The action of the drug on the human body is called Pharmacodynamics in Medical terminology. To produce its effect and to change the pathological process that is happening the body and to reduce the symptom or cure the disease, the medicine has to function in a specific way. The changes it does to the body at cellular level gives the desired result of treating a disease. Drugs act by stimulating or inhibiting a receptor or an enzyme or a protein most of the times. Medications are produced in such a way that the ingredients target the specific site and bring about chemical changes in the body that can stop or reverse the chemical reaction which is causing the disease.
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Rayor binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α1 receptors, and dopamine D2L and D3 receptors.
The therapeutic activity of Rayor in migraine is generally attributed to the agonist effect at 5-HT1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine. One theory suggests that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release. In addition, Rayor possesses oxytocic properties.
How should I take Rayor?
It is important to use Rayor properly. Make sure that you read the patient directions carefully before using Rayor.
Do not use nasal Rayor for a headache that is different from your usual migraine. Instead, check with your doctor.
To relieve your migraine as soon as possible, use nasal Rayor as soon as the headache begins. Even if you get warning signals of a coming migraine (an aura), you should wait until the headache pain starts before using nasal Rayor.
Lying down in a quiet, dark room for a while after you use Rayor may help relieve your migraine.
If you feel much better after a dose of nasal Rayor, but your headache comes back or gets worse after a while, you may use more nasal Rayor. However, use Rayor only as directed by your doctor. Do not use more of it, and do not use it more often, than directed.
Your doctor may direct you to take another medicine to help prevent headaches. It is important that you follow your doctor's directions, even if your headaches continue to occur. Headache-preventing medicines may take several weeks to start working. Even after they do start working, your headaches should occur less often, and they should be less severe, and easier to relieve. This can reduce the amount of nasal Rayor or other pain medicines that you need. If you do not notice any improvement after several weeks of headache-preventing treatment, check with your doctor.
Dosing
The dose of Rayor will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Rayor. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
For nasal dosage form (nasal solution):
For migraine headaches:
Adults—One spray (0.5 mg) in each nostril. After 15 minutes, another spray (0.5 mg) in each nostril should be used.
Children—Use and dose must be determined by your doctor.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Rayor administration
Administration of drug is important to know because the drug absorption and action varies depending on the route and time of administration of the drug. A medicine is prescribed before meals or after meals or along with meals. The specific timing of the drug intake about food is to increase its absorption and thus its efficacy. Few work well when taken in empty stomach and few medications need to be taken 1 or 2 hrs after the meal. A drug can be in the form of a tablet, a capsule which is the oral route of administration and the same can be in IV form which is used in specific cases. Other forms of drug administration can be a suppository in anal route or an inhalation route.
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Use this medication exactly as prescribed by your doctor. Never use more than your prescribed dose of Rayor nasal. Follow the directions on your prescription label. Tell your doctor if the medicine seems to stop working as well in treating your migraine attacks. Rayor is not for daily use.
Rayor nasal spray is absorbed quickly through your nasal passages and is for use only in the nose. The nasal spray liquid should not be injected into the body.
Your doctor may want to give your first dose of Rayor nasal in a hospital or clinic setting to quickly treat any serious side effects that occur.
Rayor nasal comes in a bottle (vial) with a nasal sprayer attachment. Do not open the vial and attach the sprayer until you are ready to use the medication. A new vial and sprayer should be used for each new headache episode.
Before using the medication, prime the nasal spray by pumping exactly 4 sprays into the air.
Use the first dose of Rayor as soon as you notice headache symptoms, or after an attack has already begun. Use one spray in each nostril, and after 15 minutes use a second spray in each nostril, for a total of 4 sprays.
Do not tilt your head back while you are using the nasal spray, and do not sniff through your nose during use or just after use. Throw away the vial and sprayer after you finish using it to treat one headache episode, or no longer than 8 hours after opening the vial.
If you still have migraine symptoms after using a total of 4 sprays, call your doctor before using any more. Do not use more than 6 total sprays of Rayor nasal in any 24-hour period. Do not use more than 8 total sprays of this medication over a period of 7 days.
If you use Rayor nasal long-term, your doctor may want to check your heart function periodically using an electrocardiograph or ECG (sometimes called an EKG), a machine that measures electrical activity of the heart. This will help your doctor determine if it is still safe for you to use this medication. Do not miss any scheduled visits to your doctor.
Do not give this medication to anyone else, even if they have the same headache symptoms you have. Rayor can be dangerous if it is used to treat headache in a person who has not been diagnosed by a doctor as having true migraine headaches.
Store Rayor nasal at room temperature away from moisture and heat. Do not refrigerate or freeze the nasal spray. Do not use any stored Rayor if the expiration date on the label has passed.
Rayor pharmacology
Pharmacokinetics of a drug can be defined as what body does to the drug after it is taken. The therapeutic result of the medicine depends upon the Pharmacokinetics of the drug. It deals with the time taken for the drug to be absorbed, metabolized, the process and chemical reactions involved in metabolism and about the excretion of the drug. All these factors are essential to deciding on the efficacy of the drug. Based on these pharmacokinetic principles, the ingredients, the Pharmaceutical company decides dose and route of administration. The concentration of the drug at the site of action which is proportional to therapeutic result inside the body depends on various pharmacokinetic reactions that occur in the body.
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Mechanism of Action
Rayor binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. The therapeutic activity of Rayor in migraine is generally attributed to the agonist effects at 5-HT1D receptors.
Pharmacodynamics
Significant elevation in blood pressure has been reported in patients with and without a history of hypertension.
Rayor possesses oxytocic properties.
Pharmacokinetics
Absorption
The mean time from dosing to maximum plasma concentration following Rayor administration was approximately 0.5 hours.
Distribution
Rayor mesylate is 93% plasma protein bound. The apparent steady-state volume of distribution is approximately 800 liters.
Elimination
Metabolism
Four Rayor mesylate metabolites have been identified in human plasma following oral administration. The major metabolite, 8'-β-hydroxy Rayor, exhibits affinity equivalent to its parent for adrenergic and 5-HT receptors and demonstrates equivalent potency in several venoconstrictor activity models, in vivo and in vitro. The other metabolites, i.e., dihydrolysergic acid, dihydrolysergic amide, and a metabolite formed by oxidative opening of the proline ring, are of minor importance. Following nasal administration, total metabolites represent only 20% to 30% of plasma AUC. The systemic clearance of Rayor mesylate following intravenous and intramuscular administration is 1.5 L/min. Quantitative pharmacokinetic characterization of the four metabolites has not been performed.
Excretion
The major excretory route of Rayor is via the bile in the feces. The total body clearance is 1.5 L/min, which reflects mainly hepatic clearance. Only 6% to 7% of unchanged Rayor is excreted in the urine after intramuscular injection. The renal clearance (0.1 L/min) is unaffected by the route of Rayor administration.
The mean apparent half-life of Rayor nasal administration in healthy subjects is approximately 12 hours.
Specific Populations
No studies have been conducted on the effect of renal or hepatic impairment, gender, race, ethnicity, or pregnancy on Rayor pharmacokinetics.
Drug Interaction Studies
CYP3A4 Inhibitors
Rare reports of ergotism have been obtained from patients treated with Rayor and macrolide antibiotics (e.g., clarithromycin, erythromycin) and from patients treated with Rayor and protease inhibitors (e.g., ritonavir), presumably due to inhibition of CYP3A metabolism of ergotamine.
Other Drugs
The pharmacokinetics of Rayor did not appear to be significantly affected by the concomitant use of a local vasoconstrictor.
Multiple oral doses of the β-adrenoceptor antagonist propranolol, used for migraine prophylaxis, had no significant influence on the Cmax, tmax, or AUC of Rayor doses up to 4 mg. However, propranolol may potentiate the vasoconstrictive action of ergotamine.
The effect of oral contraceptives on the pharmacokinetics of Rayor has not been studied.
References
EPA DSStox. "Dihydroergotamine: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
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