Pharmacology of CNS Depressants and Migraine Treatments

Orexin Receptor Antagonist Prototype

Suvorexant (Belsomra).

Orexin Receptor Antagonist MOA

Blocks orexin receptors → ↓ wakefulness.

Orexin Receptor Antagonist Use

Sleep induction.

Muscle Relaxants Common

Baclofen (Lioresal) · Cyclobenzaprine (Flexeril) · Dantrolene (Dantrium).

Muscle Relaxants MOA

Centrally acting CNS depressants; Dantrolene = direct skeletal muscle action.

ADHD & Narcolepsy Therapies Prototype

Amphetamine sulfate (Adzenys).

Obesity Management Anorexiant

Phentermine (Lonamin) MOA: ↑ DA/NE → appetite suppression + ↑ BMR.

Anorexiant

Phentermine (Lonamin)

MOA of Phentermine

↑ DA/NE → appetite suppression + ↑ BMR.

Use of Phentermine

BMI > 30 (or > 27 w/ comorbidities).

Side Effects of Phentermine

↑ BP · Palpitations · Anxiety · Agitation · HA · Dizziness.

Contraindications for Phentermine

CV dz · Uncontrolled HTN · MAOI · Eating disorder.

Nursing considerations for Phentermine

Morning dose · Avoid caffeine · Schedule IV.

Orlistat

Lipase inhibitor → ↓ fat absorption.

Contrave ER

Naltrexone + Bupropion.

Saxenda

Liraglutide: GLP-1 agonist (also for T2DM as Victoza).

Serotonin Agonists

Triptans.

Prototype Triptan

Sumatriptan (Imitrex).

MOA of Triptans

5-HT receptor agonist → cranial vasoconstriction → ↓ inflammatory peptides.

Use of Triptans

Abort migraine attacks (first-line).

Side Effects of Triptans

Tingling · Flushing · Injection pain · Vasoconstriction.

Monitor for Triptans

↓ freq/duration/intensity = therapeutic response.

Ergot Alkaloid

Ergotamine (Ergomar).

MOA of Ergotamine

Constriction of cerebral vessels.

Use of Ergotamine

Tx & prevention of migraine (rare now).

Side Effects of Ergotamine

N/V · Cold/clammy hands/feet · Muscle pain · Dizziness.

CGRP Inhibitors

Injectables: Erenumab (Aimovig) · Galcanezumab (Emgality) · Fremanezumab (Ajovy) · Eptinezumab (Vyepti).

Oral acute CGRP Inhibitors

Rimegepant · Ubrogepant (Ubrelvy).

Use of CGRP Inhibitors

Migraine prevention & acute tx.

Methylxanthines

Aminophylline / Theophylline / Caffeine.

MOA of Methylxanthines

Stimulate medullary resp centers.

Major Depressive Disorder

≥ 5 symptoms ≥ 2 weeks - depressed mood, anhedonia, insomnia or hypersomnia, weight change, fatigue, poor concentration, worthlessness, suicidality.

Goal of therapy

↑ 5-HT / NE / DA activity → relieve symptoms and prevent relapse.

Response time

2-4 weeks (minimum).

Selective Serotonin Reuptake Inhibitors (SSRIs)

Prototype: Fluoxetine (Prozac) | Others: Sertraline, Paroxetine, Citalopram, Escitalopram.

SSRIs MOA

Block neuronal reuptake of serotonin → ↑ 5-HT levels.

SSRIs Uses

Depression, OCD, PTSD, Anxiety, Panic, PMDD.

SSRIs SE

GI upset, Insomnia, Headache, Sexual dysfunction, Weight gain, Emotional blunting, SIADH, Serotonin syndrome.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Prototype: Venlafaxine (Effexor) | Others: Desvenlafaxine, Duloxetine (Cymbalta).

SNRIs MOA

Block reuptake of 5-HT and NE.

SNRIs Uses

Depression, GAD, Neuropathic pain, Fibromyalgia.

SNRIs SE

HTN, ↑ HR, Dry mouth, Sweating, Constipation, Blurred vision, N/V.

Tricyclic Antidepressants (TCAs)

Prototype: Imipramine (Tofranil) | Others: Amitriptyline, Nortriptyline.

TCAs MOA

Block reuptake of NE and 5-HT + anticholinergic & antihistamine actions.

TCAs Uses

Depression, Nocturnal enuresis, Neuropathic pain.

TCAs SE

Sedation, Orthostatic hypotension, Anticholinergic effects, Weight gain, QT prolongation.

TCA Toxicity

3 C's → Cardiotoxicity, Convulsions, Coma.

Monoamine Oxidase Inhibitors (MAOIs)

Prototype: Phenelzine (Nardil) | Others: Isocarboxazid, Tranylcypromine.

MAOIs MOA

Inhibit MAO enzyme → ↑ NE, 5-HT, DA.

Atypical Antidepressants - Bupropion (Wellbutrin)

MOA: Block DA and NE reuptake.

Atypical Antidepressants - Trazodone

MOA: Blocks 5-HT reuptake + H₁ and α₁ block.

Mood Stabilizer - Lithium Carbonate

MOA: Alters Na⁺ transport, ↓ NE/DA release, Stabilizes neuronal excitability.

Lithium Therapeutic Range

0.5 - 1.2 mEq/L.

Lithium Toxicity

Toxic > 1.5 mEq/L: Coarse tremor, Confusion, GI upset, Ataxia, Seizure, Death.

GI distress

Gastrointestinal discomfort or issues.

Fatigue

Extreme tiredness or lack of energy.

Weight gain

An increase in body weight.

Fine tremor

A small, rapid, and involuntary muscle contraction.

Antipsychotics

Medications used to treat psychotic disorders such as schizophrenia.

Psychotic Disorders

Mental disorders characterized by a disconnection from reality.

Schizophrenia

A severe mental disorder characterized by delusions, hallucinations, and disorganized thinking.

Core symptoms of schizophrenia

Disorganized thought, inappropriate affect, altered behavior, social withdrawal.

Positive symptoms

Symptoms such as hallucinations, delusions, disorganized speech, and agitation.

Negative symptoms

Symptoms such as flat affect, avolition, anhedonia, alogia, and poor hygiene.

Cognitive symptoms

Symptoms affecting attention, memory, and judgment.

Therapeutic goals for schizophrenia

Acute: reduce aggression and normalize sleep/eating; Secondary: improve self-care and socialization; Long term: coping, prevent relapse, maintain function.

Effect onset of antipsychotics

1-2 months, gradual.

1st Generation Antipsychotics (FGA)

Also known as typical antipsychotics, e.g., Chlorpromazine (Thorazine) and Haloperidol (Haldol).

MOA of FGA

Block post-synaptic dopamine receptors.

Side effects of FGA

Extrapyramidal symptoms (EPS), neuroleptic malignant syndrome (NMS), and other effects like EKG changes and hypotension.

EPS

Extrapyramidal symptoms including dystonia, parkinsonism, akathisia, and tardive dyskinesia.

Neuroleptic Malignant Syndrome (NMS)

A life-threatening condition characterized by fever, rigidity, altered mental status, increased heart rate, and blood pressure.

2nd Generation Antipsychotics (SGA)

Also known as atypical antipsychotics, e.g., Clozapine (Clozaril) and Quetiapine (Seroquel).

MOA of SGA

Block dopamine and serotonin receptors.

Tolerance

The need for an increased dose to achieve the same effect.

Physical dependence

Experiencing withdrawal symptoms if the substance is stopped.

Psychological dependence

Craving the pleasurable effects of a substance.

Chlordiazepoxide (Librium)

BZD for ETOH withdrawal; Sedative + anticonvulsant; BBW - Resp depression with opioids.

Flumazenil (Romazicon)

BZD antidote; Competitive receptor antagonist; BBW - May cause seizures in dependent pt.

Disulfiram (Antabuse)

Alcohol deterrent; Blocks acetaldehyde metabolism → N/V, palpitations if ETOH used; BBW - Avoid ETOH 12 h before/after · Fatal rxn possible.

Methadone (Methadose)

Opioid agonist; Replaces opioid → prevent withdrawal · Reduce cravings; BBW - Use only in certified program · QT prolongation monitor.

Buprenorphine + Naloxone (Suboxone)

Partial agonist/antagonist; Reduces craving · Blocks euphoria; BBW - Misuse → resp depression / death.

Naltrexone (ReVia, Vivitrol)

Opioid antagonist / ETOH dependence; Blocks receptors → ↓ craving · No "high"; Give after detox 7-10 d · Monitor LFTs.

Acamprosate (Campral)

Alcohol maintenance; Modulates GABA & glutamate; ↓ relapse · Start post-detox · Avoid renal failure.

Withdrawal Syndromes - ETOH

Symptoms include: Tremors, Agitation, N/V, Tachycardia, HTN, Seizures, Delirium tremens; Tx: BZD (Librium / Lorazepam) · Thiamine · IV fluids.

Withdrawal Syndromes - Opioids

Symptoms include: Craving, Muscle ache, Diarrhea, Rhinorrhea, Yawning, Piloerection; Tx: Methadone or Buprenorphine · Clonidine for symptoms.

Withdrawal Syndromes - Stimulants

Symptoms include: Depression, Fatigue, Sleep disturbance, ↑ appetite; Tx: Supportive · No specific antidote.

SAMHSA Helpline

1-800-662-HELP (24/7 treatment referral).

Behavioral therapy + Medication

Highest success rates for treatment.

Parasympathetic Nervous System (PNS)

Regulates 'Rest & Digest' functions.

Cholinergic drugs

Stimulate the PNS (increase ACh effects).

Anticholinergic drugs

Block ACh, reducing PNS activity and allowing SNS-like effects.

Direct-acting Cholinergic Drugs

Bind directly to muscarinic receptors and activate them.

Indirect-acting Cholinergic Drugs

Block acetylcholinesterase → increased ACh levels.

Nicotinic receptors

Receptors that respond to acetylcholine and are found in the autonomic ganglia and neuromuscular junction.

Muscarinic receptors

Receptors that respond to acetylcholine and are primarily found in the parasympathetic nervous system.

Cholinergic Stimulation Effects - GI

Increases secretions and motility.

Cholinergic Stimulation Effects - GU

Increases urination.

Cholinergic Stimulation Effects - Eyes

Causes miosis and decreases intraocular pressure.

Cholinergic Stimulation Effects - Glands

Increases salivation and sweating.