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Drugs That Affect The: Nervous System
Topics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
But first... A colorful review of  neurophysiology!
Nervous System CNS PNS Somatic Autonomic Parasympathetic Sympathetic
Analgesics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Opioids ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Actions of Opioid Receptors Response Mu Kappa Analgesia   Respiratory  Depression  Sedation   Euphoria  Physical Dependence     GI motility  
Actions at Opioid Receptors Drugs Mu Kappa Pure Agonists -morphine, codeine, meperidine (Demerol ® ), fentanyl (Sublimaze ® ), remifentanil (Ultiva ® ), propoxyphene (Darvon ® ), hydrocodone (Vicodin ® ), oxycodone (Percocet ® ) Agonist Agonist Agonist-Antagonist - nalbuphine (Nubaine ® ), butorphanol (Stadol ® ) Antagonist Agonist Pure Antagonist - naloxone (Narcan ® ) Antagonist Antagonist
General Actions of Opioids ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Non-opioid Analgesics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
NSAID Properties Drug Fever Inflammation Pain Aspirin    Ibuprofen    Acetaminophen  
Aspirin Mechanism of Action ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Aspirin Effects ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Acetaminophen (Tylenol ® ) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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
Anesthetics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Anesthetics ,[object Object],[object Object],[object Object],[object Object]
Anti-anxiety & Sedative-hypnotic  Drugs ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Chemically different,  Functionally similar
Mechanism of action ,[object Object],[object Object],[object Object],[object Object],[object Object]
Benzodiazepines vs. Barbiturates Criteria BZ Barb. Relative Safety High  Low Maximal CNS depression Low High Respiratory Depression Low High Suicide Potential Low High Abuse Potential Low High Antagonist Available? Yes No
Benzodiazepines ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Barbiturates Subgroup Prototype Typical Indication Ultra-short acting thiopental (Pentothol ® ) Anesthesia Short acting secobarbital (Seconal ® ) Insomnia Long acting phenobarbital (Luminal ® ) Seizures
Barbiturates ,[object Object],[object Object],[object Object],[object Object],[object Object]
Anti-seizure Medications ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Anti-Seizure Medications ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Ion Diffusion ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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
Action Potential Components Membrane Potential (mV) -50 -70 0 +30 Time (msec) Threshold Potential Resting Membrane Potential Na +  equilibrium Action Potential Depolarization! Hyperpolarized
Membrane Permeability Membrane Potential (mV) -50 -70 0 +30 Time (msec) Threshold Potential Resting Membrane Potential Na +  Influx K +  Efflux
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!
What Happens to the Frequency of Action Potentials If the Membrane Gets Hyperpolarized? Membrane Potential (mV) -50 -70 0 +30 Time (msec) It  decreases!
Clinical Correlation ,[object Object],[object Object],What is a seizure? What would be the  effect on the membrane of    Cl -  influx  during a seizure? Hyperpolarization & …    seizure activity!
Gamma Amino Butyric Acid Receptors GABA  Receptor Exterior Interior Cl  - Hyperpolarized!
GABA+Bz Complex Bz  Receptor GABA  Receptor Exterior Interior Cl  - Profoundly Hyperpolarized!
Are You Ready for a Big Surprise? Many CNS drugs act on GABA  receptors to effect the frequency  and duration of action potentials!
SNS Stimulants ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Amphetamines ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],MOA: promote release of norepinephrine, dopamine
Methylphenidate (Ritalin ® ) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Methylxanthines ,[object Object],[object Object],[object Object],[object Object],[object Object]
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!
News You Can Use… Source Amount of Caffeine ,[object Object],[object Object],[object Object],40 – 180 mg/cup 30 – 120 mg/cup Decaffeinated Coffee 2 - 5 mg/cup Tea 20 – 110 mg/cup Coke 40 – 60 mg/12 oz
Psychotherapeutic Medications ,[object Object],[object Object],[object Object],[object Object],[object Object],Monoamines
Anti-Psychotic Drugs (Neuroleptics) ,[object Object],[object Object],[object Object],[object Object],Two Chemical Classes: ,[object Object],[object Object],[object Object],[object Object]
Other Uses for Antipsychotics ,[object Object],[object Object],[object Object],[object Object],[object Object]
Antipsychotic MOA ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Therapeutic effects Uninteded effects
Antipsychotic Side Effects ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Extrapyramidal Symptoms Reaction Onset Features Acute dystonia Hours to 5 days Spasm of tongue, neck, face & back Parkinsonism 5 – 30 days Tremor, shuffling gait, drooling, stooped posture, instability Akathesia 5 – 60 days Compulsive, repetitive motions; agitation Tarditive dyskinesia Months to years Lip-smacking, worm-like tongue movement, ‘fly-catching’
Treatment of EPS ,[object Object],[object Object],[object Object]
Antipsychotic Agents ,[object Object],[object Object],[object Object],[object Object]
Antidepressants ,[object Object],[object Object],[object Object],[object Object],[object Object]
Tricyclic Antidepressants (TCAs) ,[object Object],[object Object],[object Object]
TCA Side Effects ,[object Object],[object Object],[object Object],[object Object],[object Object]
Selective Serotonin Reuptake Inhibitors (SSRIs) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Monoamine Oxidase Inhibitors (MAOIs) ,[object Object],[object Object],[object Object],[object Object],[object Object]
MAOI Side Effects ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
MAOI & Dietary Tyramine
Antidepressant Mechanism TCAs & SSRIs Block Here
Antidepressants Agents ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Parkinson’s Disease ,[object Object],[object Object],[object Object],[object Object],Control GABA release
Parkinson’s Disease
Parkinson’s Symptoms: ,[object Object],[object Object],[object Object],[object Object],[object Object]
Parkinson’s Treatment ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Levodopa ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Levodopa Mechanism
Other Agents ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Drugs That Affect the Autonomic Nervous System Word of Warning Carefully review the A&P material & tables on pages 309 – 314 and 317 – 321!
PNS Drugs ,[object Object],[object Object],[object Object]
Acetylcholine Receptors Figure 9-8, page 313, Paramedic Care, V1
Cholinergic Agonists ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Cholinergic agents cause  SLUDGE ! HINT!   These effects are predictable by knowing PNS physiology (table 9-4)
Direct Acting Cholinergics ,[object Object],[object Object],[object Object]
Indirect Acting Cholinergics ,[object Object],[object Object],[object Object]
Reversible ChE Inhibitors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Irreversible ChE Inhibitors ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Anticholinergics ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Hot as Hell Blind as a Bat Dry as a Bone Red as a Beet Mad as a Hatter
Neuromuscular Blockers ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Warning! ,[object Object],[object Object],[object Object],[object Object],[object Object]
SNS Drugs ,[object Object],[object Object],[object Object],[object Object],[object Object]
Alpha 1  Agonists ,[object Object],[object Object],[object Object]
Alpha 1  Antagonism ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Beta 1  Agonists ,[object Object]
Beta Antagonists ( β  Blockers) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Adrenergic Receptor Specificity Drug α 1 α 2 β 1 β 2 D opaminergic Epinephrine Ephedrine Norepinephrine Phenylephrine Isoproterenol Dopamine Dobutamine terbutaline

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Cns drugs outline

  • 1. Drugs That Affect The: Nervous System
  • 2.
  • 3. But first... A colorful review of neurophysiology!
  • 4. Nervous System CNS PNS Somatic Autonomic Parasympathetic Sympathetic
  • 5.
  • 6.
  • 7. Actions of Opioid Receptors Response Mu Kappa Analgesia   Respiratory Depression  Sedation   Euphoria  Physical Dependence   GI motility  
  • 8. Actions at Opioid Receptors Drugs Mu Kappa Pure Agonists -morphine, codeine, meperidine (Demerol ® ), fentanyl (Sublimaze ® ), remifentanil (Ultiva ® ), propoxyphene (Darvon ® ), hydrocodone (Vicodin ® ), oxycodone (Percocet ® ) Agonist Agonist Agonist-Antagonist - nalbuphine (Nubaine ® ), butorphanol (Stadol ® ) Antagonist Agonist Pure Antagonist - naloxone (Narcan ® ) Antagonist Antagonist
  • 9.
  • 10.
  • 11. NSAID Properties Drug Fever Inflammation Pain Aspirin    Ibuprofen    Acetaminophen  
  • 12.
  • 13.
  • 14.
  • 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
  • 16.
  • 17.
  • 18.
  • 19.
  • 20. Benzodiazepines vs. Barbiturates Criteria BZ Barb. Relative Safety High Low Maximal CNS depression Low High Respiratory Depression Low High Suicide Potential Low High Abuse Potential Low High Antagonist Available? Yes No
  • 21.
  • 22. Barbiturates Subgroup Prototype Typical Indication Ultra-short acting thiopental (Pentothol ® ) Anesthesia Short acting secobarbital (Seconal ® ) Insomnia Long acting phenobarbital (Luminal ® ) Seizures
  • 23.
  • 24.
  • 25.
  • 26.
  • 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!
  • 32.
  • 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!
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  • 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!
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  • 47. Extrapyramidal Symptoms Reaction Onset Features Acute dystonia Hours to 5 days Spasm of tongue, neck, face & back Parkinsonism 5 – 30 days Tremor, shuffling gait, drooling, stooped posture, instability Akathesia 5 – 60 days Compulsive, repetitive motions; agitation Tarditive dyskinesia Months to years Lip-smacking, worm-like tongue movement, ‘fly-catching’
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  • 56. MAOI & Dietary Tyramine
  • 57. Antidepressant Mechanism TCAs & SSRIs Block Here
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  • 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!
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  • 68. Acetylcholine Receptors Figure 9-8, page 313, Paramedic Care, V1
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  • 82. Adrenergic Receptor Specificity Drug α 1 α 2 β 1 β 2 D opaminergic Epinephrine Ephedrine Norepinephrine Phenylephrine Isoproterenol Dopamine Dobutamine terbutaline