CENTRALLY ACTING ANTI-HYPERTENSIVE DRUGS

Centrally acting antihypertensive drugs
1-Clonidine hydrochloride
2-methyldopa
3-Moxonidine

Clonidine monochloride
clonidine monochloride is used in the treatment of hypertension. This drugs may cause several complications if it is not being withdrawn gradually or used by those who is in the following condition:
- history of depression
- acute pophyria
- pregnancy- since it may lower fetal heart rate.
- Breast feeding
This drug may also cause drowsiness. Thus,handling machinery after taking this drug should be avoided.

This drug may cause several sides effects such as dry mouth, sedation, depression, fluid retention, bradycardia, raynaud’s phenomenon, headache, dizziness, euphoria, nocturnal unrest, rash nausea, constipation and rarely impotence.

Clonidine monochloride should not be taken together with these following drugs:
ACE inhibitors, adrenergic neurone blockers, alcohol, aldesleukin, alpha blockers, anaesthetics, analgesics, angiotensin II, antidepressants, antipsychotics, anxiolytics and hypnotics, beta blockers, calcium channel blockers, corticosteroids, diazoxide, diuretics, dopaminergics, methyldopa, moxisylyte, moxonidine, muscle relaxants, nitrates, oestrogens, prostaglandins, sympathomimetics, vasodilator antihypertensive.

Dose:
By mouth: 50-100 micrograms 3 times daily, increased every second or third day; usually maximum dose 1.2 mg daily.

These are the examples of clonidine monochloride.

Manufacturer / DistributorAlpharma USPD Pharma Pac Southwood American Health Dispensing Solutions
Clonidine HClStrength(s)0.1 MG


Manufacturer / DistributorAlpharma USPD American Health
Clonidine HCl Clonidine HClStrength(s) Strength(s)0.2 MG 0.3 MG


Clonidine HClStrength(s)0.1 MGManufacturer / DistributorMylan Quality Care Prod Allscripts Phys Total Care DRx PD-Rx Pharm DHS, Inc. Direct Dispensing Innovative Pharm Sol DispenseXpress


Clonidine HClStrength(s)0.2 MGManufacturer / DistributorMylan Phys Total Care DHS, Inc. Direct Dispensing Dispensing Solutions Innovative Pharm Sol DispenseXpress


Clonidine HClStrength(s)0.3 MGManufacturer / DistributorMylan Quality Care Prod Phys Total Care Direct Dispensing Dispensing Solutions Innovative Pharm Sol

Clonidine HClStrength(s)0.2 MGManufacturer / DistributorRugby

Clonidine HClStrength(s)0.1 mgManufacturer / DistributorActavis U.S. (Purepac Pharmaceutical Company)


Clonidine HClStrength(s)0.1 mgManufacturer / DistributorMylan Pharmaceuticals Inc

Clonidine HClStrength(s)0.2 mgManufacturer / DistributorMylan Pharmaceuticals Inc

Methyldopa
This drug is used in the treatment of hypertension.

Cautions:
Monitor blood counts and liver function before treatment and at interval during first 6-12 weeks or if unexplained fever occurs, history of depression, positive direct Coomb’s test in up to 20%of patients(may affect blood cross-matching),interference with the laboratory tests, hepatic impairment, and renal impairment

Contra-indication of methyldopa:
Depression, active liver disease, phaeocchromocytoma, acute porphyria

Methyldopa may causes several side effects. these are the example of methyldopa side effects:
Gastro-interstinal disturbances, dry mouth, stomatitis, sialadenitis, bradycardia, exacerbation of angina, postural hypotension, oedema, seation, headache, dizziness, asthenia, myalgia, arthralgia, paraesthesia, nightmares, mild psychosis, depression, impaired mental acuity, parkinsonism, bell’s palsy, abnormal liver function test, hepatitis, jaundice, pancreatitis, haemolytic anemia, bone marrow depression, leucopenia, thrombocytopenia, eosinophilla, hypersensitivity reactions includes lupus erythematousus-like syndrome, drug fever, myocarditis, pericarditis, rashes, nasal congestion, failure of ejaculation, impotence

Dose:
Initially 250mg 2-3 times daily, increased gradually at intervals of at least two days, maximum 3 grams daily.
Elderly, initially 125 twice daily, increased gradually, maximum 2 grams daily.

Interactions with the other drugs:
ACE inhibitors, adrenergic neurone blockers, alcohol, aldesleukin, alpha blockers, anaesthetics, analgesics, angiotensin II, antidepressants, antipsychotics, anxiolytics and hypnotics, beta blockers, calcium channel blockers, corticosteroids, diazoxide, diuretics, dopaminergics, clonidine, moxisylyte, iron, lithium,moxonidine, muscle relaxants, nitrates, oestrogens, prostaglandins, sympathomimetics, vasodilator antihypertensive.

These are the examples of methyldopa:

MethyldopaStrength(s)250 mgManufacturer / DistributorIVAX Corporation
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MethyldopaStrength(s)250 mgManufacturer / DistributorEndo Laboratories LLC

MethyldopaStrength(s)250 MGManufacturer / DistributorLederle Std Prod

MethyldopaStrength(s)500 MGManufacturer / DistributorLederle Std Prod


MethyldopaStrength(s)250 MGManufacturer / DistributorWest Point


MethyldopaStrength(s)125 MGManufacturer / DistributorWest Point


MethyldopaStrength(s)500 MGManufacturer / DistributorWest Point

MethyldopaStrength(s)500 MGManufacturer / DistributorTeva

MethyldopaStrength(s)250 MGManufacturer / DistributorMylan

MethyldopaStrength(s)500 mgManufacturer / DistributorMylan Pharmaceuticals Inc

Moxonidine:

Indications: mild to moderate essential hypertension.

Cautions:
Avoid abrupt withdrawal (if concomitant treatment with beta blocker has to be stopped, discontinue beta blocker first, then moxonidine after a few days).
Susceptibility to angle closure glaucoma, renal impairment(avoid if creatinine clearance less than 30ml/minute).

Contra-indications:
History of angioedema, conduction disorder,bradycardia, life-threatening arrhythmia, severe heart failure, severe coronary artery disease, raynaud’s syndrome, intermittent claudication, epilepsy, depression, parkinson’s disease, and pregnancy.

Side effect:
Dry mouth, headache, fatigue, dizziness, nausea, sleep disturbance, asthenia, vasodilation, rarely skin reactions, very rarely angle-closure glaucoma.

Dose:
200 micrograms once daily in the morning, increased if necessary after 3 weeks to 400 micrograms daily in 1-2 divided doses
Maximum 600 micrograms daily in 2 divided doses(maximum single dose 400 micrograms)

How moxonidine treat hypertension? This is the mechanism.

Moxonidine reduces sympathetic outflow of the brain Moxonidine interacts with imidazoline I1-receptors in the rostroventrolateral medulla and thereby inhibits sympathetic outflow of the brain. This area of the brain is involved in the baroreceptor reflex which is important for adaptation of the body to postural changes. For example, a reduced venous return to the heart activates cardiopulmonary receptors leading to a rise in sympathetic outflow. Unfortunately, this mechanism adjusts to long term changes in blood pressure, i.e. baroreceptor resetting, and does not respond anymore to a pathologically raised high blood pressure, i.e. hypertension.It appears that moxonidine interacts with neurons within this pathway and thereby reduces sympathetic outflow. However, no effects on postural reflexes have been observed. If, however, lifestyle factors raise sympathetic outflow of the brain, moxonidine appears to downregulate the sympathetic activity by interfering with the medullar centers involved in the baroreceptor reflex.
An increased sympathetic activity not only results in hypertension but also favours insulin resistance. The chain of events is shown for the example of hypertension which often is mediated by a greater activation of peripheral alpha-1 adrenergic receptors:

A moxonidine-mediated reduction in the sympathetic outflow of the brain results in a smaller number of norepinephrine molecules released from sympathetic nerve terminals. Thus, there will be less vasoconstriction due to reduced alpha-1 adrenoceptor effects. In addition, various functions of the body such as insulin sensitivity are expected to be affected in a beneficial manner.