General Anesthetics (Week 8) PDF

GENERAL ANESTHETICS Prepared By: Justine C. Almodal, PTRP  CONTENTS 01 02 ANALGESIA AND ANESTHESIA ANTI-INFLAMMATORY 03 ANTI-ARTHRITIS  01 GENERAL & LOCAL ANESTHESIA GENERAL ANESTHESIA: REQUIREMENTS Loss of consciousn...

GENERAL ANESTHETICS Prepared By: Justine C. Almodal, PTRP  CONTENTS 01 02 ANALGESIA AND ANESTHESIA ANTI-INFLAMMATORY 03 ANTI-ARTHRITIS  01 GENERAL & LOCAL ANESTHESIA GENERAL ANESTHESIA: REQUIREMENTS Loss of consciousness and sensation Amnesia Skeletal muscle relaxation Inhibition of sensory and autonomic reflexes A minimum of toxic side effects Rapid onset of anesthesia STAGES OF GENERAL ANESTHESIA STAGE I: conscious and somewhat aware of ANALGESIA what is happening STAGE II: Unconscious and amnesiac but EXCITEMENT appears agitated and restless (DELIRIUM) STAGE III: Desirable for the surgical SURGICAL procedure and begins with the ANESTHESIA onset of regular , deep respiration Cessation of spontaneous respiration. The ability of the STAGE IV: medullary vasomotor center to MEDULLARY regulate blood pressure is also PARALYSIS affected and cardiovascular collapse ensues General Anesthetics: Classification and use according to route of administration  GENERAL ANESTHETICS INHALED INTRAVENOUS Volatile Liquids Barbiturates Desflurane (Suprane) Methohexital (brevital sodium) Enflurane (Ethrane) Thiopental (Pentothal) Halothane (Fluothane) Isoflurane (Forane) Methoxyflurane (Penthrane) Sevoflurane (Ulthane) Gas Benzodiazepines Nitrous Oxide (Nitrogen Diazepam (Valium) Monoxide) Lorazepam (Ativan) Midazolam (Versed) Opioids Etomidate (Amidate) Ketamine (Ketalar) Propofol (Diprivan) KETAMINE This agent produces a somewhat different type of condition known as dissociative anesthesia. ○ The Pt is awake but is sedated and usually unable to recall events that occured when the ketamine was in effect. ○ Useful during short diagnostic or surgical procedures (e.g endoscopy) or during invasive procedures in children or certain high-risk patient. GENERAL ANESTHESIA: MOA Decrease activity of neurons in the reticular activating system= Unconscious and lack of memory Inhibit activity in the spinal cord= Immobility and inhibit motor responses to painful stimuli Bind to GABA receptors which contains a chloride ion channel= influx of chloride ions GENERAL ANESTHESIA: MOA Also binds to excitatory acetylcholine receptors= Inhibition of receptors Opioids decrease the transmission in nociceptive pathway Ketamine and certain inhaled agents (NO) binds to N-methyl-D Aspartate (NMDA) receptor= Inhibit excitatory effects of glutamate GENERAL ANESTHESIA: MOA ADJUVANTS IN GENERAL ANESTHESIA NEUROMUSCULAR BLOCKERS Skeletal muscle paralysis is essential during surgical procedures. The patient must be relaxed to allow proper positioning on the operating table and to prevent spontaneous muscle contraction from happening during the surgery  NEUROMUSCULAR BLOCKERS GENERIC NAME TRADE NAME NONDEPOLARIZING BLOCKERS Tubocurarine Tracrium Atracurium Nuromax Doxacurium Mivacron Mivacurium Pavulon Pancuronium Arduan Rapacuronium Raplon Rocuronium Zemuron Vecuronium Norcuron DEPOLARIZING BLOCKER Anectine, Others Succinylcholine LOCAL ANESTHETICS Produce a loss of sensation in specific body part or region Occurs before performing a relatively minor surgical procedure ○ ADVANTAGES: Relatively rapid recovery and lack of residual effects Don’t interfere with cardiovascular, respiratory and renal functioning ○ DISADVANTAGES: Length of time required to establish an anesthetic effect and the risk that analgesia will be incomplete or insufficient for the respective procedure. TYPES OF LOCAL ANESTHETICS A local anesthetic is chosen depending on factors such as : ○ The operative site and nature of the procedure ○ The type of regional anesthesia desired (Single peripheral nerve block or spinal anesthesia) ○ Pt size and general health ○ The duration of action of the anesthetic. CLINICAL USE OF LOCAL ANESTHESIA 1. Topical Administration Applied directly to the surface of the skin, mucous membranes, cornea and other regions to produce analgesia Ex: Wound cleansing, Myringotomy, circumcision and cataract surgery. CLINICAL USE OF LOCAL ANESTHESIA 2. Transdermal Administration Drugs is applied to the surface of the skin with the intent that the drug will absorb into underlying tissues. May be enhanced by the use of electrical current (Iontophoresis) or Ultrasound (Phonophoresis) Ex: Lidocaine, transdermal patch CLINICAL USE OF LOCAL ANESTHESIA 3. Infiltration Anesthesia The drug is injected directly into the selected tissue allowing it to diffuse to sensory nerve endings within that tissue. Saturates the area such as skin laceration for performing surgical repair suturing. CLINICAL USE OF LOCAL ANESTHESIA 4. Peripheral Nerve Block The anesthetic is injected close to the nerve trunk so that transmission along the peripheral nerve is interrupted. Minor (e.g Ulnar, Median) or Major (Brachial, Lumbosacral) Prolonged administration can produce localized muscle pain and necrosis CLINICAL USE OF LOCAL ANESTHESIA 5. Central Neural Blockade The anesthetic is injected within the spaces surrounding the spinal cord ○ Epidural nerve blockade: Refers to injection of drug into the epidural space ○ Caudal block: Injecting the local anesthetic into the lumbar epidural space via the sacral hiatus ○ Spinal nerve blockade: Injection within the subarachnoid space; Also referred to as “Intrathecal anesthesia” CLINICAL USE OF LOCAL ANESTHESIA 6. Sympathetic Block Especially useful in cases of complex regional pain syndrome (CRPS) One approach is to inject the local anesthetic into the area surrounding the sympathetic ganglion that innervates the affected limb. CLINICAL USE OF LOCAL ANESTHESIA 7. Intravenous Regional Anesthesia (Bier block) Anesthesia is injected into peripheral vein located in a selected limb (arm or leg) A tourniquet is also applied proximally on the limb to localize the drug temporarily within the extremity  MECHANISM OF ACTION Local anesthetics work by blocking action potential propagation along neuronal axons → Inhibit the opening of membrane sodium channels → prevents AP propagation along the portion of the axon SYSTEMIC EFFECTS OF LOCAL ANESTHESIA The most important systemic effects involve the CNS and cardiovascular system ○ Impaired respiratory function ○ Decrease cardiac excitation, HR and force of contraction Somnolence, confusion, agitation, excitation and seizures can occur if sufficient amounts reach the brain via the bloodstream  02 ANALGESIA  Analgesic drug therapy and certain rehabilitations share a common goal: Pain relief Most frequently taken by patients who are treated in rehabilitation setting Opioid and Nonopioid Analgesics OPIOID ANALGESICS Group of naturally occuring, semisynthetic and synthetic agents that are characterized by ability to relieve moderate to severe pain. Characterized by their ability to produce physical dependence and are classified as controlled substance. OPIUM POPPY CLASSIFICATION OF SPECIFIC AGENTS 1. Strong Agonists Used to treat severe pain Interact primarily with mu receptors in the CNS  STRONG AGONIST GENERIC NAME TRADE NAME Actiq, Duragesic, Fentanyl** Sublimaze Hydromorphone** Hydrostat, Dilaudid Levorphanol Levo-Dromoran Meperidine Demerol Methadone Dolophine, Methadose Morphine** MS contin, Roxanol, Statex Oxymorphone** Numorphan CLASSIFICATION OF SPECIFIC AGENTS 2. Mild-to-Moderate Agonists Used to treat moderate pain Doesn’t have as high affinity or efficacy as strong agonists agents.  MILD-TO-MODERATE AGONISTS GENERIC NAME TRADE NAME Codeine** Paveral Hydrocodone** Hycodan OxyContin, Roxicodone Oxycodone** other Propoxyphene Darvon CLASSIFICATION OF SPECIFIC AGENTS 3. Mixed Agonist-Antagonists Exhibit some agonist and antagonist like activity at the same time because of the drugs have the ability to act differently at specific classes of opioid receptors Less S/E  MIXED AGONIST-ANTAGONISTS GENERIC NAME TRADE NAME Butorphanol Stadol** Buprenorphine Buprenex Nalbuphine Nubain** Pentazocine Talwin** CLASSIFICATION OF SPECIFIC AGENTS 4. Antagonists Block all opioid receptors with a particular affinity for the mu variety. Used to treat opioid overdoses and addiction  ANTAGONISTS GENERIC NAME TRADE NAME Naloxone Narcan Naltrexone ReVia, Vivitrol Nalmefene MECHANISM OF ACTION 1. Spinal Effects MECHANISM OF ACTION 2. Supraspinal (Brain) Effects MECHANISM OF ACTION 3. Peripheral Effects PROBLEMS AND ADVERSE EFFECTS NONSTEROIDAL ANTI-INFLAMMATORY DRUGS Pharmacological properties: ○ Decrease inflammation ○ Relieve mild to moderate pain (Analgesia) ○ Decrease elevated body temperature (Antipyresis) ○ Decrease blood clotting by inhibiting platelet aggregation ASPIRIN: PROTOTYPICAL NSAID Commonly known as Acetylsalicylic acid Reprepresents major form of group of drugs known as salicylates Inhibit the synthesis of a group of endogenous compounds known collectively as the “Prostaglandin‘ PROSTAGLANDINS, THROMBOXANES & LEUKOTRIENES These compounds appear to be hormones that act locally to help regulate cell function under normal and pathologic conditions Thromboxanes and Leukotrienes are derived from the same precursor as the prostaglandins; often referred to as “Eicosanoids” Prostaglandins and leukotrienes are pro-inflammatory CYCLOOXYGENASE (COX) Responsible for the formation of prostaglandins COX 1 COX 2 Pain and inflammation (+) Prostacyclin: For Protective lining of the vasodilation and stomach inhibit platelet (+) Thromboxane: aggregation in the Increase platelet activity coronary and carotid arteries NSAIDS DRUGS NON-SELECTIVE SELECTIVE NSAID NSAID Inhibit both COX-1 and Inhibit COX-2 and spare COX 1 COX-2 AGENTS: Aspirin, Ketoprofen, Ibuprofen, AGENTS: Celecoxib, Naproxen and Mefenamic Rofecoxib, Etodolac acid S/E: Gastric upset, gastric ulceration and gastric S/E: Cardiac arrest and stroke bleeding  03 ANTI-ARTHRITIS RHEUMATOID ARTHRITIS Is a chronic, systemic disorder that affects many different tissues in the body but is primarily characterized by synovitis and destruction of articular tissue. Autoimmune disease PATHOPHYSIOLOGY The initiating factor in RA is unknown Underlying basis consist of autoimmune response in genetically susceptible individuals Precipitating factor such as virus, infectious agent or environmental trigger (cigarette/tobacco) appears to initiate the formation of antibodies that are later recognized by the host as antigens. Initiates a complex chain of events involving a variety of immune system components such as mononuclear phagocytes, T-lymphocytes and B-Lymphocytes PATHOPHYSIOLOGY DRUG THERAPY IN RA Nonsteroidal Anti-inflammatory Drugs (NSAID) Glucocorticoids Disease Modifying Anti-Rheumatic Drugs (DMARDS) DRUG THERAPY IN RA DRUG THERAPY IN RA DRUG THERAPY IN RA AZATHIOPRINE Azasan, Imuran MOA: ○ Impair synthesis of DNA and RNA precursors (but is unclear exactly how) ○ Inhibit many aspects of B and T cell functions thereby impairing immune responses mediated by these cells A/E: ○ Fever ○ Chills ○ Sore throat ○ Fatigue ○ Loss of appetite ○ Nausea and vomiting LEFLUNOMIDE Arava MOA: ○ Inhibit the synthesis of RNA precursors (pyrimidine) in lymphocytes ○ Blocks a key enzyme responsible for RNA synthesis A/E: ○ GI distress ○ Allergic reaction (Skin rashes) ○ Hair loss ○ Impair liver function METHOTREXATE Folex, Rheumatrex MOA: ○ Affects immune function by inhibiting folic acid metabolism thereby limiting the proliferation of lymphocytes and other cells that cause immune response in RA A/E: ○ Loss of appetite, nausea and other forms of GI distress ○ Pulmonary problems ○ Hematologic d/o ○ Liver dysfunction ○ Hair loss OSTEOARTHRITIS MC form of joint disease Non-inflammatory, Non-systemic and non-erosive Characterized by articular degeneration secondary to decrease proteoglycan. ACETAMINOPHEN Often the first drug used to treat OA (+) Control pain , (-) Anti-inflammatory effects Used to treat mild-to-moderate OA Non-selective NSAID Disadvantages: ○ Do not alter progressive course of joint destruction and osteoarthritic changes ○ Impair bone healing VISCOSUPPLEMENTATION Uses a substance known as hyaluronan (Hyaluronic acid) ○ Restore the normal viscosity of synovial fluid→ reduce joint stress→ limit progression of articular destruction in OA Temporarily attenuate the progressive the changes in joint structure and function typically seen in OA Delay the need for more invasive surgical treatments such as joint replacement GLUCOSAMINE AND CHONDROITIN SULFATE Dietary supplements Help protect articular cartilage and halt or reverse joint degeneration in OA Stabilize cartilage turnover and suppress the production of cytokines that contribute to pain and destructive changes in OA Inconclusive effects in all clinical trials. THE END Thank you for listening!