OPIOIDS AND DERIVATIVES HISTORY and CLASSIFICATION • Opium -17th century --------heroin/morphine • Classification – Snorting – Skin popping

– Mainlining Opioids - as a class it exert their pharmacological effects at opioid receptor. Opiates – alkaloid extracts of the opium poppy. Opium – the parent crude from naturally occuring compounds, derived from the milky exudates of the unripe capsule of papaver somniferum. MEDICINAL CHEMISTRY • Opioids are composed of six-membered saturated heterocyclic rings forming the phenantrene nucleus to which is attached a piperidine ring.Derivatives majority have isoquinoline ring. • Esterification of the phenolic functions, such as in the formation of diacetylmorphine results in compound with increased lipid solubility and increased potency and toxicity. • MECHANISM OF TOXICITY • The mechanism of opiate toxicity is an extension of its pharmacology and is directly related to interaction with stereospecific and saturable binding sites or receptors in the CNS and other tissues. • Three receptor classes: – mu-receptor – Kappa-receptor – Delta-receptor – TOXICOKINETICS • Morphine is rapidly absorbed from an oral dose, i.m. and sc injection.Thus, morphine levels rise slowly, persist longer and decline slowly. • Heroin rapidly biotransformed. • Codeine is extensively metabolized. • SIGN AND SYMPTOMSHypothermia • Mioisis • CNS depression • Respiratory depression • Frothy,noncardiogenic,pulmonary edema • Loss of consciousness • Hypoventilation • Bradycardia • Hypotension • Decreased GI motility • Increased ADH secretion • CLINICAL MANAGEMENT OF ACUTE OVERDOSE • Maintenance of vital functions, including respiratory and cardiovascular integrity is of paramount importance in the clinical management of acute opioid toxicity. • Gastric lavage and induction of emesis • Opioid antagonist – Naloxone – available as an inj. Only.a 2mg bolus rep every 5 min followed by 0.4 mg every 2-3 minutes prn.up to 24mg total – Naltrexone – available as oral tab only at 50mg dose. It is also indicated for alcohol dependence. It will induce hepatocellular injury if given in excess.

Nalmefene – available in 100 mcg/ml and 1mg/ml ampule. Indicated for partial or complete reversal of natural or synthetic opioid effects. Some antagonist of kappa,mu receptor • Nalbuphine • Butorphanol - Pentazocine

TOLERANCE and WITHRAWAL • Addiction – involves compulsive psychoactive drug use with an overwhelming involvement in the securing and using of such drug. • Compulsive drug use – involves the psychological need to procure and use drugs,often referred as “craving”. • Habituation – refers to psychological dependence. • Physical dependence – involves the need for repeated administration in order to prevent withrawal syndrome. • SPECIFIC OPIOID DERIVATIVES • Codeine ( methylmorphine ) – In combination with other ingredients as an analgesic and antitussive in prescription for cough,cold, antihistaminic and expectorant. – About 120mg codeine is equivalent to 10mg morphine. Diphenoxylate – a synthetic opiate related to mepiridine, is combined with atropine ( Lomotil ) for diarrhea. The toxicity of this combination is due to the presence of anticholinergic.The narcotic toxicity demonstrates as miosis, respiratory depression, severe cases is coma. • • Fentanyl – marketed in the form of medicated patches for management of pain, the transdermal system can release up to 200mcg/hr. Meperidine – first synthetic opioid, equianalgesic with Morphine. – Chronic oral ingestion of tablets is associated with CNS stimulation resulting in tremors, muscle twitching, nystagmus,convulsion. – Naloxone for chronic meperidine use Pentazocine – Derivative of morphine with 3-4 times potency and same addictive potential. – Continued injection resulted in serious pulmonary artery occlusion, pulmonary hypertension,neurologic complication Tramadol – centrally acting synthetic analog of codeine. In overdose, the effects are similar to those of other opioids with convulsions. Clonidine – shares some pharmacological properties and clinical features with opioids. Overdose occurs within 60-90 min after ingestion producing bradycardia,hypotension, arrhythmias, CNS depression, decreased respiration and miosis.

METHODS OF DETECTION • EMIT – enzyme-linked immunoassay technique • RIA - radioimmunoassays

smokers. Short-acting beta-blocker ( esmolol ) useful in management of myocardial tachyarrhythmias Short-acting benzodiazepines (midazolam) Controlled the seizure in patient with an ingestion of 1g or more of caffeine. Substitutions on the aromatic ring and the side chain yield a variety of compounds whose pharmacological and toxicological profiles. Treatment for ADHD and short-term depression. OCCURRENCE • Brewed coffee boast the highest amounts of caffeine ( up to 100mg ). TOLERANCE AND WITHRAWAL • Caffeine withrawal is associated with chronic use and is demonstrated abruptly within 12-24 hours after the last dose. There is demonstrated tolerance to the diuretic action and the insomnia produced with Theophylline. reaching peak distribution within 2 hours. but no tolerance develops to the CNS stimulation or bronchodilation. . speed. • Symptoms: headache.hyperphagia.lassitude.Metabolic variability among different age group. TOLERANCE AND WITHRAWAL • Chronic use of amphetamine leads to psychological dependence. dexies.Deep depression follows interruption of chronic use. • Instant and decaffeinated coffees contain less ( up to 75 and 5mg ) • Cola beverage possesses dose of stimulant ( 55mg ) • Cup of hot cocoa a dose of 200mg theobromine TOXICOKINETICS • Xanthines are well absorbed orally.SYMPATHOMIMETICS • AMPHETAMINES AND AMPHETAMINE-LIKE AGENTS Amphetamine – use in weight reduction and control of obesity. TOXICOKINETICS • Amphetamine compounds are weak bases that are well absorbed orally. 4-5 hours in adult smokers SIGN AND SYMPTOMS AND CLINICAL MANAGEMENT OF CAFFEINE TOXICITY • Adverse effects of excessive caffeine intake ( LD is 510 g ) ( above 10mg/kg ) – CNS stimulation – Insomnia – Restlessness – Sensory disturbance – Delirium – Increased skeletal muscle tension – Tachycardia – PVC’s – Diarrhea – Peptic ulcer – GI bleeding • • • • Caffeine can neutralize the desired therapeutic effects of diuretics.fatigue.anxiety.drug craving behavior. METHODS OF DETECTION • Urine drug screening tests • TLC • RIA • HPLC • EMIT XANTHINE DERIVATIVES • SOURCE AND MEDICINAL CHEMISTRY – The compounds contain the purine nucleus.Characterized by prolonged sleep. The drug eliminated by the kidney with a half-life of 3-15 hours in nonsmokers.beta-blockers and sedative-hypnotics. predominantly throughout the length of the basic environment of the small intestine. and their relative potencies.craving behavior that will last for about one week. consisting of a benzene ring and ethylamine side chain. – Caffeine and Theophylline from the tea leaves of Thea sinensis and Theobroma cacao. MEDICINAL CHEMISTRY • Beta-phenethylamine parent structure of the sympathomimetic amines.The stimulant/euphoric effects improved their popularity and gave rise to common street names : ups. bennies. • Tolerance to the anorexic effect as well as to the improvement of mood. • Withrawal syndrome depends on the extent of habituation but varies between several hours to several days after discontinuation of the drug. antihypertensive agents. – Caffeine most active component of coffee and coffee beans of Coffea arabica also found in Cola accuminata and Cola nitida (nuts). and individuals with pathologic complications is probably due to variable levels of CYP450 and N-acetyltransferase systems.

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