302 The effects of alcohol on the brain

Question 1

Which molecules in the brain are directly affected by alcohol?

Answer 1

Decreased glutamate

Increased Mu opiates, cannabinoids, and GABA

Question 2

What effects of alcohol are related to GABA?

Answer 2

-Anxiolytic (short term)
-Frontal lobe inhibition: Disinhibition, Poor planning, Impulsivity
-Ataxic: Difficulty walking when intoxicating
-Sedating
-Amnesic – including alcohol induced blackouts

Chronic administration causes excess inhibition and downregulation of GABA receptors

Question 3

What are the effects on GABA receptors after cessation of alcohol after chronic use?

Answer 3

There are few GABA receptors because of downregulation so endogenous GABA can’t activate many receptors therefore there is a net excitatory effect because glutamate goes unchecked

Therefore by day 2 of cessation, there are seizures and by day 3 there are delirium tremens

Question 4

What are the symptoms of delirium tremens?

Answer 4

Agitation
Global confusion
Disorientation
Hallucinations
Fever
Autonomic hyperactivity: sweating, dehydration, tachycardia

Question 5

How is delirium tremens treated?

Answer 5

Supportive care and treatment of comorbidities

Question 6

What is the mortality rate of delirium tremens?

Answer 6

5% mortality rate
-Usually secondary to cardiovascular collapse or infection

50% associated with comorbid infection or trauma

Question 7

What are the aims of pharmacological management of alcohol withdrawal in hospital?

Answer 7

-Primary aim
Prevent seizures

-Secondary aims
Reduce unpleasant withdrawal effects
Restore sleep
Increase chance of completion of detoxification

Question 8

What are the medications of choice for management of alcohol withdrawal?

Answer 8

Chlordiazepoxide and Diazepam

Question 9

Which medications is given for minor withdrawal symptoms and prevention of seizures and delirium tremens in alcohol withdrawal?

Answer 9

Reducing regimen of benzodiazepine

Question 10

Which medication is given for generalised tonic-clonic withdrawal seizures in alcohol withdrawal?

Answer 10

Diazepam 10mg PR

Question 11

Which medication is given to treat delirium tremens in alcohol withdrawal?

Answer 11

Lorazepam 2mg PO

2nd line – lorazepam 2mg IM for management of agitation

Question 12

Name some alcohol related brain damage types

Answer 12

-Wernicke’s/Korsakoff’s delirium leading to frontal lobe dysfunction and personality changes
-Head injury
-Secondary microvascular stroke/related disorders

Question 13

What is the classical tried of Wernicke’s encephalopathy?

Answer 13

Confusion
Ataxia
Oculo-motor abnormalities
Eg. Nystagmus and 6th nerve palsy

A medical emergency with 20% mortality if untreated

Question 14

Deficiency of which vitamin causes Wernicke’s encephalopathy?

Answer 14

Thiamine (B1)

It’s important as a co-enzyme for several enzymes and without it cells die

Question 15

Which areas of the brain are primarily affected by thiamine depletion?

Answer 15

Cerebellum: Balance and coordination
Frontal lobe: personality and executive function

Memory

Question 16

How should Pabrinex be administered?

Answer 16

Administer thiamine (in pabrinex) before food or IV dextrose otherwise residual thiamine stores will preferentially be used on carbohydrate metabolism which pulls what little remains away from the brain

This can precipitate Wernicke’s

Question 17

How does alcohol dependence cause thiamine deficiency?

Answer 17

-Inadequate nutritional intake
-Changes to gastric villi and impaired absorption

Question 18

What is Korsakoff’s amnesic syndrome?

Answer 18

An abnormal mental state in which memory and learning are affected out of all proportion to other cognitive functions in an otherwise alert and responsive patient, resulting from thiamine deficiency

Symptoms:
Persistence of any Wernicke’s symptoms such as ataxia
Anterograde amnesia
Retrograde amnesia
Confabulation

Not all Wernicke’s will progress to Korsakoff’s

Not psychotic (formally called Korsakoff’s psychosis)

Question 19

What is the prognosis of Korsakoff’s amnesia?

Answer 19

Historically believed that no recovery

But:
25% no recovery
25% slight recovery
25% significant recovery
25% complete recovery

Prognosis better with abstinence
Prevention is better than cure

Question 20

What are the personality changes associated with chronic alcoholism?

Answer 20

-A loss of social, and sometimes sexual, inhibitions
-Tendency to irritability
-Facile jocularity
-Abusiveness

Question 21

What is Facile jocularity?

Answer 21

Making lotss of jokes

Question 22

What changes in body increase risk of falls with chronic alcohol use?

Answer 22

Seizures
Intoxication
Cerebellar dysfunction
Peripheral neuropathy

Question 23

What changes in the body increase the risk of bleeding with chronic alcohol use?

Answer 23

Friable vessels
Clotting factors
Platelet changes