Transcript cholinergic

 Antidotal therapy involves antagonism
chemical inactivation of an absorbed poison
or
 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
PHYSICAL
THE VITAL SIGNS AND
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
 PARASYMPATHETIC
 SYMPATHETIC
 CHOLINERGIC
ACETYLCHOLINE
 ADRENERGIC NOREPINEPHRINE
•
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)
DEFECATION
URINATION
MIOSIS
•ANTIDOTE: atropine /
pralidoxime
•Administer activated
charcoal orally
BRONCHOSPASM / BRADYCARDIA
EXCESSIVE SALIVATION
LACRIMATION
SEIZURES, SECRETIONS, SWEATING
THINK: ANTI AND ATROPINE
•
•
•
•
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•
ANTIHISTAMINES
ANTIPSYCHOTICS
ANTISPASMODICS
ANTIEMETICS
ANTIPARKINSON
TCAs
PLANTS: Atropa belladonna, JIMSON
WEED (Datura stramonium), HENBANE
(Hyoscyamus niger)
ANTICHOLINERGIC (ATROPINE,
ANTIHISTAMINES, TCA's)
•
•
•
•
•
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•
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)
•
•
•
•
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•
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
ANTIDOTE:
naloxone
DEATH
WITHDRAWAL
WITHDRAWAL: (ALCOHOL, NARCOTICS, SEDATIVE
- HYPNOTICS, antiHTN DRUGS
• DIARRHEA
•
CRAMPS
• MYDRIASIS
•
LACRIMATION
• TACHYCARDIA
•
SEIZURES
• HYPERTENSION
•
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
Somatostatin analogue
/ inhibit insulin
Peripheral neuropathy
due to pyridoxine
depletion