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| Names | |
|---|---|
| IUPAC name 2-(1,4-Dioxaspiro[4.5]decan-2-ylmethyl)guanidine | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| KEGG | |
| MeSH | C004945 |
PubChem CID | |
| UNII | |
CompTox Dashboard (EPA) | |
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| Properties | |
| C10H19N3O2 | |
| Molar mass | 213.281 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
Guanadrel is an antihypertensive agent. [1] It is used in the form of its sulfate.
Guanadrel is a postganglionic adrenergic blocking agent. Uptake of guanadrel and storage in sympathetic neurons occurs via the norepinephrine pump; guanadrel slowly displaces norepinephrine from its storage in nerve endings and thereby blocks the release of norepinephrine normally produced by nerve stimulation. The reduction in neurotransmitter release in response to sympathetic nerve stimulation, as a result of catecholamine depletion, leads to reduced arteriolar vasoconstriction, especially the reflex increase in sympathetic tone that occurs with a change in position. Guanadrel is rapidly and well absorbed from gastrointestinal tract. [2]
In 1981 the JAMA reported guanadrel as an effective step II or step III treatment of hypertension. [3]
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.
Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken by mouth or by injection into a vein. The formulation that is taken by mouth comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken by mouth.
Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.
The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cells that secrete catecholamines, including epinephrine (adrenaline), norepinephrine (noradrenaline), and a small amount of dopamine, in response to stimulation by sympathetic preganglionic neurons.
Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal, menopausal flushing, diarrhea, spasticity, and certain pain conditions. It is used by mouth, by injection, or as a skin patch. Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.
Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.
Methyldopa, sold under the brand name Aldomet among others, is a medication used for high blood pressure. It is one of the preferred treatments for high blood pressure in pregnancy. For other types of high blood pressure including very high blood pressure resulting in symptoms other medications are typically preferred. It can be given by mouth or injection into a vein. Onset of effects is around 5 hours and they last about a day.
The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms that helps to maintain blood pressure at nearly constant levels. The baroreflex provides a rapid negative feedback loop in which an elevated blood pressure causes the heart rate to decrease. Decreased blood pressure decreases baroreflex activation and causes heart rate to increase and to restore blood pressure levels. Their function is to sense pressure changes by responding to change in the tension of the arterial wall The baroreflex can begin to act in less than the duration of a cardiac cycle and thus baroreflex adjustments are key factors in dealing with postural hypotension, the tendency for blood pressure to decrease on standing due to gravity.
Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955, the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone. The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available In 2012.
Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α-adrenergic antagonist.
Moxonidine (INN) is a new-generation alpha-2/imidazoline receptor agonist antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. It is also a growth hormone releaser. It is manufactured by Solvay Pharmaceuticals under the brand name Physiotens & Moxon.
Secondary hypertension is a type of hypertension which by definition is caused by an identifiable underlying primary cause. It is much less common than the other type, called essential hypertension, affecting only 5-10% of hypertensive patients. It has many different causes including endocrine diseases, kidney diseases, and tumors. It also can be a side effect of many medications.
Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself, and uptake is essential for the drug's action. Once guanethidine has entered the nerve, it is concentrated in transmitter vesicles, where it replaces norepinephrine. It may also inhibit the release of granules by decreasing norepinephrine.
The alpha-2 (α2) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.
Bretylium (also bretylium tosylate) is an antiarrhythmic agent. It blocks the release of noradrenaline from nerve terminals. In effect, it decreases output from the peripheral sympathetic nervous system. It also acts by blocking K+ channels and is considered a class III antiarrhythmic. The dose is 5–10 mg/kg and side effects are high blood pressure followed by low blood pressure and ventricular ectopy.
A sympatholytic drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD. In some cases, such as with Guanfacine, they have also shown to be beneficial in the treatment of ADHD.
Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).
The sympathoadrenal system is a physiological connection between the sympathetic nervous system and the adrenal medulla and is crucial in an organism's physiological response to outside stimuli. When the body receives sensory information, the sympathetic nervous system sends a signal to preganglionic nerve fibers, which activate the adrenal medulla through acetylcholine. Once activated, norepinephrine and epinephrine are released directly into the blood by postganglionic nerve fibers where they act as the bodily mechanism for "fight-or-flight" responses. Because of this, the sympathoadrenal system plays a large role in maintaining glucose levels, sodium levels, blood pressure, and various other metabolic pathways that couple with bodily responses to the environment. During numerous diseased states, such as hypoglycemia or even stress, the body's metabolic processes are skewed. The sympathoadrenal system works to return the body to homeostasis through the activation or inactivation of the adrenal gland. However, more severe disorders of the sympathoadrenal system such as Pheochromocytoma can affect the body's ability to maintain a homeostatic state. In these cases, curative agents such as adrenergic agonists and antagonists are used to modify epinephrine and norepinephrine levels released by the adrenal medulla.
The modern history of hypertension begins with the understanding of the cardiovascular system based on the work of physician William Harvey (1578–1657), who described the circulation of blood in his book De motu cordis. The English clergyman Stephen Hales made the first published measurement of blood pressure in 1733. Descriptions of what would come to be called hypertension came from, among others, Thomas Young in 1808 and especially Richard Bright in 1836. Bright noted a link between cardiac hypertrophy and kidney disease, and subsequently kidney disease was often termed Bright's disease in this period. In 1850 George Johnson suggested that the thickened blood vessels seen in the kidney in Bright's disease might be an adaptation to elevated blood pressure. William Senhouse Kirkes in 1855 and Ludwig Traube in 1856 also proposed, based on pathological observations, that elevated pressure could account for the association between left ventricular hypertrophy to kidney damage in Bright's disease. Samuel Wilks observed that left ventricular hypertrophy and diseased arteries were not necessarily associated with diseased kidneys, implying that high blood pressure might occur in people with healthy kidneys; however, the first report of elevated blood pressure in a person without evidence of kidney disease was made by Frederick Akbar Mahomed in 1874 using a sphygmograph. The concept of hypertensive disease as a generalized circulatory disease was taken up by Sir Clifford Allbutt, who termed the condition "hyperpiesia". However, hypertension as a medical entity really came into being in 1896 with the invention of the cuff-based sphygmomanometer by Scipione Riva-Rocci in 1896, which allowed blood pressure to be measured in the clinic. In 1905, Nikolai Korotkoff improved the technique by describing the Korotkoff sounds that are heard when the artery is ausculted with a stethoscope while the sphygmomanometer cuff is deflated. Tracking serial blood pressure measurements was further enhanced when Donal Nunn invented an accurate fully automated oscillometric sphygmomanometer device in 1981.
Adrenergic release inhibitors are a class of drugs which inhibit the release of epinephrine (adrenaline) and/or norepinephrine (noradrenaline) from adrenergic nerve terminals and are used as antihypertensives. Examples of these agents include bethanidine, bretylium, debrisoquine, guanadrel, guanazodine, guancydine, guanethidine, guanoclor, and guanoxan. Most agents of this class are guanidinium compounds and have little capacity to cross the blood–brain barrier.
