C04252 Pharmacy

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The development of Clonidine as a prophylaxis for migraine.



Migraine can be described as a mild to severe headache.

Migraine is a result of neurological changes in the brain. This causes migraine-related headaches and other symptoms.

Research shows that migraine headaches are positively related to light, sound, and smell.

The intensity of migraine can be increased by excessive light, disturbing sounds, and foul or repugnant odors (1).

You may experience nausea or vomiting.

Patients may complain of pain in one side of their brain, while others report pain on both sides.

A migraine-related pain can often be described as a throbbing, pounding sensation.

It is inappropriate to label all headaches as migraine. There is another type of headache that is caused by tension. This is called muscle contraction of the neck, scalp and face (2).

Boehringer Ingelheim Pharma set out to find a peripherally active, adrenergic compound to relieve nasal congestion in the form nose drops. Helmut Stahle was assigned this task.

It was thought that decongestive drugs are derived from the imidazoline structure.

Clonidine was discovered by him when he introduced chlorine atoms to the 2- and 6-positions of the phenyl rings.

Clonidine is more antihypertensive than decongestant ((5)), it was discovered.

Clonidine can be used to lower blood pressure. It is also used for prophylaxis of migraine headaches vascular, the management of vasomotor symptoms related with menopause, and in combination with benzodiazepines to treat alcohol withdrawal. Also, it is used to treat attention deficit hyperactivity (ADHD), open-angle and secondary blindness, and attention-deficit hyperactivity.

Clonidine stimulates the centrally active beta 2A subtype alpha adrenergic nerve receptors in the brainstem. This causes a decrease in sympathetic outflow to the central nervous system.

Clonidine, an imidazole derivative, is metabolized by cytochrome P450.

Clonidine can be used in combination with other drugs to lower blood pressure.

Clonidine can also be used for neuropathy, smoking cessation, attention disorder, neuropathy, menopause symptoms, diabetic diarrhoea and restless leg syndrome.

Clonidine was approved for use in the United States in 1974. It is still used in many applications.

Clonidine is most commonly used to treat hypertension. However, it can also be used in cancer pain management, attention deficit disorder, and menopausal flushing.

Clonidine is used primarily in the NHS for hypertension and menopausal flushing.

Clonidine can be used unlicensed to treat Tourette syndrome, migraine, sedation, withdrawal symptoms, as well as to relieve symptoms such as alcohol withdrawal, nicotine addiction, and narcotic withdrawal.

Clonidine is available as a tablet, injection or 100mcg (25mcg), and 150mcg (150mcg).

Adults can take 50-100mcg of Clonidine three times daily. The dose can be gradually increased the second or third day to maintain control.

Side effects include fatigue, sedation and bradycardia.

Clonidine tablets have a duration of action of 3-5hrs and a half-life between 12-16 hours. In severe cases of impaired renal function, it can last up to 41 hours.

Clonidine is usually prescribed before bed because of its sedating properties.

Clonidine activates presynaptic Auto Receptors in locus Coeruleus, and decreases norepinephrine production.

Its antihypertensive effects are linked to a decrease in plasma levels norepinephrine.

Clonidine extended-release tablet is used in the USA as an adjunctive therapy for children with attention deficit hyperactivity disorder.

Sudden withdrawal can lead to rebound hypertension from a rebound in sympathetic flow.

Clonidine therapy should be tapered gradually to reduce rebound side effects.

(2) Sudden withdrawal may cause agitation, restlessness and palpitation in patients who are taking high doses.

Galactose intolerance patients should be aware that Catapres (Clonidine), tablet contains lactose monohydrate.

Clonidine and its metabolites can be extensively excreted in urine. Dosage should be adjusted according the response. It may also show variability in patients suffering from renal impairment.

Clonidine is excreted in urine approximately 70% as an unchanged parent drug, and 20% with the faeces administered drug.

Clonidine may cause reduced lacrimation in patients who wear contact lenses.

Clonidine can be purchased as Catapres injection and Catapres tablet by Boehringer Ingelheim. There are also generics available on the market.

Clonidine was first used in 1966.

The drug was first developed for the treatment of hypersensitivity. It was originally known as Catapres.

Clonidine was initially widely used to treat nicotine withdrawal, opium withdrawal and other conditions.

Clonidine was later approved by the U.S Food & Drug Administration for use in high blood pressure treatment.

Clonidine also helped lower blood pressure by acting on the nerve cells in the brain (3).

Clonidine was developed in migraine prophylaxis. This clinical was consolidated by clonidine.

Clonidine was administered at 25 micrograms per day. This reduced the average number of migraine attacks by 2.26 to 3.94 per month.

The average number of migraine attacks fell from 4. to 1.88 after the 50 microgram dosage was increased.

The 25 microgram dosage showed 44% reduction in attacks. However, it was the same for 46% and 10% of patients who experienced increased attacks.

The 50 microgram dosage group saw 58% of patients report fewer attacks, while the 40% reported no changes.

The remaining 1% had a higher incidence of attacks.

The duration of attacks was also considered in both doses.

The 25 microgram dose reduced the pain duration in 38% of patients. It was unchanged for 60% of the patients and it was elevated in the remaining 22%.

In the same manner, pain duration was reduced in patients who took 50 mg of clonidine. However, it was not affected in patients who were 46% and 46% respectively. The effects of clonidine in 2% patients also decreased.

The increased dose of Clonidine had side effects such as nausea and sedation. However, sedation was seen in 22% of patients.

This trial is important for the prophylaxis and treatment of migraine with an effective dose of Clonidine (7).

Clonidine can be used to treat migraines. This is because migraines are caused by low levels of serotonin. These chemicals regulate the pain in the nervous systems.

Migraines can also be caused by changes in the brainstem or interactions with the trigeminal nervous.

The brain’s level of serotonin drops and this causes the trigeminal nervous to release neuropeptides (meninges), which move to the brain’s outer part, causing migraine pain (4).

The positive correlation between migraine and hypertension is that migraine pain increases with increased hypertension.

Clonidine, an imidazole derivative, is widely used in treating hypertension.

Numerous studies have shown that low-dose clonidine can reduce hypertension and migraine.

The above information can help you to conclude that migraine pain can be a serious condition. If not treated medically, it can cause impairment in your ability to concentrate and daily work.

Clonidine is the most effective medication, out of all the available medications.

Because clonidine acts directly on the central nervous system, brain cells and can be taken in small amounts, it can be used to treat migraines.

Refer to

StaEhle H. A historical perspective on the development of Clonidine.

BaillieA re’s Best practice and research.

Sprenger T., Goadsby P.J. Current practice and future directions for the acute and prevention of migraine.

The Lancet Neurology.

2010 Mar 31;9(3),285-98.

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