History of Scopolamine and Its Epidemiology - Research Paper Example

? "Scopolamine" Introduction Scopolamine is an alkaloid responsible for inducing anticholinergic effects. Scopolamine is used as a sedative to control vomiting and in ophthalmology for the dilatation of pupils, essential during the eye examination, while scopolamine transdermal is utilized in motion sickness. Scopolamine is a tropane alkaloid of plant origin, belongs to the Solanaceae (nightshade) family particularly Datura sp. Scopolamine is a secondary metabolite obtained from these plants. The drug is also called as hyoscine, with muscarinic antagonistic outcomes. Effective dose of the drug is imperative, as overdose of scopolamine results in delirium, paralysis of eyes, delusions, stupor and in certain cases, may result in death of the individuals. Etymology of scopolamine highlights that the term scopolamine was coined after the plant Scopolia where as hyoscine is coined from the scientific nomenclature of henbane called Hyoscyamus niger. Scopolamine is a competitive antagonist at the M1 receptor (muscarinic acetylcholine receptor) and therefore it is known as anticholinergic or anti-muscarinic drug (White et al, 2007). History of Scopolamine Scopolamine was the foremost component in Asthmador, to contradict smoking it was made available in the market between the years 1950s and 1960s. The drug also enables the individual to overcome asthma and bronchitis. Between 1940 and 1960, scopolamine was used to induce labour in the twilight sleep. The drug aids in eliminating pain as scopolamine influences brain functions responsible for self-awareness and self-control resulting in psychosis (Dictionary Definition). Tracing the history of the drug, in 1940, crime fiction's classic novel, "Farewell My Lovely", mentioned scopolamine in a private sanatorium. Later, in the year 1957, the drug had to suffer a small degree of disrepute through the film "I Was a Teenage Werewolf". Scopolamine was used in World War II action classic "The Guns of Navarone" (1961); and in "Where Eagles Dare" (1968), as a Schutzstaffel truth serum. Scopolamine gained popularity in media for its enormous actions, "That'll Be The Day" (1974), TV series, episode 1; in Rober Ludlum's Matarese Dynasty (1979). It was used in kidnappings in X files "Red Museum" (1990). Scopolamine was also used in "The Mars Records" (2000). While in the year 2007, episode of a TV show, "Airborne" mentioned an individual wearing scopolamine patch (Dictionary Definition). Epidemiology of Scopolamine Anticholinergic drug called scopolamine is responsible for causing serious illness or death if ingested. History of the drug scopolamine reveals that the drug has always been misused throughout the United States, which resulted in poisoning due to innocence, lack of awareness and poor understanding of the user. The incidents of Jimson weed poisoning was reported in Texas, NYC and California between June- November 1994 (Epidemiologic Notes and Reports Jimson Weed Poisoning Texas, New York, and California, 1994). Pharmacology of Scopolamine Scopolamine is an alkaloid obtained from Solanaceae family. Datura and Scopola carniolica are the chief members from which scopolamine is derived from these plants and act as antimuscarinic in a similar manner as atropine with more impact on central nervous system. Therefore, the drug plays an important role in anaesthesia, in urinary incontinence, as an antispasmodic, act as a mydriatic as well as cycloplegic agent. It is the drug of choice in motion sickness. The drug is used for the treatment of excessive salivation, sialorrhoea, colicky abdominal pain, diverticulitis, bradycardia as well as for irritable bowel syndrome (Drug Bank). Pharmacodynamics of Scopolamine The drug is a muscarinic antagonist. The structure of scopolamine is similar to the neurotransmitter acetylcholine. The drug act by blocking the muscarinic acetylcholine receptors (M1). The drug is classified as an anticholinergic drug. The drug stops nausea and vomiting which occur due to motion sickness. Mode of action of Scopolamine Scopolamine interferes with the transmission of nerve impulses by acetylcholine in the parasympathetic nervous system. Under normal conditions, balance of the body is maintained by the vestibular portion of the ear. Due to motion some individuals becomes disoriented as a result of this the vestibule transmits the signal by means of nerves to the brain (vomiting centre). Scopolamine prevents this neuronal communication by blocking the action of acetylcholine, i.e. communication between vestibule and vomiting center of the brain could not be established due to the action of scopolamine. The drug can act directly on the vomiting center. It is prescribed to take the drug prior to the commencement of an effectual motion sickness (Drug Bank). Bioavailability of scopolamine is 10-50%. Route of elimination, as parent is less than 10% of the total dose of excretion in the urine while metabolites over 108 hours, the half life of the drug is 4.5 hours (Drug bank). Medical Use of Scopolamine The chief source of the drug is Hyoscyamys niger. The drug displays direct effect on the CNS, low dose acts as depressant resulting in amnesia, fatigue, drowsiness, N- REM sleep while the high dose brings excitation. The drug is anticholinergic with more potent action on eye and secretory gland with shorter duration of action. These actions are in contrast to the Atropine action (Tripathi, 2008). Drug scopolamine has three primary medical uses- a. for the treatment of nausea (even post-operative nausea) and motion sickness; b. for the treatment of intestinal cramping; c. for ophthalmic purposes, in eye drops for the induction of mydriasis and cycloplegia. The drug is used as a narcotic painkiller, preanesthetic agent, rarely in Parkinsonism and occasional sleep aid. Other uses of drug involves breaking of nicotine addiction (Dictionary Definition). Scopolamine is used for central action in- Parkinsonism- Central anticholinergics are less effective than levodopa. They are used in mild cases in drug induced extra pyramidal syndromes and as adjuvant to levodopa. Motion sickness- Hyoscine is the most effective drug for motion sickness. It is particularly valuable in highly susceptible individuals and for vigorous motions. The drug should be given prophylactically (0.2 mg. oral), because administration after symptoms have setin is less effective, action lasts 4-6 hours. A transdermal preparation applied behind the pinna 4 hours before the journey has been shown to protect for 3 days. Side effects with low oral doses and transdermal medication are few but sedation and dry mouth may occur. Hyoscine and other anticholinergics are not effective in other types of vomiting (Tripathi, 2008). Hyoscine has been used to produce sedation and amnesia during labour and to control maniacal states. It had earned a reputation as a lie detector during world war II. Its amnesic and depressant action was believed to put the subject off guard in the face of sustained interrogation and sleep deprivation so that he come out with the truth (Tripathi, 2008). Adverse Effects and Toxicity Side effects are quite common with the use of atropine and its congeners; are due to facets of its action other than for which it is being used. they cause inconvenience but are rarely serious. Belladonna poisoning may occur due to drug overdose or consumption of seeds and berries or belladonna/datura plant. Children are highly susceptible. Manifestations are die to exaggerated pharmacological actions (Tripathi, 2008). In contrast to atropine, hyoscine produces central depression at therapeutic doses and symptoms include drowsiness and fatigue. Toxic doses of hyoscine produce stimulation of the CNS in a similar manner to atropine. However, hyoscine does not stimulate the medullary centres and therefore does not produce the increases in respiration rate or blood pressure seen with atropine. Hyoscine may produce CNS stimulation rather than depression at therapeutic doses if used in the presence of pain without opioid analgesics; symptoms include excitement, restlessness, hallucinations, or delirium. Patients who experience drowsiness should not drive or operate machinery. Caution has been advised in elderly patients and in patients with impaired liver, or kidney function, as adverse CNS effects have been stated to be more likely in these patients. There have been rare reports of an increase in frequency of seizures in epileptic patients. Criminal/ Abuse of Scopolamine Hyoscine has been used by criminals to incapacitate and produce anterograde amnesia in their victims in crimes such as drug-facilitated rape (‘date rape’), robbery, and kidnapping. A powder, known locally as burundanga, has been blown into the victim’s face or given in drinks, chocolate, or chewing gum. Dry mouth, difficulty in swallowing and talking. Dry, flushed and hot skin specially over face and neck, fever, difficulty in micturation, decreased bowel sounds, a scarlet rash may appear. Dilated pupil, photophobia, blurring of near vision, palpitation. Excitement, psychotic behaviour, ataxia, delirium, dreadful visual hallucinations, hypotension, weak and rapid pulse, cardiovascular collapse with respiratory depression. Convulsions and coma occur in severe poisoning (Tripathi, 2008). Although bilateral mydriasis has occurred with the use of transdermal hyoscine, development of a unilateral fixed dilated pupil (anisocoria) may be due to contamination of a finger with hyoscine in handling the device, and then rubbing the eye. Effects on mental function- reports reveal There have been reports of psychotic reactions associated with the transdermal use of hyoscine. Psychotic reactions have also occurred after instillation of hyoscine eye drops. Effects on the oesophagus- A patient developed pain on swallowing after 4 days of treatment with hyoscine. Endoscopy showed oesophageal ulceration, which healed completely after 8 weeks of esomeprazole treatment (Philcox, 2007). Diagnosis Methacholine 5 mg or neostigmine 1 mg s.c. fails to induce typical muscarinic effects (Tripathi, 2008). Contra indications Atropinic drugs are absolutely contraindicated in individual with a narrow iridocorneal angle may precipitate acute congestive glaucoma. However, marked rise in intraocular tension is rare in patients with wide angle glaucoma. Caution is advocated in elderly males with prostatic hypertrophy- urinary retention cannot occur (Tripathi, 2008). Interactions Absorption of most drugs is slowed because atropine delays gastric emptying. This results in slower absorption and greater peripheral degradation of levodopa- less of it reaches the brain. This does not occur when a peripheral decarboxylase inhibitor is combined. On the other hand, extent of digoxin and tetracycline absorption may be increased due to longer transit time in the gastrointestinal tract. Antacids interfere with absorption of anticholinergics. Antihistaminics, tricyclic antidepressants, phenothiazines, disopyramide, pethidine have anticholinergic property- additive side effects occur with atropinic drugs. MAP inhibitors interfere with metabolism of anticholinergic antiparkinsonian drugs delirium may occur (Tripathi, 2008). Routes of administration Administration of scopolamine is performed through transdermal patches or by oral route or given subcutaneous, ophthalmic route or by means of intravenous routes. The transdermal patch is given as a preventive mode for nausea and vomiting while other routes involving oral, ophthalmic and intravenous forms involve scopolamine hydrobromide (Dictionary Definition). Scopolamine: Grown, Manufactured, Transported and Marketed Scopolamine is a plant product obtained from burundanga since Inca's era in South America. The plant product is given the shape of scopolamine medicine in the process of biosynthesis which commences with L-ornithine decarboxylated to putrescine by ornithine decarboxylase enzyme. Putrescine methylated to N-methylputrescine by enzyme N-methyltransferase. N-methylputrescine deaminated to 4-methylaminobutanal by putrescine oxidase enzyme. 4-methylaminobutanal undergoes spontaneous ring formation to N-methyl- pyrrolium cation, which condenses with acetoacetic acid to produce hygrine. A rearrangement is done to form tropinone. Tropinone is converted to tropine by Tropinone reductase. Tropine condenses with phenylalanine-derived phenyllactate to littorine. Littorine is rearranged to hyoscyamine aldehyde by cytochrome Cyp80F1. Epoxidation of hypscyamine yields scopolamine in the presence of enzyme 6beta-hydroxyhyoscyamine epoxidase (Ziegler, 2008). The two leading manufacturers are Boca pharmacal inc and Private formulations inc (Drug Bank). The drug is marketed in the form of disc for transdermal use, in liquid form it is marketed for intravenous administration while for intramuscular and intravenous administration it is marketed in the form of solution. For oral administration the drug is marketed as tablets. The market is large for scopolamine, as motion sickness patches. Marina Biotech, Inc. is known to sale intranasal scopolamine (News Detail). Treatment & Rehabilitation If poison has been ingested, gastric lavage should be done with tannic acid (KMnO4 is ineffective in oxidizing atropine). The patient should be kept in dark quiet room. Cold sponging or ice bags are applied for reducing body temperature. Serin, THA and physostigmine. Physostigmine 1-3 mg s.c. or i.v. antagonises both central and peripheral effects but has been found to produce hypotension and arrhythmias in some cases. As such, its utility is controversial. Neostigmine and DFP do not antagonise the central effects. Other general measure (maintenance of blood volume, assisted respiration, diazepam to control convulsions) should be taken as appropriate (Tripathi, 2008). References Hebert, T. J., Cashion, M. F., Dohanich, G. P. (1994). Effects of hormonal treatment and history on scopolamine inhibition of lordosis. Physiol Behav, 56(5), 835-9. Dictionary Definition. (n.d.) Retrieved from http://scopolamine.askdefine.com/ Drug Bank. (n.d.) Retrieved from http://www.drugbank.ca/drugs/DB00747 Epidemiologic Notes and Reports Jimson Weed Poisoning Texas, New York, and California, 1994. (n.d.) Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/00035694.htm. News Detail. (n.d.) Retrieved from http://www.pharmaloco.com/news_detail/Nastech+Reacquires+the+US+Marketing+Rights+t o+Intranasal+Sco/20665/faq.php Philcox, S., Keegan, A. (2007). A case of hyoscine-related oesophagitis. Med J Aust 186, 650–1. Tripathi, S. K. (2008). Essentials of Medical Pharmacology. 6th ed. Jaypee Publication. White, P. F., Tang, J., Song, D. et al. (2007). Transdermal Scopolamine: An Alternative to Ondansetron and Droperidol for the Prevention of Postoperative and Postdischarge Emetic Symptoms. Anesthesia and Analgesia, 104 (1), 92–96. Ziegler, J. Facchini, P. J. (2008). Alkaloid Biosynthesis: Metabolism and Trafficking. Annual Review of Plant Biology, 59(1), 735–769. Read More