Agents for Migraine include-

Ergotamine derivatives include-
 Dihydrergotamine mesylate, Ergotamine tartarate, Methysergide maleate


Drug interaction- Summary

Betablocker+ methylsergide-                                                                                   peripheral ischemia manifested
                                           
Betablockers and methylsrgide-                                                                                    concurrent methylsergide therapy may result in peripheral
ischema manifested by cold extremities with possible
 peripheral gangrene

Vascular headache

 Agents for Migraine - Ergotamine derivatives include-

Dihydrergotamine mesylate, Ergotamine tartarate, Methysergide maleate

Adverse reactions occur in upto 30% to 50% of patients

Ergotamine tartrate -
nausea and vomiting occur.
Numbness and tingling of fingers and toes, muscle pain, in the extremities,
pulselessness, weakness in the legs
precordial pain
transcient tachycardia
localized edema and itching

Dihydroergotamine injection-
serious cardiac events, including some have been fatal following use of dihyroergotamine injection.
but extremely rare.
Events reported- coronary artery vasospasm, transient myocardial ischemia, MI ,
ventricular tachycardiaventricular fibrillation,

Pregnancy, women who may become pregnant (powerful uterine stimulant actions of ergotamine and dihydroergotamine may cause fetasl harm
Hypersensitivity to ergot alkaloids or component of formulation
peripheral vascular disease, severe arteriosclerosis, thrombophebitis, hepatic or renal impairment severe pruritus, coronary artery disease, hypertension , sepsis.

Do not give dihydroergotamine to patients with ischemic heart disease, angina pectoris,history of MI

Serious adverse effects associated with coadministration of dihydroergotamine with potent
CYP3A4  inhibitors ( eg. protease inhibitors, macrolide antibiotics  resulting in vasospasm that led to cerbral ischemia and /or ischemia of extremities.
Use of potent CYP3A4  ( ritonavir, indiavir, erythromycin, clarithromycin, troleandomycin, ketoconazole,itraconazole ) is therfore contraindicated

Dihydroergotamine may increase blood pressre, do not give to patients with uncontrolled
hypertension

Do not use dihydroergotamine , 5-HT1 agonists eg.sumiatriptan , ergotamine containg or
ergor medication or methysergide within 24 of each other.

Do not administer dihydroergotamine to patients with hemiplegic or basilar migraine

Do not administer dihyroergotamine to nursing mothers.


Special precautions:
Risk of myocardial ischemia and or MI and other cardiac events-
Do not use dihydroergotamine in patients with documented ischemic or vasopastic coronary artery
disease

Cardiac events and fatalities-
No deaths have been reported in patients using dihydroergotamine. The potential for adverse reactions exits.

Drug-associated cerebrovascular events and fatalities-
Cerbral haemorrhage ,subarchnoid , stroke, and other cerebrovascular events have been
reported in patients treated with dihydroergotamine, some have resulted in fatalities. it should be noted that patients with migraine may be at risk of certain cerbrovascular events eg. stroke, hemorrhage, transcient ischemic attack.

Elevation in blood pressure-
Significant increase in blood pressure has been reported in rare occassions in patients with or without history of hypertension treated with dihydroergotamine.

Coronary artery vasospasm-
Dihydroergotamine may cause coronary artery vasospasm. Patients who experience signs or symptoms suggestive of angina should be evaluted.

Drug abuse and dependence-
Patients who take ergotamine for extended periods of time may become dependent upon and require progressively increasing doses for relief of vascular headache and prevention of dysporic effects that follow withdrawal.

Indications:

Vascular headache

Dosage:

Adults- 4 to 8mg daily,take with meals. There must be a drug free interval of 3 to 4 weeks after every 6 months course of treatment.

Obstructive uropathy

Drugs causing adverse reactions-

1. Intrarenal- cytotoxics

2. Extrarenal - methysergide

METHYSERGIDE- AGENTS FOR MIGRAINE

 1.May cause GI upset; take with food or milk.

2. Caution patients regarding caloric intake

3. May cause drowsiness; use caution when driving or performing tasks requiring alertness, coordination and physical dexterity.

4. Continuous administration should not exceed 6 months. There must be a drug free interval of 3 to 4 weeks after 6 month course of treatment. Do not stop taking suddenly; reduce dosage gradully during last 2 to 3 weeks of each treatment course to avoid " headache rebound".

5. Notify physician of cold, numb or painful extremities, leg cramps, when walking, girdle, flank or chest pain, painful urination or shortness of breath.

6. Allergy- Tell your doctor if you had any unusual reaction to methysergide or to any ergot medicines

7. Pregnancy- Studies with methysergide have not been done in either human or animals

8. Breast feeding- This medicine passes into breast milk, and may cause unwanted effects such as vomiting, diarrhea, weak pulse, unstable blood pressure, and convulsions (seizures) in nursing babies.

9. Children- Can cause serious side effects i any patient.It is important that you discuus with the childs doctor, the good that this medicine can do as well as the risks of using it

 10. Older adults- Elderly people are specially sensitive to the effects of methylsergide. This may increase chance of side efects during treatment

11. Other medicines-Inform your  doctor about   other prescription medicines or OTC medicines you are taking.

12. Other medical problems- Your doctor may want to know about  your other medical problems especially- Arthiritis or Heart or blood vessel disease or Infection or Itching or Kidney disease or Liver disease or Lung disease -chance of seriuos sideefects may be increased High blood pressure or Stomach ulcer - methysergide can make your condition worse

13. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

14. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

15. Date Expired  medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

 Pharmacology:

Methysergide is a semisynthetic ergot derivative. It has no intrinsic vasoconstrictor properties and its mechmanism of action has not been established. It inhibit or blocks the effects of serotonin, a substance which may be involved in the mechanism of vascular headaches.

Food has significant effect on oral 5-HT1 agonists bioavailability, but delays sumatriptans Tmax by aaproximately 30 minutes and rizatriptans time to reach peak concentration by 1 hour.

AUC and Cmax of eletriptan are increased approximately 20% to 30% following oral admin. of a high fat meal.

Pregnancy:

Contrindicated in pregnancy due to oxytocic properties

Lactation:

Ergot derivatives in the milk of nursing mothers have caused symptoms of ergotism (eg. vomiting, diarrhea) in the infant

Children:

Not recommended for use in children