1. Pharmacology Drugs That Affect The: Nervous System dr shabeel pn

3. But first... A colorful review of neurophysiology!

4. Nervous System CNS PNS Somatic Autonomic Parasympathetic Sympathetic

7. Actions of Opioid Receptors    GI motility  Physical Dependence  Euphoria   Sedation  Respiratory Depression   Analgesia Kappa Mu Response

8. Actions at Opioid Receptors Antagonist Antagonist Pure Antagonist - naloxone (Narcan ® ) Agonist Antagonist Agonist-Antagonist - nalbuphine (Nubaine ® ), butorphanol (Stadol ® ) Agonist Agonist Pure Agonists -morphine, codeine, meperidine (Demerol ® ), fentanyl (Sublimaze ® ), remifentanil (Ultiva ® ), propoxyphene (Darvon ® ), hydrocodone (Vicodin ® ), oxycodone (Percocet ® ) Kappa Mu Drugs

11. NSAID Properties   Acetaminophen    Ibuprofen    Aspirin Pain Inflammation Fever Drug

15. Acetaminophen Metabolism Acetaminophen Non-toxic metabolites Major Pathway Minor Pathway P-450 Toxic metabolites Non-toxic metabolites Induced by ETOH Glutathione Depleted by ETOH & APAP overdose

20. Benzodiazepines vs. Barbiturates High Low Abuse Potential No Yes Antagonist Available? High Low Suicide Potential High Low Respiratory Depression High Low Maximal CNS depression Low High Relative Safety Barb. BZ Criteria

22. Barbiturates Seizures phenobarbital (Luminal ® ) Long acting Insomnia secobarbital (Seconal ® ) Short acting Anesthesia thiopental (Pentothol ® ) Ultra-short acting Typical Indication Prototype Subgroup

27. Where Does Diffusion Take the Ion? Exterior Interior K + 5 mM Cl - Low Cl - High K + 150 mM Na + 15 mM Na + 150 mM O U T I N I N

28. Action Potential Components Membrane Potential (mV) -50 -70 0 +30 Time (msec) Threshold Potential Resting Membrane Potential Na + equilibrium Action Potential Depolarization! Hyperpolarized

29. Membrane Permeability Membrane Potential (mV) -50 -70 0 +30 Time (msec) Threshold Potential Resting Membrane Potential Na + Influx K + Efflux

30. What Happens to the Membrane If Cl - Rushes Into the Cell During Repolarization? Membrane Potential (mV) -50 -70 0 +30 Time (msec) Threshold Potential Resting Membrane Potential Na + Influx K + Efflux It gets hyperpolarized!

31. What Happens to the Frequency of Action Potentials If the Membrane Gets Hyperpolarized? Membrane Potential (mV) -50 -70 0 +30 Time (msec) It decreases!

33. Gamma Amino Butyric Acid Receptors GABA Receptor Exterior Interior Cl - Hyperpolarized!

34. GABA+Bz Complex Bz Receptor GABA Receptor Exterior Interior Cl - Profoundly Hyperpolarized!

35. Are You Ready for a Big Surprise? Many CNS drugs act on GABA receptors to effect the frequency and duration of action potentials!

40. A patient is taking theophylline and becomes tachycardic (SVT). You want to give her adenosine. Is there an interaction you should be aware of? How should you alter your therapy? Methylxanthines blocks adenosine receptors. A typical dose of adenosine may not be sufficient to achieve the desired result. Double the dose!

47. Extrapyramidal Symptoms Lip-smacking, worm-like tongue movement, ‘fly-catching’ Months to years Tarditive dyskinesia Compulsive, repetitive motions; agitation 5 – 60 days Akathesia Tremor, shuffling gait, drooling, stooped posture, instability 5 – 30 days Parkinsonism Spasm of tongue, neck, face & back Hours to 5 days Acute dystonia Features Onset Reaction

56. MAOI & Dietary Tyramine

57. Antidepressant Mechanism TCAs & SSRIs Block Here

60. Parkinson’s Disease

64. Levodopa Mechanism

66. Drugs That Affect the Autonomic Nervous System Word of Warning Carefully review the A&P material & tables on pages 309 – 314 and 317 – 321!

68. Acetylcholine Receptors Figure 9-8, page 313, Paramedic Care, V1

82. Adrenergic Receptor Specificity terbutaline Dobutamine Dopamine Isoproterenol Phenylephrine Norepinephrine Ephedrine Epinephrine D opaminergic β 2 β 1 α 2 α 1 Drug