Pcp lsd .pptx

Clinical Toxicology Drugs abuse… Hallucinogenic agents : PCP &LSD  CNS Stimulant: Amphetamines & Strychnine Lec=3 Phencyclidine (PCP, 1-phenylcyclohexyl Piperidine) was developed in the late 1950s, and marketed as Sernyl. Early animal studies reported the drug to have strong analgesic activi...

Clinical Toxicology Drugs abuse… Hallucinogenic agents : PCP &LSD  CNS Stimulant: Amphetamines & Strychnine Lec=3 Phencyclidine (PCP, 1-phenylcyclohexyl Piperidine) was developed in the late 1950s, and marketed as Sernyl. Early animal studies reported the drug to have strong analgesic activity with sympathomimetic and CNS stimulant and depressant action. It is chemically related to the dissociative anesthetic ketamine, but is much more toxic. Since in some cases the drug produced postanesthetic confusion and delirium of prolonged duration. A significant proportion of patients showed severe adverse reactions during emergence, including agitation and hallucinations Some suffered from psychosis for up to 10 days PCP was therefore quickly withdrawn. It is commonly sold on the street as tablets (about 5 mg), capsules, powder, aqueous or alcoholic solution, or as “rock salt” crystal. It is often mixed with parsley, mint, oregano or marijuana. Sometimes “crack” is dipped in PCP and smoked (“tragic magic”), or cannabis is dipped in PCP (“love boat”). It appears under a variety of exotic names including Angel Dust, Dust and Crystal Joints Toxicokinetics PCP is well absorbed following all routes of administration. Maximum plasma PCP concentrations are observed 5 to 15 min after smoking. It is a lipophilic weak base and its volume of distribution is high . Since it is highly lipid soluble, it accumulates in brain and adipose tissue. Metabolism of the latter causes release of PCP which contributes to the recurrence of symptoms. PCP can be detected in urine up to 20 to 30 days (usually 2 weeks). Blood concentrations of PCP as low as 10 ng/mL may be associated with behavioral effects listed in Table 17.4. Concentrations greater than 100 ng/mL are usually associated with coma, which may result in death due to secondary complications such as seizure and respiratory depression. Doses of PCP resulting in blood concentrations of 200 to 250 ng/mL and greater are probably uniformly fatal.  Usual fatal dose approximately 100 mg or more. Neurologic signs of PCP at low doses or after chronic administration of doses that provide blood concentrations up to 100 ng/mL include: horizontal and vertical nystagmus, variable pupil size with depressed light reflex, and occasional blurred or double vision. Additionally, ataxia, tremors, slurred speech, muscle weakness, drowsiness, and increased respiratory rate and depth are observed . Sudden and dramatic mood changes are also seen along with delusion disoriented thought process, and sometimes visual  hallucinations. The chronic PCP user generally requires 24 to 48 hr to return completely to normal Phencyclidine Toxicity  PCP toxicity is manifested by a stuporous, comatose state in which the patient is responsive only to deep pain. Important diagnostic features of intoxication include the presence of vertical and horizontal nystagmus, which are associated with hypertension in a comatose also muscular rigidity . Massive oral overdoses of up to 1 g street grade PCP have resulted in periods of stupor and coma of several hours to 5 days in duration. Delayed and prolonged respirations and apnea may follow. Intoxication is also marked by sustained hypertension and tachycardia, and general motor seizures preceded by muscle tremors and rigidity PCP-induced psychosis described as aggressive, and/or disorganized behavior with or without paranoia lasting from less than 4 hr to as long as several days Restless and combative behavior and thought patterns are usually complete in one week, but severe cases may require 12 to 18 months to return to pre drug status. Death due to secondary complications such as seizure and respiratory depression. Management of Acute Poisoning  PCP is a common cause of psychotic, drug related emergency room admissions Since there is no specific antidote, treatment of acute PCP intoxication is focused on supportive and symptomatic care. Complete recovery may require several weeks or longer.  There has been some success with placing the agitated, psychotic individual in an attended, quiet, and darkened room, Diazepam has been used successfully to treat hyperactivity and agitation of the intoxicated patient.  Phenothiazines (e.g., chlorpromazine) and butyrophenones (haloperidol) are not recommended for initial treatment of PCP intoxication because they lower the seizure threshold, hyperthermia and may produce severe hypotension . However, they have been recommended to treat persistent phencyclidine induced psychosis. severe hypertensive crisis treated with a rapidly acting vasodilator, such as diazoxide or nitroprusside. Renal damage is sometimes a complication of PCP because of profound involuntary muscular activity, which can lead to diffuse muscle injury and myoglobinuria. To reduce the possibility of acute renal failure, diuretics, such as furosemide, have been used. Physical restraints should be used only when necessary to keep muscle injury minimized and, hence, help prevent onset of renal damage PCP ,It is extremely lipid soluble, and a weak base with a pKa between 8.6 and 9.4. The drug also undergoes enterohepatic circulation.  As a result, when PCP enters the acidic environment of the stomach, it becomes trapped in ionized form, which may be efficiently removed by gastric suction and adding 30 to 40 g of activated charcoal every 6 to 8 hr .  In severe PCP intoxication, urine acidification to a pH between 5.0 and 5.5 with ammonium chloride will greatly enhance elimination of this basic drug. Once urinary pH is approximately 5, furosemide can be given to promote diuresis.  Haemodialysis and haemoperfusion are not beneficial. Lysergic Acid Diethylamide (LSD) Lysergic acid diethylamide (LSD) does not occur naturally but is a semisynthetic preparation ergot alkaloids .LSD produces opposing actions of powerful central stimulation with slight depression. Although it has no legitimate medical use today, the colorless, odorless, and tasteless compound is the most powerful hallucingenic agent known, whose experimental value has proven it to be a model for psychosis. The substance is available “on the street” in liquid, powder, and microdot dosage forms.  The average dose is 100 mg, but doses as high as 1,500 mg have been reported with no major complications. There have been reports of chronic users ingesting amounts as high as 10,000 mg without suffering serious complications. The reason for an abuser of LSD to use such a high dose may be due to tachyphylaxis, or rapid production of tolerance, which occurs with repeated administration. A significant increase in dose may be necessary in 3 to 4 days after continued use. An interesting element in LSD abuse is that recovery from tolerance occurs just as rapidly. LSD produced mood changes range from euphoria to dysphoria. The user may feel euphoric, displaying hilarious laughter at times, with the mood swiftly changing to sadness and crying episodes LSD acutely affects sensory perception. Although it acts on the auditory, tactile, olfactory, senses, the most marked effects are on visual perception. Colors of objects become more intense. Flat surfaces assume depth. Fixed objects begin to undulate and flow. Since there is alteration in time perception, these visual changes seem to continue forever. .  LSD also causes disruption of ego function and the fear of selfdestruction. Body parts may feel unnatural or foreign.  LSD affects both sympathetic and parasympathetic nervous systems, but sympathetic activities predominate. Therefore, as a sympathomimetic agent, some of the characteristics of LSD include marked mydriasis, hyperthermia, tachycardia, and hypertension. piloerection, hyperglycemia, LSD toxicity When hallucinogens, such as LSD, are taken in a so-called "therapeutic” dose, a temporary psychotic state or trip results. Usually an experienced user is knowledgeable about adjusting the amount of drug needed to obtain this desired experience On occasion, hallucinogens produce bad trips or adverse reactions . This has been attributed to first-time users’ lack of experience in relating observed effects as pleasurable ,or contamination during synthesis . Adverse effects fall into three categories:  Panic reactions The person can no longer think rationally and feels he will not be able to come to with himself. It is important during these episodes that the individual be reminded that what he is experiencing is drug induced, and that the bad trip will not last forever.  One of the more widely publicized chronic reactions to LSD use is the Flashback. They are characterized as recurrence of the LSD experience in the absence of ingestion ,they occur more frequently in users who have previously experienced bad trips and constantly abuse this drug, but flashbacks have also been reported after a single LSD exposure o Flashbacks can be brief or last several hours. One study showed that flashbacks occur more frequently just before going to sleep and while under severe stress . Three categories of flashbacks have been described;  Perceptual—seeing vivid colors, hearing sounds from previous trips.  Somatic— paresthesia, tachycardia.  Emotional— feelings of loneliness, panic, and depression. The most serious are the emotional flashbacks, because persistent feelings of fear, loneliness, and other emotions can lead to suicid  Another danger that has the hallucinogen abuser is occurrence of Prolonged Psychosis states of paranoia and schizophrenia have been reported, even after the general state of intoxication subsided Management of Acute Overdose  In general, the victim who experiences adverse effects to hallucinogens should be placed in a quiet environment to minimize external stimuli that could aggravate the psychotic state.    Rapid lowering of blood pressure to normal can be achieved with a vasodilator. Convulsions and anxiety are usually managed successfully with diazepam. Bad trips, panic reactions, and psychotic episodes generally respond well to treatment with anti-anxiety agents,and haloperidol. After recovery, psychiatric consultation is mandated.. CNS Stimulants  Amphetamine-like Drugs  Methylxanthine Derivatives  Strychnine  Cocaine  Camphor, Traditionally, drugs, such as amphetamine and strychnine, produce strong convulsant activity. However, other drugs may act as moderate CNS stimulants . Amphetamine and Amphetamine-like Drugs Numerous derivatives of amphetamine have been used over the years to modify a variety of medical conditions, legitimate or otherwise. Today, approved uses include management of narcolepsy, hyperkinesis (hyperactivity) in children, and short-term treatment of obesity. Drugs with amphetamine like activity Amphetamine ,Benzphelamine ,Chloiphentermine ,Dextroamphetamine Diethylpropion ,Methamphetamine ,Phendimetrazine tartrate Phenmetrazine,Phentermine ,Phenylproparralamine Mechanism of Toxicity Amphetamine induces CNS stimulation, mainly by causing release of catecholamines (epinephrine, norepinephrine, dopamine) into central synaptic spaces and inhibiting their reuptake into nerve endings, endogenous neurotransmitters remain present within the synapses in higher concentration and for longer than normal time. All neurons that normally respond to stimulation are affected. One problem frequently encountered by amphetamine users is tolerance to some of the central effects, such as the anorexiant and euphoric actions. Therefore, users may need to increase the dose, sometimes approaching several hundred milligrams daily. Tolerance does not occur to all central actions, however. Toxic psychosis may appear after months of continued use. If use is continued in these individuals, the convulsive threshold may actually be lowered, and fatalities become a greater problem. Characteristics of Poisoning Amphetamine causes a variety of dose related signs and symptoms. Most toxic effects are extensions of pharmacologic actions. stimulation and require immediate attention. • Amphetamine-induced psychosis with euphoria and hallucinations is common. Hallucinations are generally perceived as unpleasant. be auditory in nature (mostly in patients using amphetamines chronically), or visual (more common after a single large dose). • Respiratory and Sympathomimetic cardiovascular effects include functions are tachypnea, stimulated. tachycardia, hypertension, flushing, and diaphoresis. This leads eventually to depression of both systems once the neurotransmitter has been depleted. • Hyperpyrexia may be significant believed to be caused by druginduced peripheral vasoconstriction, but whether fatal hyperpyrexia is produced centrally or peripherally is not known. Hyperpyrexia common cause of death . The acute lethal dose in adults has been reported at 20 to 25 mg/kg, and in children, 5 mg/kg as 1 + and 2+ may be experienced even with therapeutic doses and are generally not causes of great concern. Conditions listed as 3-f and 4-t- reflect severe CNS stimulation and require immediate attention  Phenothiazines have amphetamine-induced been which recommended is due to for treatment excess of dopamine. Chlorpromazine has also been shown to reverse hyperthermia, convulsions, and hypertension associated with amphetamine toxicity without causing depression. The dose is repeated every 30 min as needed.  Haloperidol has been advocated also since it produces less respiratory depression and reduced chance for sustained hypotension and reflex tachycardia. Both drugs are direct antagonists to amphetamine.  Barbiturates antagonize amphetamine, but only when given in anesthetic doses. Diazepam is preferred. Convulsions are usually associated with increased body temperature. Management of hyperthermia may include use of a hypothermic blanket or placing the patient in a cool, quiet room. Salicylates may be helpful in temperature reduction.  Once the patient has been stabilized, gastric decontamination should be considered. Recall that emetics are contraindicated in patients experiencing seizures.  A suggested management protocol for ingestion of a large amount of amphetamine that occurred within 4 hr includes emesis with syrup of ipecac. Gastric lavage is recommended when emesis is contraindicated. After 4 hr, activated charcoal is preferred over emesis.  Renal clearance of amphetamine is enhanced by acidification of urine with ammonium chloride.  Additional Measures General measures of supportive and symptomatic care must be stressed. The victims should be placed in a quiet environment, away from sensory stimulation, as this may precipitate further convulsions. In severe toxicity, aggressive care to manage hypertension, tachycardia, seizures, and hyperthermia are given high priority. Management of acute CNS stimulants poisoning Strychnine Strychnine is an indole alkaloid obtained from the dried seeds of Nux vomica ,from the plant, Strychnos nux-vomica. Strychnine, in doses of 0.5 to 1.0 mg, was formerly used in a variety of medications intended for internal stimulant use. Today, its legitimate use is mainly confined to pesticide products that are intended to control rodents. Fatal poisoning in adults, especially from the ingestion of tonic tablets, results from ingesting 30 to 100 mg and, in children, from accidental ingestion of rodenticide (15-mg can be a lethal dose). Mechanism of Toxicity Strychnine inhibits the postsynaptic receptor for glycine, an inhibitory neurotransmitter, allowing for the development of spinal convulsions of the tonic type (characterized as extensor thrusts). Strychnine exerts its toxic abilities by blocking postsynaptic conduction in the inhibitory spinal Renshaw motor neurons, where it interferes with ascending and descending motor tracts, resulting in convulsions of spinal cord origin. Characteristics of Poisoning Early stages are characterized by a grimacing stiffness of the neck and face, followed by increased reflex excitability that is precipitated by sensory stimulation. Tonic convulsions (traditionally demonstrated as arched back or opisthotonus) are followed by coordinated extensor thrusts. Convulsions occur as full contractions of all voluntary muscles, including thoracic, abdominal, and diaphragmatic, which ultimately suppress respiration. Convulsive episodes are continuous or intermittent, with depression and sleep interspersed, depending on the depth of toxicity, and the patient is generally conscious and in pain. After several full convulsions medullary paralysis due to hypoxia is the cause of death. Stiffness of facial and neck muscles Hypereactive reflexes Lactic acidosis Opisthotonos Tetanic convulsions Respiratory paralysis Asphyxia Death Treatment must be instituted swiftly and is aimed at preventing convulsions, maintaining ventilation, and administration of an anticonvulsant/skeletal muscle relaxant, such as diazepam. Successful treatment with diazepam (10 mg i.v., repeated as needed) Gastric lavage is only indicated when the compound is suspected to be in the stomach contents and if convulsions have subsided.