Lesson B3 - Pharmacology

Question 1

The sedative-hypnotic agents are central nervous system (CNS)

Answer 1

depressants.

Question 2

These drugs produce dose-dependent CNS depression ranging from: antianxiety effect → sedation → hypnosis (sleep) →

Answer 2

general anesthesia.

Question 3

The magnitude of CNS depression produced by a drug at a particular dose determines whether the agent is considered

Answer 3

as an antianxiety agent, a sedative, or a hypnotic at that dose.

Question 4

The first agents to be introduced into clinical medicine as sedatives and hypnotics were the

Answer 4

bromides in the mid 19th century.

Question 5

Antianxiety relief

Answer 5

The benzodiazepines are the drugs of choice.

Question 6

Sedative (reduce sensory-motor function, reduce tension):

Answer 6

The wide margin of safety of
the benzodiazepines allows these drugs to be used in clinical situations where sedation is
required.

Question 7

Hypnotic (sleep):

Answer 7

The short-acting benzodiazepines are the drugs most widely used as
hypnotics.

Question 8

Anticonvulsant agent for certain types of epilepsy:

Answer 8

Phenobarbital has been used to control
generalized tonic-clonic and partial seizures. Some of the benzodiazepines are useful in
absence seizures and status epilepticus.

Question 9

Treatment of skeletal muscle spasm:

Answer 9

Benzodiazepines reduce elevated skeletal muscle

tone and are useful in neuromuscular disorders, e.g. cerebral palsy.

Question 10

Treatment of alcohol withdrawal syndrome:

Answer 10

Most of the benzodiazepines are useful in the
treatment of alcohol withdrawal. There is cross-dependence on the two agents, diazepam
substituting for alcohol. Diazepam is the drug of choice.

Question 11

These receptors are highest in density in the cerebral cortex, cerebellum and limbic system.
These drugs:

Answer 11

(a) Increase synaptic inhibition and thus dampen neuronal responses.

By activating the benzodiazepine receptor, they enhance the action of gamma- aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS. The sites of action include the cerebellum, cerebral cortex, limbic system, reticular activating system, and the spinal cord. They act on the same structure as GABA, but not on the GABA receptor.

Question 12

benzodiazepines

Answer 12

1. They possess a very high therapeutic index.
2. They produce relief from anxiety
3. They can decrease aggression.
4. They produce sedation and amnesia.
5. Some members of this group are effective hypnotics (drowsiness, facilitates onset and
   maintenance of sleep).
6. They produce minimal suppression of rapid-eye-movement (REM)-type sleep with
   hypnotic benzodiazepines (e.g. flurazepam) at normal doses.
7. They produce skeletal muscle relaxation (e.g. diazepam).
8. They have anticonvulsant action (e.g. diazepam for status epilepticus), i.e. an acute
   episode of seizures.

Question 13

Pharmacokinetics: This is the pharmacological property for which there are appreciable
differences among the various benzodiazepines. They have different

Answer 13

durations of action, which
is determined by rate of liver metabolism and formation or lack of pharmacologically active
metabolites.

Question 14

Benzodiazepines

Answer 14

(e.g. diazepine, flurazepam

Diazepam is used as an anxiolytic and anticonvulsant. Flurazepam is
used as a hypnotic.

Question 15

Barbiturates

Answer 15

e.g. phenobarbital)

Question 16

Routes of administration: Benzodiazepines are usually taken as a capsule or tablet, but some
are available

Answer 16

e for intravenous use.

Question 17

Benzodiazepines- Effects of short-term use – low to moderate doses: CNS; the desirable effects are the relief
from

Answer 17

anxiety and tension, relaxation and calmness. Other effects may include mild to moderate
impairment of motor coordination, drowsiness, lethargy, fatigue, and impairment of thinking and
memory. Respiratory depression has been observed following rapid intravenous
administration. Gastrointestinal symptoms are nausea, constipation, dry mouth and abdominal
discomfort.

Question 18

Benzodiazepines-Effects of short-term use – higher doses:

Answer 18

The major effects of higher doses are drowsiness,
over-sedation and sleep. Prior to sleep, the clinical picture may resemble an intoxicated state.
The subject would have blurred vision, incoordination, slow reflexes, and impaired thought.

Question 19

Benzodiazepines-Effects of long-term use:

Answer 19

The effects of long-term use varies between individuals. Some
individuals can take large amounts for long periods of time without any major evidence of
intoxication, while others will demonstrate the symptoms of chronic sedative-hypnotic
intoxication. These are: impaired thinking, poor memory and judgement, disorientation, slurred
speech, incoordination, and weak muscles.

Question 20

Lethality: The benzodiazepines are among the drugs most commonly involved in overdose.
Fortunately, the wide margin of safety for these drugs means

Answer 20

that deaths from overdoses are very

rare.

Question 21

Tolerance develops to the sedative and impairment of coordination effects of the
benzodiazepines. Tolerance to the anxiolytic effect

Answer 21

is less common

Question 22

Physical dependence/withdrawal: It is generally acknowledged that, for the millions of
patients who take benzodiazepines for short periods (up to a few months), the risk of physical
dependence is

Answer 22

low

Question 23

Psychological dependence (addiction) may develop in some users, but by no means all. There 
is a persistent

Answer 23

craving for the drug, even when it no longer produces an effect.

Question 24

Patterns of use: The benzodiazepines are among the most widely

Answer 24

prescribed drugs in the world

Question 25

Diazepam and

lorazepam are the preferred drugs and are often used in combination with

Answer 25

alcohol to enhance the

effect of alcohol.

Question 26

Potential for abuse: Benzodiazepines have a low

Answer 26

abuse liability-They have weaker

reinforcing properties than barbiturates, alcohol, opioids and stimulants

Question 27

Benzodiazepines inherent

harmfulness is

Answer 27

low-The margin of safety is high; they may make one uncoordinated, but
they do not depress respiration at these doses and do not often lead to death.

Question 28

The clinical uses for the barbiturates are limited. The short-acting ones are used to induce

Answer 28

anesthesia, and phenobarbital (a long-acting agent) is used as an antiepileptic.

Question 29

The action of the barbiturates is

Answer 29

less selective than that of the benzodiazepines on the CNS.

Question 30

barbiturates potentiate the effect of GABA at its receptor, enhancing the inhibitory effect of GABA, but they do not bind to

Answer 30

the benzodiazepine receptor but have their own binding sites. Through this
mechanism they modulate the chloride channel.

Question 31

The pharmacological properties/effects of the barbiturates are:

Answer 31

1. They possess a low therapeutic index. The dose required to produce a beneficial effect is
   close to the dose that will produce a toxicity.
2. The barbiturates demonstrate a full spectrum of dose-dependent CNS depression.
   Antianxiety → sedation → hypnosis → general anesthesia → death.
3. When used as a hypnotic (e.g. secobarbital), they suppress REM-type sleep. REM sleep is
   essential so that we do not wake up feeling “not having slept”.
4. Some of the long-acting barbiturates are effective in suppressing epileptic seizures.
5. Thiopental, an ultrashort-acting drug, is used to induce general anesthesia. It also
   suppresses respiration, but the patient is artificially ventilated.
6. Respiratory depression is a major problem and is dose-dependent.
7. The cardiovascular system is depressed by high doses. The response usually seen is a
   slowing of the heart and lowering of blood pressure

Question 32

Barbiturates are classified according to their duration of action:

Answer 32

Long-acting (1-2 days), e.g. phenobarbital.
Short-acting (3-8 hours), e.g. secobarbital (seconal).
Ultrashort-acting (20 minutes), e.g. thiopental.

Question 33

Barbiturates-Routes of administration: For medical use in epilepsy, the usual route is

Answer 33

oral

Question 34

Barbiturates-Effects of short-term use – low doses:

Answer 34

Low doses usually result in tranquillity, relaxation, mild euphoria, and reduced interest in one’s surroundings

Question 35

Barbiturates-Effects of short-term use – moderate doses:

Answer 35

Moderate doses induce sleep. Prior to sleep, there
is a period of increased activity (the drug inhibits an inhibitory pathway), a pleasurable state of
intoxication, and euphoria.

Question 36

Barbiturates-Effect of short-term use – high doses:

Answer 36

Sleep is highly probable and the subject may lose

consciousness.

Question 37

Barbiturates-Effects of long-term use:

Answer 37

Chronic inebriation is the term which best describes long-term use.
Memory, judgement and thinking are impaired

Question 38

Lethality with barbiturates is common, especially when combined with alcohol. There are no
specific antidotes for barbiturate poisoning as there is

Answer 38

with the opioid

Question 39

Tolerance can develop very rapidly to sleep induction and

Answer 39

the mood effects of the barbiturates,
often within a few weeks of nightly administration. Tolerance develops more slowly to the
impaired motor coordination and slowed reaction time.

Question 40

Psychological dependence (addiction) on barbiturates can result from regular use, irrespective 
of the

Answer 40

dose

Question 41

Physical dependence/withdrawal usually follows abrupt discontinuance of the barbiturates.
The syndrome following withdrawal after low doses presents as

Answer 41

disturbances.

Question 42

Patterns of use: Barbiturates are prescribed much less in 2010 than 40 years ago. Illicit use
continues to be a problem. Barbiturates are sometimes combined with heroin and the mixture
given intravenously to obtain a pleasurable

Answer 42

“high”

Question 43

Potential for abuse: The abuse liability of the barbiturates is equal to or

Answer 43

greater than alcohol.

Question 44

The inherent harmfulness of the barbiturates is

Answer 44

very high

Question 45

Flumazenil is a GABAA receptor antagonist and blocks the effect of the

Answer 45

benzodiazepines

Question 46

Zolpidem is a new GABA receptor agonist and may have advantages over the

Answer 46

benzodiazepines as a hypnotic as it does not disturb sleep patterns (REM sleep) to the same extent as the
benzodiazepines.

Question 47

Buspirone does not act on the GABA receptor, but rather at the 5-HT receptor. It is used in
generalized

Answer 47

anxiety states and may have an advantage over other sedatives in that it does not
appear to have an additive effect with other sedative-hypnotic drugs.

Question 48

Chloral hydrate is an old drug that was once widely used as a

Answer 48

hypnotic