UNIT 9 PPT Flashcards
(27 cards)
CLASSIFICATION OF ANTIDOTES
According to mode of action…
- Physiological/ pharmacological antidote
- Physical antidote
- Chemical antidote
- It counteracts the effects of a poison by producing the opposite pharmacological effects.
Ex: ACHE inhibitor -> Atropine
- Pharmacological antidotes may neutralize or antagonize the effects of a toxicant.
- This type of antidote may act by following 5 mechanisms:
- ________
- ________
- ________
- ________
- ________
PHYSIOLOGICAL/ PHARMACOLOGICAL ANTIDOTE
- Preventing the formation of toxic metabolites
- By facilitation of more rapid or complete elimination of a toxicant
- By competing with the toxicant’s action at a receptor site.
- By blocking receptors responsible for the toxic effect.
- By aiding in the restoration of normal function.
- The agent which is used to interfere with poison through physical properties, not change their nature is known as physical antidote.
a) _________: Adhesion of atoms, ions, or molecules from a gas, liquid, or dissolved solid to a surface.
- This process creates a film of the adorbate on the surface of the adsorbent.
- Ex: Activate charcoal (Universal Antidote)
b) _________: A mixture of egg and milk make a coat over the mucosa.
c) _________: 10% alcohol or 10% glycerine solution -> Carbolic acid (Phenol).
PHYSICAL ANTIDOTE
a. Adsorbing
b. Coating
c. Dissolving
- interacts specifically with a toxicant or neutralize the toxicant.
Ex: Metal chelators combine with metals to form complexes that can be eliminated by the kidneys.
- It mainly acts by 2 mechanisms:
i. __________
ii. _________
CHEMICAL ANTIDOTE:
i. Complex formation
ii. Metabolic conversion
- Antidote makes a complex with the toxicant making it unavailable to cross the membrane or to interact with the receptors.
- Ex: ______________ are sulfhydryl compounds that bind metals such as arsenic, and lead)
i. Complex formation
- DMSA (dimercaprol and dimercaptosuccinic acid
[CHEMICAL ANTIDOTE]
- ______________________
- _______ interact with hemoglobin and cyanide to form __________, which is less toxic than cyanide and interfere with the cyanide access to __________ system.
Nitrate + Oxyhemoglobin -> Methemoglobin + Cyanide -> Cyanomethemoglobin (less toxic)
ii. Metabolic conversion:
- Detoxification to less toxic product
- Nitrate
- cyanomethemoglobin
- cytochrome oxidase
[CHEMICAL ANTIDOTE]
- _______________
- Some antidotes accelerate the detoxification of a poison
Ex: __________ acts as a glutathione substitute which combines with hepatotoxic paracetamol metabolites and detoxifies them.
- Ex: ________ accelerates the conversion of cyanide to nontoxic _________
Cyanide - (Toxic)
Thiosulfate - (antidote)
Thiocyanate - (Nontoxic)
ii. Metabolic conversion:
Accelerated Detoxification to less toxic product:
- Acetyl cysteine
- Thiosulfate
- thiocyanate
[CHEMICAL ANTIDOTE]
MECHANISM OF ACTION
- _____________
- Specific or nonspecific binding
- Enhanced elimination
2._____________
- Competitive inhibition
- ____________
- Conversion to less toxic metabolites - ____________
- Atropine
- HIET
- Direct antagonism
- Decrease the active toxin level
- Block the site of action
- Decrease toxic metabolites
- Counteract effects of toxin
A). Involves specific and nonspecific binding
SPECIFIC
1. _________
2. _________
3. _________
NONSPECIFIC
1. _________
2. _________
B). Involves enhanced elimination
1. Hemadsorption
2. Urinary alkalinization
- DECREASE THE ACTIVE TOXIN LEVEL
SPECIFIC
1. Chelation
2. Immunotherapy
3. Bioscavenger therapy
NONSPECIFIC
1. Activated charcoal
2. Intra-lipid therapy
- Ex: Either Ethanol or Fomepizole inhibits the metabolism of methanol and ethylene glycol (antifreeze) to toxic metabolites by competing for the same enzyme __________ (ADH)
A. Competitive inhibition of the enzyme
- alcohol dehydrogenase
[2. BLOCK THE SITE OF ACTION]
- BLOCK THE SITE OF ACTION
- ____________________
- Some antidotes displace the poison from specific receptor sites, thereby antagonizing the effects completely
Examples:
- Opioid overdose -> Naloxone antagonizes the effects of opioids at stereo-specific opioid receptor sites
- Benzodiazepine overdose -> Flumazenil
B. Competitive inhibition of the receptor
[2. BLOCK THE SITE OF ACTION]
- DECREASE TOXIC METABOLITES
A. Binding of the toxic metabolite
B. Conversion to less toxic metabolite
- Sodium Thiosulfate to Cyanide poisoning
C. Inert Complex Formation
- Some antidotes interact with the poison to form an inert complex which is then excreted from the body.
Ex:
a) ________ for heavy metals
b) ________ for thallium
c) ________ for digoxin
d) ________ for cyanide etc.
C. Inert Complex Formation
[3. DECREASE TOXIC METABOLITES]
a) Chelating agents for heavy metals
b) Prussian blue for thallium
c) Specific antibody fragments for digoxin
d) Dicobalt edetate for cyanide etc.
- Muscarinic effects of _____________ -> Atropine
- CCB (Calcium Channel Blocker) and BB (Beta-Blocker) overdose -> _____________
- INH (Isoniazid) -> _____________ (______)
- Warfarin -> __________
- MTX (Methotrexate) -> ____________
- ## COUNTERACT EFFECTS OF TOXINExamples
- Muscarinic effects of OP (Organophosphate Poisoning) -> Atropine
- CCB (Calcium Channel Blocker) and BB (Beta-Blocker) overdose -> HIET (Hyperinsulinemia-Euglycemia Therapy)
- INH (Isoniazid) -> Pyridoxine (Vit. B6)
- Warfarin -> Vit. K
- MTX (Methotrexate) -> Folinic acid
- Antidote binds to the receptor site of poison and block its action
Ex: Muscarinic effects of OP (Organophosphate Poisoning) -> Atropine
Atropine blocks the effects of _________ agents such as __________ at Muscarinic receptor sites.
- Receptor Site Blockade
= anticholinesterase
= Organophosphates
[4. COUNTERACT EFFECTS OF TOXIN]
Antidote bypasses the toxic effect of poison
Ex: Use of 100% Oxygen in cyanide poisoning
Cyanide -> ___________ -> Cells are unable to use Oxygen due to cyanide’s inhibition of ___________ (enzyme in cellular respiration)
- Toxic Effect bypass
= cytochrome oxidase
= histotoxic hypoxia
[4. COUNTERACT EFFECTS OF TOXIN]
- Synthetic polyamino polycarboxylic acid
Aka:
-> Calcium disodium edetate
-> Calcium sodium EDTA
- Calcium disodium versenate
- Mainly used to complex di- and trivalent metal ions.
- Side Effects: Nausea, Diarrhea, Abdominal pain, Renal damage
- EDTA (Ethylene Diamine TetraAcetic acid)
Ca Calcium Disodium EDTA (CaNa,EDTA)
- CaNa3,DTPA
- ZnNa3DTPA
- Plutonium and other transuranic elements like Americium, Curium (Radiation from Dirty bomb)
- Poor GI absorption
- Calcium/Zinc Trisodium Diethlene TriaminePentaAcetate
(DTPA)
aka:
-> B-B-dimethylcysteine
->3-mercapto-D-valine
- Chelating agent for Pb, Hg, and Cu poisoning
Pharmacologic profile:
- Well absorbed in the GIT
- Low incidence of ADRs
: Thrombocytopenia, Leukopenia
- CI: Patients allergic to PCN
- D-Penicillamine (DPA)
- Has 3-C backbone + 2 sulfhydryl (-SH) and a hydroxyl (-OH) group
- Oily, clear, colorless liquid
- Pungent, unpleasant odor (mercaptan)
- Used since 1949 in cases of heavy metal poisoning
Common ADRs:
- Fever
- Conjunctivitis
- Lacrimation
- Constricted feeling
- Headache
- Paresthesia
- Nausea
- Pain at the injection site
- Dimercaprol/ British Anti-Lewisite (2,3-dimercapto-1-propanolol)
- Dimercaprol/ British Anti-Lewisite
- ____________
- Least toxic among dithiol compounds
- Hydrophilic
- 95% protein bound - ____________
- For Hg-intoxication
- Not for Pb-toxicity
- Meso-2,3-Dimercaptosuccinic acid (DMSA)
- Sodium-2,3-Dimercaptopropane-1-Sulfonate (DMPS)
Dimercaprol/ British Anti-Lewisite
➤ New DMSA Analogues
- ____________
- MIADMSA
- DMSA + Isoamyl Alcohol - ____________
- MmDMSA - ____________
- McHDMSA
Dimercaprol/ British Anti-Lewisite
➤ New DMSA Analogues
- Monoisoamyl DMSA
- MIADMSA
- DMSA + Isoamyl Alcohol - Monomethyl DMSA
- MmDMSA - Monocyclohexyl DMSA
- McHDMSA
Desferrioxamine (DFO)
- Secreted by Streptomyces pilosus
- Trivalent iron
- low affinity for other metals
- For ________ and ________
- DFO completely covers the surface of Fe3+ during complex formation, thereby preventing iron-catalyzed free radical reactions.
Desferal
- thalassemia
- Al-poisoning
___________
Aka: L1, CP20
- Iron-chelator alternative to DFO in the transfusional iron overload.
- Less expensive
Deferiprone
