Plant Toxicity Lecture Notes PDF

Al-Mustaqbal University College of Pharmacy 5th stage Clinical Toxicology Lecture:4 Plant Toxicity Dr.Iman Ghanim Hameed  Plant Toxicity A poisonous plant is defined as a plant that when touched or ingested in sufficient quantity can be harmful or fatal to...

Al-Mustaqbal University College of Pharmacy 5th stage Clinical Toxicology Lecture:4 Plant Toxicity Dr.Iman Ghanim Hameed  Plant Toxicity A poisonous plant is defined as a plant that when touched or ingested in sufficient quantity can be harmful or fatal to an organism or any plant capable evoking a toxic and/or fatal reaction. Examples on poisoning plants like mashroom, foxglove, castor bean, free tobacco...etc. 2  MUSHROOM POISONING Mushrooms are the fruiting bodies of a group of higher fungi. Mushroom toxicity occurs after the ingestion of mushrooms that contain toxins which are similarly appearing to non-toxic mushrooms. There are thousands of species of mushrooms, but only about 100 species can cause symptoms when eaten by humans, and only 15-20 species are potentially lethal when ingested. No simple rule exists for distinguishing edible mushrooms from poisonous one. In more than 95% of mushroom toxicity cases, poisoning occurs as a result of misidentification of the poisonous mushroom from edible one. 3  PATHOPHYSIOLOGY Each poisonous mushroom species contains one or more toxins. The severity of mushroom poisoning may vary, depending on: 1. The geographic location where the mushroom is grown 2. The amount of toxin delivered 3. Genetic characteristics of the mushroom Boiling, cooking, freezing, or processing may not alter some mushroom’s toxicity. 4  PATHOPHYSIOLOGY Mushroom poisoning can be classified into the following 3 categories on the basis of the time from ingestion to the development of symptoms : 1. Early symptom category 2. Late symptom category 3. Delayed symptom 5  PATHOPHYSIOLOGY Early symptom category: first 6 hours  of ingestion and include gastrointestinal, allergic, and neurologic syndromes. Late symptom category: appear between 6-24 hours after ingestion and may include hepatotoxic and nephrotoxic syndromes. Delayed symptom category: more than 24 hours after ingestion and include mostly nephrotoxic syndromes. 6  MUSHROOM TOXINS Mushroom toxins include but not limited to the following: 1. Amatoxin--- Cyclopeptides 2. Gyromitrins (monomethylhydrazine)  inhibits a number of hepatic systems, including cytochrome P-450 and glutathione, and causes hepatic necrosis  inhibits pyridoxine kinase and interferes with all the pyridoxine-requiring enzymes in the body, including those involved in the synthesis of gamma-aminobutyric acid (GABA).  The reduction of GABA concentrations in the brain leads to CNS hyperexcitability and convulsions. 2-Orellanine Its main effects are on the renal tubular system, where it causes necrosis with relative sparing of the glomerular apparatus. 3- Muscimol and ibotenic acid (is structurally similar to GABA and acts as a GABA- receptor agonist. 4-Norleucine (Nephrotoxins) 5- Muscarine 7  Amatoxins Amatoxins are powerful toxins. Ingested amounts as low as 0.1 mg/kg are sufficient to be lethal. A single full-grown specimen of A. phalloides, weighing 20 g, contains about 5–8 mg of amatoxin and is, therefore, potentially lethal.  Amatoxins It is a cyclic octapeptides that are synthesized by Amanita species. Amatoxins are absorbed rapidly from the GIT. These toxins may be detected in the urine as early as 90–120 min after ingestion of the mushrooms. At least 5 subtypes of amatoxins are known, the only significant human toxin being alpha-amatoxin, which inhibits RNA polymerase II and protein synthesis.  Muscarine Muscarine stimulates M1 and M2 types of postganglionic cholinergic receptors (muscarinic receptors) in the autonomic nervous system. This action results in parasympathetic stimulation similar to that caused by the release of endogenous acetylcholine at postganglionic receptors of smooth muscle and exocrine gland.  Muscarine Muscarine-containing mushrooms typically produce cholinergic symptoms such as sweating, facial flushing, salivation, lacrimation, vomiting, abdominal cramps, diarrhea, urination, and miosis; occasionally, bradycardia, hypotension, and dizziness develop. Symptoms typically occur within 1 hour of ingestion and last for 4-24 hours. In most cases, they resolve without drug therapy or with a dose of atropine.  Complications Of Mushroom Toxicity Respiratory: Aspiration pneumonia may occur with mushroom poisonings and involves loss of airway protective reflexes. Neurologic: Convulsions are common in gyromitrin poisoning, but they also may be due to hypoxia, acidosis, and metabolic abnormalities; cerebral edema may be a complication of hypoxia, acidosis, trauma, and hepatic failure.  Complications Of Mushroom Toxicity Hepatic: Hepatic failure and hypoglycemia are complication of amatoxin and gyromitrin poisonings. Renal: Renal failure is a common complication of norleucine and orellanine poisoning but also may be due to hypoperfusion and shock. Hematologic: Methemoglobinemia and hemolysis may complicate gyromitrin poisoning. Others: Trauma may complicate hallucinogenic mushroom poisoning. Hypovolemia and electrolyte disturbances may complicate any mushroom poisoning  Treatment OF MUSHROOM TOXICITY 1. Early volume resuscitation (fluid rehydration) is important for liver and renal toxic syndromes. 2. Gut decontamination, including whole-bowel irrigation. 3. Multiple doses of activated charcoal (regardless of the timing of presentation) should be administered repeatedly to interrupt enterohepatic circulation of these toxins. 4. Endotracheal intubation is recommended in all patients at risk of aspiration, and mechanical ventilation should be initiated in all patients with hypoxia, acidemia, and shock.  TREATMENT OF MUSHROOM TOXICITY 5. Agitation, commonly observed with hallucinogenic mushrooms, is treated with benzodiazepines. 6. Severe muscarinic symptoms may be treated with the infusion of small doses of atropine. 7. Patients with severe poisoning from disulfiram-containing mushrooms may benefit from fomepizole which blocks alcohol dehydrogenase and, hence, the formation of the toxic aldehyde.  TREATMENT OF MUSHROOM TOXICITY 8. Renal failure, commonly observed with norleucine and orellanine poisoning, may have to be treated with hemodialysis. 9. Conventional indications for dialysis include fluid overload (with pulmonary edema), severe hyperkalemia, and acidosis. 10. Blood transfusions may be required in patients with hemorrhagic diarrhea, blood loss, and severe hemolytic anemia.  TREATMENT OF MUSHROOM TOXICITY 11. Blood pressure support with dopamine and norepinephrine may be required when crystalloids and colloid infusions fail. 12. Hypoglycemia is treated with infusions of 10% dextrose.  THANK YOU FOR YOUR ATTENTION