* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Fatality From Spasmo-Proxyvon® Addiction: A Few Cases
Survey
Document related concepts
Pharmaceutical marketing wikipedia , lookup
Orphan drug wikipedia , lookup
Drug design wikipedia , lookup
Polysubstance dependence wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Drug discovery wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Prescription costs wikipedia , lookup
Neuropharmacology wikipedia , lookup
Pharmacognosy wikipedia , lookup
Prescription drug prices in the United States wikipedia , lookup
Psychopharmacology wikipedia , lookup
Transcript
47 Case Report Fatality From Spasmo-Proxyvon® Addiction: A Few Cases Venkata Raghava S,* Vijay Kautilya D, Bheemappa Havanur, Devadass PK ABSTRACT Ever since the information technology revolution hit India in a big way, substance abuse has been rising in incidence by leaps and bounds, mainly because of the ease with which such substances can be procured through the Internet. There has been a significant shift from conventional drugs of abuse such as cannabis and heroin to newer drugs such as designer amphetamines, phencyclidine, and ketamine. But because these drugs are covered by the Narcotic Drugs and Psychotropic Substances Act, there has been a recent trend towards abuse of pharmaceutical agents such as pentazocine, propoxyphene and buprenorphine. Spasmo-Proxyvon® is a popular brand of antispasmodic from Wockhardt which contains paracetamol (acetaminophen), dicyclomine, and dextropropoxyphene. This combined drug formulation sold as gelatin capsules is easily available, and is increasingly being abused for its opioid effect. A few cases of such addiction resulting in death are being reported. Case 1 A 31-year-old male developed rigor all on a sudden while in his bathroom, which persisted for 10-15 minutes even after coming out of the bathroom, and died thereafter. Autopsy revealed bluish-coloured semi-digested rice particles in the stomach with unusual smell, and congestion of the mucosa. Intestinal mucosa was also congested. Blood and viscera samples were sent for chemical analysis to the Forensic Science Laboratory. Testing revealed the presence of dextropropoxy-phene. Key Words: Spasmo-Proxyvon®; Dextropropoxyphene; Acetaminophen; Paracetamol; Dicyclomine Case 2 A 20-year-old male developed sudden anxiety, followed by shivering at his house. On taking him to a local hospital, he was declared “brought dead.” As per the history furnished by the police, he was a known drug addict for many years. External examination revealed multiple, transverse, linear, parallel scars on the back of the left forearm, measuring 4-5 cm in length. Stomach contained partly digested orange-coloured rice and chicken meal, with some blue coloured particles. The contents had an unusual smell, and the gastric mucosa appeared congested. Chemical analysis revealed the presence of dextropropoxyphene in the samples sent. Introduction Spasmo-Proxyvon® is a popular antispasmodic drug from Wockhardt that is increasingly being abused of late.1 This paper highlights three cases of death due to addiction to Spasmo-Proxyvon®. Autopsies were conducted in the Department of Forensic Medicine of Victoria, Bowring & Lady Curzon Hospital, Bengaluru. Case 3 A 45-year-old male was found dead at a bus-stand. History furnished by the police suggested he had been absconding from his home due to drug addiction for the past few years. Some strips of Spasmo-Proxyvon® tablets were found in his trouser pockets. Autopsy revealed bluish discolouration of the stomach mucosa, with un- Dept. of Forensic Medicine & Toxicology, Bangalore Medical College & Research Institute, Bengaluru. * Author for correspondence: [email protected] 48 JOURNAL OF THE INDIAN SOCIETY OF TOXICOLOGY (JIST) usual smell of the contents. Intestinal mucosa showed dark discolouration. Chemical analysis of blood and viscera samples revealed the presence of dextropropoxyphene. In all three cases the cause of death was opined as “respiratory failure as a result of consumption of a substance containing dextropropoxyphene”. Discussion Spasmo-Proxyvon® is one of the most commonly prescribed antispasmodic drugs in India, manufactured by Wockhardt, and contains 2 acetaminophen (i.e., paracetamol 400 mg), dicyclomine hydrochloride (10 mg), propoxyphene napsylate (100 mg), and permitted blue dye in gelatin capsule form. It is a schedule ‘H’ drug, and should not be sold without prescription. But in reality, it is easily available over the counter.3 SpasmoProxyvon® is indicated for the relief of spasmodic pains due to renal colic, abdominal muscle cramps, irritable bowel syndrome, etc. Dextropropoxyphene is a synthetic opioid chemically dissimilar to morphine, but quite similar in analgesic action and adverse effect profile to codeine, except that it is a poor antitussive, and probably less constipating. It is primarily metabolized in the liver.4 It has a half-life of 6 to 12 hours. However, its metabolite, norpropoxyphene (NPP) has a half-life of 30 to 36 hours. After oral ingestion, onset of effects is usually within 1 hour, with peak plasma concentrations achieved within 2-2½ hours. Repeated doses (at intervals of 6 hrs), lead to increasing plasma concentrations, eventually reaching a plateau at/ after the 9th dose (about 48 hrs).5 In parts of Southern India, it was noted that the key ingredient in these preparations has changed from dextropropoxyphene hydrochloride to dextropropoxyphene napsylate. There are some key differences between these formulations: ■ First, the napsylate salt form is water-insoluble. Hence, it cannot be abused by the parenteral route (ie. by injection). ■ Second, approximately 100 mg of dextropropoxyphene napsylate is equivalent to 65 mg of dextropropoxyphene HCl. ■ Third, the onset of action of the napsylate salt is slightly longer (about an hour) than that of the HCl salt. V O L 006 ISSUE 002 JUL-DEC 2 010 Normally the therapeutic concentration for dextropropoxyphene is about 0.4 mg/L, and plasma concentration in serious toxicity is found to be over 1 mg/L5. Convulsions and delirium are the major effects of overdose. Adverse effects on chronic use comprise impairment of mental performance, drowsiness, lethargy, blurred vision, miosis, decreased appetite, inhibition of the cough reflex (antitussive effect), respiratory depression, and constipation.6 Dicyclomine (dicloverine) is a synthetic tertiary amine, which is a muscarinic receptor antagonist. It has a direct, smooth muscle relaxant action, in addition to antispasmodic and antiemetic properties. Atropinic side effects are usually not present at antispasmodic doses. It is commonly used for treating irritable bowel syndrome, motion sickness, morning sickness, rectal urgency, abdominal cramps, dysmenorrhoea, etc.4 Overdose can cause atropinic effects such as dry mouth, dilated pupils, palpitations, psychotic behaviour, delirium, hallucinations, CVS collapse and respiratory depression. It is contraindicated in people with narrow iridocorneal angle and prostatic hypertrophy. The normal therapeutic dose is 10-20 mg orally, three or four times a day.4 Acetaminophen (paracetamol) is a para-aminophenol derivative, and is an analgesic- antipyretic with poor antiinflammatory action. It has a central analgesic action (raising the pain threshold). Plasma half-life is about 2-3 hours, and effective oral dose lasts 3-5 hours. It is one of the most commonly used over-the-counter analgesicantipyretic drugs, used in doses of 0.5-1 gm three times a day. Adverse effects are rare, as the drug is well tolerated, but chronic use can cause analgesic nephropathy. Acute poisoning can cause centrilobular hepatic necrosis, hypoglycaemia, etc. Fulminant hepatic failure and death are likely if the plasma levels are above 200 mcg/ ml at 4 hrs, and 30 mcg/ml at 15 hrs of ingestion.7 The maximum doses for the constituents of SpasmoProxyvon® are as follows: ■ Acetaminophen: 2-4 grams/day ■ Dextropropoxyphene HCl: 390 mg/day ■ Dextropropoxyphene napsylate: 600 mg/day ■ Dicyclomine: No available safety data for doses above 80 mg/day.7 CASE REPORT: FATALITY FROM SPASMO-PROXYVON ADDICTION Spasmo-Proxyvon® costs less than Rs.12 for each strip. Just three tablets dissolved in soda water gives the user the desired euphoria, which lasts for more than three hours. The effect is said to be stronger when it is dissolved in soft drinks. Tolerance develops in the user over a period of time, who ends up using the drug in higher doses than usual, eventually leading to fatality. Sometimes the drug user dissolves the capsule in water and injects it intravenously, not knowing that the napsylate form of propoxyphene is water-insoluble and settles under the veins causing gangrene due to vascular compromise. Each “shot” is made from four to six capsules. Unlike heroin, the effect of each shot lasts three minutes, making an addict take a dozen shots a day. As multiple shots into the same vein is painful, addicts use different veins, causing multiple abscesses in various parts, over a period of time. With the realization of these problems, the government is in the process of implementing more stringent measures to prevent easy accessibility.8 However, it needs to be seen whether these measures will bear fruit, and the incidence of abuse along with associated problems will come down in the future. 49 REFERENCES 1. Ignatius Pereira. Rampant abuse of allopathic drugs. The Hindu, Friday, June 18, 2004. 2. Spasmo-Proxyvon® [cap], Class - Antispasmodics. CIMS Beta India. URL: http://www.cimsasia.com/Page.aspx?menuid = mng&name = SPASMO-PROXYVON + cap&h = spasmo, proxyvon & CTRY = IN & searchstring = spasmo + proxyvon. 3. Ambika Sharma. Schedule H drugs being sold without prescription. The Tribune, Wednesday, January 4, 2006. 4. Tripathi KD. Essentials of Medical Pharmacology. 5th edn, 2003. Jaypee Brothers Medical Publishers, New Delhi. p426. 5. Dart RC. Medical Toxicology. 3rd edn, 2003. Lippincot Williams & Wilkins, Philadelphia. 6. Miller RL. Propoxyphene. In: The Encyclopedia of Addictive Drugs. 2002. Greenwood Press, London. 390-393. 7. Brunton L, Parker K, Blumentel D, Buxton L (editors). Goodman & Gillman’s Manual of Pharmacology and Therapeutics. 11th edn, 2008. McGraw Hill. 445. 8. Neha Dixit. Hacked by the needle. Tehelka Magazine, Vol 5, Issue 14, April 12, 2008.