Pharm Neuro Part 1 B

Prescription sleep aids: drug class

Non-benzodiazepine hypnotics

Non-benzodiazepine hypnotics: why the name

Act on benzodiazepine receptors; safe and effective for initiating sleep

Sleep aids: 3 drugs (generic/trade)

Zolpidem (Ambien); eszopiclone (Lunesta); zaleplon (Sonata)

Zolpidem (Ambien) dose

PO; 5 or 10 mg at bedtime

Eszopiclone (Lunesta) dose

PO; 1, 2, or 3 mg tablet at bedtime

Zaleplon (Sonata) dose

PO; 5 or 10 mg capsule at bedtime

Sleep aids: max duration and why

Not >7-10 days; habit-forming

Sleep aids: use with caution in

Elderly; respiratory dysfunction

Sleep aids: controlled substance schedule

Schedule IV (benzodiazepine-like)

Sleep aids: receptor selectivity

Highly selective for the GABA-1 receptor complex

Sleep aids: mechanism of action

Bind GABA-1 receptors → enhance chloride conductance → CNS depression

Sleep aids vs. benzodiazepines: receptor site

Act on different GABA receptor subunits

Sleep aids: other name

Nonbenzodiazepine GABAergics

Sleep aids: effect on neurons

Reduce excitability and responsiveness to stimulating signals

Sleep aids vs. benzodiazepines: properties

Strong hypnotic; weak anxiolytic, muscle relaxant, and anticonvulsant

Sleep aids: absorption

Rapid, oral

Sleep aids: distribution

Zaleplon minimally protein-bound; zolpidem 92% protein-bound

Sleep aids: metabolism

Liver, CYP3A4

Sleep aids: excretion

Kidney

Sleep aids: clinical use

Sedation during episodes of insomnia

Sleep aids: CV adverse reactions

Increased BP; chest discomfort; palpitations

Sleep aids: EENT adverse reactions

Blurry vision; red eye; altered depth perception

Sleep aids: GI adverse reactions

xerostomia

Sleep aids: MSK adverse reactions

Arthralgia; back pain; myalgia

Sleep aids: neuro adverse reactions

Headache; abnormal dreams; sleepwalking; hallucinations; lethargy

Sleep aids: contraindications

Hypersensitivity; pregnancy

Sleep aids: black box warning

Rare serious injuries from complex sleep behaviors: sleepwalking, sleep driving, other activities while not fully awake

Sleep aids: additive effects with

Benzodiazepines and alcohol

Drugs that increase sleep aid blood levels (CYP3A4 inhibitors)

Ketoconazole; erythromycin; clarithromycin; protease inhibitors

Transient sleep problems: first-line approach

Sleep hygiene programs before prescribing

Sleep aids: why take a careful OTC/herbal history?

Patients often self-treat with OTC sleep aids; avoids interactions

Sleep aids: max use without careful re-evaluation

2 weeks (acute) or 3 months (chronic)

Sleep aids: special populations

Avoid in alcoholism; use lower doses in elderly

Sleep aids: patient education - what not to combine

Alcohol; OTC sleep aids; other CNS depressants

Sleep aids: onset of action

About 20 minutes

Sleep aids: when to take

Directly before bed, only if able to sleep at least 4 hours

Sleep aids: hours of sleep patients should plan for

6-8 hours, or don't use them

Sleep aids: patient education - next-day effects

Possible daytime drowsiness; avoid driving and hazardous activities until effects known

Sleep aids: result of use >2 weeks

Likely withdrawal symptoms and psychological dependence

Sleep aid withdrawal symptoms

Fatigue; nausea/vomiting; flushing; uncontrolled crying; GI upset; panic attacks; nervousness

Migraine: nature of the condition

Complex condition from the interplay of several factors

Migraine: sex difference

Women affected 2-3x more than men

Migraine in women: common timing

Around menstruation or when taking estrogen-containing oral contraceptives

Migraine triggers

Alcohol; strong or blinking lights; fatigue; certain foods; strong smells

3 categories of migraine

With aura (classic); without aura (common); complicated (with focal neuro deficits)

Migraine with aura: other name

Classic migraine

Migraine without aura: other name

Common migraine

Complicated migraine: definition

Migraine with focal neurological deficits

Does migraine category change drug treatment?

No; classification matters for diagnosis, but management is the same

Migraine pathophysiology

Serotonin drops → cerebral vessels expand → throbbing pain; inflammation around vessels triggers migraine

Migraine medications: 2 purposes

Abort an attack or prevent attacks (prophylaxis)

Migraine therapy: overall goal

Minimize impact on quality of life and ability to work

Migraine: first-line drugs

Simple analgesics: aspirin, acetaminophen, NSAIDs

Migraine: next step after simple analgesics

Triptans or ergotamine

Do tension headaches respond to triptans/ergotamine?

No; only migraines respond

FDA-approved drugs for migraine prevention

Beta-blockers propranolol (Inderal) and timolol (Blocadren); divalproex (Depakote); Botox

Migraine: key factor in treatment

Patient education

Migraine trigger diary

Patient tracks potential triggers; usually takes several months

Goal of migraine prophylaxis

Minimize triggers and cut migraine incidence by at least 50%

Migraine: realistic expectation

May never be migraine-free; correct medication use can control frequency

2 migraine drug classes

Serotonin receptor agonists (triptans); ergotamines

Sumatriptan (Imitrex): routes

PO; SC; nasal spray

Sumatriptan (Imitrex): PO dose

25-100 mg initially; repeat every 2 hr up to 24 hr; max 300 mg/day; 4 headaches/month

Sumatriptan (Imitrex): SC and nasal doses

6 mg SC or 20 mg nasal spray

Zolmitriptan (Zomig)

PO, ODT; 2.5 mg; repeat in 2 hr if headache returns; max 10 mg/24 hr

Rizatriptan (Maxalt)

PO, ODT; 5-10 mg at onset; repeat in 2 hr if needed; max 30 mg/24 hr

Almotriptan (Axert)

PO; 6.25 or 12.5 mg once; may repeat once in 2 hr

Eletriptan (Relpax)

20 or 40 mg at onset; may repeat once in 2 hr

Naratriptan (Amerge)

PO; 1 or 2.5 mg at onset; repeat in 4 hr if needed

Frovatriptan (Frova)

PO; 2.5 mg with fluids; may repeat in 3 hr

Treximet: components and dose

Naproxen 500 mg + sumatriptan 85 mg PO; no more than 2 tablets in 24 hr

Triptans: mechanism of action

Selective serotonin receptor agonists in cranial arteries → vasoconstriction; reduce neurogenic inflammation

Triptans: onset

Quick, about 30 minutes

Triptans: distribution

Minimal protein binding

Triptans: metabolism

Primarily hepatic

Triptans: excretion

Urine, as an indole acetic metabolite

Triptans: clinical use

Migraine relief: abort an attack or prophylaxis

Triptans: CV adverse reaction

Chest pain

Triptans: derm adverse reactions

Tingling; warm sensation; flushing

Triptans: GI adverse reactions

Abdominal discomfort; nausea; vomiting

Triptans: GU adverse reaction

Hematuria

Triptans: MSK adverse reactions

Neck, joint, throat, and jaw pain

Triptans: neuro adverse reactions

paresthesia; dizziness

Triptans + SSRIs

Possible serotonin syndrome

Triptans: CV contraindications

Ischemic heart disease; PVD; cerebrovascular syndromes; uncontrolled HTN

Why are triptans contraindicated in heart disease?

They can constrict coronary arteries

Triptans: pregnancy

Contraindicated

Triptans and ergotamines: timing rule

No triptan within 24 hours of an ergotamine derivative

Triptans and MAOIs: rule

Not concurrently, and not within 2 weeks of stopping an MAOI

Triptans in children

May be used; get a pediatric consult first

Triptans: where to give the first dose and why

In the office: monitor for CV events/hypersensitivity and check self-administration technique

Triptans: patient education - when to take

At any sign of an impending migraine or during an attack

Triptans: patient education - second dose

Allowed if symptoms return, at least 2 hours after the first

Triptans: max doses per 24 hours and why

2; more are unlikely to help and may cause side effects

Triptans: patient education - alcohol

Can aggravate the headache

Ergotamine (Ergostat, Ergomar) dose

1 tab SL at start of attack; may repeat in 30 min; max 3 tabs per attack

Dihydroergotamine (DHE 45) dose

IV/IM; 1 mg; repeat 1 dose/hr to total 3 mg

Dihydroergotamine (Migranol) dose

Intranasal; 1 spray in each nostril at onset; repeat in 15 min

Ergotamine/caffeine (Cafergot) dose

PO; 2 tabs at onset, then 1 tab every 30 min, up to 6 per attack

Ergotamines: mechanism of action

Act on serotonin receptors in cranial arteries → vasoconstriction; reduce neurogenic inflammation