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Ricin is a glycoprotein lectin composed of 2 chains, linked by a disulfide bond B chain: binds to galactose-containing glycoproteins and glycolipids expressed on the surface of cells
facilitates the entry of A chain into cytosol.
A chain: inhibits protein synthesis by irreversibly inactivating eukaryotic ribosomes through removal of a single adenin residue from the 28S ribosomal RNA loopprevents chain elongation of polypeptides and leads to cell death
Ingestion
No literature reports of poisoning from ingesting of purified ricin All reports refer to castor bean ingestion Median lethal dose (LD50) in mice is 30mg/kg, or approximately
Symptoms
Symptom onset within 4 6 hours but may be as late as 10 hours Initial symptoms nonspecific: colicky abdominal pain, vomiting, diarrhea, heartburn, and oropharyngeal pain Fluid losses lead to electrolyte imbalances, dehydration, hypotension and circulatory collapse
Unless treated, death can be expected to occur within 35 days, however in most cases a full recovery can be made.
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History of Opium
Opioids have been the mainstay of pain treatment for thousand of years, and they remain so today The search for a safe, orally active, and non-addictive analgesic based on the opiate structure is one of the oldest fields in medicinal chemistry The opiates are perhaps the oldest drugs known to humanity The first undisputed reference to opium is found in the writings
Because of morphines poor oral bioavailability, it was little used in medicine until the hypodermic syringe was invented in 1853 Morphine was used during the American Civil War and the Franco-Prussian war. Due to poor understanding about:
Safe dose levels Effects of long-term use And increased risks of addiction, tolerance and respiratory
depression
Many casualties were either killed by overdoses or became addicted to the drug
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Toxicities of morphine
Dangerous side effects are those of tolerance and dependence
Respiratory depression Most common cause of death from morphine overdose is suffocation Addiction Clinical observation and experimental studies have indicated that a single exposure to morphine could induce tolerance and dependence
Recent study shows that prolonged ventral tegmental area (VTA) dopamine neuron activities (DA) and opiate receptor desensitization followed single morphine exposure This may underlie the development of dependence and tolerance that may associate with the acute analgesic tolerance and acute addiction of morphine Withdrawal symptoms associated with morphine
Anorexia, Weight loss, Pupil dilation, Chills, Excessive sweating,
Strychnine
The Strychnine tree (Strychnos nux-vomica L.) also known as Nux vomica, is an evergreen tree native to Southeast Asia, a member of family Loganiaceae. It is a major source of the highly poisonous alkaloids strychnine and brucine, derived from the seeds inside the
Acts on spinal cord, brain, motor and sensory nerve centres, causing a condition of excessive irritation & excitability, which inturn causes muscular inco-ordination and paralysis.
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Toxicty of paracetamol
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alcohol ingestion
Acute alcohol ingestion is not a risk factor for hepatotoxicity and may even be protective by competing with acetaminophen for
CYP2E1
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glutathione.
NAPQI is thus free to react with the next most convenient substances, like protein and lipid. This process may be prevented, interrupted, and reversed NAPQI-derived organ damage
Management
Administration of N-acetylcysteine : a glutathione precursor Limits the formation and accumulation of NAPQI
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Salicylate overdose
Fatal intoxication can occur after the ingestion of 10 to 30 g by
adults and as little as 3 g by children Most patients show signs of intoxication when the plasma level exceeds 40 to 50 mg/dL (2.9 to 3.6 mmol/L) Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes Stimulation of the chemoreceptor trigger zone in the medulla causes nausea and vomiting Direct toxicity of salicylate species in the CNS
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Salicylate overdose
Activation of the respiratory center of the medulla results in tachypnea, hyperventilation, respiratory alkalosis
Salicylate toxicity
Prominent features of poisoning by methyl salicylate include central excitation, intense hyperpnoea, and hyperpyrexia. The odor of the drug can be detected easily on the breath and in the urine and vomitus.
Salicylate toxicity
In high doses, toxic effects on the CNS, consisting of stimulation followed by depression.
Salicylate toxicity
Metabolic acidosis is caused by accumulation of acids as a result of three processes.
Toxic concentrations of salicylates displace plasma HCO3 vasomotor depression caused by toxic doses of salicylates impairs renal function, with consequent accumulation of
Salicylate toxicity
The same series of events also causes alterations of water and electrolyte balance
Clinical features
Early symptoms of aspirin toxicity include tinnitus, fever, vertigo, nausea, hyperventilation,
vomiting, diarrhoea More severe intoxication can cause altered mental status,
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Management
Activated Charcoal
IV fluids Supplemental glucose Hemodialysis Alkalinizing the serum ionizes the salicylate, which
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Barbiturates
Include phenobarbitone (long acting), pentobarbitone (intermediate) , thiopental (ultra-short acting). Potentiate GABA-induced activities by prolonging the duration of Cl- channel opening Reduce glutamate-induced depolarization
Toxicty
Severe poisoning is likely to occur when more than 10 times the full hypnotic dose is ingested at once.
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Symptoms
Neurologic:
lethargy & impairment in thinking coma hypothermia decreased pupillary light reflex nystagmus respiratory depression - the most common cause of death Cardiovascular:
tachycardia or bradycardia
hypotension
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ABCs.
Treatment
Check for hypothermia & if present, warm the patient to avoid precipitating a fall in blood pressure. Perform GI decontamination once the airway is protected and
Alkalinization of the urine with sodium bicarbonate to enhance the elimination of phenobarbital and, likely, other longacting barbiturates by ion trapping. Urinary alkalinization is not recommended for short-acting barbiturate toxicity. Aggressively initiate fluid therapy if the patient is hypotensive
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Benzodiazepines
Increase the frequency of Cl- channel opening by promoting the binding of GABA to the GABAA receptors.
Biotransformation of Benzodiazepines
* Active metabolite
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Symptoms
Drowsiness, nystagmus
confusion, slurred sppech Ataxia, Coma, weakness, amnesia, hypotension respiratory depression
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Treatment
Flumazenil is the drug of choice to reverse effects of bzd
It is an antagonist for the benzodiazepine binding site. ABCs Single-dose activated charcoal is recommended for GI decontamination
in patients who present within 4 hours of ingestion or in symptomatic patients when the time of ingestion is unknown.
Digoxin
Sources positive intropic (prescription) drug for CHF
Manifestations of toxicity: CV toxic effects: Heart block and arrhythmias GIT effects: Anorexia, nausea, vomiting, diarrhea and abdominal
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Treatment
Digoxin Fab fragments (Digibind ) are generally indicated for
Thalidomide
Synthesized by W. Kunz and others in 1956 Distributed in Europe, Australia, and Canada Marketed as safe, potent, non-barbiturate sedative and antiemetic Not approved by the FDA for use in the US
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Birth Defects
Amelia
phocomelia hypoplasticity of the bones absence of bones external ear abnormalities facial palsy Eye abnormalities (anophthalmos, microphthalmos) Congenital heart defects Alimentary, urinary, and genital malformations
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Phenytoin
Effective against all types of partial and tonic-clonic seizures, but not absence seizures. Exerts anti-seizure activity without causing general
depression of the CNS. Toxic effects Depression of the CNS occurs particularly in the cerebellum
Inhibition of insulin secretion so that hyperglycemia and glucosuria results Behavioral changes, such as confusion, hallucination Phenytoin causes teratogenic during pregnancy.
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Tricyclic antidepressants
Mechanism of action:
They block the uptake of catecholamine leading to their accumulation at the receptor sites and potentiating of their activity. Inhibition of reuptake in synapse of NA and 5-HT They possess anticholinergic, antihistaminic, 1-receptor blocking
activity
Toxic Effects Dry mouth, blurring of vision, retention of urine, glaucoma, constipation, postural hypotension, arrhythmias, tremors, mild parkinsonian syndrome and hypersensitivity reactions.
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Food poisoning
Any illness resulting from the consumption of food There are two types of food poisoning: food infection and
food intoxication.
Food infection refers to the presence of bacteria or other microbes which infect the body after consumption. Food intoxication refers to the ingestion of toxins contained within the food, including bacterially produced exotoxins.
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Causes
Improper handling, preparation, or food storage. large variety of toxins that affect the environment chemicals
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