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Nervous System Pharmacology

Nervous System Pharmacology. Overview. Narcotics Sedatives Antidepressants Cholinergic Anticholinergic Neuromuscular Blockades. Narcotic Analgesics. Morphine Sulfate Nalbuphine. Opiate Receptors and effect of Agonist. http://www.csam-asam.org/pdf/misc/OpiatePharm.ppt. Morphine Sulfate.

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Nervous System Pharmacology

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  1. Nervous System Pharmacology

  2. Overview • Narcotics • Sedatives • Antidepressants • Cholinergic • Anticholinergic • Neuromuscular Blockades

  3. Narcotic Analgesics • Morphine Sulfate • Nalbuphine

  4. Opiate Receptors and effect of Agonist http://www.csam-asam.org/pdf/misc/OpiatePharm.ppt

  5. Morphine Sulfate • Class: Opiate Analgesic • Description: Decreases venous return (Pre-load) / Analgesia • Indications: • CP with MI • Pulmonary edema • Localized injuries

  6. Morphine Sulfate • Adverse Reactions • Hypotension • Attributed to decrease in pain • Possibly from Histamine Release • Tachycardia • Bradycardia • Respiratory Depression • Drug Interaction • CNS Depressants may potentiate effects • MAO inhibitors may cause paradoxical excitation

  7. Morphine Sulfate • Precautions • Crosses the placenta very easily • May worsen bradycardia in an inferior wall MI

  8. Morphine for Heart Attack Pain Linked to Risk of Death May 11, 2005 > -- While many patients hospitalized for a heart attack have long been treated with morphine to relieve chest pain, an analysis has shown that these patients have almost a 50 percent higher risk of dying, says a report in the American Heart Journal. Dr. Meine says. "Morphine, on the other hand, doesn't do anything about what is actually causing the pain. It just masks it, and may, in fact, make the underlying disease worse. http://www.mercyhealthplans.com/savvyshopper/healthheadlines/050511.aspx

  9. Nalbuphine • Synthetic analgesic • Very similar indications / precautions as MS

  10. Narcotic Antagonist • Narcan

  11. Anesthetics • CNS Depressants • Types of anesthesia • General • Stage 1: Anesthesia w/o amnesia • Stage 2: Delirious and excited with irregular respirations • Stage 3: Return of normal respiration • Stage 4: Toxic stage • Regional • Local (Topical)

  12. Anesthetic – Nitrous Oxide • Combination of oxygen and nitrous oxide • Self administration results in CNS depression • Oxygen tension in blood increased = decreased hypoxia • Indications: • Severe pain / anxiety / apprehension

  13. IV Anestehtic • Etomidate (Amidate) • Nonbarbituate hypnotic / Anesthetic • Works on the reticular activating system to produce anasthesia • Used in conscious sedation prior to intubation

  14. Epilepsy and Seizures • More than 2 million people have recurrent seizures • Most develop seizure activity during early childhood • Seizures that develop after 20 YOA are usually the result of a lesion or trauma

  15. Epilepsy and Seizures • Uncontrolled electrical discharge in the brain • Focal – Isolated to the lesion area • General – Involves entire cerebrum • Classifications: • Generalized Tonic-Clonic (Formerly grand mal) • Absence seizures (Formerly petit mal) – staring • Complex partial seizures – (psychomotor or temporal lobe) blank stare followed by random activity • Simple partial seizures – Begin in one area with no LOC • Febrile seizures -

  16. Sedatives & Hypnotics • CNS Depressants that produce calming effects • Calm = sedative • Sleep = Hypnotic • Benzodiazepines • Barbituates Reticular Activating System Anxiolytics

  17. Benzodiazepines • Diazepam (Valium) • Acts on the limbic (emotions), thalamic, and hypothalamic regions (Arousal) • Induce GABA in the CNS • Seizures / Decrease anxiety due to cardioversion or TCP • Adverse reactions: • Hypotension • Respiratory depression • Psychomotor impairment • Drug interaction • Precipitation may occur if administered with other drugs • Precaution necessary in geriatric and pregnant patients

  18. Benzodiazepines • Midazolam Hydrochloride (Versed) • Conscious sedation to relieve apprehension or impair memory prior to intubation • Adverse reactions • Respiratory depression • Blurred vision • Hypotension • Drug interactions • Should not be used in patients who have taken other CNS depressants

  19. Benzodiazepines • Lorazepam (Ativan) • Anti-anxiety and anti-convulsant • Slow onset (20 – 30 mins) • Long duration (6 – 8 hours) • Respiratory depression and hypotension may ensue • Caution with existing CNS depressant use

  20. Benzodiazepine Antagonist • Flumazenil (Romazicon) • Antagonizes Benzodiazepine receptors • Reverses sedation and decreases impairment • Does not work to antagonize opiate receptors

  21. Withdrawal S/S • Benziazepines act on the GABA receptors • This causes the cell to become hyperpolarized and it is no longer stimulated, hence the result is sedation and muscle relaxation • The body normally uses the GABA receptor to balance the CNS • When the flumazenil is administered, the body is unable to compensate for the rapid loss of the inhibitory control mechanism

  22. Barbituates • CNS depressant • Mild sedation to deep anesthesia • Potentiate the effects of GABA • Tend to reduce REM sleep • Withdrawal may result in significant REM sleep with dreams and nightmares

  23. Barbituates • Categorized by their lipid solubility & therefore duration of action • Ultra Short Acting – Pentothal • IV anesthetic • Short Acting – pentobarbitol • Insomnia • Intermediate – Amobarbitol • Insomnia • Long Acting – Phenobarbitol (Luminal) • Selective action on motor cortex that acts as an anticonvulsant

  24. Anticonvulsants • Phenytoin (Dilantin) • Promotes Na efflux from hyperactive neurons and results in stabilizing threshold and decreasing excitability • Indications: • Major motor seizures • Contraindications • AV blocks and bradycardias

  25. Eclampsia and Pre-eclampsia • Approximately 5% of pregnancies involve pre-eclampsia (elevated BP) • .5 to 2% progress to eclampsia (Seizures and coma • No definitive cause has been determined • Possible genetic, immunologic, entrance of toxins from fetus in distress • Progresses to CNS dysfunction

  26. Anticonvulsants • Magnesium Sulfate • Electrolyte / Anticonvulsant • Blocks the release of ach at the neuromuscular junction • Results in muscle relaxation • Uses: • Seizure from eclampsia • Stops seizures in 95% of cases • Torsades de pointes • Refractory V-fib

  27. Magnesium Sulfate • Contraindications • Heart Blocks & Mis • Adverse Reactions • Hypotension • Depressed reflexes • Bradycardia • Circulatory collapse

  28. Psychotherapeutic Drugs • All classes effect potential chemical imbalances in the brain • Important neurotransmitters • Epi • NorEpi • Ach • Dopamine • Serotonin

  29. Antipsychotic • Haloperidol Lactate (Haldol) • Thought to block Dopamine receptors in the brain, altering mood and behavior • Usually administered IM (Onset within 30 – 60 minutes) • Indications: Psychotic / agitated patients • Concerns: • May induce dystonias, akthisia • Hypotension • Vision problems • Physical restraint in conjunction with chemical restraint

  30. Tricyclic Antidepressants • Effect the uptake of neurotransmitters (Epi, Serotonin, & Dopamine) in the brain to allow them to stay “active” for a longer period of time

  31. Common Tricyclics • Amitriptyline (Elavil) • Iminpramine (Tofranil) • Nortriptyline (Pamelor)

  32. Tricyclic Overdose • The major concern is the possible cardiac dysrhythmia • Initial CNS stimulation followed by CNS depression • Hydrogen Ion binding theory • Tricyclics can be more readily secreted by the body if urine is more alkaline • Sodium Bicarbonate increases the pH to facilitate faster secretion of the toxin

  33. SSRI • Selective Serotonin Reuptake Inhibitor • When a neurotransmitter is released, one of the following will happen: • Diffusion throughout the body • Broken down by an enzyme • Reuptake • SSRIs inhibit the reuptake of serotonin for prolongued stimulation

  34. Common SSRIs • Fluoxetine (Prozac, Sarafem) • Sertraline (Zoloft) • Paroxetine (Paxil)

  35. MAO Inhibitors • Monoamine Oxidase is an enzyme that inactivates neurotransmitters in the brain • By inhibiting this enzyme, the result is an increase in the amount of neurotransmitters and increased stimulation • Theory: Up regulation (additional receptors form) of receptors in brain result in decreased stimulation

  36. Unfortunately, monoamine oxidase doesn't just destroy those neurotransmitters; it's also responsible for mopping up another amine called tyramine, a molecule that affects blood pressure. So when monoamine oxidase gets blocked, levels of tyramine begin to rise, too. And that's when the trouble starts. • While a hike in neurotransmitters is beneficial, an increase in tyramine is disastrous. Excess tyramine can cause a sudden, sometimes fatal increase in blood pressure so severe that it can burst blood vessels in the brain.

  37. Foods that contain tyramine beer, ale, robust red wines, Chianti, vermouth, homemade breads, cheese, crackers (with cheese), sour cream, bananas, red plums, figs, raisins, avocados, fava beans, Italian broad beans, green bean pods, eggplant, pickled herring, liver dry sausages, canned meats, salami, yogurt, soup cubes, commercial gravies, chocolate, and soy sauce.

  38. Common MAO Inhibitors • Phenelzyne (Nardil) • Tranylcypromine (Parnate)

  39. Drugs That Affect the CNS • Cholinergic (Parasympathomimetics) • Myasthenia Gravis • Cholinesterase Inhibotors • Pyridostigmine and neostigmine • Cholinergic Blocking (Parasympatholytics) • Anticholinergics such as atropine, ipatropium bromide • Adrenergic (Sympathomimetics) • Adrenergic Blocking (Sympatholytics)

  40. Neuromuscular Blockades • Selective paralysis of skeletal muscle with no impact on skeletal or smooth muscle • Facilitate intubation and decrease “bucking” • Work by either competing with ACH or by depolarizing the ACH receptor and rendering the muscle unable from subsequent stimulation

  41. Neuromuscular Blockades • Pancuronium (Pavulon) • Succinylcholine (Anectine) • Vecuronium (Nocuron)

  42. Pancuronium (Pavulon) • Binds to the Ach receptors in the neuromuscular junction • As Ach accumulates, pancuronium will be displaced and muscle tone will be regained (Does not cause depolarization) • Use: Surgery, intubation prep • Concerns: • Hypotension • Tachycardia COMPETETIVE

  43. Succinylcholine (Anectine) • Quick onset and brief duration (1 – 2 minutes onset / 4 – 6 minutes duration) • Causes membrane depolarization, so fasciculation's may occur • Malignant Hyperthermia • Inherited disease • Reaction to certain anesthetics • Decreased re-uptake of calcium in the sarcoplasmic reticulum • Prolonged contraction • Contraindications: • Burns greater than 24 hours old • Spinal cord injury greater than 24 hours old • Known neuromuscular diseases • Renal failure • Hyperthermia Depolarizing

  44. Succinylcholine (Anectine) • Adverse Effects • Bradycardia • Prolongued paralysis • Dose: • Ages 10 and up ….. 1.5mg/kg • If not relaxed in 2 – 3 minutes, a repeat dose of .5mg/kg

  45. Vecuronium (Norcuron) • Depolarizing neuromuscular blockade • Used for ventilatory difficulty secondary to bucking or combativeness in intubated patients • Contraindications: • Non-intubated patients and hypersensitivity

  46. Lidocaine in RSI • Controversy exists as to whether or not it decreases ICP prior to the ET placement

  47. Maryland RSI • Midazolam (Versed) • Etomidate • Lidocaine • Succinylcholine (Anectine) • Vecuronium (If bucking occurs and Versed wears off)

  48. Maryland RSI • Indications • (1) Inability to tolerate laryngoscopy, and: (a) GCS less than or equal to 8 with respiratory rate less than or equal to 8 or greater than or equal to 35 or (b) GCS less than or equal to 8 with oxygen saturation less than or equal to 90% on non-rebreather face mask • (2) On-line medical direction for RSI may be requested in the following situations: (a) GCS less than or equal to 8 with clenched jaw, inability to adequately suction airway, and without above respiratory parameters (b) Respiratory extremis with contraindications to nasotracheal intubation (respiratory rate greater than or equal to 35 with air hunger, use of accessory muscles, and oxygen saturation less than or equal to 90% on non-rebreather face mask)

  49. Maryland RSI • Contraindications (1) Conditions that may cause hyperkalemia: (a) Burns greater than 24 hours old (b) Spinal cord injury greater than 24 hours old (c) Known neuromuscular disease (Guillain-Barré Syndrome, myasthenia gravis, amyotrophic lateral sclerosis, muscular dystrophy) (d) Chronic renal failure on hemodialysis/ Presence of hemodialysis access (2) Age less than 10 (3) History of malignant hyperthermia

  50. Maryland RSI • Preparation (1) Pre-oxygenate with 90-100% oxygen. (2) Monitor oxygen saturation with pulse oxymetry and ECG. (3) Ensure functioning IV and fluid therapy as per protocol. (4) Evaluate for difficult airway. (5) Perform focused RSI neurologic exam. (6) Prepare equipment (a) Intubation kit (b) Bag Valve Mask (BVM) (c) Suction (d) RSI kit (i) Prepare medications (ii) Combitube, Cricothyroidotomy equipment (e) Capnograph

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