Pharmacotherapy II: Stimulants and Sedatives PDF

Pharmacotherapy II: Stimulants & Sedatives Augsburg PA Program, 2025 Miranda LaCroix, MSPAS, PA-C  Learning Objectives 1. Classify representative stimulants and sedative drugs by their DEA schedule and potential for abuse. 2. List the 4 classes of sedative-hypnotic drugs. 3. Di...

Pharmacotherapy II: Stimulants & Sedatives Augsburg PA Program, 2025 Miranda LaCroix, MSPAS, PA-C  Learning Objectives 1. Classify representative stimulants and sedative drugs by their DEA schedule and potential for abuse. 2. List the 4 classes of sedative-hypnotic drugs. 3. Discuss an overview of the pharmacologic effects of benzodiazepines. 4. Describe the tolerance/dependence associated with benzodiazepines, benzodiazepine-like drugs, and barbiturates. 5. Explain the distribution and metabolites of benzodiazepines and why this is important. 6. Summarize the key prescribing considerations for benzodiazepines and benzodiazepine-like drugs.  Learning Objectives 7. Given a patient scenario, select the best medication for insomnia considering the time course (onset/duration) and dependency potential, including the use of antidepressants, antihistamines, and melatonin. 8. Identify the general black box warnings associated with amphetamines. 9. Given a patient scenario, select the best medication considering the pharmacologic effects and patient-care concerns across the lifespan. 10. Outline the basic considerations of attention-deficit/hyperactivity disorder in children. 11. Differentiate between stimulant and non-stimulant medication choices for the treatment of ADHD.  Learning Objectives 12.For the following representative medications (included on the Unit Representative Medication List), know the medication class, mechanism of action, indications, adverse effects, contraindications, interactions (common), monitoring (if needed), and patient education. Alprazolam Ramelteon Diazepam Suvorexant Lorazepam Modafinil Midazolam Methylphenidate Zolpidem Dextroamphetamine-amphetamine Zaleplon Atomoxetine Secobarbital  Drug Enforcement Administration (DEA) Schedule Low Schedule Examples V Preparations containing limited Robitussin AC, Lomotil, Motofen, Lyrica, quantities of certain narcotics. Parepectolin Potential for abuse IV Low potential for abuse & Xanax, Soma, Darvon, Darvocet, Valium, Ativan, dependence Talwin, Ambien, Tramadol III Low-moderate potential for physical Tylenol with Codeine, Ketamine, Anabolic & psychological dependence Steroids, Testosterone II Potentially leading to severe Hydrocodone (Vicodin), Cocaine, psychological or physical Methamphetamine, Methadone, Hydromorphone dependence (Dilaudid), Meperidine (Demerol), Oxycodone (Oxycontin), Fentanyl, Dexedrine, Adderall, Ritalin I No current accepted medical use Heroin, Lysergic Acid Diethylamide (LSD), Marijuana (Cannabis), 3,4- methylenedioxymethamphetamine (Ecstasy), Methaqualone, Peyote High  Insomnia Persistent difficulty falling asleep or staying asleep Slow energy, difficulty concentrating, fatigue Clinical Presentation May stem from depression, anxiety, stress, or pain May be caused by sedatives & stimulants use, alcohol abuse May be due to hormone imbalance: ↑cortisol, ↓estrogen, ↓progesterone Non-pharmacological: vigorous morning exercise, sleep hygiene, stimulus control, sleep restriction, relaxation training, cognitive behavioral therapy for insomnia, biofeedback, chronotherapy Pharmacological: melatonin receptor agonists: ramelteon (Rozerem); Management benzodiazepine receptor agonists (BZRAs): zolpidem (Ambien); dual orexin receptor antagonist (DORA): suvorexant (Belsomra); low-dose tricyclic antidepressants: doxepin (Silenor); benzodiazepines Herbal/off-label: melatonin; sedating antidepressants: amitriptyline, mirtazapine, trazodone (Milipaxin); OTC: diphenhydramine, doxylamine  Sedative-Hypnotic Drugs Drug Classes: Benzodiazepines Non-Benzodiazepines Benzodiazepine Receptor Agonists Barbiturates Other CNS Depressants/Miscellaneous Melatonin Receptor Agonists Orexin Receptor Antagonist Antihistamines  Benzodiazepines Example Drugs: Alprazolam (Xanax), Diazepam (Valium), Lorazepam (Ativan), Midazolam (Nayzilam) MOA: Act in CNS – enhances the effects of GABA, increasing inhibition and blocks thalamic, hypothalamic, and limbic arousal Indications: Agitation, Seizures, Insomnia, RSI, Alcohol Withdrawal, Sedation, Panic Disorder, Palliative/End of Life Sedation Adverse effects: Transient drowsiness, sedation, depression, lightheadedness, disorientation, constipation, diarrhea, dry mouth, nausea, memory loss, confusion  Benzodiazepines Contraindications Myasthenia gravis, acute narrow angle glaucoma, pregnancy, lactation Caution in impaired liver or kidney function Concurrent use of alcohol needs extra caution Major interactions: Patient Education/Clinical Pearls Drug dependence and withdrawal may result when abruptly discontinued Use cautiously in the elderly and slowly titrate  Benzodiazepines & Metabolites BZDs and their metabolites are highly protein bound Widely distributed in the body and preferentially accumulate in lipid- rich areas such as the central nervous system and adipose tissue Some BZDs exert additional action via production of active metabolites, Diazepam produces the active metabolites oxazepam, desmethyldiazepam, and temazepam Metabolites can further increase the duration of drug action especially in some patient groups such as the elderly and those with extensive liver disease  Benzodiazepine Receptor Agonists Examples Drugs: Zolpidem (Ambien), Eszopiclone (Lunesta) , Zaleplon (Sonata) MOA Similar to benzos but instead mimic the action of GABA Time Frame to Response 10-15 min, can last 2-3hrs (zolpidem IR) Adverse Effects Drowsiness, headache, dizziness Contraindications Caution with complex behaviors (driving), impaired hepatic/renal function, addiction prone patients, and pregnancy/lactation  Barbiturates Example Drugs: Secobarbital (Seconal), Methohexital (Brevital), Amobarbital (Amytal), Phenobarbital (Luminal) MOA: Enhance the effects of GABAA by ↑ the duration Cl- channels are open, but unlike benzodiazepines, they can cause the channels to open even in the absence of BAGA Indications: Insomnia (short-term), anticonvulsants, anesthesia induction, anxiety (panic attack) Adverse effects: Sedation, disinhibition, hypnosis, ↓ concentration, anesthesia, headache, anorexia, nausea, vomiting, comma  Barbiturates Contraindications Avoid taking with barbiturates, BZDs, during pregnancy, while breastfeeding, & in individuals with acute intermittent porphyria (AIP) Use with caution in individuals with hepatic or renal impairment, or cardiovascular conditions Major interactions: Cytochrome P450 induction → ↑ metabolism of other medications such as BZDs, phenytoin, quinidine, warfarin Patient Education/Clinical Pearls: Chronic use → tolerance & dependence Treat overdose with sodium bicarbonate (NaHCO3)  Melatonin Receptor Agonists Example Drug: Ramelteon (Rozerem) MOA Synthetic derivative that has high selectivity and affinity for melatonin receptors, which blocks the receptors Leads to shorter sleep onset Adverse Effects Fatigue, dizziness, fatigue, nausea, and exacerbated insomnia Contraindications Severe sleep apnea, severe hepatic impairment, and angioedema Caution in mild to moderate hepatic impairment, depression, severe COPD Notes Avoid administration with a high fat meal Dual Orexin Receptor Antagonist Example Drug: Suvorexant (Belsomra) MOA Selective dual orexin receptor agonist (DORA) with a binding mechanism to both orexin receptors, thus inhibiting the arousal system. Leading to sleep induction and maintenance Adverse Effects Headache, somnolence, dizziness Contraindications Narcolepsy, alcohol use Caution in obese female patients, depression, other CNS depressants, and impaired respiratory function 3A4 inhibitors are not recommended  Sedative-Hypnotic Drugs Safety Common Adverse Class Drug(s) Name Mechanism of Action Indications Considerations & Monitoring/Pt. Ed. Effects Contraindications Benzodiazepines Alprazolam, Central nervous Agitation, Seizures, Transient Do not take prior to Habit forming and can Diazepam, system (CNS) Insomnia, RSI, drowsiness, driving or operating lead to dependence & Lorazepam, depressant. Act by Alcohol Withdrawal, sedation, heavy machinery addiction Midazolam enhancing the main Sedation, Panic depression, Ataxia can precipitate *Avoid taking alcohol inhibitory Disorder, lightheadedness, falls in the elderly & other medications neurotransmitter Palliative/End of disorientation, that depress the CNS gamma- Life Sedation constipation, *Avoid in individuals (barbiturates, opioids, aminobutyric acid diarrhea, dry with liver impairment TCAs), the (GABAA), by mouth, nausea, combination can lead binding to its memory loss, Avoid during to reparatory receptor and ↑ the confusion pregnancy & depression & coma frequency of Cl- breastfeeding Treat overdose with channels opening C/Is: myasthenia flumazenil → ↓ CNS gravis, respiratory excitability insufficiency, severe Manage withdrawal liver impairment, with lower doses of acute narrow-angle benzodiazepines glaucoma, untreated open-angle glaucoma  Sedative-Hypnotic Drugs Safety Mechanism of Common Class Drug(s) Name Indications Considerations & Monitoring/Pt. Ed. Action Adverse Effects Contraindications Barbiturates Secobarbital Enhance the Insomnia (short- Sedation, Avoid taking with Chronic use → (Seconal), effects of term), disinhibition, barbiturates, tolerance & Methohexital GABAA by ↑ the anticonvulsants, hypnosis, ↓ BZDs, during dependence (Brevital), duration Cl- anesthesia concentration, pregnancy, while breastfeeding, & in Cytochrome P450 Amobarbital channels are induction, anesthesia, individuals with induction → ↑ (Amytal), open, but unlike anxiety (panic headache, acute intermittent metabolism of Phenobarbital benzodiazepines attack) anorexia, porphyria (AIP) other medications (Luminal) , they can cause nausea, such as BZDs, the channels to vomiting, comma Use with caution phenytoin, open even in the in individuals with quinidine, warfarin absence of hepatic or renal BAGA impairment, or Treat overdose cardiovascular with sodium conditions bicarbonate (NaHCO3  Sedative-Hypnotic Drugs Safety Mechanism of Common Adverse Class Drug(s) Name Indications Considerations & Monitoring/Pt. Ed. Action Effects Contraindications Benzodiazepine Zolpidem Act on the Sleep onset or Drowsiness, Angioedema, Monitor for Receptor Agonists (Ambien); gamma- sleep headache, anaphylaxis. addiction, opioid Eszopiclone aminobutyric acid maintenance dizziness Caution with use, or substance (Lunesta); (GABA) receptor insomnia complex behaviors use disorder. Zaleplon (Sonata) → influx of (driving, operating Avoid in the intracellular heavy machinery), elderly. chloride → impaired Metabolized more inhibition of the hepatic/renal slowly by females. CNS function, pregnancy/lactatio n Melatonin Ramelteon Synthetic Sleep onset Fatigue, dizziness, Severe sleep Avoid taking with Receptor Agonist (Rozerem) derivative that has insomnia nausea, apnea, severe high-fat meal, it high selectivity & exacerbated hepatic won't absorb. affinity for insomnia impairment, melatonin angioedema, receptors, which depression, blocks the severe COPD receptors → to shorter sleep onset  Sedative-Hypnotic Drugs Safety Mechanism of Common Adverse Class Drug(s) Name Indications Considerations & Monitoring/Pt. Ed. Action Effects Contraindications Dual Orexin Suvorexant Binds to both Sleep onset or Headache, Narcolepsy, Many drug Receptor Agonist (Belsomra) orexin receptors sleep maintenance somnolence, alcohol use, interactions → sleep induction insomnia dizziness obesity, & maintenance. depression, other CNS depressants, & impaired respiratory function Supplements Melatonin Starts cascade of Insomnia, jet lag, Daytime Use with caution events to start shift work sleepiness, in pts with hepatic sleep attention impairment impairment Antihistamines Benadryl, Histamine Allergies, Anticholinergic Caution in Cetirizine receptor Angioedema, (dry mouth, dry elderly, (Zyrtec), antagonist Insomnia (short eyes, urinary glaucoma, hx of Fexofenadine term) retention, etc), asthma, urinary (Allegra) CNS sedation or obstruction excitation  Case Study Clinical Scenario: Write a prescription for the management of this patient. A 75yo F presents to her PCP with chief complaint of insomnia. She reports once she falls asleep, she has no problems. Actually falling asleep, however, is a problem. She has tried normalizing her night routine and having a consistent bedtime, but this has not helped. Insomnia Treatment Insomnia Treatment  Case Study Revised Clinical Scenario: Write a prescription for the management of this patient. A 40yo F presents to her PCP with chief complaint of insomnia. She reports once she falls asleep, she has no problems. Actually falling asleep, however, is a problem. She has tried normalizing her night routine and having a consistent bedtime, but this has not helped. Attention Deficit/Hyperactivity Disorder Clinical Presentation Symptoms present before age 12 ≥ 5 symptoms of inattention: making careless mistakes, inability to pay close attention to detail, not listening, failing to follow on tasks & instructions, poor organization, avoids tasks requiring sustained mental effort, easily distracted, forgetful… And/or ≥ 5 symptoms of hyperactivity/impulsivity: fidgeting, squirming, feelings of restlessness, excessively talking, difficulty waiting turns, interrupting… ≥ 2 settings: home, school, work ≥ 6 months Symptoms impair social, academic, occupational activities Management Behavioral therapy Stimulants : methylphenidate, amphetamines Nonstimulants: norepinephrine reuptake inhibitors (atomoxetine); ⍺2-adrenergic receptor agonists (guanfacine, clonidine)  Treatment of ADHD Stimulants Non-Stimulants Amphetamines Norepinephrine reuptake Methylphenidate inhibitors Dextroamphetamine- Atomoxetine amphetamine ⍺2-Adrenergic Receptor Agonists (guanfacine, clonidine)  Amphetamines Example drugs: Modafinil (Provigil), Methylphenidate (Ritalin, Concerta), Dextroamphetamine-amphetamine (Adderall) MOA: Promotes wakefulness, blocking the reuptake of dopamine & norepinephrine at the presynaptic neuron → improved focus & ↓ impulsivity Indication: ADHD, Narcolepsy, MS related fatigue Adverse effects: HTN, palpitations, headache, anxiety, nausea, vomiting, diarrhea, weight loss, decreased appetite Contraindications: Impaired liver function, mitral valve prolapse, arrhythmias or heart disease, hx of substance abuse Major interactions: Reduces the effectiveness of oral or steroidal contraceptives Patient Education/Clinical Pearls: high potential for abuse  Selective Norepinephrine Reuptake Inhibitor Example drug: Atomoxetine (Strattera) MOA: Selective Norepinephrine Reuptake Inhibitor Indication: ADHD, Orthostatic HOTN Adverse effects: Children: SI, aggression, growth reduction, headache, abdominal pain, ↓ appetite, sleepiness, N/V, priapism Adults: nausea, dry mouth, ↓ appetite, sleepiness, tiredness Contraindications: Use w/ or w/in 14 days of MAOI, Closed angle glaucoma, Current or hx of pheochromocytoma, Severe cardiac or vascular disorders Patient Education/Clinical Pearls: Response rate is lower compared to stimulants Amphetamines: Black Box Warning Amphetamines have high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants can result in overdose and death, and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing an amphetamine, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. Thank You