Moxonidine (icon) is a new generation centrally acting antihypertensive

Antihypertensive

The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...

 drug licensed for the treatment of mild to moderate essential hypertension

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

. It may have a role when thiazides, beta-blockers, ACE inhibitor

ACE inhibitor

ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...

s and calcium channel blocker

Calcium channel blocker

A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...

s are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance

Insulin resistance

Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...

 syndrome, apparently independent of blood pressure reduction. It is manufactured by Solvay

Solvay (company)

Solvay S.A. is a Belgian chemical company with its head office in Ixelles, Brussels, Belgium. It was founded in 1863 by Ernest Solvay to produce sodium carbonate by the solvay process. Since then the company has diversified to two major sectors of activity: chemicals and plastics...

 Pharmaceuticals under the brand name Physiotens.

Mechanism of actions

Moxonidine is a selective agonist

Agonist

An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

 at the imidazoline receptor

Imidazoline receptor

Imidazoline receptors are receptors for clonidine and other imidazolines.-Classes:There are three classes of imidazoline receptors:* I1 receptor – mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure, * I2 receptor – an allosteric binding site of monoamine oxidase and is...

 subtype 1 (I₁). This receptor subtype is found in both the rostral ventro-lateral pressor and ventromedial depressor areas of the medulla oblongata

Medulla oblongata

The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the medulla...

. Moxonidine therefore causes a decrease in sympathetic nervous system

Sympathetic nervous system

The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

 activity and, therefore, a decrease in blood pressure

Blood pressure

Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

.

Compared to the older central-acting antihypertensives, moxonidine binds with much greater affinity to the imidazoline I₁-receptor than to the α₂-receptor. In contrast, clonidine

Clonidine

Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...

 binds to both receptors with equal affinity.

In addition, moxonidine may also promote sodium

Sodium

Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 excretion, improve insulin resistance and glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 tolerance and protect against hypertensive target organ damage, such as kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 disease and cardiac hypertrophy.

Pharmacodynamic properties

Effects on insulin resistance

In all animal models of insulin resistance, moxonidine had striking effects on the development of insulin resistance, hyperinsulinaemia and impaired glucose homeostasis. Given the importance of insulin resistance as a risk factor for cardiovascular disease, it is of considerable relevance that it has been shown to improve insulin sensitivity.

Based on animal models, it has demonstrated that moxonidine is capable of:

• normalising plasma insulin levels
• improving glucose uptake in peripheral cells
• lowering lipid levels
• decreasing food intake and reducing weight gain in obese animals.

Renal function

Evidence is accumulating to show that sympathetic overactivity is substantially involved in the development and progression of chronic renal failure, contributing to a poor overall cardiovascular prognosis. Moxonidine has been shown to reduce structural renal damage in various models of renal failure.

Cardiac structure

In spontaneously hypertensive rats, moxonidine significantly reduced total heart weight, left ventricular weight and the ratio of ventricular weight to body weight compared with an untreated control group.

Safety pharmacology

Routine toxicology studies have provided no evidence that moxonidine has any teratogenic, mutagenic or carcinogenic potential. No evidence has been found of serious adverse effects on organs or organ systems, and the drug has not been shown to have deleterious effects on perinatal or postnatal growth and development.

Cautions

Moxonidine should be avoided in patients with moderate to severe renal impairment. Abrupt discontinuation of the drug should also be avoided. If concomitant treatment with a beta blocker has to be stopped, the beta blocker should be discontinued first, then moxonidine after a few days.

Drug interactions

Concomitant administration of moxonidine and a thiazide diuretic such as hydrochlorothiazide

Hydrochlorothiazide

Hydrochlorothiazide, abbreviated HCTZ, HCT, or HZT, is a first-line diuretic drug of the thiazide class that acts by inhibiting the kidneys' ability to retain water. This reduces the volume of the blood, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is...

 is not indicated, as both drugs' hypotensive effects may be enhanced.

Contra-indications

It is contraindicated if there has been a past history of angioedema

Angioedema

Angioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...

; heart conduction disorders (e.g. sick sinus syndrome

Sick sinus syndrome

Sick sinus syndrome, also called sinus node dysfunction, is a group of abnormal heart rhythms presumably caused by a malfunction of the sinus node, the heart's primary pacemaker...

, second- or third-degree heart block

Heart block

A heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....

); bradycardia

Bradycardia

Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...

; severe heart failure or coronary artery disease, severe liver or renal impairment. Also: Raynaud's syndrome, intermittent claudication

Intermittent claudication

Intermittent claudication is a clinical diagnosis given for muscle pain , classically in the calf muscle, which occurs during exercise, such as walking, and is relieved by a short period of rest.Claudication derives from the Latin verb claudicare, "to limp".-Signs:One of the hallmarks of arterial...

, epilepsy

Epilepsy

Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

, depression, Parkinson's disease

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system...

, glaucoma

Glaucoma

Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

. Use in pregnancy is discouraged. Moxonidine passes into breast milk.

Excess mortality has been seen in patients with symptomatic heart failure.

Side-effects

Noteworthy side effect

Adverse drug reaction

An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s include dry mouth, headache, fatigue, dizziness, nausea, sleep disturbances (rarely sedation), asthenia, vasodilatation, and rarely, skin reactions.