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ANTIDOTES

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

Major drugs involved in poisoning

Paracetamol. Aspirin. Benzodiazepines. SSRIs. Anticonvulsants. Other analgesics including NSAIDs.

Poisoing by substances other than drugs:

Petroleum distillates. Nature toxins as mushrooms. Industrial chemicals. Toiletries. Household products. Agrochemicals.

Management

Supportive Correct hypoxia, hypotension, dehydration, hypo-

hyperthermia, and acidosis Control seizures If comatose consider;

DON’T( Dextrose,O2,Naloxone,Thaimine). Monitor

PR, BP, ECG, Oxygenation, GCS General

Absorption Elimination Specific antidotes

Principles of therapy: Specific pharmacological intervention

Direct chemical antagonism e.g acid-base Receptor competition e.g. nalorphine in morphine

overdose Blockade of receptors that causes the toxic effects e.g.

atropine in organophosphate poisoning, Flumazenil in benzodiazepine poisoning.

Restoration of normal function using an agent exerting a direct opposite effect e.g. barbiturate in CNS stimulant poisoning

Antidotes in most common use in clinical toxicology:

Paracetamol: n-acetyl cysteine or methionine. Opioid: Naloxone. Iron: desferroxamine.

Paracetamol Overdose: Treatment.

N-acetyl cysteine is the drug of choice. It effectively prevents hepatotoxicity if given within 8

hours. It is strongly effective if given within 16 hours & may be

effective up to & beyond 24 hours. Because this therapy may be effective 24 hours after

ingestion, the presence of any measurable acetaminophen or biochemical evidence of hepatic injury at 24 hours is an indication to start N-acetyl cysteine therapy.

Barbiturates poisoning: treatment.

Treatment of the critically ill patient involves mechanical ventilation, resuscitation of CV status, gastric lavage & activated charcoal (after securing the airway) & supportive care in an ICU.

An alkaline diuresis with sodium bicarbonate is specifically indicated for phenobarbital, which is a weak acid that is excreted unchanged in the urine.

Multiple-dose activated charcoal every 4 -6 hours is also specifically indicated for phenobarbital, as it diffuses into the GIT lumen.

Charcoal hemoperfusion & hemodialysis have a role in barbiturate overdose for critical patients who do not respond to conservative therapy.

The benzodiazepines poisoning.

Extremely popular & have replaced other sedative-hypnotics.

Diazepam, lorazepam, & midazolam, have major therapeutic roles as IV drugs for in-hospital use as anticonvulsants, preanesthetics & sedatives.

Although common agents of overdose, cause only coma & ataxia; mortality is rare & supportive care is all that usually necessary.

The antidote FLUMAZENIL is reserved only for reversing pure in-hospital benzodiazepine conscious analgesia & reversing coma in zolpidem overdose.

Cyanide poisoning.

The cyanide antidote kit contains amyl nitrite, ampules of sodium thiosulfate, & ampoules of sodium nitrite.

The body has a natural enzyme, rhodanese, that can complex cyanide & sulphur to form thiocyanate, which is only mildly toxic.

IV sodium thiosulfate provides the sulphur necessary to produce thiocyanate & is relatively safe.

Because sodium nitrite causes hypotension & methemoglobinemia, its use is reserved for the most critical cases.

The new antidote hydroxycobalamin (initial adult dosage 5 g IV), not yet approved, is a safer alternative.

Iron poisoning.

Management of iron poisoning includes gastric lavage with normal saline.

Whole-bowel irrigation may be indicated after ingestion of sustained-release capsules.

The treatment of choice is the antidote deferoxamine, which chelates free serum iron in the plasma to form ferrioxamine, which is readily excreted

Methanol & ethylene glycol poisoning.

Signs & symptoms develop over a 24-hour period & may include infarction of the putamen.

Severe high anion gap metabolic acidosis Treatment emphasizes IV ethanol, sodium bicarbonate &

haemodialysis.

The organophosphates poisoning.

Emergency management includes decontamination of the skin,& removal of clothes; establishing an airway & ensuring proper ventilatory support , cardiac monitoring; & administering the specific antidote pralidoxime & the physiologic antidote atropine.

Atropine should be given as a physiologic antidote to reverse the muscarinic effects & to dry the excessive pulmonary secretions seen in patients with respiratory distress.

Atropine use requires cardiac monitoring& proper oxygenation.

Pralidoxime is the treatment of choice for organophosphate poisoning & should be begun on clinical grounds before return of any blood studies.

To be effective, pralidoxime must be given in the first 48 hours before irreversible binding of acetylcholinesterase occurs.

The organophosphates poisoning.

The initial dose is 1 g IV given over 15 to 30 minutes

Pralidoxime may obviate the need for high-dose atropine therapy & reduce the incidence of late-onset paralysis.

Neither therapies exclude the use of the other.

The organophosphates poisoning.

The carbamate insecticides include carbaril, methomyl, & propoxur - are reversible cholinesterase inhibitors.

They produce clinical effects similar to those of the organophosphates but without CNS signs;

They are considerably more benign & shorter duration.

Atropine is the drug of choice for carbamate poisoning.

Pralidoxime is not indicated because the carbamate-cholinesterase complex is quite reversible.