Local and General Anesthetics Flashcards
Local anesthetics - MoA
Reversible inhibition of action potential conduction by binding to sodium channels and decreasing the nerve membrane permeability to sodium. Nonpolar lipophilic form of the anesthetic molecule passes through the neuronal membrane and switches to the polar, hydrophilic form, in the cytoplasm of the neuron. This cationic form of the anesthetic binds to the cytoplasmic side of the sodium channel protein and prolongs the inactivation state of the sodium channel. With sodium channels blocked, the action potential cannot propagate along the neuronal fibers and sensory input is lost.
Local anesthetics - Indication
Topical: skin (pruritus), mucous membrane (pain caused by oral, nasal, laryngeal, rectal disorders or surgery), cornea (before diagnostic or surgical procedures, removal of foreign bodies and cataract surgery). Before venipuncture or minor surgery.
Infiltration (injecting directly into subc tissue): minor surgical procedures (suturing), removal of foreign bodies. Dental procedures. Epinephrine can be added to decrease the dose and prolong the duration of action.
Ionophoresis (uses a small electric current to force molecules of the anesthetic into the tissue): dental procedures.
- Zingo: needle-free device. Delivers powdered Lidocaine by rapid gas pressure
Nerve Block & Field Block: forms of regional anesthesia. Anesthetize an area of the body by blocking the conductivity of sensory nerves from that area. Local anesthetic is injected into or adjacent to a peripheral nerve or nerve plexus
Spinal Intrathecal: block somatosensory and motor fibers during surgery on lower limb or pelvic structures. Injected into subarachnoid, intrathecal space below the level spinal cord terminates.
Epidural: inject local anesthetic into the lumbar or caudal epidural (extradural) space. Labor and delivery.
Why does ester-type local anesthetics cause more frequently hypersensitivity?
They are metabolized by PABA which can cause allergic reactions.
Local anesthetics- Adverse effects
Caused by their absorption into the systemic circulation and subsequent alteration of CNS, cardiovascular and other organ system function.
CNS stimulation: restlessness, tremor, euphoria
CNS inhibition: drowsiness and sedation.
Toxicity: Headache, paresthesias and nausea
Higher cons: seizures –> coma
Death due to resp failure
Cardiavascular effects: hypotension, cardiac depression
Vasodilators block vasoconstriction induced by SNS
Antiarrhythmic activity: toxic doses –> cardiac conduction suppression, tachyarrhythmia (wide QRS)
Blockade of autonomic ganglia and neuromuscular transmission –> Loss of visceral and skeletal muscle tone –> potentiate effect of neuromuscular blocking drugs (atracurium) + caution in pt w myasthenia gravis.
Hypersensitivity reactions.
Spinal anesthesia: headache (ass w CSF leakage from the lumbar puncture) and respiratory depression (if anesthetic ascends too high up the spinal cord). Risk of infection or meningitis (entry into the CNS)
Ester-Type local anesthetics + Potency and duration of action
Cocaine - Medium Procaine - Short Chloroprocaine - Short Tetracaine - Long Benzocaine - Medium Proparacaine - Short All have low potency
Cocaine- MoA
Both local anesthetic and CNS stimulant. Causes vasoconstriction as a result of its sympathomimetic effect.
Cocaine - Indication
Occasionally used to anesthetize internal structures of the nose –> helps prevent bleeding after nasal surgery.
Procaine and Chloroprocaine - MoA
Metabolized to PABA
Procaine and Chloroprocaine - Indication
Procaine: infiltration, nerve block, spinal anesthesia
Chloroprocaine: epidural, infiltration and nerve bock anesthesia
Procaine and Chloroprocaine - Adverse effects
Allergic reactions
Tetracaine - Indication
Infiltration anesthesia
Also available in topical spray and gel formulations in combo with butamben (butyl aminobenzoate) and benzocaine
Benzocaine - Indication
Topical anesthetic
Sunburn
Pruritus and other skin conditions.
Anesthetize mucus membrane (available in cough lozenges and spray to relive cough)
Benzocaine - Adverse effects
Hypersensitivity reactions which can exacerbate preexisting dermatitis.
Proparacaine - Indication
Instillation during eye surgery and other opth procedures.
Amide-Type Local anesthetics + Potency and duration of action
Lidocaine - Short Etidocaine - Long Bupivacaine - Medium Mepivacaine - Short Ropivacaine - Long Levobupivacaine Prilocaine - Short Dibucaine
All have intermediate potency except Bupivacaine (high) and Ropivacaine (high)
Lidocaine - Indication
Infiltration
Nerve block
Epidural
Spinal anesthesia
Etidocaine - Indication
Infiltration and nerve block anesthesia
Bupivacaine - Indication
Obstetric anesthesia
Postsurgical pain (Liposome-encapsulated for long acting analgesia)
Epidural, infiltration, nerve block and spinal anesthesia
Bupivacaine - Adverse effects
Cardiac depression
Mepivacaine - Indication
Epidural, infiltration, nerve block and spinal anesthesia
Ropivacaine - Indication
Epidural, infiltration, nerve block anesthesia
Levobupivacaine - MoA
Isolated S(-)stereoisomer of racemic bupivacaine
Levobupivacaine - Indication
Epidural anesthesia for labor and delivery.
Prilocaine - MoA
Is a congener of lidocaine, it is converted to O-toluidine, a toxic metabolite that can cause methemoglobinemia if it accumulates.
Prilocaine - Indication
Limited to topical and infiltration anesthesia
Prilocaine - Adverse effects
Methemoglobinemia
Dibucaine - Indication
Ointment to relieve pain and itching of hemorrhoids(piles) and other problems in the rectal area.
General Anesthetics
Diethyl ether
Cyclopropane
General Anesthetics - MoA
Increase GABA and glycine inhibitory effects and decrease excitatory effects by blocking serotonergic, nicotinic and glutaminergic neurotransmission (Glutamate- NMDA/AMPA)
Diethyl ether - Adverse effects
Postop nausea and vomiting
Cyclopropane - Adverse effects
Cardiac arrhythmia, dizziness, nausea, vomiting
Inhalation anesthetics - MoA
They bind to specific amino acid residues in the transmembrane portions of the gamma-aminobutyric acid (GABAa) receptor-chloride ion channel. They increase the chloride influx and potassium efflux from neurons. Both of these actions cause hyperpolarization of neuronal membranes and reduce membrane excitability. They also reduce sodium and calcium influx, this prevents nerve firing and release of neurotransmitters.
Induction stages
1: neurons in the spinal cord are prevented from firing and analgesia and conscious sedation occur.
2: Depression of inhibitory neurons in CNS –> increased excitement, involuntary muscle movements, HR, BP and respiration
3: suppression of the reticular-activating system, loss of consciousness, loss of muscle tone and inhibition of spinal reflexes
4: Medullary paralysis. Respiratory and cardiovascular failure
Nonhalogenated anesthetics
Nitrous oxide
Nitrous oxide - Indication
Minor surgery and dental procedures
Component of balanced anesthesia in comb w another anesthetic.
Produces more analgesia
Nitrous oxide - Adverse effects
Chronic exposure: Megaloblastic anemia
´´laughing gas´ ´causes mild euphoria when adm.
Halogenated anesthetics
Halothane Enflurane Isoflurane Desflurane Sevoflurane
Halogenated anesthetics - Adverse effects
Hepatotoxicity (halothane hepatitis), Malignant hyperthermia (muscle fiber breakdown, rhabdomyolysis and renal failure )–> discontinue + treatment w dantrolene; prevents Ca release from SR (necessary to prevent fatality)
Respiratory and cardiovascular depression
Uterine relaxation
Decreased BP and CO
Halothene - Adverse effects and Contraindication
Toxicity of liver: halothane hepatitis (results from a reactive intermediate metabolite that acetylates liver proteins and produces an immune reactions that is fatal in half of all cases.
Cardiac dysrhythmias (sensitized heart to catecholamine)
Hypersensitivity reaction and hepatitis
Airway irritation
Bronchodilation
Reduced CO
Contra:
Converted to reactive intermediate metabolites that can produce hypersensitivity and hepatitis –> person who is anesthetized with halothane should not be reexposed to it for 6-12 months
Enflurane
Isoflurane
Desflurane
Sevoflurane - MoA
Exhibit more rapid induction and recovery than halothane. They undergo less metabolic degradation.
Enflurane
Isoflurane - Adverse effects
Little cardiac arrhythmias
Produce more muscle relaxation –> reduces the needed for muscle relaxant.
Bronchodilation
They cause more respiratory depression
At high concentration: CNS excitation –> seizures.
Enflurane: reduce CO
Isoflurane: reduce systemic vascular resitance
Desflurane
Sevoflurane - Adverse effects
Desflurane: : Irritating to the resp tract; limits the concentrations of this agent that can be adm during induction.
Sevoflurane: renal toxicity
Both: Reduced systemic vascular resistance
Parenteral anesthetics
Barbiturates: Thiopental, Methohexital Benzodiazepine: Midazolam Opioids: Fentanyl, Sufentanil, Alfentanil, Remifentanil Propofol, Fospropofol Etomidate Ketamine
Parenteral anesthetics - Indication
Preanesthetic sedation
Induction of anesthesia
Perioperative analgesia
Anesthesia for minor surgical and dignositic procedures
Thiopental, Propofol, Fospropofol and Etomidate - MoA
Potentiate GABA activity at the GABAA receptor chloride ion channel
Thiopental, Propofol - Indication
Primarly used for induction of anesthesia, their use is followed by the adm of an inhalation anesthetic to mainatain anesthesia.
Thiopental - Adverse effects
Hangover (accumulated in fat and muscle –> more slowly eliminated from body)
Depression of cardiovascular and respiratory function
Propofol - Adverse effects
Depression of cardiovascular and respiratory function
Fospropofol - MoA and Indication
Phosphorylated prodrug of propofol.
Used in emergency department for rapid induction of anesthesia or for conscious sedation.
Methohexital - Indication and Adverse effects
Rapid induction of anesthesia
Apnea, bronchospasm, respiratory depression
Etomidate - Indication
Emergency department: rapid induction of anesthesia or for conscious sedation
Etomidate - Adverse effects
Adrenal suppression
Transient skeletal muscle movements
Fentanyl - MoA
Opioid agonist
Fentanyl - Indication
Moderate to severe pain
Strong analgesic given iv or epidurally in combo with other drugs for surgical or obstetric analgesia and anesthesia.
Provide anesthesia during cardiac surgery
Produce neuroleptanesthesia (twilight sleep) in comb w droperidol
Used with or without a local anesthetic for epidural adm or by the spinal intrathecal route during labor or to provide postoperative analgesia.
Fentanyl - Adverse effects
Neuroleptanesthesia: chest wall rigidity (due to effect on basal ganglia)
Respiratory depression
Sufentanil - Indication
Used with or without a local anesthetic for epidural adm or by the spinal intrathecal route during labor or to provide postoperative analgesia.
Alfentanil
Remifentanil - Indication
Iv, for induction or for ambulatory surgery
Remifentanil - Adverse effect
respiratory depression
Ketamine - MoA
Block the action of excitatory amino acids, primarily glutamate at NMDA receptors.
Ketamine - Indication
Dissociative anesthesia (IV) (dissociated from environment without complete loss of consciousness)
Most often used in pediatric patients (less likely to experience the unpleasant effects during recovery) and is given in combo with a benzodiazepine for anesthesia during minor surgical or diagnostic procedures.
Status epilepticus
Ketamine - Adverse effects
Dissociative anesthesia: Analgesia Reduced sensory perceptions Immobility Amnesia
During recovery; delirium, hallucinations, irritational behavior
Hypersalivation, Tachycardia, Hypertension
Increased BP
Midazolam - Indication
Preoperative sedation, endoscopy + other diagnostic procedures
Antidode for Midazolam + Adverse effects
Flumazenil
Amnesia
