Lecture 12 - Alcohols Flashcards
What is an osmol gap?
difference between the measured osmolality and the calculated osmolarity
Osmolarity
measure of the total number of particles in one liter of solution (molar concentrations) - usually calculated
Osmolality
differs from osmolarity only in that the number of particles is expressed per kg of solution (molal concentrations) - usually measured
_____ is usually calculated
osmolarity
____ is usually measured
osmolality
What is the formula for calculated osmolarity (mosm) ?
2 x [Na+] + [glucose] + [BUN]
**concentrations are in mmol/L
What is BUN ?
blood urea nitrogen
What is the normal values of BUN ?
3.0 - 7.1 mmol/L (8-20 mg/dL)
What does the measurement of osmolality tell us?
freezing point depression
Serum osmolality may be _______ by contributions of circulation alcohols and other low MW substances.
increased
What is the formula for osmol gap ?
difference between osmol measured and osmol calculated
What is the normal range for osmol gap?
10 +/- 6 mOsm
*in an intoxication of alcohol, this will go very high
Ethanol:
how much is eliminated by enzymatic oxidation?
90-95%
Ethanol:
how much is excreted unchanged?
5-10% excreted unchanged (kidney, liver, lungs)
What is the ratio of alcohol in alveolar air to blood?
1: 2100 alveolar air/blood
* small but fixed ratio - can very accurately estimate blood levels from how much is in the breath
Ethanol elimination happens through what kind of kinetics?
michaelis-menten
What is the rate of elimination in occasional drinkers?
100-125 mg/kg/h
What is the rate of elimination in habitual drinkers/alcoholics?
175 mg/kg/h
alcohol induces it’s own _____
enzymes
Chronic alcoholics have higher _______ than others
metabolism
Ethanol:
_____ CNS depressant at low doses
selective
Ethanol:
_____ CNS depressant at high doses
general
Ethanol:
describe the multifactorial mechanism of action
- membrane fluidification
- enhancement of GABA-nergic function
- inhibition and up regulation of NMDA (N-methyl-D-aspartate) receptors and increase in dopamine release
What is functional tolerance?
ppl can stand the effect of CNS depression better (can have high levels of alcohol without showing impairment)
Ethanol:
In non-tolerant individuals, impairment of judgment can be detected at levels as low as ______
25 mg/dL
What is the lethal dose of ethanol in adults?
5-6 g/kg
What is the legal dose of ethanol in children?
3 g/kg
What are some signs and symptoms of acute intoxication?
-flushed faces
-tachycardia
-increased sweating
-mydriasis (dilation)
-muscular incoordination
-ataxia
etc.
*more on slide 13
Describe mild ethanol intoxication (50mg/dL)
-decreased inhibition and slight incoordination
Describe mild-moderate ethanol intoxication (100 mg/dL)
- slow reaction time
- altered sensory ability
Describe mild-moderate ethanol intoxication (150mg/dL)
- altered though processes
- personality/behaviour changes
Describe moderate ethanol intoxication (200mg/dL)
- mental confusion
- nausea
- vomiting
Describe severe ethanol intoxication (300mg/dL)
- hypothermia
- hypoglycemia
- seizures
Describe potentially lethal ethanol intoxication (700 mg/dL)
- unconsciousness
- decreased reflexes
- respiratory depression
What are metabolic derangements from ethanol?
- hypoglycemia
- metabolic acidosis (due to lactate and/or ketoacids)
- hypomagnesemia
Describe management of the intoxicated patient
- uncomplicated ethanol OD (monitoring, sedatives if patient antisocial)
- glucose, oxygen, thiamine
- confirm alcohol intoxication with levels (ALWAYS ORDER ETHANOL LEVELS)
- finger stick glucose level
- electrolytes (magnesium)
- anion gap and osmol gap
Interventions:
Will emesis work?
- usually person is already vomiting
- don’t want to induce it, patient can go into a coma and have problems with aspiration pneumonitis
Interventions:
Will gastric lavage work?
only if you ingest a lot
Interventions:
Will activated charcoal work?
- alcohol doesn’t bind well to AC
- usually not used for alcohol
Interventions:
Will hemodialysis work?
-it is effective
-ethanol has small Vd and can be removed
:)
Describe complications of alcoholic liver disease
- fatty liver
- alcoholic hepatitis
- alcoholic cirrhosis
How much alcohol causes FAS (fetal alcohol syndrome) ?
any amount can affect the fetus
How does acute intoxication of alcohol affect phenytoin?
transient increase in plasma level phenytoin
How does alcoholism affect phenytoin, methadone, tolbutamide, isoniazide, and warfarin?
induces enzymes, increases clearance, creates shorter half-lives for these drugs
(therefore would reduce drug levels)
What drugs produce additive effects with alcohol?
- anti-histamines
- barbiturates
- sedative-hypnotics
Alcohol causes increased _______ toxicity
acetaminophen
What is the alcohol/acetaminophen toxicity called?
alcohol-APAP syndrome
Cimetidine ______ alcohol levels
increases
through a decrease in first pass metabolism and inhibition of P450 enzymes
What drugs can cause a disulfiram reaction with alcohol?
- tolbutamide
- carbamates
- metronidazole
What is a disulfiram reaction?
- flushing of skin
- increased HR
- SOB
- n/v
- headache
- visual disturbance
How do you treat alcohol withdrawal?
- syndrome that ranges from mild-severe effects (i.e. from agitation to “delirium tremens” and seizures)
- habituation of the organism to the CNS depressant effects, uncompensated state of overstimulation (upregulation of NMDA receptors)
- symptomatic treatment
Describe the treatment of the alcoholic patient
- diagnosis
- serotonin uptake inhibitors
- naltrexone
- acamprosate calcium
- bromocriptine
- lithium
- disulfiram ???
- non-pharm
How can methanol be absorbed?
- inhaled
- through skin
Methanol:
What is the order of kinetics at high and low concentrations?
- Zero-order kinetics at high concentrations
- First-order at low concentrations
How is methanol eliminated?
10-20% eliminated unchanged by the lungs
3% unchanged in the urine
*primarily liver metabolism
How is methanol metabolized?
Methanol –(ADH) –> formaldehyde –(ALDH)–> formic acid
Methanol:
Affinity of ADH for ethanol is __ times greater than its affinity for methanol
4
Methanol:
The conversion of formaldehyde to formic acid is very ____
rapid (half life of 1-2 minutes)
Methanol:
No accumulation of formaldehyde in the ____
blood
Methanol:
What is formate metabolism dependent upon?
The presence of tetrahydrofolate to form 10-formyl tetrahydrofolate that can be metabolized to water and carbon dioxide
Methanol:
What is the half life of formate?
as long as 20 hours in humans
What is the antidote for methanol?
ethanol
*better to have ethanol than methanol in your system
Describe the toxicity of methanol and it’s metabolites
- Methanol has low toxicity
- Formaldehyde and formic acid are the toxic metabolites
Methanol toxicity will cause _____ _____
metabolic acidosis
What are some indirect effects of methanol toxicity
- mitochondria toxicity
- binding to cytochrome oxidase
- interference with the intracellular respiration
- tissue hypoxia
- anaerobic metabolism
- increased ration NADH to NAD+, lactate production
How does methanol cause ocular toxicity?
- caused directly by FORMIC ACID
- acidosis increases toxicity by favouring diffusion (vision can improve if acidosis is corrected)
- inhibition of retinal and optic nerve mitochondrial function (interference with cytochrome oxidase and with Na+/K+ ATPase system) (hypoxia, depletion of retinal and optic nerve ATP)
What formate concentration causes ocular toxicity?
> 20-30 mg/dL
_____ is the primary site of ocular toxicity with methanol
retina
What are the secondary sites of ocular toxicity with methanol?
retinal ganglion cells and retrotubular optic nerve
Describe the symptoms of ocular toxicity associated with methanol
- blurred vision
- “snow field” vision
- fundoscopic examination shows hyperaemia of the optic disc and retinal edema
- reduced pupillary response to light
Permanent sequelae:
- optic atrophy
- peripheral constriction of visual fields
- central scotoma
- reduced visual acuity
- loss of color vision
- blindness
What is the treatment for methanol toxicity?
- Standard supportive care
- Correction of academia (IV sodium bicarbonate)
- Fomepizole or ethanol
- fomepizole is the antidote
- iv folinic acid
- hemodialysis
What is the action serum level of methanol to do hemodialysis
> 25 mg/dL
Why are we less worried if methanol is taken with ethanol?
bc ethanol will inhibit methanol metabolism
What do we need to assess if there is a methanol toxicity?
- the circumstances
- time after ingestion
- ethanol co-ingestion (b/c then you are less worried bc of inhibition of methanol metabolism)
- evaluation of acidosis, osmol gap, ethanol and methanol levels, anion gap
Describe folic acid vs folonic acid
- Folic acid is reduced in vivo to tetrahydrofolic acid by dihydrofolic acid reductase
- Folinic acid is the 5-formyl tetrahydrofolic acid
Why is folinic acid preferred?
since it does not require metabolic reduction
_______ or _______ as the antidote for ethylene glycol
- ethanol
- fomepizole
Ethylene Glycol:
how much is eliminated through hepatic metabolism
80%
Ethylene Glycol:
how much is unchanged in the urine
20%
Ethylene Glycol:
What is the action serum level for hemodialysis
> 25mg/dL with acidosis or renal insufficiency
What is the treatment for Ethylene Glycol toxicity?
- Ethanol (serum concentration of 100 mg/dL)
- Fomepizole (competitive inhibitor of ADH)
- Thiamine and pyridoxine (100mg and 50mg IV every 6 hours)
- Folates
- Hemodialysis
What is fomepizole
competitive inhibitor of ADH
