toxicology of alcohols

7/30/2019 Toxicology of Alcohols

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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


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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.

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

measurement of levels in exhaled air remains the primary methodof assessing the level of intoxication.

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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.

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Patients who are comatose and who exhibit evidence of

respiratory depression should be

intubated to protect the airway and to provide ventilatoryassistance.

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.

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Ethanol

H-C-H

H

H-C-H

OH

Ethanol

H-C-H

H

C-H

O

H-C-H

H

C-OH

O

Acetaldehyde Acetic Acid

ADH ALDH

ADH = Alcohol DehydrogenaseALDH = Aldehyde Dehydrogenase

Ethanol perturbs the balance between excitatory and inhibitory

influences (GABA, Glutamate, proteins) in the brain, resulting in

anxiolysis, ataxia, and sedation. 5


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Methanol

Results in formation of formaldehyde and formic acid.

Formic acid causes nerve damage; its effects on the retina andoptic 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


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Methanol Metabolism

H-C-OH

H

H

Methanol

H-C-OH

H

O

Formaldehyde

H-C-H

H

O

Formic Acid

ADH ALDH

ADH: Alcohol Dehydrogenase

ALDH: Aldehyde Dehydrogenase

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Fomepizole

Blocks alcohol dehydrogenase

Has replaced ethanol as the agent of choice in

known or suspected exposures Minimal adverse effects

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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

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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

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Management

1. Decontamination (Reduce absorption)

Nasogastric aspiration, Activated charcoal, Gastric lavage,

Emesis

2. Enhanced cyanide metabolism

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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.

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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

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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


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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

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Pathophysiology - Cardiovascular

Myocardial depression consequence of

hypoxic stress

cytochrome a3 dysfunction

CO binding to cardiac myoglobin

Arterial hypotension

myocardial depression

NO-related peripheral vasodilatation

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Pathophysiology - Neurovascular

CO in circulation associated with massive increase in NO inperivascular tissues

NO released from vascular endothelial cells and platelets

Production of oxygen radicals from impaired mitochondrialfunction

Reaction of NO with oxygen radicals to form peroxynitrite

( ONOO- )

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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

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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

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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

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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.

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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

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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 Poison24


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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

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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

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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

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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.

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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 somebenefits:

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)

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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


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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


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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.

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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


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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

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toxicology of alcohols

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