Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
General and Local Anesthetics قاسم صالح النعيمي. د.م.أ General anesthetics General anesthesia is a reversible state of central nervous system (CNS) depression, resulting in loss of perception and response to external stimuli. General anesthesia is essential to surgical practice, because it renders patients analgesic, amnesic, and unconscious, and provides muscle relaxation and suppression of undesirable reflexes. Because no single agent provides all desirable properties, several categories of drugs are used in combination to produce optimal anesthesia. Adjuncts to inhalation anesthesia Adjuncts to anesthesia are drugs employed to complement the beneficial effects of inhalation anesthetics and to counteract their adverse effects. Some adjunctive agents are administered before surgery, some during surgery, and some after surgery. Preanesthetic medications PA medications are administered for 3 main purposes: • Reduction of anxiety. • Production of perioperative amnesia. • Relief of preoperative and postoperative pain. Preanesthetic medications includes: 1.Benzodiazepines, like diazepam, to reduce anxiety and promote amnesia. 2.Opioids (e.g. morphine), to relieve preoperative and postoperative pain. 3.Anticholinergic drugs. E. g. atropine, may be given to decrease the risk of bradycardia during surgery, prevent excessive bronchial secretions associated with anesthesia. 4.Neuromuscular blocking agents. Performance of most surgical procedures requires that skeletal muscles be relaxed; neuromuscular blocking agents (e.g. succinylcholine, pancuronium) are given to induce relaxation. By using neuromuscular blockers, we can reduce the dose of general anesthetic. Preanesthetic medications Postanesthetic medications: 1.Analgesic. Analgesics are needed to control postoperative pain. If pain is severe, opioid are indicated. For mild pain, aspirin-like drugs may suffice. 2.Antiemetics. Patients recovering from anesthesia often experience nausea and vomiting. This can be suppressed with antiemetics. Examples: ondansetron, and promethazine. 3.Muscarinic agonists. Abdominal distention (from atony of the bowel) and urinary retention are potential postoperative complications. Both conditions can be relieved through stimulation of muscarinic receptors. The muscarinic agonist employed most frequently is bethanechol. General anesthetics Classification • Inhalation anesthetics. • Intravenous anesthetics. Inhalation Anesthetics: Inhaled gases are a mainstay of anesthesia and are used primarily for the maintenance of anesthesia after administration of an IV agent. 1.Volatile liquids: halothane, enflurane, isoflurane, sevoflurane. 2. Gases: nitrous oxide. Mechanism of action : The general anesthetics increase the sensitivity of the γ aminobutyric acid (GABAA) receptors to the neurotransmitter, GABA . This causes a prolongation of the inhibitory chloride ion current after a pulse of GABA release resulting in diminished of postsynaptic neuronal excitability . Other receptors are also affected by volatile anesthetics. For example, the activity of the inhibitor glycine receptors in the spinal motor neurons is increased. In addition, the inhalation anesthetics block the excitatory postsynaptic current of the nicotinic receptors. The mechanism by which the anesthetics perform these modulatory roles is not understood. Halothane -Halothane is the prototype of the volatile inhalation anesthetics. - Halothane is a high-potency anesthetic. -Induction of anesthesia is smooth and relatively rapid. - Halothane is only weakly analgesic. Consequently, when this agent is used for surgical anesthesia, coadministration of a strong analgesic is usually required. The analgesic most commonly employed are opioid (e.g. morphine) and nitrous oxide. - Muscle relaxation. Although halothane has muscle relaxant actions, the degree of relaxation produced is generally inadequate for surgery. Accordingly, concurrent use of a neuromuscular blocking agent (e.g. pancuronium) is usually required. - Halothane is not hepatotoxic in pediatric patients (unlike its potential effect on adults). Adverse effects 1-CVS: 1. Hypotension. Halothane causes hypotension by 2 mechanisms: a-The drug has a direct depressant effect on the myocardium; the resultant decrease in contractility can reduce cardiac output by 20% to 50%. b. Halothane increases vagal tone, thereby slowing heart rate and reducing cardiac output even further. 2.Sensitization of the heart to catecholamines. Some anesthetics, most notably halothane, can increase the sensitivity of the heart to stimulation by catecholamines. While in this sensitized state the heart may develop dysrhythmias in response to catecholamines. 2-Respiratory depression. 3. Malignant hyperthermia. MH is a rare but potentially fatal reaction that can be triggered by all inhalation anesthetics. MH is characterized by muscle rigidity and a profound elevation of temperature. 4. Aspiration of gastric contents. During the state of anesthesia, reflexes that normally prevent aspiration of gastric contents into the lung are abolished.Aspiration of gastric fluids can cause bronchospasm and pneumonia. 5.Hepatotoxicity. Rarely, patients receiving inhalation anesthesia develop serious liver dysfunction. Rarely halothane produces hepatitis, sometimes progressing to massive hepatic necrosis and death. Hepatotoxicity is thought to result from an autoimmune process triggered by reactive metabolites of halothane that have formed complexes with liver proteins. Nitrous oxide: - NO is a gas anesthetic Has very low anesthetic potency. Has very high analgesic potency. Because of its low anesthetic potency, It is never employed as a primary anesthetic agent (cannot produce surgical anesthesia alone). - Because of its high analgesic potency, nitrous oxide is employed with great regularity as an adjuvant to other inhalation agents to provide supplemental analgesia. - In certain settings, nitrous oxide can be used alone. When administered alone, nitrous oxide is employed for analgesia-not anesthesia. Nitrous oxide alone is used for analgesia in dentistry and during delivery. The most important toxic effect of nitrous oxide is postoperative nausea and vomiting. Intravenous anesthetics: IV anesthetics cause the rapid induction of anesthesia. This is often described as occurring within one "arm-brain circulation time,” or the time it takes the drug to travel from the site of injection (usually the arm) to the brain, where it has its effect. IV anesthetics may be used as the sole agents for short procedures or administered as infusions to help maintain anesthesia during longer procedures. Three drug families are employed as anesthetics: 1- Barbiturates (Thiopental). 2- Benzodiazepines (Diazepam, lorazepam and midazolam.) 3- Opioids. (Fentanyl). Thiopental: - Thiopental is a short acting barbiturate. Employed for induction of anesthesia. Analgesic and muscle relaxant effects are weak. Has rapid onset of action and short duration of action. Act rapidly to produce unconsciousness. Unconsciousness occurs 10 to 20 seconds after IV injection. If thiopental is not followed by inhalation anesthesia, the patient will wake up in about 10 minutes. Thiopental is highly lipid soluble and therefore enters the brain rapidly to begin its effects. Anesthesia is terminated as thiopental undergoes redistribution from the brain and blood to other tissues. Pharmacological effects: Thiopental has minor effects on the cardiovascular system, but it may contribute to severe hypotension in patients with hypovolemia or shock. All barbiturates can cause apnea, coughing, chest wall spasm, laryngospasm, and bronchospasm. [Note: The latter is of particular concern for asthmatic patients. Benzodiazepines The benzodiazepines are used in conjunction with anesthetics to sedate the patient. The most commonly used is midazolam [mi-DAZ-olam]. Diazepam [dye-AZ-uh-pam] and lorazepam [lore-AZ-uh-pam] are alternatives. All three facilitate amnesia while causing sedation, enhancing the inhibitory effects of various neurotransmitters, particularly GABA. Minimal cardiovascular depressant effects are seen, but all are potential respiratory depressants (especially when administered intravenously). Opioid ( Fentanyl). Fentanyl is an opioid drug. It is administered in combination with a neuroleptic drug known as droperidol ( Neuroleptic opioid combination). Neuroleptic analgesia is a state that is produced by the administration of this combination. It is characterized by quiescence, indifference to surroundings and insensitivity to pain; the patient appears to be sleep but is not (i.e. complete loss of consciousness does not occur). Neuroleptic analgesia is employed for diagnostic and minor surgical procedures( e.g. bronchoscopy, repeated changing of burns dressings). For some procedures, the combination of fentanyl plus droperidol is supplemented with nitrous oxide. The state produced by this three-drug regimen is called neuroleptic anesthesia. Neuroleptic anesthesia produces more analgesia and a greater reduction of consciousness occurs with neuroleptic analgesia. Neuroleptic anesthesia can be used for major surgical procedures. Local anesthetics Classification: • Esters: contains an ester linkage in their structure. Examples: procaine (novocaine), benzocaine, cocaine, tetracaine. • Amides: contains an amide linkage. Examples: lidocaine (xylocine), dibucaine. Mechanism of action: Local anesthetics stop axonal conduction by blocking sodium channels in the axonal membrane. By blocking sodium channels, local anesthetics prevent sodium entry into axon, thereby preventing the propagation of action potential, and bring conduction to a halt. Selectivity of anesthetic effects: Local anesthetics are nonselective modifiers of neuronal function. That is, these drugs will block action potential in all neurons to which they have access. The only way that we can achieve selectivity is through delivery of the anesthetic to a limited area. Onset of action of local anesthetics: Before anesthesia can occur, the anesthetic must diffuse from its site of administration to its sites of action inside the axon membrane; anesthesia is delayed until this movement has occurred Onset and duration of action of local anesthetics are influenced by several factors. These include : - tissue pH, - molecular size of the drug, - nerve morphology, - concentration, and - lipid solubility of the drug. Of these, the most important are pH of the tissue and molecular size of the drug. At physiologic pH, these compounds are charged. The ionized form interacts with the protein receptor of the sodium channel to inhibit its function and, thereby, achieve local anesthesia. The pH may drop in sites of infection, which causes onset to be delayed or even prevented. Higher concentration and greater lipid solubility improve onset to some degree. Anesthetics of small size, high lipid solubility, and low ionization cross the axon membrane rapidly. In contrast, anesthetics of large size, low lipid solubility, and high ionization cross slowly. Use of anesthetics with vasoconstrictors: Local anesthetics cause vasodilation, which leads to rapid diffusion away from the site of action and results in a short duration of action when these drugs are administered alone. By adding the vasoconstrictor epinephrine to the local anesthetic, the rate of local anesthetic diffusion and absorption is decreased. This both minimizes systemic toxicity and increases the duration of action. Adverse effects: 1-CNS: When absorbed in sufficient amounts, local anesthetics cause CNS excitation followed by depression. 2-CVS: When absorbed in sufficient amounts, local anesthetics can affect the heart and blood vessels. In the heart, local anesthetics suppress excitability in the myocardium and conducting system, and thereby can cause bradycardia, heart block, reduced contractile force, and even cardiac arrest. In blood vessels, anesthetics relax vascular smooth muscle; the resultant vasodilation can cause hypotension. 3-Allergic reactions: Allergic reactions are much more likely with the ester type anesthetics than with the amides. Examples: allergic dermatitis and anaphylaxis. Clinical uses of local anesthetics: Local anesthetics may be administered in 2 ways: • Topically, for surface anesthesia. • By injection, for 1) infiltration anesthesia, 2)nerve block anesthesia, 3)intravenous regional anesthesia, 4)epidural anesthesia, and5) spinal anesthesia. 1)Surface anesthesia: Surface anesthesia is accomplished by applying a local anesthetic to the skin or a mucous membrane. The agents employed most commonly are lidocaine, tetracaine, and cocaine. Local anesthetics are applied to the skin to relieve pain, itching, and soreness of various causes, including infection, thermal burns, sunburn, wounds, abrasions, and insect bites. Application may be made to mucous membranes of the nose, mouth, pharynx, trachea, bronchi and vagina. In addition, local anesthetics may be used to relieve discomfort associated with hemorrhoids, anal fissures, and pruritus ani. 2)Infiltration anesthesia: Infiltration anesthesia is achieved by injecting a local anesthetic directly into the immediate area of surgery or manipulation. 3)Nerve block anesthesia: Nerve block anesthesia is achieved by injecting a local anesthetic into or near the nerves that supply the surgical field, but at a site distant from the field itself. An advantage of this technique is that anesthesia can be produced using doses that are smaller than those needed for infiltration anesthesia. 4)Intravenous regional anesthesia: IRA is employed to anesthetize the extremities (hands, feet, arms, lower leg, but not the entire leg-because too much anesthesia would be needed). Anesthesia is produced by injection into a distal vein of an arm or leg. Lidocaine, without epinephrine is the preferred agent for intravenous regional anesthesia. 5)Epidural anesthesia: EA is achieved by injecting a local anesthetic into the epidural space. A catheter placed in the epidural space allows administration by bolus or continuous infusion. Following administration, diffusion of anesthetic across the dura into the subarachnoid space blocks conduction in nerve roots and the spinal cord itself. Diffusion through intervertebral foramina blocks nerves located in the paravertebral region. With epidural administration, anesthetic can reach the systemic circulation in significant amounts. Lidocaine and bupivacaine are popular drugs for epidural anesthesia. 6)Spinal (subarachnoid) anesthesia: Spinal anesthesia is produced by injecting local anesthetic into the subarachnoid space. Injection is made in the lumbar region below the termination of the cord. Spread of anesthetic within the subarachnoid space determines the level of anesthesia achieved. Anesthetics employed most commonly are bupivacaine, lidocaine, and tetracaine.