Vigrol Forte

Uses

Caffeine is a stimulant present in tea, coffee, cola beverages, analgesic drugs, and agents used to increase alertness. It is also used in to prevent and treat pulmonary complications of premature birth.

Caffeine is indicated for the short term treatment of apnea of prematurity in infants and off label for the prevention and treatment of bronchopulmonary dysplasia caused by premature birth. In addition, it is indicated in combination with sodium benzoate to treat respiratory depression resulting from an overdose with CNS depressant drugs. Caffeine has a broad range of over the counter uses, and is found in energy supplements, athletic enhancement products, pain relief products, as well as cosmetic products.

Pseudoephedrine is a decongestant of the mucous membranes of the upper respiratory tract, especially the nasal mucosa, sinuses and eustachian tube. It is used for the symptomatic relief of allergic rhinitis (hay fever), vasomotor rhinitis, the common cold, influenza (flu) and ear congestion caused by ear inflammation or infection. Pseudoephedrine can also be used as a bronchodilator.

Pseudoephedrine is a stereoisomer of Ephedrine with similar but less potent pharmacological activity. It has nasal and bronchial decongestant activity.

Vigrol Forte 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 PerformanceAllergic Disorder, Bronchial Asthma, Common Cold, Cough, Depression, Fever, General Anesthesia Induced Hypotension, Headache, Joint Pain, Myasthenia Gravis, Narcolepsy, Nasal Congestion, Rhinorrhoea, Sore Throat, Dry cough

How Vigrol Forte 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.

Ephedrine is a direct and indirect sympathomimetic amine. Ephedrine activates adrenergic α and β-receptors as well as inhibiting norepinephrine reuptake, and increasing the release of norepinephrine from vesicles in nerve cells. These actions combined lead to larger quantities of norepinephrine present in the synapse, for longer periods of time, increasing stimulation of the sympathetic nervous system. Ephedrine's stimulation of α-1 receptors causes constriction of veins and a rise in blood pressure, stimulation of β-1 adrenergic receptors increase cardiac chronotropy and inotropy, stimulation of β-2 adrenergic receptors causes bronchodilation.

Dosage

Vigrol Forte dosage

As a decongestant and symptomatic treatment for upper respiratory tract infections the recommended dose is:

Adults: 1 tablet every 4 to 6 hours, up to maximum of 240 mg in 24 hours

Children:

• 6-12 years of age: 1/2 tablet every 4 to 6 hours daily
• 2-5 years of age: 1/4 tablet every 4 to 6 hours daily
• Less than 2 years of age: This drug is not advised unless specifically recommended by a physician.

Side Effects

Serious adverse effects associated with the use of Pseudoephedrine are rare. Symptoms of central nervous system excitation may occur, including sleep disturbances and, rarely, hallucinations have been reported. Skin rashes, with or without irritation, have occasionally been reported.

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.

Patients experiencing an overdose of ephedrine will present with rapidly increasing blood pressure. Manage overdose with blood pressure monitoring, and possibly the administration of parenteral antihypertensives. The LD₅₀ in mice after oral administration is 785mg/kg, after intraperitoneal administration if 248mg/kg, and after subcutaneous administration is 425mg/kg.

Precaution

Although Pseudoephedrine has virtually no pressor effects in normotensive patients, it should be used with caution in patients suffering mild to moderate hypertension. As with other sympathomimetic agents, Pseudoephedrine should be used with caution in patients with hypertension, heart disease, diabetes, hyperthyroidism, elevated intraocular pressure and prostatic enlargement. Caution should be exercised when using the product in the presence of severe hepatic impairment or moderate to severe renal impairment.

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.

Oral ephedrine has an average volume of distribution of 215.6L.

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.

Oral ephedrine reaches an average C_max of 79.5ng/mL, with a T_max of 1.81h, and a bioavailability of 88%.

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.

Oral ephedrine has a plasma elimination half life of approximately 6 hours, but there is a large degree of inter-patient variability.

Clearance

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

Oral ephedrine has a clearance of 23.3L/h but there is a high degree of inter-patient variability.

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.

Ephedrine is mainly eliminated in the urine. Approximately 60% is eliminated as the unmetabolized parent compound, 13% as benzoic acid conjugates, and 1% as 1,2-dihydroxypropylbenzene.

Pregnancy & Breastfeeding use

Although Pseudoephedrine has been in widespread use for many years without apparent ill consequence, there are no specific data on its use during pregnancy. Caution should therefore be exercised by balancing the potential benefit of treatment to the mother against any possible hazards to the developing foetus. Pseudoephedrine is excreted in breast milk in small amounts but the effect of this on breast-fed infants is not known.

Contraindication

Pseudoephedrine is contraindicated in-

• Hypersensitivity of individuals to this drug
• Severe hypertension and coronary artery disease
• Concurrent use of Mono Amine Oxidase Inhibitor (MAOI) drugs

Acute Overdose

As with other sympathomimetic agents, symptoms of overdosage include irritability, restlessness, tremor, convulsions, palpitations, hypertension and difficulty in micturition. Necessary measures should be taken to maintain and support respiration and control convulsions. Gastric lavage should be performed if indicated. If desired, the elimination of Pseudoephedrine can be accelerated by acid diuresis or by dialysis.

Innovators Monograph

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