Lesson B8 - Pharmacology

Question 1

The major reason for the extensive use and abuse of

alcohol is

Answer 1

its ready availability and the permissive attitudes of society

Question 2

alcohol is an old drug. It was the first sedative-hypnotic drug to be used by

Answer 2

ancient physicians. The use of fermented beverages can be traced back to 8000 B.C., when mead was
prepared from honey.

Question 3

Traditionally, alcohol has been used for three major purposes.

Answer 3

In medicine as a sedative and hypnotic.
∙ For religious and other occasions, e.g. sacramental use by Christians and Jews.
∙ Recreational purposes.

Question 4

The terms “alcohol” and “ethanol” are used

Answer 4

interchangeably

Question 5

Ten to 13 ml of absolute alcohol is the amount metabolized by

Answer 5

the liver each hour.

Question 6

Ethanol is absorbed rapidly from the

Answer 6

stomach and the upper small intestine (the major site of

absorption).

Question 7

The overall absorption rate for a given dose of ethanol is affected by:

Answer 7

(a) Stomach-emptying time, or the time required for the alcohol to reach the small intestine.
(b) Ethanol concentration in the G.I. tract.

Question 8

Ethanol distributes throughout the total body water and readily distributes across the

Answer 8

blood-brain barrier.

Question 9

In pregnant women who drink alcoholic beverages, ethanol is readily transferred across the

Answer 9

placenta and distributes throughout the total body water of the fetus.

Question 10

Over 95% of ethanol in the body is eliminated by biotransformation, primarily in the

Answer 10

liver

Question 11

The remaining 5% is excreted in the

Answer 11

breath, urine and sweat.

Question 12

Aldehyde dehydrogenase (ADH) converts alcohol to acetaldehyde, and in turn aldehyde 
dehydrogenase converts acetaldehyde (ALDH) to

Answer 12

acetic acid. Acetic acid is then further
metabolized by a number of tissues. Disulfiram and calcium carbimide (drugs used to treat
alcohol abuse) inhibit aldehyde dehydrogenase, and as a result, acetaldehyde accumulates and
the individual will feel ill and presumably stop abusing alcohol to stop the adverse effects of
acetaldehyde.

Question 13

The metabolism of alcohol is unusual as it occurs at a constant rate, irrespective of the blood
alcohol concentration. A constant amount of alcohol is metabolized each hour. This is because

Answer 13

ADH becomes rate-limiting or saturated at 20 mg of alcohol per 100 ml of blood (saturation is a
term used when a process is running at full capacity)

Question 14

Ethanol is classified as a general central nervous system (CNS)

Answer 14

depressant.

Question 15

Acute use of ethanol

more obviously affects the CNS, whereas

Answer 15

chronic, high-dose use affects many organ systems of

the body including the CNS, cardiovascular system, gastrointestinal tract and liver.

Question 16

Chronic,

maternal use of high-dose ethanol can adversely affect the

Answer 16

fetus, including teratogenesis, which

can manifest as the fetal alcohol syndrome or fetal alcohol effects.

Question 17

Ethanol produces dose-dependent depression of CNS function:

disinhibition → sedation → hypnosis → general anesthesia →

Answer 17

coma

Question 18

Low dose: Disinhibition (inhibition of an inhibitory pathway in the CNS).
This is usually manifested by increased social
interaction, e.g

Answer 18

talking

Question 19

High dose: Sedation → hypnosis → general anesthesia → coma →

Answer 19

death

Question 20

A change in sleep pattern often occurs. The changes are an increase in slow-wave sleep and a

Answer 20

decrease in rapid-eye-movement sleep. A reduction in rapid-eye-movement sleep is associated with a feeling of having “slept poorly”.

Question 21

The mechanism of action of alcohol is not understood. At high concentrations of alcohol, it was believed that the drug acted as a

Answer 21

general anesthetic

Question 22

At lower alcohol

concentrations, alcohol binds to the GABA receptor and augments

Answer 22

GABA-mediated neuronal

transmission.

Question 23

Alcohol is a CNS depressant, but at low dose the response observed is one of

Answer 23

disinhibition.

Question 24

Drinkers feel gregarious,

Answer 24

jovial, relaxed and more self-confident.

Question 25

As the dose increases, the individual may demonstrate exaggerated

Answer 25

emotional responses

Question 26

Blackouts: This is the phenomenon where the drinker does not remember events while under the influence of

Answer 26

alcohol

Question 27

Psychiatric effects: Low doses of alcohol (one to three drinks) causes relaxation, while heavy drinking (five drinks or more) often leads to

Answer 27

depression, irritability and over-sedation

Question 28

Drinking and driving: Alcohol is one of the major causes of

Answer 28

automobile accidents.

Question 29

Violence: Individuals who drink heavily are more prone to violence than non-drinkers. Men who are heavy drinkers are six times more likely to assault their wives/significant others than

Answer 29

non-drinkers

Question 30

The other risks associated with excessive use of alcohol is associated with

Answer 30

respiratory | depression, coma and death.

Question 31

Central nervous system: There are a number of neurological and mental disorders associated with chronic alcohol

Answer 31

abuse. Alcohol damages the axons of the brain, resulting in fewer connections between neurons. This causes alcoholic dementia. Dementia can be defined as a global decrease in cognitive functioning, affecting memory, judgement, and thinking.

Question 32

Alcohol increases the metabolism of vitamin B1 (thiamine), resulting in thiamine deficiency. There are two conditions which result from alcohol-induced thiamine deficiency –

Answer 32

Werniche’s encephalopathy in which the patient becomes drowsy, confused and cannot walk properly, and Korsakoff’s psychosis, a severe form of dementia.

Question 33

The peripheral nervous system is also subject to alcohol damage. Alcohol damages the axons in the peripheral nervous system, resulting in a

Answer 33

peripheral neuropathy that is manifested by loss | of feeling in the feet and is often accompanied by burning pain and difficulty in walking.

Question 34

Chronic use of ethanol, especially in high doses, can lead to a state of drug dependence, often referred to as

Answer 34

alcoholism. Ethanol drinking is a serious problem when it interferes with home life, job or scholastic performance, finances or personal mental/physical health.

Question 35

Tolerance is defined as a state in which repeated administration of the same dose of drug (ethanol) has progressively less effect, or a state in which the dose of drug needs to be increased to obtain the same quantity of effect as was produced by

Answer 35

the original dose.

Question 36

During chronic use of ethanol, there is a decreased intensity of ethanol action or a shortened duration of action. A larger dose of ethanol is needed to produce the original pharmacologic effect. Recently, it has been reported that individuals can

Answer 36

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

Question 37

Mechanism:

Answer 37

1. Metabolic (dispositional, pharmacokinetic) tolerance due to increased ethanol metabolic rate. During chronic consumption of ethanol, the same dose produces a lower blood ethanol concentration or maintains the blood ethanol concentration above a certain level for a shorter time. 2. Cellular (functional, pharmacodynamic) tolerance. The CNS adapts to the effects of ethanol.

Question 38

The consensus is that

Answer 38

cellular tolerance plays a greater role in the overall development of tolerance. The extent or rate of development of tolerance depends on the individual, dose of ethanol, and frequency of ethanol administration.

Question 39

It is important to note that, normally, minimal tolerance develops to the

Answer 39

lethal dose of | ethanol.

Question 40

Physical dependence is defined as an abnormal physiologic state brought about by repeated administration of a drug that leads to the appearance of a characteristic and specific group of symptoms when drug administration is stopped or

Answer 40

decreased

Question 41

Cross-tolerance:

Answer 41

1. between ethanol and sedative hypnotics | 2. ethanol and general anesthetics

Question 42

The basis of physical dependence on ethanol primarily involves the CNS. Withdrawal from ethanol (CNS depressant) produces

Answer 42

excitability of the CNS (arousal, stimulation).

Question 43

The ethanol withdrawal syndrome can be treated effectively by oral administration of diazepam, a benzodiazepine-type sedative-hypnotic drug. The pharmacological basis for this therapy involves the principle of

Answer 43

cross-dependence, in which the withdrawal syndrome following cessation of use of a particular drug is suppressed by administration of a second drug of the same or similar pharmacological classification.

Question 44

Psychological dependence is defined as a compulsion that requires periodic or continuous administration of a drug to produce pleasure or to

Answer 44

avoid discomfort.

Question 45

The dependence liability is

Answer 45

moderate

Question 46

Acute use: Low doses of acute use lead to vasodilation (flushing) of the vessels to the skin, resulting in a feeling of warmth. High doses of alcohol can depress the cardiovascular system and lead to alterations in the

Answer 46

normal rhythm of the heart.

Question 47

Chronic use: Low chronic doses of alcohol can reduce the risk of coronary heart disease and stroke. High chronic doses can lead to alcoholic cardiomyopathy (destruction of or poor heart muscle) . In addition, there is an increased incidence of

Answer 47

hypertension and stroke.

Question 48

Low doses of alcohol will stimulate gastric secretion, and hence the use of a small dose of alcohol before a meal to stimulate digestion and enhance appetite. Higher doses of alcohol will irritate the lining of the stomach, causing inflammation and erosion (known as

Answer 48

gastritis).

Question 49

Chronic high doses of alcohol leads to alcoholic liver disease, a major cause of hospitalization and deaths in North America. There are three stages to alcoholic liver disease.

Answer 49

In stage 1, the liver cells accumulate fat, causing the liver to enlarge (fatty liver). This stage is usually asymptomatic and is reversible if the alcohol is stopped. Stage 2 is alcoholic hepatitis. The liver cells are damaged and inflamed. The stage of alcoholic hepatitis can be asymptomatic or there can be severe liver function impairment. With abstinence, hepatitis is usually

Question 50

Epidemiologic and laboratory animal studies have demonstrated that ethanol is a

Answer 50

teratogen

Question 51

Chronic, maternal use of high-dose ethanol throughout pregnancy can produce teratogenic effects in the embryo/fetus, which can manifest postnatally as the

Answer 51

Fetal Alcohol Syndrome.

Question 52

Drugs Used in the Treatment of Alcoholism: Disulfiram and Calcium Carbimide (Calcium Cyanamide) These drugs are used as pharmacological adjuncts to psychotherapy or group therapy, and are referred to as alcohol-deterrent or alcohol-sensitizing drugs. These drugs inhibit hepatic aldehyde dehydrogenase and result in

Answer 52

increased acetaldehyde concentration if the patient drinks ethanol, thereby producing cardiovascular/respiratory changes that are perceived as aversive.

Question 53

Alcohol and Drug Interactions 1. Acute ethanol use during drug therapy (body contains ethanol). )

Answer 53

1AIngestion of ethanol and other CNS depressants leads to an additive effect or synergism of CNS depression. B) Ethanol inhibits biotransformation (metabolism) of certain drugs

Question 54

Alcohol and Drug Interactions-Chronic ethanol use followed by drug therapy (no ethanol in body)

Answer 54

Ethanol causes proliferation (increase in growth) of the smooth endoplasmic reticulum of the liver cell, leading to increased activity of the liver drug-metabolizing enzyme system. There will be increased biotransformation of certain drugs (e.g. sedative-hypnotics, phenytoin), if there is no co-existing ethanol-induced liver injury