Pharmacology: anti anxiety and hypnotic drugs

Question 1

Describe the normal processing of information in the brain, versus the processing of information in anxiety

Answer 1

Information normally goes from sensory thalamus via cortex and sometimes hippocampus to the amygdala, where an emotional response is produced

In anxiety, information shortcuts from the sensory thalamus to the amygdala - missing the context and interpretation of stimulus

Question 2

What are the two neurotransmitters implicated in anxiety?
What happens to the ratio of these in anxiety?

Answer 2

Glutamate and GABA
Not enough yo GABA GABA makes me anxious. Too little GABA, too much glutamate

Question 3

Glutamate and GABA: describe
- Whether they are excitatory or inhibitory
- Their ionotropic receptors
- Their GPCRs

Answer 3

Question 4

Anxiety treatments:
- First line treatments?
- Second line treatments?
- Short term treatments?
- Other options for difficult to treat anxiety?

Answer 4

First line: SSRIs, CBT
Second line: SNRIs, TCA’s
Short term: benzodiazepines
Difficult to treat: antipsychotics, antiseizure, beta blockers

Question 5

BENZODIAZEPINES
- Mechanism of action?

Answer 5

GABA-A receptors are ionotropic, enabling Cl- influx into neurons –> hyperpolarisation.

Benzodiazepines bind to an allosteric site on GABA-A receptors. So when GABA binds, there’s increased Cl- inlux and hyperpolarisation.

Question 6

BENZODIAZEPINES
- Naming?
- Examples?

Answer 6

-azepam
Diazepam (valium), temazepam, clonazepam

Question 7

BENZODIAZEPINES
Absorption
- Well absorbed or not?
- Route of administration?

Distribition
- Water or lipid soluble? Consequences?
- Can some forms be strongly protein bound?

Answer 7

Well absorbed, orally
Lipid soluble - can cross the BBB, high volume of distribution (accumulate in body fat)
Yes

Question 8

BENZODIAZEPINES
Metabolism and excretion
- Describe it’s conjugation, and how this assists with excretion
- Can different types have different half lives/durations of action?
- Are there various active metaboiltes?

Answer 8

Conjugated with glucuronide or OH; more water soluble –> renally excreted.
Yes
Yes

Question 9

BENZODIAZEPINES
Indications?

Answer 9

Acute anxiety reduction (anxiolytic)

Induce sleep (treat insomnia - however doesn’t produce quality, restful sleep as lack of REM sleep)

Inhibit seizures (given intranasally or rectally - fast, patient can’t swallow)

Induce skeletal muscle relaxation (to treat muscle spasm - but not an approved indication)

Anterograde amnesia

Palliative care (clonazepam)

Question 10

BENZODIAZEPINES
Adverse reactions?

Answer 10

CNS depression
Sometimes paradoxical aggression and irritability
Tolerance
Withdrawal

Question 11

BENZODIAZEPINES - ADRs
CNS depression
- Examples?
- Do they interact with other CNS depressants and alcohol?

Withdrawal
- Effects of withdrawal?

Answer 11

Drowsiness, confusion, amnesia, impaired coordination, hangover effect
Yes

Heightened anxiety, rebound REM sleep, tremor, tinitus, weight loss

Question 12

BENZODIAZEPINES
Antidote? MOA?

Answer 12

Flumazenil - competitive antagonist at the allosteric site.

Question 13

HYPNOTIC DRUGS
Indication?

Answer 13

Insomnia - hypnotic drugs help you sleep

Question 14

HYPNOTIC DRUGS
3 examples?

Answer 14

Z drugs (zolpidem, zopiclone)
Melatonin receptor agonists (melatonin)
Suvorexant

Question 15

HYPNOTIC DRUGS
Z drugs - zolpidem and zopiclone
- MOA
- ADRs?

Answer 15

Non benzodiazepines that bind to the same allosteric site, to modulate GABA-A signalling
Don’t have anxiolytic effect, but do have tolerance/dependence problems.

Question 16

HYPNOTIC DRUGS
Suvorexant
MOA?

Answer 16

Orexins are neuropeptides implicated in the sleep wake cycle. Their levels are high in daylight/wakefulness, and low at night/sleepy

Suvorexant is an orexin receptor antagonist