4) Removal of poison/toxic agent from the body Antidotes Any agent/substance that neutralizes (oppose) a poison (drug, toxic agent, heavy metal, pesticide, …) or counteract or minimize its harmful effects without causing damage to the body. Classes: 1) Physical 2) Chemical 3) Dispositional 4) Receptor Specific 5) Pharmacological or Physiological

Antidotes 1) Physical Antidotes These substances prevents the absorption of poison by their presence (act locally & not systemically), e.g., a) Demulcents (fats,oils,egg albumin & Milk (is diluting agent that contains proteins to absorb poison), all are used as antidotes for corrosive and irritant poisoning, b) Activated charcoal (Antagonize adsorption) is used for strychnine and mineral poisoning (Charcoal – Absorbs poison) c) Bentonite & Fuller’s Earth for Paraquat/Diquat (herbicides) poisoning (toxic to the GI, kidney, liver, heart & lung)

Antidotes 2) Chemical Antidotes * Produce antagonism through chemical reactions * Local & Systemic a) Local -Neutralizers - Sodium Bicarbonate (NaHCO3) for Fe++ (to form Ferrous carbonate- not absorbed) - Magnesium Oxide (MgO) for mild acids - Starch for Iodine (give blue color)

Antidotes 2) Chemical Antidotes b) Systemic (Reverses toxicity systemically) * Chelating agents (Attach to toxin, chelates it &↓ availability) 1) Succimer, (2,3 Di-mercapto-succinic Acid (DMSA) , (Brand Name: Chemet), given PO, (a Pb chelator), used for treating lead (Pb) poisoning, it works by trapping lead in the body and removing it in the urine. 2) Dicarboxylic Acid (Succinic Acid Derivative). Chelates Pb especially in children, (few SE) 3) British Anti Lewisite (BAL)– (Dimercaprol), Contains 2 Sulfhydryl Group Developed by the British to act as an antidote to toxic warfare gases Good Chelating agent against Hg & Pb – (for acute toxicity) 

Antidotes 2) Chemical Antidotes 4) Ca++ Disodium EDTA (iv administration) -Prevents chelation of Ca++ but chelates other ions & heavy metals (Pb, Cadmium, Hg) -Ca++ Na2EDTA + BAL are more effective when blood Pb > 70ug/dl 5) Deferoxamine Chelates iron 6) Cupramine (Penicillamine) Chelates Cupper 7) Protamine SO4 Systemic antidote for Heparin overdose 8) Digoxin immune FAB (Digibind, DigiFab, Ovine) Systemic antidote for Digoxin overdose (>2ng/ml) or life threatening

Antidotes 2) Chemical Antidotes 9) Botulinum toxin: most toxic agent known to mankind. (Botox, BTX-A) used therapeutically to correct: uncontrollable blinking, crossed eyes, inhibit sweating, facial wrinkles, chronic migraine (all approved by FDA) * Toxicity in adult is treated with antitoxin * Toxicity in infants is treated with botulism immune globulin 10) Scorpion, snake – Vaccine for anti scorpion Venom & anti snake venom

Antidotes 2) Chemical Antidotes Tetanus leads to death in about 1 in 10 cases. Several vaccines are used to prevent tetanus among children and adults (passive protection) Mild cases can be treated with: Tetanus immunoglobulin IV/IM Metronidazol, IV for 10 days Diazepam Sever cases: human tetanus Immu. globulin intrathecally (Improve from 4% to 35%) Tracheotomy, magnesium (IV) infusion (for spasms) & Diazepam 11) Tetanus – (lockjaw) caused by Gram-positive anaerobic bacterium Clostridium tetani *is a painful tightening of the muscles, all over the body. It can lead to "locking" of the jaw so Patient cannot open his mouth or swallow.

Antidotes 3) Dispositional Antidotes *Reverses the action of the poison by effecting their metabolism & excretion a) Metabolism  toxicity of metabolites  or  than parent compound Toxic agents: Methanol – wood alcohol, contains 1 C & produces more toxic metabolites Toxic as compared to ethanol – grain alcohol Methanol → Formaldehyde (1C) → Formic Acid (1C) ↓ No further metabolism, Formic Acid accumulates & leads to Acidosis, Electrolytes imbalances, CNS depression similar to Diabetes Keto-Acidosis (DKA)

Antidotes 3) Dispositional Antidotes (metabolism) To counteract methanol & prevent its metabolism give ETOH (Ethanol) ETOH is metabolized by the same enzyme & will produce competition for the methanol ETOH has a grater affinity for the alcohol dehydrogenase  Ethanol → Formaldehyde (1C) → Acetaldehyde (2C) → Acetic Acid (2C) → CO2 + H2 Which prevents Methanol Poisoning (Ethanol – CNS depression) Methanol that remains, will be excreted by the lungs & kidneys Formaldehyde (if accumulated) causes blindness Formic acid sever acidosis & coma

Antidotes 3) Dispositional Antidotes (Excretion) b) Excretion: any agent that Accelerates the excretion of toxic substance – if possible 1) Bromides (Br): Salts with some toxicity at high dose -CNS depressant - Excreted by kidneys - Cl will enhance/push Br excretion – Cl produced dispositional mechanism, well tolerated 2) Strontium (Sr): Earth metal belonging to the Ca++ family -Very toxic -Ca++ displaces Sr, forcing Excretion – dispositional mechanism 3) Thallium: a rodentcidies & pesticide, very toxic and lethal - KCl is displacing thallium and enhance its excretion

Antidotes 3) Dispositional Antidotes (Excretion) * Diuresis in Special Conditions:         -Ion trapping is forced removal of a substance by trapping it in the urine ( concentration in urine) -Ion trapping changes the pH of urine 6.5-6.7 *Ion trapping is done in Specific Conditions depends on: -Alkaline Poison -Acidic Poison * Functioning renal system (can not be used with renal failure )

Antidotes 3) Dispositional Antidotes (Excretion) a) ACIDIC POISON: * Salicylates and Barbiturates ·  Alkaline urine by using IV infusion of NaHCO3 1-2 mEq/kg ·   Make sure pH of urine > 8 ·   it renders the urine alkaline and will ionize acidic drugs/ poison b)  BASIC POISON: * Cocaine alkaloid with nitrogen & Amphetamines · Acidify urine by using ascorbic acid or NH4Cl, IV infusion To acidify the urine pH < 5, which will Ionize basic drugs

4) Pharmacological Antidotes * These are most specific due to their Pharmacological action–only affect poison- least Side effects – (very few) Receptor antidotes (AKA receptor Antidotes/blockers, displacing) Atropine: - Antidote for muscarinic compounds - Antidote for nerve gases - Organophosphates (highly toxic), Death occurs within minutes - Sarin & Tabun (nerve gas, inhibit cholinesterase & ACh accumulates leading to a massive Cholinergic response)

4) Pharmacological Antidotes 2) Neostigmine (Cholinergic agonist) Antidote for muscle relaxant, Tubocurarine – blocks the Neuro muscular junction competitively Only peripheral effect Antidote for Cholinesterase inhibitor→ ACh accumulates Quaternary ammonium – No CNS SE because don’t cross BBB Preferred over Physostigmine (Tertiary ammonium with possible CNS effects) Antagonize Atropine overdose – at peripheral & CNS levels 3) Naloxone/Naltrexone (Pure opioid antagonists) - Antidote for Morphine or other narcotic analgesic overdose - Use caution due to precipitation of withdrawal

5) Physiological Antidotes Agents that produce effects opposite to that of the poison, but not on the same receptor 1) Epinephrine -Used for anaphylactic shock – Bee stick - sever cardiovascular collapse & bronchoconstriction - EP reverses this by ↑ BP & causing bronchodilation 2) Tetrahydrofolinic Acid (Leucovorin), (Reduced form of folic acid) - used as an antidote for Methotrexate (Drug used for cancer treatment, lupus, arthritis) Ulcer toxicity Loss of hair ↓ blood count & ↓ platelet Give Folinic Acid ( a derivative of Folic Acid)

Removal of the absorbed portion of the poison * This process entails some risk because poison is being removed from the systemic circulation This process is done only when: 1) Patient is seriously poisoned w/seriously- known toxic agent 2) The level of poison in body ↑ 3) Is done by: a) Natural way OR b) artificial way

Removal of the absorbed portion of the poison a) Natural way: Induce diuresis & speed route of elimination for the xienobiotics (metabolism Or excretion) · b) Artificial way (Artificial or Mechanical) 1) Peritoneal dialysis (Least risky, Easy to perform, Sometimes used in cases of renal failure 2) Extracorporeal (outside the body) Hemodialysis  -Involves removal of blood from body, purified, then given back though a vein 3) Hemoperfusion (Most risky, no dialysis involved, blood is perfuse through an absorbing substance, e.g., charcoal) * Requirements: -Used only if severe toxicity exists – Ex. if Pt. is in coma -Used only if High blood level are present -Used only when high level of Poison present in BODY