Drugs That Promote WAKEFULNESS Flashcards
Drugs that cause AWAKEfulness
Will target the following pathways
3
- Potentate the ascending arousal pathway signalling at =
Ach, histamine, 5Ht, NA, OREXIN - Dampen the VLPO
- Enhance process S markers
Presentation of Narcolepsy
- Sleep wake disregulation
- Catalepsy (loss of muscle tone or control, triggered by emotions) accompanied by a state of consciousness
- Hallucinations
- Sleep paralysis and disturbed sleep
- Motor, cognitive psychiatric, metabolic and autonomic disturbances
3 narcolepsy disease profiles
- NARCOLEPSY TYPE 1
. Calaplexy
. Orexin deficiency - NARCOLEPSY TYPE 2
. No cataplexy
. Orexin deficiency not present - NARCOLEPSY UNSPECIFIED
Not NT1 or NT2
Pathophysiology of narcolepsy
- Genetic predisposition»_space;> trigger event that leads to selective, immune mediates destruction of orexin-producing neurons (selective loss)»_space; OR AND
antibodies of anti streptococcal infections from flu and vaccines
Management approaches
Structured night time sleep
Scheduled and prn napping
Wake promoting agents
Cataplexy = antidepressants (TCA, SSRI, NRIs, pitolisant
List meds to improve wakefulness
- Modafinil, armodafinil,
- Dexamfetamine, methylphenidate
- Sodium oxybate
- Solriamfetol
moa of MODANAFIL, armodafinil
Competitive binding to cell membrane transporters for
DA in VPAG area and for
NE in the VLPO area
=
Stimulates:
Histamine release
Orexin release
MODANAFIL, armodafinil
Use caution in ….
. CVD
. Hx of psychiatric disorders
. Hx of substance abuse
. Hepatic disease + elderly
. Avoid in woman of childbearing age unless contraception used
When can modanafil be used (as per PBS subsidy)?
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
Moa of amphetamines
Sympathomimetic amines with CNS stimulant activity
Leads to increase DA and NE in synaptic spaces by blocking reuptake by competitive inhibition of transporters
Amfetamines contraindicated in…
. Hyperthyroidism
. Tourette syndrome
. Glaucoma
. Cardiac conditions
. Severe depression, anorexia nervous, psychosis, agitation or suicidal tendencies
.
- Psychiatric disorder
- CV disorder
- History of substance misuse
- Glaucoma
Reasons that pose as UNACCEPTABLE RISK in taking dexamfetamine
4
Repeat q
Psychiatric disorder
CVD
History of substance misuse
Glaucoma
Sodium oxybate
Moa
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
Which class is sodium oxybate in?
Schedule 8
Dosing regimen and routine of sodium oxybate
Take first dose 2 hours after eating food
Take it while in bed and lay down immediately after dosing. Remain in bed
Solriamfetol
Moa
Inhibits DA/NE reuptake through DAT/NET
Pitolisant
Moa
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
Adenosine MOA
Adenosine A1 receptors inhibit neuronal transmission.
This is done by
Binding to adenosine receptors A1 and blocks adenosine actions = awake
Treatment of cataplexy
. Clomipramine TCA (indicated)
Off label use::
. Fluoxetine, fluvoxamine (SSRI)
. Venlafaxine, duloxetine (SNRI)
. Atomexetine (NRI)
Is sodium oxybate registered in Australia?
No
Which have a high abuse potential?
Amfetamines or modafinil/armodafinil ??
Amfetamines
What is narcolepsy
Rare
Hypothalamic disorder
Sodium oxybate
C/I
- In combination with sedative hypnotics or alcohol
- Ppl with
Succinic semialdehyde dehydrogenase deficiency - History of substance misuse
