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- 1. Pharmacology Pharmacology Pharmacology Drugs That Affect The: Nervous System Drugs That Affect The: Nervous System
- 2. Topics Topics Topics • Analgesics and antagonists • Anesthetics • Anti-anxiety and sedative-hypnotics • Anti-seizure / anti-convulsants • CNS stimulators • Psychotherapeutics • ANS/PNS/SNS agents • Analgesics and antagonists • Anesthetics • Anti-anxiety and sedative-hypnotics • Anti-seizure / anti-convulsants • CNS stimulators • Psychotherapeutics • ANS/PNS/SNS agents
- 3. A colorful review of neurophysiology! A colorful review of neurophysiology! But first... But first... But first...
- 4. Nervous System Nervous System Nervous System CNS CNS PNS PNS Somatic Somatic Autonomic Autonomic Parasympathetic Parasympathetic Sympathetic Sympathetic
- 5. Analgesics Analgesics Analgesics • Decrease in sensation of pain. • Classes: – Opioid. • Agonist. • Antagonist. • Agonist-antagonist. – Non-opioids. • Salicylates. • NSAIDs. • Adjuncts. • Decrease in sensation of pain. • Classes: – Opioid. • Agonist. • Antagonist. • Agonist-antagonist. – Non-opioids. • Salicylates. • NSAIDs. • Adjuncts.
- 6. Opioids Opioids Opioids • Generic reference to morphine-like drugs/actions – Opiate: derivative of opium • Prototype: morphine – Morpheus: god of dreams • Act on endorphin receptors: – Mu (most important) – Kappa • Generic reference to morphine-like drugs/actions – Opiate: derivative of opium • Prototype: morphine – Morpheus: god of dreams • Act on endorphin receptors: – Mu (most important) – Kappa
- 7. Actions of Opioid Receptors Actions of Opioid Receptors Actions of Opioid Receptors Response Mu Kappa Analgesia ; ; Respiratory Depression ; Sedation ; ; Euphoria ; Physical Dependence ; ⇓ GI motility ; ;
- 8. Actions at Opioid Receptors Actions at Opioid Receptors 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. General Actions of Opioids General Actions of Opioids General Actions of Opioids • Analgesia • Respiratory depression • Constipation • Urinary retention • Cough suppression • Emesis • Increased ICP – Indirect through CO2 retention • Analgesia • Respiratory depression • Constipation • Urinary retention • Cough suppression • Emesis • Increased ICP – Indirect through CO2 retention • Euphoria/Dysphoria • Sedation • Miosis – Pupil constriction • ⇓ Preload & afterload – Watch for hypotension! • Euphoria/Dysphoria • Sedation • Miosis – Pupil constriction • ⇓ Preload & afterload – Watch for hypotension!
- 10. Non-opioid Analgesics Non Non- -opioid opioid Analgesics Analgesics • Salicylates – Aspirin (Bayer® ) * (prototype for class) • Non-Steroidal Anti-Inflammatory Drugs • Ibuprofen (Motrin®, Advil®) – Propionic Acid derivative • Naproxen (Naprosyn®) • Naproxen sodium (Aleve®) • All compete with aspirin for protein binding sites – Ketorolac (Toradol®) • Salicylates – Aspirin (Bayer® ) * (prototype for class) • Non-Steroidal Anti-Inflammatory Drugs • Ibuprofen (Motrin®, Advil®) – Propionic Acid derivative • Naproxen (Naprosyn®) • Naproxen sodium (Aleve®) • All compete with aspirin for protein binding sites – Ketorolac (Toradol®)
- 11. NSAID Properties NSAID Properties NSAID Properties Drug Fever Inflammation Pain Aspirin ; ; ; Ibuprofen ; ; ; Acetaminophen ; ;
- 12. Aspirin Mechanism of Action Aspirin Mechanism of Action Aspirin Mechanism of Action • Inhibit synthesis of cyclooxygenase (COX) – Enzyme responsible for synthesis of: • Inhibit synthesis of cyclooxygenase (COX) – Enzyme responsible for synthesis of: Prostaglandins –Pain response –Suppression of gastric acid secretion –Promote secretion of gastric mucus and bicarbonate –Mediation of inflammatory response –Production of fever –Promote renal vasodilation (⇑ blood flow) –Promote uterine contraction Prostaglandins –Pain response –Suppression of gastric acid secretion –Promote secretion of gastric mucus and bicarbonate –Mediation of inflammatory response –Production of fever –Promote renal vasodilation (⇑ blood flow) –Promote uterine contraction Thromboxane A2 –Involved in platelet –aggregation Thromboxane A2 –Involved in platelet –aggregation
- 13. Aspirin Effects Aspirin Effects Aspirin Effects Good • Pain relief • ⇓ Fever • ⇓ Inflammation Good • Pain relief • ⇓ Fever • ⇓ Inflammation Bad • GI ulceration: – ⇑ Gastric acidity – ⇓ GI protection • ⇑ Bleeding • ⇓ Renal elimination • ⇓ Uterine contractions during labor Bad • GI ulceration: – ⇑ Gastric acidity – ⇓ GI protection • ⇑ Bleeding • ⇓ Renal elimination • ⇓ Uterine contractions during labor
- 14. Acetaminophen (Tylenol®) Acetaminophen (Tylenol Acetaminophen (Tylenol® ® ) ) • NSAID similar to aspirin • Only inhibits synthesis of CNS prostaglandins – Does not have peripheral side effects of ASA: • Gastric ulceration • ⇓ Platelet aggregation • ⇓ Renal flow • ⇓ Uterine contractions • NSAID similar to aspirin • Only inhibits synthesis of CNS prostaglandins – Does not have peripheral side effects of ASA: • Gastric ulceration • ⇓ Platelet aggregation • ⇓ Renal flow • ⇓ Uterine contractions
- 15. Acetaminophen Metabolism Acetaminophen Metabolism Acetaminophen Metabolism Acetaminophen Acetaminophen Non-toxic metabolites Non-toxic metabolites Major Pathway Minor Pathway P-450 Toxic metabolites Toxic metabolites Non-toxic metabolites Non-toxic metabolites Induced by ETOH Induced by ETOH Glutathione Depleted by ETOH & APAP overdose Depleted by ETOH & APAP overdose
- 16. Anesthetics Anesthetics Anesthetics • Loss of all sensation – Usually with loss of consciousness – ⇓ propagation of neural impulses • General anesthetics – Gases • Nitrous oxide (Nitronox®), halothane, ether – IV • Thiopental (Pentothal®), methohexital (Brevitol®), diazepam (valium®), remifentanil (Ultiva®) • Loss of all sensation – Usually with loss of consciousness – ⇓ propagation of neural impulses • General anesthetics – Gases • Nitrous oxide (Nitronox®), halothane, ether – IV • Thiopental (Pentothal®), methohexital (Brevitol®), diazepam (valium®), remifentanil (Ultiva®)
- 17. Anesthetics Anesthetics Anesthetics • Local – Affect on area around injection – Usually accompanied by epinephrine • Lidocaine (Xylocaine ®), topical cocaine • Local – Affect on area around injection – Usually accompanied by epinephrine • Lidocaine (Xylocaine ®), topical cocaine
- 18. Anti-anxiety & Sedative- hypnotic Drugs Anti Anti- -anxiety & Sedative anxiety & Sedative- - hypnotic Drugs hypnotic Drugs • Sedation: ⇓ anxiety & inhibitions • Hypnosis: instigation of sleep • Insomnia – ⇑ Latent period – ⇑ Wakenings • Classes: – Barbiturates – Benzodiazepines – Alcohol • Sedation: ⇓ anxiety & inhibitions • Hypnosis: instigation of sleep • Insomnia – ⇑ Latent period – ⇑ Wakenings • Classes: – Barbiturates – Benzodiazepines – Alcohol Chemically different, Functionally similar Chemically different, Functionally similar
- 19. Mechanism of action Mechanism of action Mechanism of action • Both promote the effectiveness of GABA receptors in the CNS – Benzodiazepines promote only – Barbiturates promote and (at high doses) stimulate GABA receptors • GABA = chief CNS inhibitory neurotransmitter – Promotes hyperpolarization via ⇑ Cl- influx • Both promote the effectiveness of GABA receptors in the CNS – Benzodiazepines promote only – Barbiturates promote and (at high doses) stimulate GABA receptors • GABA = chief CNS inhibitory neurotransmitter – Promotes hyperpolarization via ⇑ Cl- influx
- 20. Benzodiazepines vs. Barbiturates Benzodiazepines vs. Benzodiazepines vs. Barbiturates 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. Benzodiazepines Benzodiazepines Benzodiazepines Benzodiazepines • diazepam (Valium®) • midazolam (Versed®) • alprazolam (Xanax®) • lorazepam (Atiavan®) • triazolam (Halcion®) Benzodiazepines • diazepam (Valium®) • midazolam (Versed®) • alprazolam (Xanax®) • lorazepam (Atiavan®) • triazolam (Halcion®) “Non-benzo benzo” • zolpidem (Ambien®) • buspirone (BusPar®) “Non-benzo benzo” • zolpidem (Ambien®) • buspirone (BusPar®)
- 22. Barbiturates Barbiturates Barbiturates Subgroup Prototype Typical Indication Ultra-short acting thiopental (Pentothol®) Anesthesia Short acting secobarbital (Seconal®) Insomnia Long acting phenobarbital (Luminal®) Seizures
- 23. Barbiturates Barbiturates Barbiturates • amobarbital (Amytal®) • pentobarbital (Nembutal®) • thiopental (Pentothal®) • phenobarbital (Luminal ®) • secobarbital (Seconal ®) • amobarbital (Amytal®) • pentobarbital (Nembutal®) • thiopental (Pentothal®) • phenobarbital (Luminal ®) • secobarbital (Seconal ®)
- 24. Anti-seizure Medications Anti Anti- -seizure Medications seizure Medications • Seizures caused by hyperactive brain areas • Multiple chemical classes of drugs – All have same approach – Decrease propagation of action potentials • ⇓ Na+, Ca++ influx (delay depolarization/prolong repolarization) • ⇑ Cl- influx (hyperpolarize membrane) • Seizures caused by hyperactive brain areas • Multiple chemical classes of drugs – All have same approach – Decrease propagation of action potentials • ⇓ Na+, Ca++ influx (delay depolarization/prolong repolarization) • ⇑ Cl- influx (hyperpolarize membrane)
- 25. Anti-Seizure Medications Anti Anti- -Seizure Medications Seizure Medications Benzodiazepines • diazepam (Valium®) • lorazepam (Ativan®) Barbiturates • phenobarbital (Luminal®) Benzodiazepines • diazepam (Valium®) • lorazepam (Ativan®) Barbiturates • phenobarbital (Luminal®) Ion Channel Inhibitors • carbamazepine (Tegretol®) • phenytoin (Dilantin®) Misc. Agents • valproic acid (Depakote®) Ion Channel Inhibitors • carbamazepine (Tegretol®) • phenytoin (Dilantin®) Misc. Agents • valproic acid (Depakote®)
- 26. Ion Diffusion Ion Diffusion Ion Diffusion • Key to neurophysiology • Dependent upon: – Concentration gradient – Electrical gradient • Modified by: – ‘Gated ion channels’ • Key to neurophysiology • Dependent upon: – Concentration gradient – Electrical gradient • Modified by: – ‘Gated ion channels’
- 27. Where Does Diffusion Take the Ion? Where Does Diffusion Take the Where Does Diffusion Take the Ion? Ion? Exterior Interior K+ 5 mM K+ 5 mM Cl- Low Cl- Low Cl- High Cl- High K+ 150 mM K+ 150 mM Na+ 15 mM Na+ 15 mM Na+ 150 mM Na+ 150 mM O U T O U T I N I N I N I N
- 28. Action Potential Components Action Potential Components Action Potential Components Mem brane Poten tial (mV) -50 +30 Threshold Potential -70 0 Time (msec) Threshold Potential Resting Membrane Potential Resting Membrane Potential Na+ equilibrium Na+ equilibrium Action Potential Action Potential Depolarization! Depolarization! Hyperpolarized Hyperpolarized
- 29. Membrane Permeability Membrane Permeability Membrane Permeability Mem brane Poten tial (mV) -50 +30 Threshold Potential -70 0 Time (msec) Threshold Potential Resting Membrane Potential Resting Membrane Potential N a + I n f l u x K + E f f l u x
- 30. Mem brane Poten tial (mV) -50 +30 Threshold Potential -70 0 Time (msec) Threshold Potential Resting Membrane Potential Resting Membrane Potential N a + I n f l u x K + E f f l u x It gets hyperpolarized! It gets hyperpolarized! What Happens to the Membrane If Cl- Rushes Into the Cell During Repolarization? What Happens to the Membrane If Cl- Rushes Into the Cell During Repolarization?
- 31. Mem brane Poten tial (mV) -50 +30 -70 0 Time (msec) It decreases! It decreases! What Happens to the Frequency of Action Potentials If the Membrane Gets Hyperpolarized? What Happens to the Frequency of Action Potentials If the Membrane Gets Hyperpolarized?
- 32. Clinical Correlation Clinical Correlation • Remember that it is the rate of action potential propagation that determines neurologic function. – Determined by frequency of action potentials. • Remember that it is the rate of action potential propagation that determines neurologic function. – Determined by frequency of action potentials. What is a seizure? What is a seizure? What would be the effect on the membrane of ⇑ Cl- influx during a seizure? What would be the effect on the membrane of ⇑ Cl- influx during a seizure? Hyperpolarization & ⇓ seizure activity!
- 33. Gamma Amino Butyric Acid Receptors Gamma Amino Butyric Acid Gamma Amino Butyric Acid Receptors Receptors GABA Receptor GABA Receptor Exterior Interior Cl - Cl - Hyperpolarized! Hyperpolarized!
- 34. GABA+Bz Complex GABA+Bz GABA+Bz Complex Complex Bz Receptor Bz Receptor GABA Receptor GABA Receptor Exterior Interior Cl - Cl - Profoundly Hyperpolarized! Profoundly Hyperpolarized!
- 35. Are You Ready for a Big Surprise? Are You Ready for a Big Are You Ready for a Big Surprise? Surprise? Many CNS drugs act on GABA Many CNS drugs act on GABA receptors to effect the frequency receptors to effect the frequency and duration of action potentials! and duration of action potentials!
- 36. SNS Stimulants SNS Stimulants SNS Stimulants • Two general mechanisms: – Increase excitatory neurotransmitter release – Decrease inhibitory neurotransmitter release • Two general mechanisms: – Increase excitatory neurotransmitter release – Decrease inhibitory neurotransmitter release • Three classes: • Amphetamines • Methylphendidate • Methylxanthines • Three classes: • Amphetamines • Methylphendidate • Methylxanthines
- 37. Amphetamines Amphetamines Amphetamines amphetamine methamphetamine dextroamphetamine (Dexedrine®) amphetamine methamphetamine dextroamphetamine (Dexedrine®) Side Effects •Tachycardia •Hypertension •Convulsion •Insomnia •Psychosis Side Effects •Tachycardia •Hypertension •Convulsion •Insomnia •Psychosis Indications •Diet suppression •⇓ Fatigue •⇑ Concentration Indications •Diet suppression •⇓ Fatigue •⇑ Concentration MOA: promote release of norepinephrine, dopamine MOA: promote release of norepinephrine, dopamine
- 38. Methylphenidate (Ritalin®) Methylphenidate (Ritalin Methylphenidate (Ritalin® ® ) ) • Different structure than other stimulants – Similar mechanism – Similar side effects • Indication: ADHD – Increase ability to focus & concentrate • Different structure than other stimulants – Similar mechanism – Similar side effects • Indication: ADHD – Increase ability to focus & concentrate
- 39. Methylxanthines Methylxanthines Methylxanthines • Caffeine • Theophylline (Theo-Dur®) • Aminophylline Mechanism of action • Reversible blockade of adenosine receptors • Caffeine • Theophylline (Theo-Dur®) • Aminophylline Mechanism of action • Reversible blockade of adenosine receptors
- 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? A patient is taking theophylline and A patient is taking theophylline and becomes tachycardic (SVT). You want to becomes tachycardic (SVT). You want to give her adenosine. Is there an interaction give her adenosine. Is there an interaction you should be aware of? How should you you should be aware of? How should you alter your therapy? alter your therapy? Methylxanthines blocks adenosine receptors. A typical dose of adenosine may not be sufficient to achieve the desired result. Methylxanthines blocks adenosine receptors. A typical dose of adenosine may not be sufficient to achieve the desired result. Double the dose! Double the dose!
- 41. News You Can Use… News You Can Use News You Can Use… … Source Amount of Caffeine Coffee •Brewed •Instant 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
- 42. Psychotherapeutic Medications Psychotherapeutic Psychotherapeutic Medications Medications • Dysfunction related to neurotransmitter imbalance. – Norepinephrine. – Dopamine. – Seratonin. • Goal is to regulate excitory/inhibitory neurotransmitters. • Dysfunction related to neurotransmitter imbalance. – Norepinephrine. – Dopamine. – Seratonin. • Goal is to regulate excitory/inhibitory neurotransmitters. Monoamines
- 43. Anti-Psychotic Drugs (Neuroleptics) Anti Anti- -Psychotic Drugs Psychotic Drugs (Neuroleptics) (Neuroleptics) • Schizophrenia – Loss of contact with reality & disorganized thoughts – Probable cause: increased dopamine release – Tx. Aimed at decreasing dopamine activity • Schizophrenia – Loss of contact with reality & disorganized thoughts – Probable cause: increased dopamine release – Tx. Aimed at decreasing dopamine activity Two Chemical Classes: Two Chemical Classes: • Phenothiazines • chlorpromazine (Thorazine ®) • Butyrophenones • haloperidol (Haldol®) • Phenothiazines • chlorpromazine (Thorazine ®) • Butyrophenones • haloperidol (Haldol®)
- 44. Other Uses for Antipsychotics Other Uses for Other Uses for Antipsychotics Antipsychotics • Bipolar depression • Tourette’s Syndrome • Prevention of emesis • Dementia (OBS) • Temporary psychoses from other illness • Bipolar depression • Tourette’s Syndrome • Prevention of emesis • Dementia (OBS) • Temporary psychoses from other illness
- 45. Antipsychotic MOA Antipsychotic MOA Antipsychotic MOA • Mechanism is similar • Strength ([]) vs. Potency (‘oomph’) – Phenothiazines – low potency – Butyrophenones – high potency • Receptor Antagonism – Dopamine2 in brain – Muscarinic cholinergic – Histamine – Norepi at alpha1 • Mechanism is similar • Strength ([]) vs. Potency (‘oomph’) – Phenothiazines – low potency – Butyrophenones – high potency • Receptor Antagonism – Dopamine2 in brain – Muscarinic cholinergic – Histamine – Norepi at alpha1 Therapeutic effects Uninteded effects
- 46. Antipsychotic Side Effects Antipsychotic Side Effects Antipsychotic Side Effects • Generally short term • Extrapyramidal symptoms (EPS) • Anticholinergic effects (atropine-like) – Dry mouth, blurred vision, photophobia, tachycardia, constipation) • Orthostatic hypotension • Sedation • Decreased seizure threshold • Sexual dysfunction • Generally short term • Extrapyramidal symptoms (EPS) • Anticholinergic effects (atropine-like) – Dry mouth, blurred vision, photophobia, tachycardia, constipation) • Orthostatic hypotension • Sedation • Decreased seizure threshold • Sexual dysfunction
- 47. Extrapyramidal Symptoms Extrapyramidal Symptoms 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’
- 48. Treatment of EPS Treatment of EPS Treatment of EPS • Likely caused by blocking central dopamine2 receptors responsible for movement • Anticholinergic therapy rapidly effective – diphenhydramine (Benadryl®) • Likely caused by blocking central dopamine2 receptors responsible for movement • Anticholinergic therapy rapidly effective – diphenhydramine (Benadryl®)
- 49. Antipsychotic Agents Antipsychotic Agents Antipsychotic Agents • chlorpromazine (Thorazine®) • thioridazine (Mellaril®) • trifluoperazine (Stelazine®) • haloperidol (Haldol®) • chlorpromazine (Thorazine®) • thioridazine (Mellaril®) • trifluoperazine (Stelazine®) • haloperidol (Haldol®)
- 50. Antidepressants Antidepressants Antidepressants • Likely cause: inadequate monoamine levels • Treatment options: – Increasing NT synthesis in presynaptic end bulb – Increasing NT release from end bulb – Blocking NT ‘reuptake’ by presynaptic end bulb • Likely cause: inadequate monoamine levels • Treatment options: – Increasing NT synthesis in presynaptic end bulb – Increasing NT release from end bulb – Blocking NT ‘reuptake’ by presynaptic end bulb
- 51. Tricyclic Antidepressants (TCAs) Tricyclic Tricyclic Antidepressants Antidepressants (TCAs) (TCAs) • Block reuptake of both NE & serotonin – Enhance effects • Similar side effects to phenothiazines • Block reuptake of both NE & serotonin – Enhance effects • Similar side effects to phenothiazines
- 52. TCA Side Effects TCA Side Effects TCA Side Effects • Orthostatic hypotension • Sedation • Anticholinergic effects • Cardiac toxicity – Ventricular dysrythmias • Orthostatic hypotension • Sedation • Anticholinergic effects • Cardiac toxicity – Ventricular dysrythmias
- 53. Selective Serotonin Reuptake Inhibitors (SSRIs) Selective Serotonin Reuptake Selective Serotonin Reuptake Inhibitors (SSRIs) Inhibitors (SSRIs) • Block only serotonin (not NE) reuptake – Elevate serotonin levels • Fewer side effects than TCS – No hypotension – No anticholinergic effects – No cardiotoxicity • Most common side effect – Nausea, insomnia, sexual dysfunction • Block only serotonin (not NE) reuptake – Elevate serotonin levels • Fewer side effects than TCS – No hypotension – No anticholinergic effects – No cardiotoxicity • Most common side effect – Nausea, insomnia, sexual dysfunction
- 54. Monoamine Oxidase Inhibitors (MAOIs) Monoamine Monoamine Oxidase Oxidase Inhibitors Inhibitors ( (MAOIs MAOIs) ) • Monoamine oxidase – Present in liver, intestines & MA releasing neurons – Inactivates monoamines – Inactivates dietary tyramine in liver • Foods rich in tyramine: cheese & red wine • Monoamine oxidase – Present in liver, intestines & MA releasing neurons – Inactivates monoamines – Inactivates dietary tyramine in liver • Foods rich in tyramine: cheese & red wine
- 55. MAOI Side Effects MAOI Side Effects MAOI Side Effects • CNS Stimulation – Anxiety, agitation • Orthostatic hypotension • Hypertensive Crisis – From increased tyramine consumption • Excessive arteriole constriction, stimulation of heart • CNS Stimulation – Anxiety, agitation • Orthostatic hypotension • Hypertensive Crisis – From increased tyramine consumption • Excessive arteriole constriction, stimulation of heart
- 56. MAOI & Dietary Tyramine MAOI & Dietary Tyramine MAOI & Dietary Tyramine
- 57. Antidepressant Mechanism Antidepressant Mechanism Antidepressant Mechanism TCAs & SSRIs Block Here
- 58. Antidepressants Agents Antidepressants Agents Antidepressants Agents TCAs • imiprimine (Tofranil®) • amitriptyline (Elavil®) • nortriptyline (Pamelor ®) SSRIs • fluoxetine (Prozac®) • paroxetine (Paxil®) • sertraline (Zoloft®) TCAs • imiprimine (Tofranil®) • amitriptyline (Elavil®) • nortriptyline (Pamelor ®) SSRIs • fluoxetine (Prozac®) • paroxetine (Paxil®) • sertraline (Zoloft®) MAOIs • phenelzine (Nardil®) Atypical Antidepressants • bupropion (Wellbutrin®) MAOIs • phenelzine (Nardil®) Atypical Antidepressants • bupropion (Wellbutrin®)
- 59. Parkinson’s Disease Parkinson Parkinson’ ’s Disease s Disease • Fine motor control dependent upon balance between excitatory and inhibitory NT – Acetylcholine = excitatory – Dopamine =inhibitory GABA= inhibitory • Fine motor control dependent upon balance between excitatory and inhibitory NT – Acetylcholine = excitatory – Dopamine =inhibitory GABA= inhibitory Control GABA release
- 61. Parkinson’s Symptoms: Parkinson Parkinson’ ’s Symptoms: s Symptoms: • Similar to EPS • Dyskinesias – Tremors, unsteady gait, instability • Bradykinesia • Akinesia in severe cases • Similar to EPS • Dyskinesias – Tremors, unsteady gait, instability • Bradykinesia • Akinesia in severe cases
- 62. Parkinson’s Treatment Parkinson Parkinson’ ’s Treatment s Treatment • Dopaminergic approach – ⇑ Release of dopamine – ⇑ [Dopamine] – ⇓ Dopamine breakdown • Cholinergic approach – ⇓ Amount of ACh released – Directly block ACh receptors • All treatment is symptomatic and temporary • Dopaminergic approach – ⇑ Release of dopamine – ⇑ [Dopamine] – ⇓ Dopamine breakdown • Cholinergic approach – ⇓ Amount of ACh released – Directly block ACh receptors • All treatment is symptomatic and temporary
- 63. Levodopa Levodopa Levodopa • Sinemet ® = levodopa + carbidopa • Increase central dopamine levels • Side effects: – Nausea and vomiting – Dyskinesia (~80% of population) – Cardiovascular (dysrythmias) • Sinemet ® = levodopa + carbidopa • Increase central dopamine levels • Side effects: – Nausea and vomiting – Dyskinesia (~80% of population) – Cardiovascular (dysrythmias)
- 65. Other Agents Other Agents Other Agents • amantadine (Symmetrel®) – ⇑ release of dopamine from unaffected neurons • bromocriptine (Parlodel®) – Directly stimulated dopamine receptors • selegiline (Carbex®, Eldepryl®) – MAOI selective for dopamine (MAO-B) • benztropine (Cogentin®) – Centrally acting anticholinergic • amantadine (Symmetrel®) – ⇑ release of dopamine from unaffected neurons • bromocriptine (Parlodel®) – Directly stimulated dopamine receptors • selegiline (Carbex®, Eldepryl®) – MAOI selective for dopamine (MAO-B) • benztropine (Cogentin®) – Centrally acting anticholinergic
- 66. Drugs That Affect the Autonomic Nervous System Drugs That Affect the Drugs That Affect the Autonomic Nervous System Autonomic Nervous System Word of Warning Carefully review the A&P material & tables on pages 309 – 314 and 317 – 321! Word of Warning Carefully review the A&P material & tables on pages 309 – 314 and 317 – 321!
- 67. PNS Drugs PNS Drugs PNS Drugs • Cholinergic – Agonists & Antagonistis (Anticholinergics) – Based on response at nicotinic(N&M) & muscarinic receptors • Cholinergic – Agonists & Antagonistis (Anticholinergics) – Based on response at nicotinic(N&M) & muscarinic receptors
- 68. Acetylcholine Receptors Acetylcholine Receptors Acetylcholine Receptors Figure 9-8, page 313, Paramedic Care, V1
- 69. Cholinergic Agonists Cholinergic Agonists Cholinergic Agonists Salivation Lacrimation Urination Defecation Gastric motility Emesis Salivation Lacrimation Urination Defecation Gastric motility Emesis Cholinergic agents cause SLUDGE! HINT! These effects are predictable by knowing PNS physiology (table 9-4)
- 70. Direct Acting Cholinergics Direct Acting Direct Acting Cholinergics Cholinergics • bethanechol (Urecholine) prototype – Direct stimulation of ACh receptors – Used for urinary hesitancy and constipation • bethanechol (Urecholine) prototype – Direct stimulation of ACh receptors – Used for urinary hesitancy and constipation
- 71. Indirect Acting Cholinergics Indirect Acting Indirect Acting Cholinergics Cholinergics • Inhibit ChE (cholinesterase) to prolong the duration of ACh stimulation in synapse • Reversible • Irreversible • Inhibit ChE (cholinesterase) to prolong the duration of ACh stimulation in synapse • Reversible • Irreversible
- 72. Reversible ChE Inhibitors Reversible ChE Inhibitors Reversible ChE Inhibitors • neostigmine (Prostigmine®) – Myasthenia Gravis at nicotinicM receptors – Can reverse nondepolarizing neuromuscular blockade • physostigmine (Antilirium®) – Shorter onset of action – Used for iatrogenic atropine overdoses @ muscarinic receptors • neostigmine (Prostigmine®) – Myasthenia Gravis at nicotinicM receptors – Can reverse nondepolarizing neuromuscular blockade • physostigmine (Antilirium®) – Shorter onset of action – Used for iatrogenic atropine overdoses @ muscarinic receptors
- 73. Irreversible ChE Inhibitors Irreversible ChE Inhibitors Irreversible ChE Inhibitors • Very rarely used clinically • Very common in insecticides & chemical weapons – VX and Sarin gas – Cause SLUDGE dammit and paralysis • Tx: atropine and pralidoxime (2-PAM®) – Anticholinergics • Very rarely used clinically • Very common in insecticides & chemical weapons – VX and Sarin gas – Cause SLUDGE dammit and paralysis • Tx: atropine and pralidoxime (2-PAM®) – Anticholinergics
- 74. Anticholinergics Anticholinergics Anticholinergics • Muscarinic antagonists – Atropine • Ganglionic antagonists – block nicotinicN receptors – Turns off the ANS! – trimethaphan (Arfonad®) • Hypertensive crisis • Muscarinic antagonists – Atropine • Ganglionic antagonists – block nicotinicN receptors – Turns off the ANS! – trimethaphan (Arfonad®) • Hypertensive crisis • Atropine Overdose – Dry mouth, blurred vision, anhidrosis • Atropine Overdose – Dry mouth, blurred vision, anhidrosis Hot as Hell Blind as a Bat Dry as a Bone Red as a Beet Mad as a Hatter Hot as Hell Blind as a Bat Dry as a Bone Red as a Beet Mad as a Hatter
- 75. Neuromuscular Blockers Neuromuscular Blockers Neuromuscular Blockers • Nicotinic Cholinergic Antagonists – Given to induce paralysis • Depolarizing – succinylcholine (Anectin®) • Nondepolarizing – tubocurarine from curare – rocuronium (Zemuron®) – vecuronium (Norcuron®) • Nicotinic Cholinergic Antagonists – Given to induce paralysis • Depolarizing – succinylcholine (Anectin®) • Nondepolarizing – tubocurarine from curare – rocuronium (Zemuron®) – vecuronium (Norcuron®)
- 76. Warning! Warning! Warning! • Paralysis without loss of consciousness! – MUST also give sedative-hypnotic – Common agents: • fentanyl (Sublimaze®) • midazolam (Versed®) • Paralysis without loss of consciousness! – MUST also give sedative-hypnotic – Common agents: • fentanyl (Sublimaze®) • midazolam (Versed®)
- 77. SNS Drugs SNS Drugs SNS Drugs • Predictable response based on knowledge of affects of adrenergic receptor stimulation • HINT: Know table 9-5, page 321 • Each receptor may be: – Stimulated (sympathomimetic) – Inhibitied (sympatholytic) • Predictable response based on knowledge of affects of adrenergic receptor stimulation • HINT: Know table 9-5, page 321 • Each receptor may be: – Stimulated (sympathomimetic) – Inhibitied (sympatholytic)
- 78. Alpha1 Agonists Alpha Alpha1 1 Agonists Agonists • Profound vasoconstriction – Increases afterload & blood pressure when given systemically – Decreases drug absorption & bleeding when given topically • Profound vasoconstriction – Increases afterload & blood pressure when given systemically – Decreases drug absorption & bleeding when given topically
- 79. Alpha1 Antagonism Alpha Alpha1 1 Antagonism Antagonism • Inhibits peripheral vasoconstriction – Used for hypertension – prazosin (Minipress®) – doxazosin (Cardura®) – phentolamine (Regitine®) • Blocks alpha1&2 receptors • Inhibits peripheral vasoconstriction – Used for hypertension – prazosin (Minipress®) – doxazosin (Cardura®) – phentolamine (Regitine®) • Blocks alpha1&2 receptors
- 80. Beta1 Agonists Beta Beta1 1 Agonists Agonists • Increases heart rate, contractility, and conductivity • Increases heart rate, contractility, and conductivity
- 81. Beta Antagonists (β Blockers) Beta Antagonists ( Beta Antagonists (β β Blockers) Blockers) • Frequently used • Lower Blood Pressure • Negative chronotropes & inotropes • Frequently used • Lower Blood Pressure • Negative chronotropes & inotropes Beta1 Selective Blockade • atenolol (Tenormin®) • esmolol (Brevibloc®) • metoprolol (Lopressor®) Beta1 Selective Blockade • atenolol (Tenormin®) • esmolol (Brevibloc®) • metoprolol (Lopressor®) Nonselective • propranolol (Inderal®) • labetalol (Normodyne®, Trandate®) • sotalol (Betapace®) Nonselective • propranolol (Inderal®) • labetalol (Normodyne®, Trandate®) • sotalol (Betapace®)
- 82. Adrenergic Receptor Specificity Adrenergic Receptor Specificity Adrenergic Receptor Specificity Drug α1 α2 β1 β2 Dopaminergic Epinephrine Ephedrine Norepinephrine Phenylephrine Isoproterenol Dopamine Dobutamine terbutaline
- 83. Web Resources Web Resources Web Resources • Web based synaptic transmission project – http://www.williams.edu/imput/index.html • Web based synaptic transmission project – http://www.williams.edu/imput/index.html
- 84. Thank You! Thank You! Thank You! • To Temple College EMS Professions for permission to use their materials • To Temple College EMS Professions for permission to use their materials