Pizofén: yjib échéhya
SUMATRIPTAN
Use
Sumatriptan, 6 mg, is injected subcutaneously. Prepacked dosage vials are available for self injection and the maximum recommended dose is 12 mg/24 hours, a second injection being administered at least 1 hour after the first. Orally sumatriptan is taken as 100 mg tablets. The maximum recommended dose is 300 mg/24 hours. It can be taken at any time during a migraine attack but is most effective if taken early on. It is used to treat acute migraine or acute cluster headaches, and relieves headache and nausea in 65-85% of attacks. It is more effective than ergotamine, but has a short half-life so headache recurs after a single dose in 30-40% of patients.
Mechanism of action
Sumatriptan is a selective agonist of 5HT1D receptors which are found predominantly in the cranial circulation. Sumatriptan causes carotid vasoconstriction in a dose-dependent manner. There is a small amount of vasoconstriction in other vascular beds, notably the coronary and pulmonary vasculature, and sumatriptan causes a significant but transient systemic pressure response.
Adverse effects
Þ Transient pain at the injection site.
Þ Flushing, dizziness, weakness.
Þ Paresthesiae.
Þ Pressure or tightness in any part of the body, particularly the chest. Chest pain is particularly worrying as it is possible that it could be due to coronary artery vasoconstriction, although there is no conclusive evidence to support this view.
Þ Nausea and vomiting after oral administra-tion.
Pharmacokinetics
Sumatriptan is rapidly absorbed after both oral and subcutaneous administration, with a Tmax of 45 and 15 min, respectively. The drug is approximately 100% bioavailable after subcutaneous injection, in comparison to 14% bioavailability after oral administration, food does not affect oral absorption. Sumatriptan undergoes substantial presystemic hepatic metabolism to an inactive indole acetic acid metabolite. Eight per cent is metabolized and 20% is excreted unchanged via the kidney. The t1/2 is 2 hours, protein binding is low and because of its lipid solubility it has a large volume of distribution.
Contraindications
Sumatriptan should not be used in patients with ischemic heart disease or Prinzmetal angina, or severe hypertension.
Drug interactions
Sumatriptan should not be combined with ergotamine, MAOI, lithium, or 5HT reuptake inhibitors.
ERGOTAMINE
Use
Ergotamine is only used in acute migraine, it is advisable to start oral, rectal or inhaltion ergotamine treatment at a dose of 1 mg only (e.g. half a cafergot suppository or three puffs of an ergotamine medihaler). The corresponding intramuscular dose is 0.25 mg.
Mechanism of action
Ergotamine has partial a-adrenergic agonsist (vasoconstrictor) actions. Structurally the lysergic acid moiety of the molecule resembles both 5HT and noradrenaline and it blocks 5HT uptake by platelets and blood vessels thus allowing 5HT to activate vasoconstrictor receptors. It is believed to act by vasoconstriction.
Adverse effects
Þ Nausea and vomiting, due to too high a dose, may be misinterpreted as due to undertreatment, a potentially disastrous error.
Þ Peripheral vascular system: coldness of extremities, Raynaud´s phenomenon, intermittent claudication, paresthesiae and digital gangrene (treatment of ergo-indiced vasospasm is by means of a vasodilator such as nitroprusside or an organic nitrate).
Þ Rebound headaches which may persist for several days following discontinuation of the drug if used excessively.
Contraindications
Ergotamine should not be used in pregnancy, and only in exceptional circimstances in patients with cardiac and peripheral vascular disease.
Pharmacokinetics
Ergotamine shows marked interindividual variations in absorption when administered orally, undergoing extensive hepatic metabolism. Less than 5% is excreted unchanged.
PIZOTIFEN
Use
Pizotifen is often the first choice in migraine prophylaxis. It is related to the tricyclic antidepressants. The initial dose is 0.5 mg (given at night as it causes drowsiness) and this can be increased up to 3 mg if necessary.
Mechanism of action
Pizotifen is a 5HT2 antagonist. It also has mild antimuscarinic and antihistamine activity.
Adverse effects
Þ Drowsiness.
Þ Appetite stimulation and weight gain.
Þ Dizziness.
Þ Muscle pain.
Pharmacokinetics
Pizotifen is well absorbed (80%) and undergoes extensive hepatic metabolism. Only 1% of a dose is excreted unchanged in the urine. The t1/2 is 26 hours and it has a large volume of distribution.
Drugs interactions
Pizofen should not be used with monoamine oxidase inhibitors, and potentiates the drowsiness and sedation of sedatives, tranquillizers and antidepressants.
METHYSERGIDE
Use
Methysergide should only be used under specialist hospital supervision because of its severe toxicity. It is highly effective as prophylaxis (up to 80% of patients) in a dose of 1-2 mg two or three times daily with meals. Initially 1 mg is given at night and the dose is slowly increased up to 2 mg 6 hourly. After 6 months it is stopped for at least 1 month. Its use is indicated only in patients who, despite other attempts at control, experience such severe and frequent migraine as substantially to interfere with their work or social activities. The smallest dose that suppresses about 75% of the headaches is used because of toxicity.
Mechanism of action
Methysergide has powerful 5HT2 blocking activity with partial agonist activity on 5HT1 receptors and also some anti-inflammatory and vasoconstrictor effects.
Adverse effects
Þ Gastrointestinal disturbances: nausea, vomi-ting, diarrhea and abdominal pain.
Þ Neurological disturbances: mild euphoria, dissociation, experiences of unreality, hyperesthesia.
Þ Weight gain and edema.
Þ Reversible vasoconstriction: angina, inter-mittent claudication, abdominal angina.
Þ Fibrosis in the peritoneum and thorax: retroperitoneal fibrosis is not clearly dose related but is related to prolonged use.
Symptoms may be minimal and progresion to end-stage renal failure may occur insidiously.
CALCIUM CHANNEL BLOCKERS
Flunarizine, 10 mg daily, is the most effective of this class of drugs in migraine prophylaxis. These drugs are useful in terminating the aura in patients who have aura without headache. Verapamil, 40 mg tds, is commonly used as prophylaxis against cluster headaches.
TRICYCLIC ANTIDEPRESSANTS
These are effective in preventing attacks in some patients independent of their mood. The probable mechanism is via 5HT and noradrenaline reuptake blockade. Amitryptyline in low dose (e.g. 10-25 mg at night) is often adequate.
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