension and bradycardia. Inhibit monoamine oxidase. Produce hypotension. Can precipitate a hypertensive crisis. Tissue Receptor Subtype Heart beta 1 Adipose tissue beta 1 beta 3?
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