Central Nervous System Pharmacology

Overview

• CNS, Psych, Controlled Substances, and Overdoses with Antidotes will all be covered

Central Nervous System

• Will be discussed in terms of the autonomic system pharmacology, analgesics, paralytics, sedatives/hypnotics, anticonvulsants, and stimulants

Parasympathetic Nervous System

• Neurotransmitter is Acetylcholine, active at both pre and post ganglionic sites
• Causes blood vessels to dilate
• Causes smooth muscles to contract
• Increases bodily secretions
• Slows heart rate
• Cholinergic receptors are nicotinic and muscarinic
  • Responses include decreased heart rate and blood pressure
  • Also responses include SLUDGEM(Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis, Miosis)
  • Can also cause decreased respiration and bronchoconstriction

Sympathetic Nervous System

• Neurotransmitters are acetylcholine (preganglionic) and norepinephrine (postganglionic)
• Adrenergic receptors: Alpha (causes vasoconstriction) and Beta (causes dilation)
  • Alpha receptors always constrict
  • Beta receptors always dilate
• Beta 1 increases cardiac ion/chrono/dromo
• Beta 2 is a vasodilator and bronchodilator
• Responses include dilated pupils, and increased heart rate, blood pressure,
  • Also responses include decreased gut motility and saliva
  • Can also cause increased respiration, by increasing the diameter of airways
• Inotropic effects increase contractility
• Chronotropic effects increase heart rate
• Dromotropic effects increase conduction

Classification of Medications

• Sympatholytic: Antagonistic, inhibiting transmission of nerve impulses in the sympathetic nervous system
  • Example: beta-blockers and alpha-blockers
• Sympathomimetic: Causes effects similar to the sympathetic nervous system
• Parasympatholytic: Blocks the effects of the parasympathetic nervous system
  • Example: Anticholinergic/Antimuscarinic
• Parasympathomimetic: Stimulates the parasympathetic nervous system

Autonomic Nervous System Pharmacology

• Cholinergics
  • Bethanechol (Urecholine)
  • Pilocarpine
  • Neostigmine (Prostigmin)
  • Physostigmine (Antilirium)
  • Anticholinergics
    • Muscarinic Receptors:
      • Atropine
      • Atrovent
    • Nicotinic Receptors:
      • Trimethaphan (Arfonad)
      • Mecamylamine (Iversine)

Sympathetic System Medications - Adrenergics

• Epinephrine
• Dopamine (Inotropin)
• Isoproterenol
• Dobutamine (Dobutrex)
• Ephedrine
• Phenylephrine (Neo-Synephrine)
• Terbutaline (Brethine)

Sympathetic System Medications - Antiadrenergics

• Beta Blockers
  • Propranolol
  • Metoprolol (Lopressor)
  • Atenolol (Tenormin)

Analgesics

• Opioid Agonists
  • Morphine (Duramorph)
  • Hydromorphone (Dilaudid)
  • Fentanyl (Sublimaze)
  • Meperidine (Demerol)
• Opioid Antagonists
  • Naloxone (Narcan)
• Opioid Agonist-Antagonists
  • Nubain
• Nonopioids
  • Aspirin, NSAIDs, Acetaminophen

Opioid Receptors

• Mu (μ)
  • Functions include supraspinal and spinal analgesia, sedation, inhibition of respiration, slowed gastrointestinal transit, and modulation of hormone and neurotransmitter release
  • Endogenous Opioid Peptide Affinity: Endorphins > enkephalins > dynorphins
• Delta (δ)
  • Functions include supraspinal and spinal analgesia, and modulation of hormone and neurotransmitter release
  • Endogenous Opioid Peptide Affinity: Enkephalins > endorphins and dynorphins
• Kappa (κ)
  • Functions include supraspinal and spinal analgesia, psychotomimetic effects, and slowed gastrointestinal transit
  • Endogenous Opioid Peptide Affinity: Dynorphins >> endorphins and enkephalins

Paralytics

• Succinylcholine (Anectine)
• Vecuronium (Norcuron)
• Rocuronium (Zemuron)

Sedatives/Hypnotics

• Benzodiazepines
  • Diazepam (Valium)
  • Lorazepam (Ativan)
  • Midazolam (Versed)
• Dissociative Agents
  • Ketamine (Ketalar)
• Barbiturates
  • Phenobarbital (Luminal)
• Miscellaneous Agents
  • Nitrous Oxide
  • Propofol (Diprivan)
  • Etomidate (Amidate)

Anticonvulsants

• Phenytoin (Dilantin)
• Carbamazepine (Tegretol)
• Valproic acid (Depakote)
• Diazepam (Valium)
• Lorazepam (Ativan)
• Phenobarbital (Luminal)
• Lamotrigine (Lamictal)
• Levetricetam (Kepra)
• Gabapentin (Neurontin)
• Midazolam (Versed)

Stimulants

• Amphetamines
  • Methamphetamine
  • Dextroamphetamine (Dexadrine)
• Methylphenidate (Ritalin)
• Methylxanthines
  • Caffeine
  • Aminophylline
  • Theophylline

Psych

• Excited Delirium and Extrapyramidal symptoms will be covered

Extrapyramidal Symptoms

• Common side effect of antipsychotic medications
  • Phenothiazines
    • Chlorpromazine (Thorazine)
  • Butyrophenones
  • Haloperidol (Haldol)
• Patients can have tremors and parkinsonism-like effects
• Treatment - Diphenhydramine (Benadryl)

Excited Delirium

• Characterized by the triad of delirium, psychomotor agitation, and physiological excitation
• Can be from mental illness and/or intoxication from drugs
• Patients can die while being restrained
• Risk Factors: young age, males, obese, hx of stimulate abuse (Cocaine and Amphetamines most common)
• Treatment - Sedation (Versed)

Controlled Substances - Schedules

• Schedule I
  • Abuse Potential: Highest
  • Example Drugs: Heroin, LSD, Marijuana, Psilocybin
  • Medicinal Use: No accepted use; limited use for research purposes
• Schedule II
  • Abuse Potential: High
  • Example Drugs: Morphine, PCP, Cocaine
  • Medicinal Use: Accepted use with restrictions
• Schedule III
  • Abuse Potential: Medium
  • Example Drugs: Selected Amphetamines, Anabolic Steroids, Codeine with aspirin
  • Medicinal Use: Accepted use
• Schedule IV
  • Abuse Potential: Low
  • Example Drugs: Diazepam, Ambien, Xanax
  • Medicinal Use: Accepted use
• Schedule V
  • Abuse Potential: Lowest
  • Example Drugs: Over the counter prescription drugs containing codeine
  • Medicinal Use: Accepted use

Overdoses and Antidotes

• Tricyclic Antidepressants
  • Blocks the reuptake of norepinephrine and serotonin
• In an overdose, arrythmias and MI can occur
• Common Medications:
  • Imipramine (Tofranil), Amitriptyline (Elavil), Desipramine (Norpramin), Nortriptyline (Pamelor)
  • Treatment is Sodium Bicarbonate
• Beta Blockers
  • Most are used to treat hypertension.
  • Examples include Atenolol (Tenormin) and Metoprolol (Lopressor)
  • Treatment - Glucagon
• Calcium Channel Blockers
  • Common examples of calcium channel blockers include; Amlodipine (Norvasc), Diltiazem (Cardizem), Felodipine, Isradipine
  • Treatment - Calcium Chloride
• Organophosphate Poisoning
  • Nerve gases VX and Sarin and Insecticides can cause this
  • SLUDGE symptoms will occur
  • Treatment - Atropine and Pralidoxime (Protopam, 2-PAM)
• Cyanide Poisoning
  • Found in burning some industrial products (silk, plastics, wool, and furniture), medications, and plants (Apricot, peach, and cherry pits, and some poisons)
  • Treatment - Amyl Nitrite and Cyanokit