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47 Case Report Fatality From Spasmo-Proxyvon ® Addiction: A Few Cases Venkata Raghava S, * Vijay Kautilya D, Bheemappa Havanur, Devadass PK Dept. of Forensic Medicine & Toxicology, Bangalore Medical College & Research Institute, Bengaluru. * Author for correspondence :
[email protected] ABSTRACT Ever since the information technology revolution hit In-dia in a big way, substance abuse has been rising in inci-dence by leaps and bounds, mainly because of the easewith which such substances can be procured throughthe Internet. There has been a significant shift from con-ventional drugs of abuse such as cannabis and heroin tonewer drugs such as designer amphetamines, phencycli-dine, and ketamine.But because these drugs are covered by the NarcoticDrugs and Psychotropic Substances Act, there has beena recent trend towards abuse of pharmaceutical agentssuch as pentazocine, propoxyphene and buprenorphine.Spasmo-Proxyvon ® is a popular brand of antispasmodicfrom Wockhardt which contains paracetamol (acetami-nophen), dicyclomine, and dextropropoxyphene. Thiscombined drug formulation sold as gelatin capsules is easilyavailable, and is increasingly being abused for its opioideffect. A few cases of such addiction resulting in deathare being reported. Key Words : Spasmo-Proxyvon ® ; Dextropropoxyphene;Acetaminophen; Paracetamol; Dicyclomine Introduction Spasmo-Proxyvon ® is a popular antispasmodic drug fromWockhardt that is increasingly being abused of late. 1 This paper highlights three cases of death due to addiction toSpasmo-Proxyvon ® . Autopsies were conducted in theDepartment of Forensic Medicine of Victoria, Bowring& Lady Curzon Hospital, Bengaluru. Case 1 A 31-year-old male developed rigor all on a sudden whilein his bathroom, which persisted for 10-15 minutes evenafter coming out of the bathroom, and died thereafter.Autopsy revealed bluish-coloured semi-digested rice par-ticles in the stomach with unusual smell, and congestionof the mucosa. Intestinal mucosa was also congested.Blood and viscera samples were sent for chemical analy-sis to the Forensic Science Laboratory. Testing revealedthe presence of dextropropoxy-phene. Case 2 A 20-year-old male developed sudden anxiety, followed by shivering at his house. On taking him to a local hospi-tal, he was declared “brought dead.” As per the historyfurnished 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 leftforearm, measuring 4-5 cm in length. Stomach contained partly digested orange-coloured rice and chicken meal,with some blue coloured particles. The contents had anunusual smell, and the gastric mucosa appeared con-gested. Chemical analysis revealed the presence of dextropropoxyphene in the samples sent. Case 3 A 45-year-old male was found dead at a bus-stand. His-tory furnished by the police suggested he had been ab-sconding from his home due to drug addiction for the past few years. Some strips of Spasmo-Proxyvon ® tab-lets were found in his trouser pockets. Autopsy revealed bluish discolouration of the stomach mucosa, with un- 48 JOURNAL OF THE INDIAN SOCIETY OF TOXICOLOGY (JIST)VOL 006 ISSUE 002 JUL-DEC 2010 usual smell of the contents. Intestinal mucosa showeddark discolouration. Chemical analysis of blood and vis-cera samples revealed the presence of dextropropoxy- phene.In all three cases the cause of death was opined as “res- piratory failure as a result of consumption of a substancecontaining dextropropoxyphene”. Discussion Spasmo-Proxyvon ® is one of the most commonly pre-scribed antispasmodic drugs in India, manufactured byWockhardt, and contains 2 acetaminophen (i.e., paracetamol 400 mg), dicyclomine hydrochloride (10 mg), propoxyphene napsylate (100 mg), and permitted bluedye in gelatin capsule form. It is a schedule ‘H’ drug,and should not be sold without prescription. But in real-ity, it is easily available over the counter. 3 Spasmo-Proxyvon ® is indicated for the relief of spasmodic painsdue to renal colic, abdominal muscle cramps, irritable bowel syndrome, etc.Dextropropoxyphene is a synthetic opioid chemically dis-similar to morphine, but quite similar in analgesic actionand adverse effect profile to codeine, except that it is a poor antitussive, and probably less constipating. It is pri-marily metabolized in the liver. 4 It has a half-life of 6 to12 hours. However, its metabolite, norpropoxyphene(NPP) has a half-life of 30 to 36 hours. After oral in-gestion, 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 in-gredient in these preparations has changed fromdextropropoxyphene hydrochloride to dextropropoxy- phene napsylate . There are some key differences be-tween these formulations: ■ First, the napsylate salt form is water-insoluble. Hence,it cannot be abused by the parenteral route (ie. byinjection). ■ Second, approximately 100 mg of dextropropoxyphenenapsylate is equivalent to 65 mg of dextropropoxy- phene HCl. ■ Third, the onset of action of the napsylate salt is slightlylonger (about an hour) than that of the HCl salt. Normally the therapeutic concentration for dextropro- poxyphene is about 0.4 mg/L, and plasma concentrationin serious toxicity is found to be over 1 mg/L 5 . Convul-sions 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 consti- pation. 6 Dicyclomine (dicloverine) is a synthetic tertiary amine,which is a muscarinic receptor antagonist. It has a di-rect, smooth muscle relaxant action, in addition to antis- pasmodic and antiemetic properties. Atropinic side ef-fects are usually not present at antispasmodic doses. Itis commonly used for treating irritable bowel syndrome,motion sickness, morning sickness, rectal urgency, ab-dominal cramps, dysmenorrhoea, etc. 4 Overdose cancause atropinic effects such as dry mouth, dilated pupils, palpitations, psychotic behaviour, delirium, hallucinations,CVS collapse and respiratory depression. It is contrain-dicated in people with narrow iridocorneal angle and pro-static hypertrophy. The normal therapeutic dose is 10-20mg orally, three or four times a day. 4 Acetaminophen (paracetamol) is a para-aminophenolderivative, and is an analgesic- antipyretic with poor anti-inflammatory action. It has a central analgesic action(raising the pain threshold). Plasma half-life is about 2-3hours, and effective oral dose lasts 3-5 hours. It is one of the most commonly used over-the-counter analgesic-antipyretic drugs, used in doses of 0.5-1 gm three timesa day. Adverse effects are rare, as the drug is well toler-ated, but chronic use can cause analgesic nephropathy.Acute poisoning can cause centrilobular hepatic necro-sis, hypoglycaemia, etc. Fulminant hepatic failure anddeath 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 Spasmo-Proxyvon ® 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 above80 mg/day. 7 49 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 threehours. The effect is said to be stronger when it is dis-solved 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. Some-times the drug user dissolves the capsule in water andinjects it intravenously, not knowing that the napsylateform of propoxyphene is water-insoluble and settles un-der the veins causing gangrene due to vascular compro-mise. Each “shot” is made from four to six capsules.Unlike heroin, the effect of each shot lasts three min-utes, making an addict take a dozen shots a day. As mul-tiple shots into the same vein is painful, addicts use dif-ferent veins, causing multiple abscesses in various parts,over a period of time.With the realization of these problems, the governmentis in the process of implementing more stringent mea-sures to prevent easy accessibility. 8 However, it needsto be seen whether these measures will bear fruit, andthe incidence of abuse along with associated problemswill come down in the future. REFERENCES 1.Ignatius Pereira. Rampant abuse of allopathic drugs. The Hindu,Friday, June 18, 2004.2.Spasmo-Proxyvon ® [cap], Class - Antispasmodics. CIMS BetaIndia. 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 prescrip-tion. The Tribune, Wednesday, January 4, 2006.4.Tripathi KD. Essentials of Medical Pharmacology. 5 th edn, 2003.Jaypee Brothers Medical Publishers, New Delhi. p426.5.Dart RC. Medical Toxicology. 3 rd edn, 2003. Lippincot Williams& Wilkins, Philadelphia.6.Miller RL. Propoxyphene. In: The Encyclopedia of AddictiveDrugs. 2002. Greenwood Press, London. 390-393.7.Brunton L, Parker K, Blumentel D, Buxton L (editors). Goodman& Gillman’s Manual of Pharmacology and Therapeutics. 11 th edn, 2008. McGraw Hill. 445.8.Neha Dixit. Hacked by the needle. Tehelka Magazine, Vol 5,Issue 14, April 12, 2008. CASE REPORT: FATALITY FROM SPASMO-PROXYVON ADDICTION
