Vascurin

Uses

Ergotamine Tartrate and caffeine are used as therapy to abort or prevent vascular headache; e.g., migraine, migraine variants or so-called “histaminic cephalalgia.”

Vascurin is also used to associated treatment for these conditions: Bronchopulmonary Dysplasia (BPD), Common Cold, Dark circles under eyes, Dyspepsia, Fatigue, Fever, Flu caused by Influenza, Headache, Migraine, Pain, Pain, Acute, Pain, Menstrual, Primary apnea of premature newborns, Respiratory Depression, Rheumatic Pain, Somnolence, Soreness, Muscle, Tension Headache, Toothache, Moderate Pain, Analgesia, Antacid therapy, Athletic Performance

How Vascurin works

The mechanism of action of caffeine is complex, as it impacts several body systems, which are listed below. The effects as they relate to various body systems are described as follows:

General and cellular actions

Caffeine exerts several actions on cells, but the clinical relevance is poorly understood. One probable mechanism is the inhibition of nucleotide phosphodiesterase enzymes, adenosine receptors, regulation of calcium handling in cells, and participates in adenosine receptor antagonism. Phosphodiesterase enzymes regulate cell function via actions on second messengers cAMP and cGMP. This causes lipolysis through activation of hormone-sensitive lipases, releasing fatty acids and glycerol.

Respiratory

The exact mechanism of action of caffeine in treating apnea related to prematurity is unknown, however, there are several proposed mechanisms, including respiratory center stimulation in the central nervous system, a reduced threshold to hypercapnia with increased response, and increased consumption of oxygen, among others. The blocking of the adenosine receptors enhances respiratory drive via an increase in brain medullary response to carbon dioxide, stimulating ventilation and respiratory drive, while increasing contractility of the diaphragm.

Central nervous system

Caffeine demonstrates antagonism of all 4 adenosine receptor subtypes (A1, A2a, A2b, A3) in the central nervous system. Caffeine's effects on alertness and combatting drowsiness are specifically related to the antagonism of the A2a receptor.

Renal system

Caffeine has diuretic effects due to is stimulatory effects on renal blood flow, increase in glomerular filtration, and increase in sodium excretion.

Cardiovascular system

Adenosine receptor antagonism at the A1 receptor by caffeine stimulates inotropic effects in the heart. Blocking of adenosine receptors promotes catecholamine release, leading to stimulatory effects occurring in the heart and the rest of the body. In the blood vessels, caffeine exerts direct antagonism of adenosine receptors, causing vasodilation. It stimulates the endothelial cells in the blood vessel wall to release nitric oxide, potentiating blood vessel relaxation. Catecholamine release, however, antagonizes this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. Finally, caffeine is shown to raise systolic blood pressure measurements by 5 to 10 mmHg when it is not taken regularly, versus no effect in those who consume it regularly. The vasoconstricting effects of caffeine are beneficial in migraines and other types of headache, which are normally caused by vasodilation in the brain.

Dosage

Vascurin dosage

Usual Adult Dose for Cluster Headache:

Oral, Sublingual: 2 mg ergotamine in fixed combination with caffeine given as quickly as possible after the first symptom of headache. Additional 1 mg doses can be given every 30 minutes until the headache has been aborted or until a total dose of 6 mg has been reached or 10 mg/week.

Rectal: 2 mg ergotamine in fixed combination with caffeine given as quickly as possible after the first symptom of headache. An additional 2 mg dose can be given 1 hour later if the first dose fails to abort the headache. The total dose should not exceed 4 mg/attack or 10 mg/week.

Usual Adult Dose for Migraine:

Oral, Sublingual: 2 mg ergotamine in fixed combination with caffeine given as quickly as possible after the first symptom of headache. Additional 1 mg doses can be given every 30 minutes until the headache has been aborted or until a total dose of 6 mg has been reached or 10 mg/week.

Rectal: 2 mg ergotamine in fixed combination with caffeine given as quickly as possible after the first symptom of headache. An additional 2 mg dose can be given 1 hour later if the first dose fails to abort the headache. The total dose should not exceed 4 mg/attack or 10 mg/week.

Side Effects

Increased BP, hypotension, rapid and weak pulse, palpitations, arrhythmias, precordial pain, coronary infarction, fibrotic thickening of the heart valves. Cerebral ischaemia and thrombosis, blurred vision, sleep disturbances, urinary retention, muscle cramps and joint pains. 

GI symptoms such as nausea, vomiting, constipation, abdominal pain. Dysaesthesia, paraesthesia, formication, tremor, convulsions, headache, extrapyramidal effects. Anxiety, depression, confusion, hallucinations, psychomotor impairment.

Toxicity

The oral LD50 of caffeine in rats is 192 mg/kg. An acute fatal overdose of caffeine in humans is about 10–14 grams (equivalent to 150–200 mg/kg of body weight).

Caffeine overdose

In the case of caffeine overdose, seizures may occur, as caffeine is a central nervous system stimulant. It should be used with extreme caution in those with epilepsy or other seizure disorders. Symptoms of overdose may include nausea, vomiting, diarrhea, and gastrointestinal upset. Intoxication with caffeine is included in the World Health Organization’s International Classification of Diseases (ICD-10). Agitation, anxiety, restlessness, insomnia, tachycardia, tremors, tachycardia, psychomotor agitation, and, in some cases, death can occur, depending on the amount of caffeine consumed. Overdose is more likely to occur in individuals who do not consume caffeine regularly but consume energy drinks.

Overdose management

For a mild caffeine overdose, offer symptomatic treatment. In the case of a severe overdose, intubation for airway protection from changes in mental status or vomiting may be needed. Activated charcoal and hemodialysis can prevent further complications of an overdose and prevent absorption and metabolism. Benzodiazepine drugs can be administered to prevent or treat seizures. IV fluids and vasopressors may be necessary to combat hypotension associated with caffeine overdose. In addition, magnesium and beta blocking drugs can be used to treat arrhythmias that may occur, with defibrillation and resuscitation if the arrhythmias are lethal. Follow local ACLS protocols.

Precaution

Not to be taken regularly or used for migraine prophylaxis. Increased risk of arterial constriction and other symptoms of ergotism. Discontinue treatment when symptoms of arterial occlusion occur e.g. numbness and tingling of the extremities. Caution when used in patients with infective hepatitis, cardiac disease or anaemia. GI tract obstructive disease, glaucoma, prostatic hypertrophy or urinary retention may be worsened by cyclizine. May increase risk of retroperitoneal and/or pleuropulmonary fibrosis. Not recommended for use with other vasoconstrictors. Elderly.

Volume of Distribution

Caffeine has the ability to rapidly cross the blood-brain barrier. It is water and fat soluble and distributes throughout the body. Caffeine concentrations in the cerebrospinal fluid of preterm newborns are similar to the concentrations found in the plasma. The mean volume of distribution of caffeine in infants is 0.8-0.9 L/kg and 0.6 L/kg in the adult population.

Elimination Route

Caffeine is rapidly absorbed after oral or parenteral administration, reaching peak plasma concentration within 30 minutes to 2 hours after administration. After oral administration, onset of action takes place within 45 to 1 hour. Food may delay caffeine absorption. The peak plasma level for caffeine ranges from 6-10mg/L. The absolute bioavailability is unavailable in neonates, but reaches about 100% in adults.

Half Life

In an average-sized adult or child above the age of 9, the half-life of caffeine is approximately 5 hours. Various characteristics and conditions can alter caffeine half-life. It can be reduced by up to 50% in smokers. Pregnant women show an increased half-life of 15 hours or higher, especially in the third trimester. The half-life in newborns is prolonged to about 8 hours at full-term and 100 hours in premature infants, likely due to reduced ability to metabolize it. Liver disease or drugs that inhibit CYP1A2 can increase caffeine half-life.

Clearance

The clearance of caffeine varies, but on average, is about 0.078 L/kg/h (1.3 mL/min/kg).

Elimination Route

The major metabolites of caffeine can be found excreted in the urine. About 0.5% to 2% of a caffeine dose is found excreted in urine, as it because it is heavily absorbed in the renal tubules.

Pregnancy & Breastfeeding use

Pregnancy: Category X. This medicine should not be used during pregnancy as it may be harmful to the unborn baby.

Lactation: Significant amounts of this medicine may pass into breast milk. It should not be used by breastfeeding mothers as it may be harmful to the nursing infant.

Contraindication

Not to be used with potent inhibitors of CYP3A4 and protease inhibitors. Hyperthyroidism, renal or hepatic impairment. Pre existing vascular disease including coronary disease, obliterative vascular disease, angina, claudication, peripheral ischaemia, Raynaud's syndrome and hypertension. Not to be used when there is sepsis. Pregnancy and lactation.

Special Warning

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Renal Dose Adjustments: Contraindicated in patients with renal dysfunction

Liver Dose Adjustments: Contraindicated in patients with liver dysfunction

Acute Overdose

Acute overdosage: 

• Symptoms: Nausea, vomiting, diarrhoea, extreme thirst, coldness, weakness, tingling and itching of the skin, rapid and weak pulse, hypotension, shock, confusion, convulsions and unconsciousness. BP may be difficult to measure; may result in fatalities. Further symptoms of peripheral vasoconstriction or CV disturbances may occur but be delayed.
• Treatment includes using activated charcoal to reduce absorption. General supportive measures should be instituted. IV vasodilators such as sodium nitroprusside infusion may be required to relieve vasospasm. Peritoneal dialysis and forced diuresis may be used to remove ergotamine from the body.

Chronic overdosage: 

• Symptoms: Peripheral ischaemia of the extremities, especially the feet and legs. Gangrene may develop in the toes and fingers. Anginal pain, tachycardia or bradycardia and BP fluctuations may occur. Excessive use may lead to pleural and peritoneal fibrosis. Rebound headache may occur and is a major withdrawal symptom following the development of ergotamine dependence.
• Treatment: IV vasodilators e.g. nitroprusside and nitroglycerin may be used to re-establish normal blood flow. Captopril may be used to reverse the effects of chronic overdosage with ergotamine.

Storage Condition

Store below 25°C.

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