Drugs That Promote WAKEFULNESS

Question 1

Drugs that cause AWAKEfulness
Will target the following pathways
3

Answer 1

1. Potentate the ascending arousal pathway signalling at =
   Ach, histamine, 5Ht, NA, OREXIN
2. Dampen the VLPO
3. Enhance process S markers

Question 2

Presentation of Narcolepsy

Answer 2

1. Sleep wake disregulation
2. Catalepsy (loss of muscle tone or control, triggered by emotions) accompanied by a state of consciousness
3. Hallucinations
4. Sleep paralysis and disturbed sleep
5. Motor, cognitive psychiatric, metabolic and autonomic disturbances

Question 3

3 narcolepsy disease profiles

Answer 3

1. NARCOLEPSY TYPE 1
   . Calaplexy
   . Orexin deficiency
2. NARCOLEPSY TYPE 2
   . No cataplexy
   . Orexin deficiency not present
3. NARCOLEPSY UNSPECIFIED
   Not NT1 or NT2

Question 4

Pathophysiology of narcolepsy

Answer 4

1. Genetic predisposition&raquo_space;> trigger event that leads to selective, immune mediates destruction of orexin-producing neurons (selective loss)&raquo_space; OR AND
   antibodies of anti streptococcal infections from flu and vaccines

Question 5

Management approaches

Answer 5

Structured night time sleep
Scheduled and prn napping

Wake promoting agents
Cataplexy = antidepressants (TCA, SSRI, NRIs, pitolisant

Question 6

List meds to improve wakefulness

Answer 6

1. Modafinil, armodafinil,
2. Dexamfetamine, methylphenidate
3. Sodium oxybate
4. Solriamfetol

Question 7

moa of MODANAFIL, armodafinil

Answer 7

Competitive binding to cell membrane transporters for
DA in VPAG area and for
NE in the VLPO area

=
Stimulates:
Histamine release
Orexin release

Question 8

MODANAFIL, armodafinil
Use caution in ….

Answer 8

. CVD
. Hx of psychiatric disorders
. Hx of substance abuse
. Hepatic disease + elderly
. Avoid in woman of childbearing age unless contraception used

Question 9

When can modanafil be used (as per PBS subsidy)?

Answer 9

Use only when dexamfetamine poses qs unacceptable risk or intolerable

And

No history of psychiatric disorder

And

Have sl

Sleep latency test or 10 minutes

Question 10

Moa of amphetamines

Answer 10

Sympathomimetic amines with CNS stimulant activity

Leads to increase DA and NE in synaptic spaces by blocking reuptake by competitive inhibition of transporters

Question 11

Amfetamines contraindicated in…

Answer 11

. Hyperthyroidism
. Tourette syndrome
. Glaucoma
. Cardiac conditions
. Severe depression, anorexia nervous, psychosis, agitation or suicidal tendencies
.

1. Psychiatric disorder
2. CV disorder
3. History of substance misuse
4. Glaucoma

Question 12

Reasons that pose as UNACCEPTABLE RISK in taking dexamfetamine

4
Repeat q

Answer 12

Psychiatric disorder
CVD
History of substance misuse
Glaucoma

Question 13

Sodium oxybate

Moa

Answer 13

Has specific binding sites on GABA-a receptors contain a4, b1, gamma subunits and acts as partial weak agonist at GABA-B receptors

Involved in release pf neurotransmitters
GLU, NE, DA, GABA

Question 14

Which class is sodium oxybate in?

Answer 14

Schedule 8

Question 15

Dosing regimen and routine of sodium oxybate

Answer 15

Take first dose 2 hours after eating food

Take it while in bed and lay down immediately after dosing. Remain in bed

Question 16

Solriamfetol

Moa

Answer 16

Inhibits DA/NE reuptake through DAT/NET

Question 17

Pitolisant

Moa

Answer 17

H3R antagonist/inverse agonist
(H3Rs play a role in cognition compared to the H1R and H2R whoes role is mainly peripheral)

Blocks histamine release

This increases ACh and DA in cerebral cortex

Question 18

Adenosine MOA

Answer 18

Adenosine A1 receptors inhibit neuronal transmission.

This is done by

Binding to adenosine receptors A1 and blocks adenosine actions = awake

Question 19

Treatment of cataplexy

Answer 19

. Clomipramine TCA (indicated)

Off label use::
. Fluoxetine, fluvoxamine (SSRI)
. Venlafaxine, duloxetine (SNRI)
. Atomexetine (NRI)

Question 20

Is sodium oxybate registered in Australia?

Answer 20

No

Question 21

Which have a high abuse potential?

Amfetamines or modafinil/armodafinil ??

Answer 21

Amfetamines

Question 22

What is narcolepsy

Answer 22

Rare
Hypothalamic disorder

Question 23

Sodium oxybate

C/I

Answer 23

1. In combination with sedative hypnotics or alcohol
2. Ppl with
   Succinic semialdehyde dehydrogenase deficiency
3. History of substance misuse