Antidotal therapy involves antagonism or chemical inactivation of an absorbed poison The pharmacodyamics of a poison can be altered by competition at a receptor (naloxone therapy in the setting of heroin overdose) Physiological antidote (glucagon in the setting of propranolol overdose) Anti-venoms and chelating agents bind and directly inactivate poisons

The biotransformation of a drug can also be altered by an antidote (fomepizole will inhibit alcohol dehydrogenase and stop the formation of toxic acid metabolites from ethylene glycol and methanol) Many drugs used in the supportive care of a poisoned patient (anticonvulsants, vasoconstricting agents, etc.) may be considered nonspecific functional antidotes Antidotes can significantly reduce morbidity and mortality rates but are potentially toxic if used for inappropriate reasons….their use requires correct identification of a specific poisoning or syndrome

THE IDENTIFICATION OF VARIOUS TOXIC SYNDROMES REQUIRES INTEGRATING OF DATA PROVIDED BY BOTH THE VITAL SIGNS AND PHYSICAL EXAMINATION TO ELICIT MANIFESTATIONS SPECIFIC TO AN INTOXICANT THIS COLLECTION OF MANIFESTATION (TOXICOLOGIC SYNDROMES) MAY ASSIST IN THE DIAGNOSIS WHEN THE AGENT IS UNKNOWN AND MAY HELP IN ANTICIPATING MANIFESTATIONS THAT WILL DEVELOP

 CHOLINERGIC  ANTICHOLINERGIC  SYMPATHOMIMETIC  NARCOTIC  WITHDRAWAL

CENTRAL NERVOUS SYSTEM:  BRAIN  SPINAL CORD PERIPHERAL NERVOUS SYSTEM  SOMATIC NERVOUS SYSTEM  AUTONOMIC NERVOUS SYSTEM

AUTONOMIC NERVOUS SYSTEM  SYMPATHETIC NOREPINEPHRINE  PARASYMPATHETIC ACETYLCHOLINE  ADRENERGIC  CHOLINERGIC

AUTONOMIC NERVOUS SYSTEM  CHOLINERGIC ACETYLCHOLINE RELEASE & BREAKDOWN FOUND AT :  ALL AUTONOMIC GANGLIA  POSTGANGLIONIC PARASYMPATHETIC FIBERS  FEW SYMPATHETIC FIBERS - SWEAT GLANDS  NEUROMUSCULAR JUNCTION  ADRENAL MEDULLA

AUTONOMIC NERVOUS SYSTEM  CHOLINERGIC RECEPTORS: MUSCARINIC: CARDIOVASCULAR, GI, URINARY, LUNGS NICOTINIC: AT ALL GANGLIA, NEUROMUSCULAR JUNCTION

AUTONOMIC NERVOUS SYSTEM  SYMPATHETIC ( ADRENERGIC ) NOREPINEPHRINE RELEASE & REUPTAKE AT MOST POSTGANGLIONIC SYMPATHETIC NEURONS RECEPTORS =  1  2  1  2  3

CHOLINERGIC

THREE WAYS TO ENHANCE CHOLINERGIC ACTIVITY: 1. CHOLINERGIC MEDICATIONS PILOCARPINE = MIOSIS (glucoma) BETHANECHOL = URINARY STIMULANT

2. ACETYL CHOLINESTERASE INHIBITORS: ORGANOPHOSPHATES & CARBAMATES 3. PLANTS: AMANITA MUSCARIA (WEAK) CLITOCYBE

DUMBELS (direct or indirect-AchEI) D EFECATION U RINATION M IOSIS B RONCHOSPASM / B RADYCARDIA E XCESSIVE SALIVATION L ACRIMATION S EIZURES, SECRETIONS, SWEATING ANTIDOTE: atropine / pralidoxime Administer activated charcoal orally

THINK: ANTI AND ATROPINE ANTIHISTAMINES ANTIPSYCHOTICS ANTISPASMODICS ANTIEMETICS ANTIPARKINSON TCAs PLANTS: Atropa belladonna, JIMSON WEED (Datura stramonium), HENBANE (Hyoscyamus niger)

ANTICHOLINERGIC (ATROPINE, ANTIHISTAMINES, TCA's) HOT AS A HARE RED AS A BEET DRY AS A BONE BLIND AS A BAT MAD AS A HATTER The bowel and bladder lose their tone ….and the heart runs alone

ANTICHOLINERGIC Mydriasis Blurred vision Fever Dry skin Flushing Ileus Urinary retention Tachycardia Hypertension Psychosis Myoclonus Seizures ANTIDOTE: physostigmine / treat symptoms

Maintain an open airway and assist ventilation if needed Treat (if they occur):  Hyperthermia….external rapid cooling  Coma  Rhabdomyolysis (Hematest-positive urine or high serum creatine phosphokinase level)…..I.V fluids, alkalinize of urine  Seizures…..benzodiazepine

A small dose of physostigmine (0.5–1 mg IV in an adult), given to patients with severe toxicity Precaution: can cause AV block, asystole, and seizures, especially in patients with tricyclic antidepressant overdose Neostigmine, a peripherally acting cholinesterase inhibitor, may be useful in treating anticholinergic-induced ileus Decontamination: administer activated charcoal orally (gastric lavage no needed)

SYMPATHOMIMETIC (COCAINE, AMPHETAMINES) MYDRIASIS TACHYCARDIA HYPERTENSION FEVER SWEATING SEIZURES ANTIDOTE: benzodiazepines

 Alpha-adrenergic syndrome (phenylpropanolamine and phenylephrine)  Hypertension with reflex bradycardia  The pupils are usually dilated  Beta-adrenergic syndrome (albuterol, metaproterenol, theophylline, and caffeine)  Beta-2–mediated vasodilation may cause hypotension. Tachycardia is common

NARCOTIC Papaver somniferum “ poppy plant”

NARCOTIC (HEROIN, METHADONE)  MIOSIS  CNS DEPRESSION  BRADYCARDIA  HYPOTENSION  HYPOVENTILATION  HYPOTHERMIA  COMA  DEATH ANTIDOTE: naloxone

WITHDRAWAL

WITHDRAWAL: (ALCOHOL, NARCOTICS, SEDATIVE - HYPNOTICS, antiHTN DRUGS DIARRHEA MYDRIASIS TACHYCARDIA HYPERTENSION CRAMPS LACRIMATION SEIZURES HALLUCINATIONS ANTIDOTE: benzodiazepines

 HYPERMETABOLIC SYNDROME  Phenol compound, dinitrophenol, pentachlorophenol herbicides  CONVULSION  RESTLESSNESS  FEVER  HYPERPNEA  TACHYCARDIA  METABOLIC ACIDOSIS

 TORSION–HEAD AND NECK SYNDROME: idiosyncratic reaction with extrapyramidal manifestation  Amantadine, H1 receptor antagonist (brompheniramine), levodopa, phenothiazines, sertraline  DYSPHONIA  OCULOGYRIC CRISIS  RIGIDITY  TREMOR  TORTICOLLIS

CASE 5: A 22 Y.O. MALE IS BROUGHT IN BY POLICE. DURING THE ARREST THEY SUSPECT HE SWOLLOWED SOMETHING. THE PATIENT REFUSES TO ANSWER YOUR QUESTIONS. T 100.8(38C) R 24 PULSE 130 B/P 148/98 DIALATED PUPILS, AGITATED, NO TRACK MARKS WHAT SUBSTANCE BEST FITS? WHY? WHAT TREATMENT? WHY?

SPECIFIC ANTIDOTES

Muscle relaxant K+ channel activator/vasodilator

Peripheral neuropathy due to pyridoxine depletion Somatostatin analogue / inhibit insulin