Anxiolytics

Question 1

Anxiety disorders?

Answer 1

1. Generalized anxiety disorder (ongoing state of excessive anxiety)
2. Panic disorder (sudden attacks of fear)
3. Phobias (strong fears of objects /situations)
4. Post traumatic stress (triggered by recall of past stressful experience)
5. Obsessive compulsive disorder (compulsive ritualistic behavior driven by irrational anxiety e.g fear of contamination)

Question 2

Medical disorders linked to anxity?

Answer 2

1. Cardiovascular: angina, arrhythmias, hypertension
2. Gastrointestinal: irritable bowel syndrome, peptic ulcers
3. Respiratory: asthma
4. Endocrine: anaemia, hypoglycaemia
5. Neurological: migraine, tremor, seizures, Parkinson’s disease

Question 3

What are anxiolytics used for?

Answer 3

Used to relieve stress, tension and anxiety brought about by complex & hectic modern life
- primary use is to induce calmness
- used along psychological approaches and antidepressants

Question 4

What is anxiety?

Answer 4

an exaggerated feeling of apprehension, uncertainty and fear.
- It is an unpleasant state of tension with an anticipation of eminent danger.

Question 5

An ideal anxiolytic should not produce?

Answer 5

1. Too much daytime sedation or drowsiness
2. Psychological or physical dependence.
3. Should have low toxicity

Question 6

Anxiety drugs are refereed to as?

Answer 6

minor tranquilizers.
- Pharmacologically, these agents, when used in high doses, resemble barbiturates and are capable of causing CNS depression.
- The main advantage over barbiturates is the high sedative-to-hypnotic ratio (margin between calmness producing dose and the hypnotic dose)

Question 7

Classification of anxiolytics?

Answer 7

1. Benzodiazepines (Chlordiazepoxide, Alprazolam, Diazepam, Lorazepam, Midazolam, Prazepam).
2. Antidepressants (SSRIs, SNRIs, TCAs, and MAOIs )
3. Some antiepileptics (Gabapentin)
4. Carbamates (Meprobamate)
5. Miscellaneous (Buspirone, Hydroxyzine, Propranolol, Chlormezanone).

Question 8

Benzodiazepines?

Answer 8

• Most commonly prescribed.
• Effective at dose levels that do not produce drowsiness
• Primarily used for relief of situational anxiety (except for midazolam, a short acting agent, used parentarally for pre and post operative sedation)

Question 9

Kinetics of benzodiazepines?

Answer 9

Good oral absorption with sleep occurring within 15 – 45 minutes
Flurazepam has fastest onset of action, converted to active metabolite, with half life of 50 -100 hours. (long duration of action), produce prolonged hang over effect.
These drugs are mainly excreted in urine

Question 10

Adverse effects of benzos?

Answer 10

Daytime drowsiness, lightheadedness, headache and slight motor incoordination.
Memory impairment , disorientation, slurred speech and depression may occur.
Tolerance
Note: Dependence is less severe than with barbiturates.

Question 11

Contraindications of benzos?

Answer 11

1. Pregnant women (foetal damage has been reported with their use in early pregnancy)
2. Additive CNS depression can occur when used with other CNS depressants (alcohol, antihistamines, barbiturates)

Question 12

Gbapentin?

Answer 12

Structural analogue of GABA .May increase the activity of GABA or inhibits its re-uptake.
- antiepileptic drugs

Question 13

Pharmacokinetics of gabapentin?

Answer 13

Not bound to proteins
Not metabolized and excreted unchanged in urine
Does not induce or inhibit hepatic enzymes (similar to lamotrigine)
Plasma t ½ 5-7 hours

Question 14

Sedatives-hypnotics?

Answer 14

The primary use of sedative –hypnotics is to induce sleep in insomnia
(A wide variety of sleep disturbances)

Question 15

Classification of sedative-hypnotics?

Answer 15

A. barbituarates
1-Long acting (12-24 hr)
Ex. Phenobarbital
2-Intermediate acting (8-12hr)
Ex. Amobarbital
3-Short acting (4-8 hr)
Ex. Pentobarbital
4-Ultrashort acting (0.5-1hr)
Ex. Thiopental

B. non-barbiturates
1. Benzodiazepine
2. Non- benzodiazepine

Question 16

Kinetics of barbiturates?

Answer 16

Absorbed from the stomach, small intestines, rectum and IM sites (in varying degrees) and readily cross the BBB.
Long acting – metabolised in the liver by oxidation of radicals

Question 17

Duration of action of barbiturates depend on?

Answer 17

Rate of hepatic degradation
Their degree of lipid solubility.
Degree of protein binding. (reduces renal clearance)
Excreted via kidneys

Question 18

Mode of action of barbiturates?

Answer 18

Barbiturates depress the sensory cortex, reduce motor activity, in higher doses, impair respiration and vasomotor function in the brainstem
In the midbrain reticular formation, barbiturates elevate the threshold for electrical stimulation
This goes on to depress the firing rate of the neurons and cortical activation is decreased, leading to
Neuronal activity in the limbic system and hypothalamus is reduced by barbiturates
Facilitation of GABA activity in the brain has been observed with barbiturates.

Question 19

Therapeutic uses of barbiturates?

Answer 19

Sedative/Hypnotic agent. (infrequently, lately has been replaced by benzodiazepines)
Short term treatment of insomnia
Control of acute convulsive state
Treatment of grand mal epilepsy
Pre & post operative sedation
Induction of anaesthesia(ultra short acting)
Management of manic reactions.

Question 20

Adverse reactions of barbiturates?

Answer 20

Hangover and drowsiness
If habitually used, it may cause insomnia
Paradoxical excitement. (restlessness, excitement or delirium especially in the elderly.)
Drug automatism (a state of amnesia resulting from barbiturate poisoning)

Question 21

Non barbiturates examples?

Answer 21

Benzodiazepine hypnotics (Flurazepam etc)
Chloral Hydrate
Paraldehyde
Glutethimide
Ethchlorovynol
Ethinamate
Methprylon
Propriomazine

Question 22

Benzodiazepine as a sedative?

Answer 22

Most commonly prescribed.
Effective at dose levels that do not produce drowsiness
Primarily used for relief of situational anxiety (except for midazolam, a short acting agent, used parentarally for pre and post operative sedation)

Question 23

CVS effects of benzos?

Answer 23

CVS effects are minor, except in severe intoxication in which the blood pressure falls.

Question 24

Analgesic action of benzos?

Answer 24

Diazepam causes transient analgesia on intravenous administration. Other benzodiazepines do not have analgesic effect. Unlike barbiturates, these agents do not cause hyperanalgesia

Question 25

Antianxiety effects of benzos?

Answer 25

Exert a specific effect on the lymbic system and therefore reduce anxiety in doses which do not produce drowsiness or sleep (unlike barbiturates)
Larger doses are sedative and ultimately produce sleep.
Benzodiazepines and meprobamate diminish aggressive behaviour in animals without causing impairement of neurological function.

Question 26

Effects of benzos?

Answer 26

Effects are exclusively the result of their action on the CNS.
All agents are qualitatively similar, but quantitatively, they have differences.
These agents produce: Sedation, hypnosis, anxiolytic activity, skeletal muscle relaxation and anticonvulsant activity.

Question 27

Anticonvulsant effects of benzos?

Answer 27

These agents raise the threshold for electrically induce seizures

Question 28

Skeletal muscle relaxant effects of benzos?

Answer 28

Induce voluntary muscle relaxation (hypotonea) without affecting normal locomotion in therapeutic doses.
They reduce rigidity in patients with cerebral palsy.
In therapeutic doses, neuromuscular transmission is not affected, but an inhibition of polysynaptic reflexes within the spinal cord occurs

Question 29

Hypnotic effects of benzos?

Answer 29

Can be used as hypnotics
In therapeutic doses, they due not suppress REM sleep, but suppresses stage 4.
Most agents decrease sleep latency and reduce the number of awakenings. The net effect is an increase in total sleep time.