Ethanol

when the concentration of ethanol in the blood is 20 to 30 mg/dl, it leads to

An increased reaction time

diminished fine motor control Impulsivity

impaired judgment
More than 50% of persons are grossly intoxicated by a concentration of 150 mg/dl. In fatal cases, the average concentration is about 400 mg/dl, although alcohol-tolerant individuals often can withstand comparable blood alcohol levels.
1

Ethanol
In the United States, most states set the ethanol level defined as intoxication at 80 mg/dl. There is increasing evidence that lowering the limit to 50 to 80 mg/dl can reduce motor vehicle injuries and fatalities significantly. Blood alcohol levels reduce at a rate of about 15 mg/dl per hour. measurement of levels in exhaled air remains the primary method

While alcohol can be measured in saliva, urine, sweat, and blood,

of assessing the level of intoxication.

Ethanol
Concentrations of alcohol in blood will be higher in women than
in men consuming the same amount of alcohol because, on average, women are smaller than men women have less body water per unit of weight into which ethanol can distribute women have less gastric ADH activity than men. For individuals with normal hepatic function, ethanol is metabolized at a rate of one standard drink (12g) every 60 to 90 minutes.

 Patients who are comatose and who exhibit evidence of respiratory depression should be intubated to protect the airway and to provide ventilatory assistance. The stomach may be lavaged, but care must be taken to prevent pulmonary aspiration of the return flow. Ethanol can be removed from blood by hemodialysis. Uses of alcohol Relieve the long-lasting pain related to trigeminal

neuralgia, inoperable carcinoma, and other conditions.

Systemically administered ethanol is confined to the treatment of poisoning by methanol and ethylene glycol.
4

Ethanol
ADH = Alcohol Dehydrogenase ALDH = Aldehyde Dehydrogenase

OH H-C-H H-C-H H Ethanol ADH

O C-H H-C-H H Acetaldehyde ALDH

O C-OH H-C-H H Acetic Acid

Ethanol perturbs the balance between excitatory and inhibitory influences (GABA, Glutamate, proteins) in the brain, resulting in anxiolysis, ataxia, and sedation.
5

Methanol
Results in formation of formaldehyde and formic acid.
Formic acid causes nerve damage; its effects on the retina and optic nerve can cause blindness. Tachypnea, CNS depression, abdominal pain and multisystem organ failure Treatment sodium bicarbonate to combat acidosis Hemodialysis

the

administration

of

ethanol,

which

slows

formate

production by competing with methanol for metabolism by alcohol dehydrogenase.

6

Methanol Metabolism
ADH: Alcohol Dehydrogenase ALDH: Aldehyde Dehydrogenase

H
H-C-OH H Methanol ADH

O H-C-H H Formaldehyde ALDH

O H-C-OH H Formic Acid

Fomepizole Blocks alcohol dehydrogenase

Has replaced ethanol as the agent of choice in

known or suspected exposures

Minimal adverse effects

Cyanide Toxicity
Potent cellular toxin with nefarious (evil) history Poisoning can occur from Occupation, accidental ingestion of pre-metabolites Sodium nitroprusside infusion

Cyanogenic glycoside plant ingestion

Inhalation of burning plastics

Biochemical Toxicology
Inhibits final step of oxydative phosphorylation (cytochromes) Pyruvate lactate (anaerobically) severe metabolic

acidosis
Alters calcium homeostasis Constricts pulmonary and coronary vessels Clinical Features: CNS: Headache, Drowsiness, Seizures, Coma

Cardiovascular: Tachycardia, Collapse/asystole

Pulmonary: Dyspnea, Tachypnea, Apnea
10

Management
1. Decontamination (Reduce absorption) Nasogastric aspiration, Activated charcoal, Gastric lavage, Emesis 2. Enhanced cyanide metabolism

11

3. Cyanide ion binding a. Cobalt containing drugs: Cyanide ions will bind to cobalt which can be supplied in the

form of either; Hydroxocobalamin, or Dicobalt edetate

b. Methaemoglobin forming drugs: Cyanide will also bind to methaemoglobin formed after administration of nittrites eg. Amylnitrite, sodium nitrite Nitrite leads to oxidation of ferrous (++) haemoglobin to ferric (+++) methaemoglobin The basis of this treatment is methaemoglobins ability to bind to cyanide ions.
12

13

Carbon Monoxide (CO)

An odorless, colorless, tasteless gas Results from incomplete combustion of carbon-containing fuels; Gasoline, wood, coal, natural gas, propane, oil, and methane Effect on hemoglobin Hemoglobin molecules each contain four oxygen binding sites Carbon monoxide binds to hemoglobin
This binding reduces the ability of blood to carry oxygen to organs

Impaired release of oxygen at tissue level

Increased minute ventilation with subsequent increased CO uptake
14

 Hemoglobin occupied by CO is called carboxyhemoglobin Hb affinity for CO 250 times affinity for O2 Body systems most affected are the cardiovascular and central nervous systems Effects of Carbon Monoxide Oxygen cannot be transported because the CO binds more readily

to hemoglobin (Hgb) displacing oxygen and forming

carboxyhemoglobin Premature release of O2 prior to reaching distal tissue leads to hypoxia at the cellular level Inflammatory response is initiated due to poor and inadequate tissue perfusion
15

 Myocardial depression from CO exposure Dysrhythmias, myocardial ischemia, MI Vasodilation from increased release of nitric oxide;

worsening tissue perfusion and leading to syncope

Carbon monoxide absorption dependent upon: Minute ventilation

Duration of exposure
Concentration of CO in the environment Concentration of O2 in the environment The lower the O2 concentration to begin with, the faster the symptoms will develop
16

Pathophysiology - Cardiovascular Myocardial depression consequence of hypoxic stress cytochrome a3 dysfunction

CO binding to cardiac myoglobin

Arterial hypotension myocardial depression NO-related peripheral vasodilatation
17

Pathophysiology - Neurovascular
CO in circulation associated with massive increase in NO in perivascular tissues NO released from vascular endothelial cells and platelets Production of oxygen radicals from impaired mitochondrial

function
Reaction of NO with oxygen radicals to form peroxynitrite ( ONOO- )

18

 Peroxynitrite binds to perivascular tissue proteins causing injury Increased capillary permeability in CNS and pulmonary

vascular beds
Endothelial injury causing expression of adherence molecules - beta 2 integrins

Leucocytes bind to injured endothelium reducing cerebral

perfusion Initiation of CNS lipid peroxidation

19

Clinical manifestations
General headache, nausea, vomiting, weakness Cardiovascular chest pain, tachypnea, tachycardia, hypotension

pulmonary edema, arrythmias, cardiac arrest

Neurologic dizziness, ataxia, seizures, coma Others retinal hemorrhages, metabolic acidosis
20

Delayed or persistent CO toxicity

Dementia, psychosis, memory deficit Parkinsonism, paralysis, Personnality changes, gait disturbance Cortical blindness, Peripheral neuropathy, urinary incontinence Neuropsychologic deficits often subtle Lesions of cerebral white matter

Patients > 30 year old more susceptible to delayed CO toxicity

21

Snake bite
Snakes are strict carnivores & venomous at birth. Snakes are deaf & almost blind. Sense of smell is high Sensitive to vibration

Immobile at temps < 8C cannot survive at > 42C

There are over 3,000 species of snakes on the Planet, but only 15% are considered to be dangerous Amount of venom released based on size of victim.

22

Types of snakes
Non Poisonous Snakes
Head-Rounded

Fangs-Not present
Pupils-Rounded Anal Plate-Double row Bite Mark-Row of small teeth.

Poisonous Snakes
Head Triangle Fangs Present

Pupils - Elliptical pupil

Anal Plate - Single row Bite Mark - Fang Mark
23

Snake Venom
Snake Venom is a Toxin (Hemotoxin, Neurotoxin, or Cytotoxin) It is excreted through a modified parotid salivary gland

Located on each side of the skull, Behind the eye

Snake venoms are a combination of proteins and enzymes The flow of venom is produced through a pumping mechanism from an alveolar sac that stores the venom, proceeds through a channel, down a tubular fang which is

hollow in the center to project the venom into the air or its prey
Though the venom is dangerous, since it is not inhaled it cannot be considered a Poison
24

 Varies widely between species and even within a species Geographic location ex. Mojave rattlesnake Age of snake

Last feeding
90% protein by dry weight and most of these are enzymes 25 different enzymes have been isolated from venoms and 10 of these occur frequently in most venoms Different venoms contain different combinations of enzymes

causing a more potent effect than any of the individual effects

The enzymes in the venom are responsible forneurotoxic, hemotoxic or cytotoxic effects
25

 Snake Venom is primarily to attack prey Immobilize kill Digest 90% water Other 10% : Proteins : enzymatic & nonenzymatic

Polypeptides
Hyaluronidase All snake venom An enzyme that splits hyaluronic acid and so lowers its viscosity Facilitates spread of other toxins
26

Clinical effects
Neurotoxicity Systemic toxicity including hypotension and shock

Coagulopathy
Renal failure Local tissue necrosis including cobra spit

Toxic Effects
Respitory paralysis, Fever, Rapid Pulse, Increased Thirst, Dizziness, Local Tissue Damage, Blurred vision, Nausea and vomiting, Diarrhea , Coma , Death

27

Supportive treatment
Elevate limb Paralysis: neostigmine and atropine Hypotension: Crystalloid, fluids and ionotropic support Oliguria & renal failure: fluids, diuretics, dopamine, dialysis

Local infection- Antibiotics

Antivenom Nausea: metoclopramide. Analgesics: paracetamol, morphine.

28

Uses of venomous Snake

Although snakes have been deemed as one of the worlds most dangerous and disgusting critters on the planet, they actually have some benefits: Help control the smaller members of the animal kingdom from becoming overpopulated Possess an oil (high Eicosapentaenoic acid) that can be harvested and is used to alleviate pain in joints, such as rheumatoid arthritis. anti-venom production and slowing of cancer growth and metastasis Also anticoagulant, antiplatelet activities Denmotoxin (77 aa polypeptide having potent postsynaptic

neuromuscular), fibrolase, contortostatin (anti-angiogenic agent)

29

Antivenin
Antivenin is made by injecting horses with toxins from venomous snakes and then monitored to make sure they survive.

Then after the horse builds up an immunity the blood is

extracted and processed into antivenin Polyvalent antivenin: Manufactured by hyper immunizing horses against venoms of four standard snakes: Cobra (naja naja),Krait (B.caerulus),Russels viper(V.russelli),Saw scaled viper(Echis carinatus). Antivenom :precaution Monitor for acute reactions: Hypotension, Urticaria &Wheeze
Tuesday, October 02, 2012 30

Bee Sting
Honey bee belong : Family- Hymenoptera ; Sub Family-Apidae Only the females have adapted a stinger from the ovipositor on the

posterior aspect of the abdomen

Venom Histamine.

Melittina

membrane

active

polypeptide

that

can

cause

degranulation of basophils and mast cells, constitutes more than 50 percent of the dry weight of bee venom Venom commonly causes pain, slight erythema, edema, and pruritus at the sting site Local reaction, Toxic manifestation and anaphylaxis, delayed reaction Serum sickness
31

Treatment
Immediate removal is the important principle and the method of removal is irrelevant. Sting site should be washed thoroughly with soap and water to minimize the possibility of infection. Intermittent ice packs at the site- diminish swelling and delay the absorption of venom while limiting edema. Oral antihistamines and analgesics may limit discomfort and pruritus. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be effective in relieving pain. Severe case: Epinephrine Methylprednisolone :to limit ongoing urticaria and edema and may potentiate the effects of other measures.
32

Scorpion sting Scorpions have a world-wide distribution. Highly toxic species are found in the Middle East, India, North Africa, South America, Mexico, and the Caribbean island of Trinidad.

Venom can open neuronal sodium channels and cause

prolonged and excessive depolarization.

33

Symptoms and sign

Somatic and autonomic nerves may be affected Initial pain and paresthesia at the stung extremity that becomes

generalised
Cranial nerve- abnormal roving eye movements, blurred vision, pharyngeal muscle incoordination and drooling and respiratory compromise. Excessive motor activity Nausea, vomiting, tachycardia, and severe agitation can also be present. Cardiac dysfunction, pulmonary edema, pancreatitis, bleeding disorders, skin necrosis, and occasionally death can occur.
34

Treatment Pain Management Ice pack Immobilization of limb Local anesthetics are better than opiates

Tetanus prophylaxis
wound care and antibiotics, Benzodiazepines for motor activity.

Stabilize Airway Breathing and Circulation

35