Plant Poisons: Digitalis, Cannabis, and LSD PDF

 Digitalis The cardiac glycosides, of which digitalis is the most commonly known, have intensive history in pharmacotherapy.  Source: Cardiac glycosides are the active principles in many plants: - Digitalis purpurea. (Purple foxglove). - Digitalis Lanata. (White foxglove). – - Medite...

 Digitalis The cardiac glycosides, of which digitalis is the most commonly known, have intensive history in pharmacotherapy.  Source: Cardiac glycosides are the active principles in many plants: - Digitalis purpurea. (Purple foxglove). - Digitalis Lanata. (White foxglove). – - Mediterranean sea onion (sea squil1). - Oleander.  Digitalis  Active principle: Digoxin, Digitoxin, Digitalin and Digitonin. - Digoxin is the most commonly prescribed digitalis preparations. - Digoxin uses include congestive heart failure and atrial arrhythmias. It is available as 0.125 and 0.25 mg tablets. Digitalis  Condition of poisoning:  Accidental: Therapeutic overdose. Children.  Suicidal.  Digitalis  Mechanism of action: I- Therapeutic dose: a- Elongate diastolic period, so improve filling of heart i.e. – ve chronotropic(↓HR.). b- Enforce systolic power - improve contraction. i.e. + ve Inotropic ( ↑ CO). c- Increase renal blood flow. II- Toxic dose: a- Cardiac poison. b- GIT affection. c- Visual Manifestations. d- CNS Manifestations.  Digitalis  Pathophysiology: 1- Stimulates vagus [Bradycardia] 2- Inhibits Na+ - K+ ATPase lead to:  Increase intracellular sodium.  Increase intracellular calcium.  Increase extracellular potassium “hyperkalemia” (in acute toxicity only while in chronic toxicity, the serum K level is usually normal or low owing to concurrent diuretic therapy).  Digitalis  Clinical presentation: A- Cardiac: Arrhythmias- [The most frequent manifestations] Tachyarrhythmias Brady arrhythmias Atrial: 1- Tachycardia 2- Flutter 1- Sinus bradycardia 3- Fibrillation. 2- A- V block Ventricular: 3- Sinus arrest. 1- Extra systoles. 2- Tachycardia. 3- Fibrillation.  Digitalis  Clinical presentation: B- GIT: [The earliest manifestation]. Anorexia, nausea, vomiting, colic and diarrhea. C- Visual: Green yellow vision [rods & Cones affection]. D- CN.S: Headache, delirium, disorientation & drowsiness. Digitalis  Cause of death: Arrhythmias and cardiac arrest.  Digitalis  Investigations: a- E.CG and continuous cardiac monitor, look for bradycardia, heart block, atrial and ventricular arrhythmias. b- Electrolytes levels: Hyperkalemia in acute toxicity and it is a primary predictor of need for antidotal therapy. Hypokalemia in chronic toxicity and it exacerbates toxicity as well. Hypercalcemia and hypomagnesemia exacerbate toxicity as well. c- Kidney function tests (renal impairment alters elimination of glycosides). d- Digoxin level Therapeutic blood level is 2ng/ml. Concentrations exceeding l5ng/ml carry serious prognosis.  Digitalis  Treatment: I- Prevention from further exposure. II- Supportive measures. III- GIT decontamination. IV- Physiological antidote.  Digitalis  Treatment: II- Supportive measures: ABC with special emphasis on supporting respiratory and cardiac functions. Treat the arrhythmias. A- Treat electrolytes disturbance: i. ↑K (Acute toxicity — insulin in 5%glucose to avoid hypoglycemia). ii. ↓K (chronic toxicity): -__KC1. iii. ↑Ca __Non Ca EDTA. B- Anti arrhythmic drugs: 1- Phenytion(250mg slow IV followed by l00mg/8hr.) 2- Lidocaine(1mg/kg loading dose followed by maintenance infusion) treat :- Atrial arrhythmias. Ventricular arrhythmias. 3- Atropine (0.5-1mg IV) treat:- Heart block. Bradycardia.  Digitalis  Treatment: III. G. I T decontamination: 1- Gastric lavage especially if vomiting is ineffective. 2- Local antidote:  Charcoal. (Multiple doses).  Cholestyramine [interrupt the enterohepatic circulation].  Digitalis  Treatment: IV- Physiological antidote: Digibind [Fab] (Digoxin- specific antibody fragments) Dose: based on total body load of digoxin. Many equations have been postulated to calculate the dose. Indication 1- Serum digoxin level above 10ng/ml in adults and >5 ng/ml in children or ingestion of > 10 mg in adults and > 4mg in children. 2- Severe cardiac arrhythmias. 3- Severe hyperkalemia (>5-5.5 mEq/L). 4- Heart block even 1st degree. Action: Reverses tissue binding (binds to digoxin and to a lesser extent, digitoxin and other cardiac glycosides and the inactive complex that is formed is rapidly excreted in urine).  Digitalis  Treatment: IV- Physiological antidote: Digoxin: Body Load (mg) = (SDC ng/ml)(5.6)(wt in kg) 1000 Each vial of antidote contains 40 mg, this will bind 0.6 mg digoxin Cannabis Sativa Cannabis is a psychoactive (psychedelic, psychotomimetics, hallocinogen) drug that has been used since ancient times for both medicinal and recreational effects. It is the most widely used illicit drug in the world. Source: - Cannabis sativa. - Cannabis indica. Cannabis Sativa  It is found in forms of: Hashish: dried resin from the flower tops. Hashish oil: dark viscous liquid or concentrate of cannabinoids obtained by solvent extraction of the crude plant material or of the resin. Bango: from dried leaves. Marijuana: Mixure of [Crushed leaves, flower, and stem] Sinsemilla: (‘without seeds’) mixture of flowering tops and leaves of cultivated, unfertilized female plants. THC 8 – 11% Cannabis Sativa  Active principle: The primary psychoactive one is delta -9- T.H.C [delta -9-Tetra hydro cannabinol], canabinol, canabidiol Cannabis Sativa  Route of administration: Smoked: in cigarettes or shisha. Ingested: alone or with coffee or tea. Inhaled: burnt in closed place (glass, cup,..) Tablets :( marinol-dronabinol’THC’) for therapeutic use as stomachic or antiemetic in cancer patients. Other therapeutic uses of cannabinoids: Asthma and glaucoma, as an antidepressant, anticonvulsant and anti-spasmodic Cannabis Sativa  Pharmacokinetics: * Absorption:- Inhalation or ingestion * Distribution: High lipid solubility. Rapidly. distributed to brain and adipose tissues. * Metabolism: by liver. * Excretion: urine and stool. Cannabis Sativa  Condition of poisoning: Accidental:- Overdose by the user. Cannabis Sativa  Mechanism of action: The exact mechanism of THC’s pharmacology remains only partially understood. Receptors for THC have been found in the basal ganglia, cerebral cortex, cerebellum and hippocampus. THC stimulates sympathetic receptors and inhibits parasympathetic receptors. THC possesses CNS stimulation & depression depending upon:  Mood of the user.  Concentration of THC.  Route of administration.  Cannabis Sativa  Clinical presentation: A) Mental: Euphoria: Floating in air, sense of well being and talkativeness. Sexual or erotic dreams. Increase special senses: Auditory [used by musicians] touch and olfactory. Dysphoria. It replaces euphoria due to depression effect. Disorientation of time:- Minutes seems hours i.e. false prolongation of time. [Sexual act is falsely lengthened]. Disorientation of space: Near objects appear far distant [car accidents]. Cannabis Sativa  Clinical presentation: B) Physical: Eyes: Dilated pupil + conjunctival congestion. CVS: Tachycardia + orthostatic hypotension. Resp: Depression of R.C. GIT: Increase appetite to sugars + dry mouth. Bladder: urinary frequency. Cannabis Sativa  Cause of death:  Central asphyxia  Car accidents. Cannabis Sativa  Investigation: * Routine investigations * Blood & urine sample: THC. Cannabis Sativa  Treatment:- of acute toxicity. 1- Supportive measures: ABCs esp- Care of respiration. 2- GIT decontamination: Gastric lavage. Charcoal. 3- Physiological antidote:- No specific antidote. 4- Symptomatic measures: Reassurance. Mild sedation (diazepam) if needed. Psychiatric follow up.  LSD Lysergic Acid Diethylamide (LSD) is an Ergot Alkaloid  psychoactive (psychedelic, psychotomimetics, hallocinogen)  Extremely potent (25 – 50 g orally produce marked behavioral effect  Odorless  Colorless  Tasteless  Liquid or Solid  Taken orally  Tachyphylaxis (rapid production of tolerance)  Rapid recovery from tolerance  Cross tolerance with mescaline & psilocybin  LSD  Source: Natural: Plant: Calviceps purpurae Synthetic: LSD  LSD  Mechanism of Action: Poorly understood, But: The primary action is on the CNS esp. changes in mood and behavior LSD affects both pyr- & extrapyramidal systems LSD affects sym- & parasympathetic systems LSD has sensory effects  LSD  C.P.:  Euphoria; hilarious laughter  Dysphoria; sadness & crying  Visual; more intense color of objects, flat surfaces assume depth, fixed objects undulate and flow  Abnormal Auditory, Tactile, Olfactory & Gustatory sense  LSD  C.P.:  Sympathetic; Mydriasis, hyperthermia, piloerection, hyperglycemia, tachycardia & hypertension  Alteration in time perception  Disruption of ego function & fear of self- destruction  Body parts feel unnatural or foreign  LSD  C.P.:  Acute panic reaction  Flashbacks  Prolonged psychosis  Schizophrenia like symptoms  LSD  Cause of Death: Suicide commonly  LSD  Management:  Quiet environment & lighted room at bed time  Reassurance  Sedation, Diazepam  Cloropromazine 50 – 100 mg I.M. (one dose) Drug Dependence Definitions: Drug of abuse: It is the use of a drug by any route (oral, smoking, snuffing, or injection) to produce mood change alteration of the level of consciousness Substance of abuse: Is any substance with pharmacologic effects used for non-medical reasons i.e. in order to produce a state of well being and to avoid discomfort This substance is usually condemned by the society Drug habituation: Is characterized by a desire to take the drug but without compulsion; some degree of psychological Dependence; detrimental effects on the p.t rather than society Drug addiction or drug dependence: It is the compulsive repeated use of a drug or substance resulting in physical, and psychological dependence Drug Dependence Mechanism of drug dependence: The most accepted theory is that: addiction may be a cellular phenomenon whether through cellular adaptation or receptors adaptation; where the cells become accustomed to the presence of the Drug, interruption of continuous administration of the drug or decrease its concentration will result in disturbed function Drug Dependence Characters of dependence: 1- Compulsive desire to take the drug 2- Tolerance 3- Physical dependence 4- Psychic dependence 5- Withdrawal symptoms 6- Detrimental effects on the individual, family and society Drug Dependence Methods of abuse of addicting drugs: 1- Nasal insufflation e.g. heroin 2- Inhalation e.g. cocaine 3- Smoking e.g. hashish 4- I.V e.g. morphine 5- Dissolving tabs then I.V injection Drug Dependence Types of addicts:  Therapeutic addicts  Professional addicts  Street addicts  Congenital addicts Thank you