S

Sedative-Hypnotics

USES

Treatment of insomnia (i.e., difficulty falling asleep initially, frequent awakening, awakening too early).

ACTION

Benzodiazepines are the most widely used agents and largely replace barbiturates due to greater safety, lower incidence of drug dependence. Benzodiazepines nonselectively bind to at least three receptor subtypes accounting for sedative, anxiolytic, relaxant, and anticonvulsant properties. Benzodiazepines enhance the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which inhibits impulse transmission in the CNS reticular formation in brain. Benzodiazepines decrease sleep latency, number of nocturnal awakenings, and time spent in awake stage of sleep; increase total sleep time. The nonbenzodiazepines zaleplon and zolpidem preferentially bind with one receptor subtype, reducing sleep latency and nocturnal awakenings and increasing total sleep time. Ramelteon is a selective agonist of melatonin receptors (responsible for determining circadian rhythms and synchronizing sleep-wake cycles).

SEDATIVE-HYPNOTICS

Name	Availability	Dosage Range	Side Effects
Benzodiazepines
Estazolam	T: 1 mg, 2 mg	A: 1–2 mg E: 0.5–1 mg	Daytime sedation, memory and psychomotor impairment, tolerance, withdrawal reactions, rebound insomnia, dependence
Flurazepam	C: 15 mg, 30 mg	A/E: 15–30 mg E: 15 mg	Headaches, unpleasant taste, dry mouth, dizziness, anxiety, nausea
Temazepam (Restoril)	C: 7.5 mg, 15 mg, 30 mg	A: 15–30 mg E: 7.5–15 mg	Same as flurazepam
Nonbenzodiazepines
Eszopiclone (Lunesta)	T: 1 mg, 2 mg, 3 mg	A: 1–3 mg E: 1–2 mg	Headaches, unpleasant taste, dry mouth, dizziness, anxiety, nausea
Ramelteon (Rozerem)	T: 8 mg	A, E: 8 mg	Headaches, dizziness, fatigue, nausea
Suvorexant (Belsomra)	T: 5 mg, 10 mg, 15 mg, 20 mg	A, E: 10–20 mg	Next day somnolence, leg weakness
Zaleplon (Sonata)	C: 5 mg, 10 mg	A: 10–20 mg E: 5 mg	Headaches, dizziness, myalgia, drowsiness, asthenia, abdominal pain
Zolpidem (Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist)	T: 5 mg, 10 mg CR: 6.25 mg, 12.5 mg SL (Edluar): 5 mg, 10 mg (Intermezzo): 1.75 mg, 3.5 mg OS: 5 mg/actuation	OS, T, SL (Edluar): 5 mg (females, elderly); 5–10 mg (males) (Intermezzo): 1.75 mg (females, elderly); 3.5 mg (males) CR: 6.25 mg (females, elderly); 6.25–12.5 mg (males)	Dizziness, daytime drowsiness, headaches, confusion, depression, hangover, asthenia

A, Adults; C, capsules; CR, controlled-release; E, elderly; OS, oral solution; SL, sublingual; T, tablets.

Skeletal Muscle Relaxants

USES

Central acting muscle relaxants: Adjunct to rest, physical therapy for relief of discomfort associated with acute, painful musculoskeletal disorders (i.e., local spasms from muscle injury).

Baclofen, dantrolene, diazepam: Treatment of spasticity characterized by heightened muscle tone, spasm, loss of dexterity caused by multiple sclerosis, cerebral palsy, spinal cord lesions, CVA.

ACTION

Central acting muscle relaxants: Exact mechanism unknown. May act in CNS at various levels to depress polysynaptic reflexes; sedative effect may be responsible for relaxation of muscle spasm.

Baclofen, diazepam: May mimic actions of gamma-aminobutyric acid on spinal neurons; do not directly affect skeletal muscles.

Dantrolene: Acts directly on skeletal muscle, relieving spasticity.

SKELETAL MUSCLE RELAXANTS

Name	Indication	Dosage Range	Side Effects/Comments
Baclofen (Lioresal)	Spasticity associated with multiple sclerosis, spinal cord injury	Initially 5 mg 3 times/day Increase by 5 mg 3 times/day q3days Maximum: 20 mg 4 times/day	Drowsiness, dizziness, GI effects Caution with renal impairment, seizure disorders Withdrawal syndrome (e.g., hallucinations, psychosis, seizures)
Carisoprodol (Rela)	Discomfort due to acute, painful, musculoskeletal conditions	250–350 mg 4 times/day	Drowsiness, dizziness, GI effects Hypomania at higher than recommended doses Withdrawal syndrome Hypersensitivity reaction (skin reaction, bronchospasm, weakness, burning eyes, fever) or idiosyncratic reaction (weakness, visual or motor disturbances, confusion) usually occurring within first 4 doses
Chlorzoxazone (Lorzone)	Discomfort due to acute, painful, musculoskeletal conditions	Initially 250–500 mg 3–4 times/day Maximum: 750 mg 3–4 times/day	Drowsiness, dizziness, GI effects, rare hepatotoxicity Hypersensitivity reaction (urticaria, itching) Urine discoloration to orange, red, or purple
Cyclobenzaprine (Flexeril)	Muscle spasm, pain, tenderness, restricted movement due to acute, painful, musculoskeletal conditions	Initially 5–10 mg 3 times/day	Drowsiness, dizziness, GI effects Anticholinergic effects (dry mouth, urinary retention) Quinidine-like effects on heart (QT prolongation) Long half-life
Dantrolene (Dantrium)	Spasticity associated with multiple sclerosis, cerebral palsy, spinal cord injury	Initially 25 mg/day for 1 wk, then 25 mg 3 times/day for 1 wk, then 50 mg 3 times/day for 1 wk, then 100 mg 3 times/day Maximum: 100 mg 4 times/day	Drowsiness, dizziness, GI effects Contraindicated with hepatic disease Dose-dependent hepatotoxicity Diarrhea that is dose dependent and may be severe, requiring discontinuation
Diazepam (Valium)	Spasticity associated with cerebral palsy, spinal cord injury; reflex spasm due to muscle, joint trauma or inflammation	2–10 mg 3–4 times/day	Drowsiness, dizziness, GI effects Abuse potential
Metaxalone (Skelaxin)	Discomfort due to acute, painful, musculoskeletal conditions	800 mg 3–4 times/day	Drowsiness (low risk), dizziness, GI effects Paradoxical muscle cramps Mild withdrawal syndrome Contraindicated in serious hepatic or renal disease
Methocarbamol (Robaxin)	Discomfort due to acute, painful, musculoskeletal conditions	Initially 1,500 mg 4 times/day Maintenance: 1,000 mg 4 times/day	Drowsiness, dizziness, GI effects Urine discoloration to brown, brown-black, or green
Orphenadrine (Norflex)	Discomfort due to acute, painful, musculoskeletal conditions	100 mg 2 times/day	Drowsiness, dizziness, GI effects Long half-life Anticholinergic effects (dry mouth, urinary retention) Rare aplastic anemia Some products may contain sulfites
Tizanidine (Zanaflex)	Spasticity	Initially 4 mg q6–8h (maximum 3 times/day), may increase by 2–4 mg as needed/tolerated Maximum: 36 mg (limited information on doses greater than 24 mg)	Drowsiness, dizziness, GI effects Hypotension (20% decrease in B/P) Hepatotoxicity (usually reversible) Withdrawal syndrome (hypertension, tachycardia, hypertonia) Effect is short lived (3–6 hrs) Dose cautiously with creatinine clearance less than 25 ml/min

B/P, Blood pressure; GI, gastrointestinal.

Smoking Cessation Agents

Tobacco smoking is associated with the development of lung cancer and chronic obstructive pulmonary disease. Smoking is harmful not just to the smoker but also to family members, coworkers, and others breathing cigarette smoke.

Quitting smoking decreases the risk of developing lung cancer, other cancers, heart disease, stroke, and respiratory illnesses. Several medications have proved useful as smoking cessation aids. Nausea and light-headedness are possible signs of overdose of nicotine warranting a reduction in dosage.

SMOKING CESSATION AGENTS

Name	Availability	Dose Duration	Cautions/Side Effects	Comments
Bupropion (Zyban)	T: 150 mg	150 mg every morning for 3 days, then 150 mg 2 times/day Start 1–2 wks before quit date Duration: 7–12 wks up to 6 mos for maintenance	History of seizure, eating disorder, use of MAOI within previous 14 days, bipolar disorder Side Effects: Insomnia, dry mouth, tremor, rash	Stop smoking during second wk of treatment and use counseling support services along with medication
Clonidine (Catapres, Catapres-TTS)	T: 0.1 mg, 0.2 mg Patch: 0.1 mg/24 hrs, 0.2 mg/24 hrs, 0.3 mg/24 hrs	Oral: 0.15–0.75 mg/day Patch: 0.1–0.2 mg daily Duration: 3–10 wks	Rebound hypertension. Side Effects: Dry mouth, drowsiness, dizziness, sedation, constipation	Abrupt discontinuation can result in anxiety, agitation, headaches, tremors accompanied or followed by rapid rise in B/P
Nicotine gum (Nicorette)	Squares: 2 mg, 4 mg	1 gum q1–2h for 6 wks, then q2–4h for 3 wks then q4–8h for 3 wks Maximum: 24 pieces/day Duration: up to 12 wks	Recent MI (within 2 wks), serious arrhythmias, serious or worsening angina pectoris Side Effects: Dyspepsia, mouth soreness, hiccups	2 mg recommended for pts smoking less than 25 cigarettes/day, 4 mg for pts smoking 25 or more cigarettes/day Chew until a peppery or minty taste emerges and then “park” between cheek and gums to facilitate nicotine absorption through oral mucosa Chew slowly and intermittently to avoid jaw ache and achieve maximum benefit Only water should be taken 15 min before and during chewing
Nicotine inhaler (Nicotrol)	Cartridge: 10 mg (delivers 4 mg nicotine)	4–16 cartridges daily; taper frequency of use over the last 6–12 wks Duration: up to 6 mos	Recent MI (within 2 wks), serious arrhythmias, serious or worsening angina pectoris Side Effects: Local irritation of mouth and throat, coughing, rhinitis	Use at or above room temperature (cold temperatures decrease amount of nicotine inhaled)
Nicotine lozenge (Nicorette Lozenges)	Lozenges: 2 mg, 4 mg	One lozenge q1–2h for 6 wks, then q2–4h for 3 wks, then q4–8h for 3 wks Duration: 12 wks Maximum: 5 lozenges in 6 hrs; 20 lozenges in 1 day	Recent MI (within 2 wks), serious arrhythmias, serious or worsening angina pectoris Side Effects: Local skin reaction, insomnia, nausea, sore throat	First cigarette smoked within 30 min of waking, use 4 mg; after 30 min of waking, use 2 mg Use at least 9 lozenges/day first 6 wks Only 1 lozenge at a time, 5 per 6 hrs and 20 per 24 hrs Do not chew or swallow
Nicotine nasal spray (Nicotrol NS)	10 mg/ml (delivers 0.5 mg/spray)	8–40 doses/day A dose consists of one 0.5 mg delivery to each nostril; initial dose is 1–2 sprays/hr, increasing as needed Duration: 3–6 mos	Recent MI (within 2 wks), serious arrhythmias, serious or worsening angina pectoris Side Effects: Nasal irritation	Do not sniff, swallow, or inhale through nose while administering nicotine doses (may increase irritation) Tilt head back slightly for best results
Nicotine patch (NicoDerm CQ)	Nicoderm CQ: 7 mg/24 hrs, 14 mg/24 hrs, 21 mg/24 hrs Nicotrol: 5 mg/16 hrs, 10 mg/16 hrs, 15 mg/16 hrs	Apply upon waking on quit date: Nicoderm CQ (greater than 10 cigarettes/day): 21 mg/24 hrs for 4 wks, then 14 mg/24 hrs for 2 wks, then 7 mg/24 hrs for 2 wks (10 or fewer cigarettes/day): 14 mg/24 hrs for 6 wks, then 7 mg/24 hrs for 2 wks	Recent MI (within 2 wks), serious arrhythmias, serious or worsening angina pectoris Side Effects: Local skin reaction, insomnia	The 16- and 24-hr patches are of comparable efficacy Begin with a lower-dose patch in pts smoking 10 or fewer cigarettes/day Place new patch on relatively hair-free location, usually between neck and waist, in the morning If insomnia occurs, remove the 24-hr patch prior to bedtime or use the 16-hr patch Rotate patch site to diminish skin irritation
Nortriptyline (Pamelor)	T: 25 mg, 50 mg, 75 mg, 100 mg	Initially 25 mg/day, increasing gradually to target dose of 75–100 mg/day 10–28 days prior to selected “quit” date, continue for 12 wks or more after “quit” day Duration: up to 12 wks	Risk of arrhythmias Side Effects: Sedation, dry mouth, blurred vision, urinary retention, light-headedness, shaky hands	Initiate therapy 10–28 days before the quit date to allow steady state of nortriptyline at target dose
Varenicline (Chantix)	T: 0.5 mg, 1 mg	Days 1–3: 0.5 mg daily; days 4–7: 0.5 mg 2 times/day; day 8 to end of treatment: 1 mg 2 times/day Duration: begin 1 wk before set quit date, continue for 12 wks. May use additional 12 wks if failed to quit after first 12 wks	Side Effects: Nausea; sleep disturbances; headaches; may impair ability to drive, operate machinery; depressed mood; altered behavior; suicidal ideation reported	Use lower dosage if not able to tolerate nausea and vomiting Use counseling support services along with medication

B/P, Blood pressure; MAOI, monoamine oxidase inhibitor; MI, myocardial infarction; T, tablets.