Lecture 12 - Alcohols Flashcards

1
Q

What is an osmol gap?

A

difference between the measured osmolality and the calculated osmolarity

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2
Q

Osmolarity

A

measure of the total number of particles in one liter of solution (molar concentrations) - usually calculated

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3
Q

Osmolality

A

differs from osmolarity only in that the number of particles is expressed per kg of solution (molal concentrations) - usually measured

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4
Q

_____ is usually calculated

A

osmolarity

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5
Q

____ is usually measured

A

osmolality

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6
Q

What is the formula for calculated osmolarity (mosm) ?

A

2 x [Na+] + [glucose] + [BUN]

**concentrations are in mmol/L

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7
Q

What is BUN ?

A

blood urea nitrogen

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8
Q

What is the normal values of BUN ?

A

3.0 - 7.1 mmol/L (8-20 mg/dL)

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9
Q

What does the measurement of osmolality tell us?

A

freezing point depression

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10
Q

Serum osmolality may be _______ by contributions of circulation alcohols and other low MW substances.

A

increased

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11
Q

What is the formula for osmol gap ?

A

difference between osmol measured and osmol calculated

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12
Q

What is the normal range for osmol gap?

A

10 +/- 6 mOsm

*in an intoxication of alcohol, this will go very high

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13
Q

Ethanol:

how much is eliminated by enzymatic oxidation?

A

90-95%

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14
Q

Ethanol:

how much is excreted unchanged?

A

5-10% excreted unchanged (kidney, liver, lungs)

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15
Q

What is the ratio of alcohol in alveolar air to blood?

A

1: 2100 alveolar air/blood

* small but fixed ratio - can very accurately estimate blood levels from how much is in the breath

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16
Q

Ethanol elimination happens through what kind of kinetics?

A

michaelis-menten

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17
Q

What is the rate of elimination in occasional drinkers?

A

100-125 mg/kg/h

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18
Q

What is the rate of elimination in habitual drinkers/alcoholics?

A

175 mg/kg/h

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19
Q

alcohol induces it’s own _____

A

enzymes

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20
Q

Chronic alcoholics have higher _______ than others

A

metabolism

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21
Q

Ethanol:

_____ CNS depressant at low doses

A

selective

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22
Q

Ethanol:

_____ CNS depressant at high doses

A

general

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23
Q

Ethanol:

describe the multifactorial mechanism of action

A
  • membrane fluidification
  • enhancement of GABA-nergic function
  • inhibition and up regulation of NMDA (N-methyl-D-aspartate) receptors and increase in dopamine release
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24
Q

What is functional tolerance?

A

ppl can stand the effect of CNS depression better (can have high levels of alcohol without showing impairment)

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25
Q

Ethanol:

In non-tolerant individuals, impairment of judgment can be detected at levels as low as ______

A

25 mg/dL

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26
Q

What is the lethal dose of ethanol in adults?

A

5-6 g/kg

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27
Q

What is the legal dose of ethanol in children?

A

3 g/kg

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28
Q

What are some signs and symptoms of acute intoxication?

A

-flushed faces
-tachycardia
-increased sweating
-mydriasis (dilation)
-muscular incoordination
-ataxia
etc.
*more on slide 13

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29
Q

Describe mild ethanol intoxication (50mg/dL)

A

-decreased inhibition and slight incoordination

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30
Q

Describe mild-moderate ethanol intoxication (100 mg/dL)

A
  • slow reaction time

- altered sensory ability

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31
Q

Describe mild-moderate ethanol intoxication (150mg/dL)

A
  • altered though processes

- personality/behaviour changes

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32
Q

Describe moderate ethanol intoxication (200mg/dL)

A
  • mental confusion
  • nausea
  • vomiting
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33
Q

Describe severe ethanol intoxication (300mg/dL)

A
  • hypothermia
  • hypoglycemia
  • seizures
34
Q

Describe potentially lethal ethanol intoxication (700 mg/dL)

A
  • unconsciousness
  • decreased reflexes
  • respiratory depression
35
Q

What are metabolic derangements from ethanol?

A
  • hypoglycemia
  • metabolic acidosis (due to lactate and/or ketoacids)
  • hypomagnesemia
36
Q

Describe management of the intoxicated patient

A
  • 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
37
Q

Interventions:

Will emesis work?

A
  • usually person is already vomiting

- don’t want to induce it, patient can go into a coma and have problems with aspiration pneumonitis

38
Q

Interventions:

Will gastric lavage work?

A

only if you ingest a lot

39
Q

Interventions:

Will activated charcoal work?

A
  • alcohol doesn’t bind well to AC

- usually not used for alcohol

40
Q

Interventions:

Will hemodialysis work?

A

-it is effective
-ethanol has small Vd and can be removed
:)

41
Q

Describe complications of alcoholic liver disease

A
  • fatty liver
  • alcoholic hepatitis
  • alcoholic cirrhosis
42
Q

How much alcohol causes FAS (fetal alcohol syndrome) ?

A

any amount can affect the fetus

43
Q

How does acute intoxication of alcohol affect phenytoin?

A

transient increase in plasma level phenytoin

44
Q

How does alcoholism affect phenytoin, methadone, tolbutamide, isoniazide, and warfarin?

A

induces enzymes, increases clearance, creates shorter half-lives for these drugs

(therefore would reduce drug levels)

45
Q

What drugs produce additive effects with alcohol?

A
  • anti-histamines
  • barbiturates
  • sedative-hypnotics
46
Q

Alcohol causes increased _______ toxicity

A

acetaminophen

47
Q

What is the alcohol/acetaminophen toxicity called?

A

alcohol-APAP syndrome

48
Q

Cimetidine ______ alcohol levels

A

increases

through a decrease in first pass metabolism and inhibition of P450 enzymes

49
Q

What drugs can cause a disulfiram reaction with alcohol?

A
  • tolbutamide
  • carbamates
  • metronidazole
50
Q

What is a disulfiram reaction?

A
  • flushing of skin
  • increased HR
  • SOB
  • n/v
  • headache
  • visual disturbance
51
Q

How do you treat alcohol withdrawal?

A
  • 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
52
Q

Describe the treatment of the alcoholic patient

A
  • diagnosis
  • serotonin uptake inhibitors
  • naltrexone
  • acamprosate calcium
  • bromocriptine
  • lithium
  • disulfiram ???
  • non-pharm
53
Q

How can methanol be absorbed?

A
  • inhaled

- through skin

54
Q

Methanol:

What is the order of kinetics at high and low concentrations?

A
  • Zero-order kinetics at high concentrations

- First-order at low concentrations

55
Q

How is methanol eliminated?

A

10-20% eliminated unchanged by the lungs

3% unchanged in the urine

*primarily liver metabolism

56
Q

How is methanol metabolized?

A

Methanol –(ADH) –> formaldehyde –(ALDH)–> formic acid

57
Q

Methanol:

Affinity of ADH for ethanol is __ times greater than its affinity for methanol

A

4

58
Q

Methanol:

The conversion of formaldehyde to formic acid is very ____

A

rapid (half life of 1-2 minutes)

59
Q

Methanol:

No accumulation of formaldehyde in the ____

A

blood

60
Q

Methanol:

What is formate metabolism dependent upon?

A

The presence of tetrahydrofolate to form 10-formyl tetrahydrofolate that can be metabolized to water and carbon dioxide

61
Q

Methanol:

What is the half life of formate?

A

as long as 20 hours in humans

62
Q

What is the antidote for methanol?

A

ethanol

*better to have ethanol than methanol in your system

63
Q

Describe the toxicity of methanol and it’s metabolites

A
  • Methanol has low toxicity

- Formaldehyde and formic acid are the toxic metabolites

64
Q

Methanol toxicity will cause _____ _____

A

metabolic acidosis

65
Q

What are some indirect effects of methanol toxicity

A
  • mitochondria toxicity
  • binding to cytochrome oxidase
  • interference with the intracellular respiration
  • tissue hypoxia
  • anaerobic metabolism
  • increased ration NADH to NAD+, lactate production
66
Q

How does methanol cause ocular toxicity?

A
  • 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)
67
Q

What formate concentration causes ocular toxicity?

A

> 20-30 mg/dL

68
Q

_____ is the primary site of ocular toxicity with methanol

A

retina

69
Q

What are the secondary sites of ocular toxicity with methanol?

A

retinal ganglion cells and retrotubular optic nerve

70
Q

Describe the symptoms of ocular toxicity associated with methanol

A
  • 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
71
Q

What is the treatment for methanol toxicity?

A
  • Standard supportive care
  • Correction of academia (IV sodium bicarbonate)
  • Fomepizole or ethanol
  • fomepizole is the antidote
  • iv folinic acid
  • hemodialysis
72
Q

What is the action serum level of methanol to do hemodialysis

A

> 25 mg/dL

73
Q

Why are we less worried if methanol is taken with ethanol?

A

bc ethanol will inhibit methanol metabolism

74
Q

What do we need to assess if there is a methanol toxicity?

A
  • 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
75
Q

Describe folic acid vs folonic acid

A
  • Folic acid is reduced in vivo to tetrahydrofolic acid by dihydrofolic acid reductase
  • Folinic acid is the 5-formyl tetrahydrofolic acid
76
Q

Why is folinic acid preferred?

A

since it does not require metabolic reduction

77
Q

_______ or _______ as the antidote for ethylene glycol

A
  • ethanol

- fomepizole

78
Q

Ethylene Glycol:

how much is eliminated through hepatic metabolism

A

80%

79
Q

Ethylene Glycol:

how much is unchanged in the urine

A

20%

80
Q

Ethylene Glycol:

What is the action serum level for hemodialysis

A

> 25mg/dL with acidosis or renal insufficiency

81
Q

What is the treatment for Ethylene Glycol toxicity?

A
  • Ethanol (serum concentration of 100 mg/dL)
  • Fomepizole (competitive inhibitor of ADH)
  • Thiamine and pyridoxine (100mg and 50mg IV every 6 hours)
  • Folates
  • Hemodialysis
82
Q

What is fomepizole

A

competitive inhibitor of ADH