Chemical Structures and Excipient Profile of Drugs

Chemical Structures and Excipient Profile of Drugs DRUG AND EXCIPIENT PROFILE CAFFEINE Chemical structure : Mol. Weight : Average: 194.1906 Melting point : 238  °C State : solid Water solubility : 2.16E+004 mg/L (at 25  °C) Half Life : 3 – 7 hours in geriatrics , 65 – 130 hours in pediatrics Protein Binding : Low protein binding (25 – 36%) Absorption : absorbed after oral and parenteral administration. The peak plasma level of caffeine ranges from 6 to 10mg/L and the mean time to reach peak concentration ranged from 30 minutes to 2 hours. Pharmacology : Caffeine is a naturally occurring xanthine derivative like theobromine and the bronchodilator theophylline. It is used as a CNS stimulant, mild diuretic, and respiratory stimulant (in neonates). Often combined with analgesics or with ergot alkaloids, caffeine is used to treat migraine and other types of headache. Over the counter, caffeine is used to treat drowsiness or mild water-weight gain. Mechanism of Action : Caffeine stimulates med ullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3†²,5†²-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. Xanthines such as caffeine act as antagonists at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of nor epinephrine or angiotensin, antagonist of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of caffeine. Blockage of the adenosine A1 receptor in the heart leads to the accelerated, pronounced â€Å"pounding† of the heart upon caffeine intake. Indication : For management of fatigue, orthostatic hypotension, and for the short term treatmen t of apnea of prematurity in neonates. Toxicity : LD 50 = 127 mg/kg (oral dose in mice) ERGOTAMINE Chemical structure : Mol. Weight : Average: 581.6615 Melting point : 213.5  °C State : solid state Water solubility : Slightly soluble Half Life : 2 hours Absorption : The bioavailability of sublingual ergotamine has not been determined. Pharmacology : Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacology of ergotamine is extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon the site, and is highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and producing depression of central vasomotor centers. The pain of a migraine attack is due to increased amplitude of pulsations in the cranial arteries, especially the m eningeal branches of the external carotid artery. Ergotamine reduces extra cranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyper perfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow. Mechanism of Action : Ergotamine acts on migraine by one of the two proposed mechanisms: 1) activation of 5-HT 1D receptors located on intracranial blood vessels, including those on arteriole-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine, and 2) Activation of 5-HT 1D receptors on sensory nerve endings of the trigeminal system which results in inhibition of pro-inflammatory neuropeptide release. Indication : For use as therapy to abort or prevent vascular type of headache, e.g., migraine, migraine variants, or so called â€Å"histaminic cephalalgia†. Toxicity : Signs of overexposure including irritation, nausea, vomiting, headache, diarrh ea, thirst, coldness of skin, pruritus, weak pulse, numbness, tingling of extremities, and confusion. CYCLIZINE