M3S2 Alcohol Flashcards

1
Q

Introduction to Alcohol

A

-aka ethanol
-1 of 3 most used non-medical drugs in Canada along side caffeine and nicotine
-consumption has decreased in the past decade, but alcohol still produces more health problems and deaths than all illicit drugs combined, resulting in enormous healthcare and social costs
-major use for extensive use and misuse of alcohol is its ready availability and the permissive attitudes to society

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

ADME of alcohol (ethanol)

A

-CHS depressant that works by slowing down brain functioning and neural activity
-ethanol is the only type of alcohol that can be safely consumed

Absorption
-absorbed rapidly from stomach (20% absorbed here) and upper small intestine (80% is absorbed here) (also passes through esophagus and large intestine)
-overall absorption rate for a given dose of ethanol is affected by:
Stomach-emptying time, or time required for the alcohol to reach the small intestine
Ethanol concentration in the gastrointestinal (GI) tract and the presence of food
-the time from the last drink to the maximal blood alcohol concentration ranges from 30 to 90 minutes

Distribution
-distributes throughout the total body water and readily gains access to the brain
-readily transfer across the placenta and distribute throughout a developing fetus

Metabolism
4 steps:
1. Alcohol dehydrogenase: ethanol converted to acetaldehyde by the enzyme alcohol dehydrogenase (ADH). This is the rate-limiting step in alcohol metabolism, meaning speed of this conversion typically sets the pace for rest of metabolism
2. MEOS: second but less important pathway, microsomal ethanol oxidizing system (MEOS), which is part of cytochrome P450 system. The MEOS contribute to the metabolism of ethanol, breaking down to acetaldehyde, especially at high doses when alcohol dehydrogenase is running at full capacity (I.e. saturated)
3. Aldehyde dehydrogenase: acetaldehyde then converted to acetate by enzyme aldehyde dehydrogenase (ALDH)
4 Acetate: aka acetic acid, further metabolized by a number of tissues into carbon dioxide and water
-> genetic variability in ethanol metabolism
-some individuals rapidly convert alcohol to acetaldehyde, causing accumulation of acetaldehyde in body (considered protective against alcoholism since accumulated acetaldehyde produces unpleasant side effects, such as a flushed face)
-second enzyme in the pathway, aldehyde dehydrogenase (ALDH) also have genetic variability in population
-> rate of ethanol metabolism
-unusual as occurs at constant rate irrespective to blood alcohol concentration (BAC)
-because alcohol dehydrogenase (ADH) becomes rate-limiting, or saturate, at 20 mg of alcohol per 100 mL of blood
-therefore, body rate of ethanol metabolism is about 120 mg ethanol/kg body weight/hour ( that is if 70 kg person metabolizes one drink per hour)

Excretion
-over 95% of ethanol is eliminated by biotransformation, particularly in liver
-remaining 5% excreted in breath, urine and sweat
-breathalyzer are used to measure the level of intoxication via excretion of ethanol in the breath

*refer to goodnotes for images

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is alcohol primarily metabolized by

A

-the enzyme alcohol dehydrogenase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Medical use of ethanol

A

Very few
-alcohol sponge applied topically to treat fever
-skin disinfectant
-as antidote in the treatment of methanol (wood alcohol) poisoning
-hand sanitizer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Clinical effect of ethanol

A

-ethanol classified as general CNS depressant
-CNS effect are proportional to blood alcohol concentration (BAC)

-to convert BAC in mg/dL to BAC represented as a percentage of weight/volume, you simply notice the decimal place three places to the left
Ex. A BAC of 100 mg/d is equal to 0.1 g per 100mL of blood or 0.1% (weight/volume)

*refer to image in on goodnotes to see conc amount verse effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

BAC and driving

A

-risk of driving and getting in an accident increases exponentially in relation to their BAC
-in 2014, approximately 29% of all fatal car accidents in Canada were associated with alcohol or alcohol and drugs combined
In Canada, for new drivers under the age of 22, a zero tolerance BAC applies. For all other drivers, having a BAC of 0.05% is a provincial offence, and having a BAC of 0.08% is a criminal offence

  • refer to graph on goodnotes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mechanism of action of alcohol

A

-affects a large number of membrane proteins that participate in signalling pathways
-however, think alcohol works through one main mechanism- by binding to the chloride ion channel adn augmenting GABA-mediated neuronal inhibition
-different binding site for alcohol than other drugs
-interaction of alcohol with chloride ion channels on dopaminergic neurons in the reward areas of the brain may explain the reinforcing effects of the drug

*refer to goodnotes for photo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Effects of short term use of alcohol (in addition to CNS)

A

CARDIOVASCULAR:
Low dose - create vasodilation (flushing) of vessels to the skin, resulting in a feeling of warmth
High dose - depress the cardiovascular system, which can lead to alterations in the normal rhythm of the heart

STOMACH:
Low dose - increased gastric secretion
High dose - irritate the lining of stomach, causing inflammation and erosion (known as gastritis). Condition causes vomiting and abdominal pain. Ulcers may be aggravated, often leading to serious gastrointestinal bleed

LIVER:
Low dose (1-3 drinks) - occasional use has no significant adverse effects on liver
High doses (>5 drinks) - acute high dose (alcohol binge) will inhibit glucose production, and in association with fasting, can lead to hypoglycaemia (low blood sugar)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Adverse effects of short term high dose alcohol use (aka binge-drinking)

A

Memory loss
-individual does not remember events while under the influence
-can be frightening and may result in individual seeking help

Psychiatric effects
-heavily drinking often leads to depression, irritability, and over-sedation
-negative mood states, in concert with impaired judgement and impulsiveness may lead to self-harm or acts of violence

Overdose
-excessive short-term alcohol consumption can also result in overdose, which is characterized by respiratory depression, coma and death
-number of comatose drinkers die each year after aspirating their own vomit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Adverse effects of chronic high dose alcohol use

A

CNS
-numerous neurological and mental disorders associated
-ex. Alcoholic dementia which is a decrease in cognitive functioning affecting memory, judgement and thinking
-alcohol damages axons of neurons within the brain, resulting in fewer connections between neurons

Cardiovascular
-can lead to alcoholic cardiomyopathy (destruction of, or poor heart muscle)
-an increased incidence of hypertension and stroke also apparent

Liver
-lead to liver disease, which a major cause of hospitalization and deaths in North America
-at early stages, can be reversible with alcohol abstinence, but later stages irreversible and liver function is severely impaired

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Effects of alcohol use during pregnancy

A

-chronic use of high-dose ethanol throughout pregnancy can produce teratogenic effects in the embryo/fetus, which can manifest postnatally as Fetal Alcohol Spectrum Disorder (FASD)
-FASD about 9 per 1000 live births
- a safe dose of ethanol in pregnancy has not been established, therefore, alcohol abstinence during pregnancy is recommended

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are some distinct facial features of individuals with FASD

A

-short palpebral fissures
-short nose
-thin upper lip
-flat mid face
-indisitinct philtrium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Alcohol and drug interactions

A

-2 ways depending on if drug and alcohol in body at same time or not

Alcohol use during drug therapy
-ingestion of ethanol and other CNS depressants leads to additive or synergistic effect of CNS depression
-inhibition of metabolism of certain drugs (ex. Sedative-hypnotics)

Chronic alcohol use before drug therapy (abstaining alcohol during drug therapy tho)
-only occur if no co-existing ethanol-induced liver injury
-increases the activity of metabolizing enzymes in the liver, resulting in increased metabolism of certain drugs (ex. Sedative-hypnotics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Alcohol potential for misuse and SUD

A

-alcohol produces both reinforcing and sedating effects in CNS

Potential for misuse
-since significant reinforcing properties, misuse potential is moderate
-ease of availability and social and legal acceptance contributes to enthanol’s misuse potential
-inherited harmfulness is moderate
-death can occur from high dose acute ethanol ingestion and chronic ingestion can have long-term effects of heath
-ethanol less inherently harmful than methanol

Tolerance
-individuals can develop tolerance more rapidly to ethanol-induced impairment of performance task when they perform that task repeatedly under the influence of ethanol

Cross-tolerance
Occurs between alcohol and
1. Sedative-hypnotics: a higher dose of a sedative-hypnotic drug is required for the desired therapeutic use
2. General anaesthetics; higher dose of anesthetic agent required for surgical anesthesia in someone who has developed alcohol tolerance

Withdrawal
Withdrawal from ethanol produces compensatory excitation of CNS (ex. Auroral stimulation)
-in severe cases of ethanol withdrawal, delirium tremens (DTs) may occur, which can involve convulsions, coma and possibly death
*refer to goodnotes image of chart and specific symptoms

Addiction
-compulsive desire to seek, obtain and drink ethanol exists
-addiction could be most powerful factor in chronic use of ethanol, contributing to SUD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the pharmacological basis for using benzodiazepines to thereat alcohol withdrawal symptoms

A

-initial therapy of alcohol withdraw syndrome is to maintain fluid and electrolyte balance, to prevent seziures
-more severe withdrawal can be treated effectively by oral administration of diazepam, a benzodiazepine
-use this as followings similar mechanism of action
-following successful withdrawal of the patient from ethanol, the dose of diazepam is decreased gradually over the course of several days to weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Drugs used to treat alcohol use disorder

A

-numerous of drugs can that used as pharmacological adjuncts to psychotherapy or group therapy, and referred to as alcohol-deterrent or alcohol-sensitizing drugs

Ex. Naltrexone
-an opioid antagonist
-effective in treatment of alcohol addiction
-diminishes the craving of ethanol and assists in the maintenance of abstinence
-blocks activation of dopaminergic reward pathways in the brain

17
Q

Summary of alcohol

A

*refer to goodnotes image

18
Q

True or false: alcohol classified at a CNS stimulant

A

False
-is a CNS depressant tho