Antimigraine drugs are the groups of drug that are used for treatment or prevention of a migraine. A migraine is a primary headache disorder characterized by recurrent headaches that are moderate to severe. Typically, the headaches affect one half of the head, are pulsating in nature, and last from two to 72 hours. Associated symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity. Up to one-third of people have an aura: typically a short period of visual disturbance that signals that a headache will soon occur. Occasionally, an aura can occur with little or no headache following it.
Classifications / Types of Antimigraine
| Ergolines |
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| 5-HT1 agonists |
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| Others |
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| Calcium channel blockers |
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| Progestogens |
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| Sympatholytics |
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| Tricyclic antidepressants |
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| Anticonvulsants |
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Mechanism of Action of Antimigraine
Their action is attributed to their agonist effects on serotonin 5‑HT1B and 5‑HT1D receptors in blood vessels (causing their constriction) and nerve endings in the brain, and subsequent inhibition of pro-inflammatory neuropeptide release, including CGRP and substance P. Triptans are selective agents for 5-HT1B and 5-HT1D and have low or even no affinity for other types of 5-HT receptors.
5-HT receptors are classified into seven different families named 5-HT1 to 5-HT7. All receptors are G protein-coupled receptors with seven transmembrane domains with the one exception of 5-HT3 receptor which is a ligand-gated ion channel. There is a high homology in the amino acid sequence within each family. Each family couples to the same second messenger systems. Subtypes of 5-HT1 are the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F receptors. All 5-HT1D receptors are coupled to inhibition of adenylate cyclase. 5-HT1Band 5-HT1D receptors have been difficult to distinguish on a pharmacological basis. After cloning two distinct genes for 5-HT1B and 5-HT1D receptors, a better insight into distribution and expression in different tissues was gained, except in brain tissue where they are overlapping in several areas
Most mammalian species, including humans, have 5-HT1D binding sites widely distributed throughout the central nervous system. 5-HT1D receptors are found in all areas of the brain but they differ in quantity at each area. An important initiator of head pain is suggested to be the activation of trigeminovascular afferent nerves which upon activation releases neuropeptides such as CGRP, substance P and neurokinin A. Also they are thought to promote neurogenic inflammatory response important for sensitization of sensory afferents, and also transmission and generation of head pain centrally. 5-HT1D has been found responsible for inhibition of neurogenic inflammation upon administration with sumatriptan and other related compounds that act on prejunctional 5-HT1D receptors.
All triptans, like the older drug dihydroergotamine, have agonistic effects on the 5-HT1D receptor. Comparison of sumatriptan and dihydroergotamine showed that dihydroergotamine has high affinity and sumatriptan has a medium affinity for 5-HT1D. Triptans have at least three modes of action. These antimigraine mechanisms are:
- vasoconstriction of pain-producing intracranial extracerebral vessels by a direct effect on vascular smooth muscle. Sumatriptan and rizatriptan have been shown to cause vasoconstriction in the human middle meningeal arteries.
- inhibition of vasoactive neuropeptide release by trigeminal terminals innervating intracranial vessels and the dura mater. The trigeminocervical complex has 5-HT1D receptors that bind dihydroergotamine and triptans in humans. Rizatriptan has been shown to block dural vasodilation and plasma protein extravasation by inhibiting the release of CGRP via activation of receptors on preganglionic trigeminal sensory nerves terminals. Sumatriptan is shown to inhibit potassium stimulated CGRP secretion from cultured trigeminal neurons in a dose dependent manner and may also inhibit the release of substance P.
- inhibition of nociceptive neurotransmission within the trigeminocervical complex in the brainstem and upper cervical spinal column. Rizatriptan has central trigeminal antinociceptive activity.
Other possibilities of triptans in antimigraine effects are modulation of nitric oxide-dependent signal transduction pathways, nitric oxide scavenging in the brain, and sodium-dependent cell metabolic activity.
Indications of Antimigraine
- Migraines
Contra-Indications of Antimigraine
- Migraine Headache with Temporary Paralysis of One Side
- Severe uncontrolled high blood pressure
- Transient ischaemic attack(TIA), peripheral vascular disease, severe hepatic impairment, concomitant administration of ergotamine, ergotamine derivatives
- Heart attack
- Myocardial infarction, angina pectoris, documented silent ischaemia, Prinzmetal’s angina
- Type of angina where Chest Pain Occurs at Rest
- Coronary artery disease
- Disease of Inadequate Blood Flow to the Heart Muscle ,abnormal heart rhythm
- Occasional Numbness or Tingling of Fingers and Toes
- Peripheral vascular disease
- Insufficiency of the vascular system of the intestine
- Severe renal impairment
- Family History of inadequate blood flow to the heart muscle
- Increased cardiovascular event risk
- Allergies to triptans-5-HT1 Antimigraine Agents
Do not take almotriptan within 24 hours before or after using another migraine headache medicine
Side Effects of Antimigraine
The most common
- Nausea/vomiting
- sleepiness
- feeling of pain or tightness in your jaw, neck, or throat;
- chest pain or heavy feeling, pain spreading to the arm or shoulder, sweating, general ill feeling;
- sudden numbness or weakness,
- Confusion, problems with vision, speech, or balance;
- headache
- dry mouth
- dizziness
- Constipation
- Weight gain/loss
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
Drug Interactions of Antimigraine
Antimigraine drugs may interact with the following drug, supplements, & may change the efficacy of the drug
- amphetamines (e.g., dextroamphetamine, lisdexamfetamine)
- atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone)
- azathioprine
- barbiturates (e.g., butalbital, pentobarbital phenobarbital)
- antipsychotics (e.g., chlorpromazine, fluphenazine, haloperidol, , quetiapine, risperidone)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- ergotamine-containing or ergot-type medications (e.g., dihydroergotamine, methysergide)
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- metoclopramide
- protease inhibitors (e.g., indinavir, lopinavir, ritonavir)
- selective norepinephrine reuptake inhibitors (SNRIs; e.g., venlafaxine)
- selective serotonin receptor agonists (SSRIs; e.g., fluoxetine, fluvoxamine, paroxetine, sertraline)
- trimethoprim
- valproic acid
- warfarin
References
