Clinical Toxicology PDF

Uruk University 5th Stage College of Pharmacy First Course Clinical Toxicology Dr. Reem Ghanim Hussein Lecturer at College of Pharmacy Uruk University...

Uruk University 5th Stage College of Pharmacy First Course Clinical Toxicology Dr. Reem Ghanim Hussein Lecturer at College of Pharmacy Uruk University 2024 - 2025 Central nervous system stimulants Amphetamine and Amphetamine like drugs Numerous derivatives of amphetamine have been used over the years to modify a variety of medical conditions. Today, they are approved in the management of narcolepsy, hyperkinesia (hyperactivity) in children and short-term treatment of obesity.  Mechanism of toxicity Amphetamine induces CNS stimulation mainly by : 1. Causing the release of catecholamines (epinephrine, norepinephrine, and dopamine) into central synaptic spaces 2. Inhibiting their reuptake into nerve endings. One problem frequently encountered by amphetamine users is tolerance to some of the central effects, such as anorexia and euphoric actions, therefore, users may need to increase the dose. If use is continued in these individuals, the convulsive threshold may actually be lowered, and fatalities become a greater problem.  Characteristic of poisoning Amphetamine causes a variety of dose related signs and symptoms. Most toxic effects are extension of pharmacological actions:- 1. C.N.S.:- Amphetamine-induced psychosis with euphoria and hallucinations is common. Hallucinations either auditory (with chronic used ) visual (after a single large dose). Tactile hallucinations are experienced occasionally. 2. Respiratory functions are stimulated. 3. Cardiovascular functions are stimulated. 4.Sympathomimetic effects include tachycardia, hypertension, flushing, and diaphoresis. 5. Hyperpyrexia may be significant, with temperatures above 109 oF (42.8 C) reported. Temperatures this high are incompatible with life and are a contributing cause of death.  Management 1. Phenothiazines have been recommended for the treatment of amphetamine-induced psychosis, which is due to excess dopamine. 2. Chlorpromazine has also been shown to reverse hyperthermia, convulsions, and hypertension associated with amphetamine toxicity without causing depression. 3. Salicylates and a hypothermic blanket or placing the patient in a cool, quiet room may be helpful in temperature reduction. Methylxanthine derivatives Three methylxanthine alkaloids are commonly encountered from natural resources: 1. Theobromine (( found in Cocoa and chocolate )) 2. Theophylline (( some of it found in Tea )) 3. Caffeine (( found in Tea and Coffee and many cola-flavored drinks are rich sources of caffeine and some of it found in Cocoa and chocolate )). In addition to their presence in foods and drinks, theophylline and caffeine are used in drug therapy.  Methylxanthines in general stimulate the CNS, induce: 1. Diuresis 2. Relax smooth muscle (notably bronchial muscles, and stimulate cardiac functions) Caffeine also augments the analgesic properties of salicylates and is contained in numerous analgesic products. Theobromine possess similar, but weaker pharmacological activity on CNS. Mechanism of Toxicity 1. Increased calcium release from intracellular sites. 2. Accumulation of cyclic nucleotides, especially cyclic AMP (cAMP)by phosphodiesterase inhibitors ((cAMP is an very important second messenger playing fundamental roles in cellular responses to many hormones and neurotransmitters)) 3. Adenosine receptor blockade (((results in increased release of norepinephrine, dopamine and serotonin and will effect on different site in the body)) Pharmacological mechanism of action  Characteristics of poisoning Theophylline has a narrow therapeutic margin, 10 to 20 μg/mL. Maintaining therapeutic blood concentration can be difficult because numerous factors as well as other drugs can stimulate or depress theophylline clearance, Rapid intravenous administration of theophylline or aminophylline (theophylline ethylene diamine) can result in death due to cardiac arrhythmias. Other manifestations of overdose include nausea and vomiting, headache, dizziness, palpitations, and tachycardia, hypotension, and precordial pain. Also, patients have reported severe restlessness and agitation. Focal and generalized seizures may appear occasionally.  Management 1. Diazepam is often recommended as first-line therapy to Theophylline-induced seizure which are difficult to manage, but it often fails to control the problem. Still diazepam should be given first. If fails to control seizures, phenobarbitone should be administered. 2. Propranolol or verapamil can usually control the Arrhythmia. These block the SA and AV nodes, and also restore coronary blood flow by reversing theophylline induced hypotension. Camphor Camphor-containing products are not generally considered by the laypeople to be toxic. Indeed, camphor has long been used externally as a rubefacient, mild analgesic, antipruritic, and counterirritant. Camphorated oil has been the largest single cause of camphor- related poisonings. Most poisonings have occurred because victims mistook it for castor oil, or other remedies that either sounded like or looked like camphorated oil, and ingested an unsuspected toxic dose.  Characteristics of poisoning Signs and symptoms of camphor poisoning may appear within 5 to 15 min after ingestion, or be delayed for several hours on a full stomach. Because it is highly lipid soluble, camphor enters the CNS quickly. Management 1. Camphor must be removed from the stomach as quickly as possible. A. Immediate emesis or gastric lavage is indicated (before convulsions and generalized stimulation occur). B. Activated charcoal should follow. C. Lavage should be continued until the odor of camphor is no longer detected. D. It has been suggested that whenever the quantity ingested is unknown, it should be assumed the amount was greater than 1 g and the patient should be vigorously treated. 2. Barbiturates have long been used to control convulsions, but diazepam is generally preferred because it produces less respiratory depression. 3. Hemodialysis will accelerate removal of camphor from the blood. 4. Succinylcholine may be used to help control muscular rigidity and spasm. 5. As with any other CNS stimulant the patient must be kept quiet and at minimum sensory input. Thank you