toxicology of alcohols
Post on 04-Apr-2018
220 Views
Preview:
TRANSCRIPT
-
7/30/2019 Toxicology of Alcohols
1/35
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
-
7/30/2019 Toxicology of Alcohols
2/35
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.
2
-
7/30/2019 Toxicology of Alcohols
3/35
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.
3
-
7/30/2019 Toxicology of Alcohols
4/35
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.
4
-
7/30/2019 Toxicology of Alcohols
5/35
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
-
7/30/2019 Toxicology of Alcohols
6/35
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
-
7/30/2019 Toxicology of Alcohols
7/35
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
7
-
7/30/2019 Toxicology of Alcohols
8/35
Fomepizole
Blocks alcohol dehydrogenase
Has replaced ethanol as the agent of choice in
known or suspected exposures Minimal adverse effects
8
-
7/30/2019 Toxicology of Alcohols
9/35
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
9
-
7/30/2019 Toxicology of Alcohols
10/35
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
-
7/30/2019 Toxicology of Alcohols
11/35
Management
1. Decontamination (Reduce absorption)
Nasogastric aspiration, Activated charcoal, Gastric lavage,
Emesis
2. Enhanced cyanide metabolism
11
-
7/30/2019 Toxicology of Alcohols
12/35
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
-
7/30/2019 Toxicology of Alcohols
13/35
13
-
7/30/2019 Toxicology of Alcohols
14/35
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
-
7/30/2019 Toxicology of Alcohols
15/35
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
-
7/30/2019 Toxicology of Alcohols
16/35
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
-
7/30/2019 Toxicology of Alcohols
17/35
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
-
7/30/2019 Toxicology of Alcohols
18/35
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- )
18
-
7/30/2019 Toxicology of Alcohols
19/35
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
-
7/30/2019 Toxicology of Alcohols
20/35
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
-
7/30/2019 Toxicology of Alcohols
21/35
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
-
7/30/2019 Toxicology of Alcohols
22/35
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
-
7/30/2019 Toxicology of Alcohols
23/35
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
-
7/30/2019 Toxicology of Alcohols
24/35
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
-
7/30/2019 Toxicology of Alcohols
25/35
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
-
7/30/2019 Toxicology of Alcohols
26/35
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
-
7/30/2019 Toxicology of Alcohols
27/35
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
-
7/30/2019 Toxicology of Alcohols
28/35
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
-
7/30/2019 Toxicology of Alcohols
29/35
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)
29
-
7/30/2019 Toxicology of Alcohols
30/35
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
-
7/30/2019 Toxicology of Alcohols
31/35
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
-
7/30/2019 Toxicology of Alcohols
32/35
-
7/30/2019 Toxicology of Alcohols
33/35
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
-
7/30/2019 Toxicology of Alcohols
34/35
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
-
7/30/2019 Toxicology of Alcohols
35/35
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
top related