Anesthesia Lecture PDF

Anesthetics General anesthetics General anesthetics Inhalation anesthetics Non-inhalation anesthetics Volatile liquids Propofol Sevoflurane Ketamine Gaseous substanc...

Anesthetics General anesthetics General anesthetics Inhalation anesthetics Non-inhalation anesthetics Volatile liquids Propofol Sevoflurane Ketamine Gaseous substances Etomidate Nitrious oxide * Midazolam Premedication agents Sedative agents Myorelaxants **Atropine Dexmedetomidine **Rocuronium *Diazepam **Suxamethonium *Midazolam Local anesthetics Lidocaine Bupivacaine Benzocaine *See. Anxiolytic agents and **cholinergic agents RSU Farmakoloģijas katedra 1 2022/2023  Anesthetics Terminology used in anesthesiology All general anesthetics (anesthesia - numbness) cause a special, medically induced, reversible condition, characterized by amnesia, loss of consciousness, and immobility. In turn, analgesic properties is not specific for all general anesthetics. Induction Anesthesia - Introductory anesthesia used to avoid the excitatory anesthetic stage and to reduce the maintenance anesthetic dose. Induction anesthetics may not always be able to provide anesthetic depth appropriate to the particular clinical situation Maintenance anesthesia provides sufficient depth of anesthesia for a specific clinical setting RSU Farmakoloģijas katedra 2 2022/2023  Anesthetics Terminology used in anesthesiology MAC - minimal alveolar concentration It is the concentration of an inhalation anesthetic that provides half of the patients with a lack of response to a surgical stimulus (skin incision). MAC - quantitative parameter of inhalation anesthetic potency, the stronger the drug, the lower the MAC Blood / gas partition coefficient Proportion between inhalation anesthetic concentration in blood and alveoli. Low coefficient ensures faster induction and fast awakening RSU Farmakoloģijas katedra 3 2022/2023  Anesthetics Concentration-dependent effects of inhalation anesthetics Inhalation anesthetics, when used alone in monotherapy, cause amnesia, at slightly higher concentrations they induce consciousness and at the highest concentration - immobility. That is why in the early days of anesthesiology, immobility was used as a criterion for controlling the depth of anesthesia. Nowadays, this is no longer a safe criterion, as during anesthesia a patient may be given muscle relaxants that provide immobilization even before the anesthetic causes a loss of consciousness. For this reason, the depth of anesthesia is controlled by EEG and hemodynamic function control RSU Farmakoloģijas katedra 4 2022/2023  Anesthetics Stages of general anesthesia Based on ether narcosis,there are 4 stages of general anesthesia Modern general anesthetics may not cause Steps 1 and 2. To minimize Stage 2 (irritability), induction anesthetics are widely used RSU Farmakoloģijas katedra 5 2022/2023  Anesthetics Non-inhalation anesthetic (NIA) IV use Propofol Allosteric modulation of GASSA receptors. Sedative, hypnotic effect Maintenance of general anesthesia Induction anesthesia Sedation Pharmacology and Physiology for Anesthesia 2019 Cerebral metabolic rate for oxygen - CMRO 2 RSU Farmakoloģijas katedra 6 2022/2023  Anesthetics Non-inhalation anesthetic (NIA) IV use Etomidate GABA-A allosteric modulation Sedative, hypnotic action Induction anesthesia Pharmacology and Physiology for Anesthesia 2019 RSU Farmakoloģijas katedra 2022/2023 7  Anesthetics Non-inhalation anesthetics (NIA) Ketamine NMDA receptor channel blocker Analgesia, * dissociative anesthesia Maintenance of general anesthesia Induction anesthesia Postoperative sedation * a cataleptic condition in which the patient's eyes are open, but he is not communicative Pharmacology and Physiology for Anesthesia 2019 RSU Farmakoloģijas katedra 8 2022/2023  Anesthetics Inhalation anesthetics Volatile liquids Sevoflurane Most often used in mixture with oxygen or oxygen/nitrous oxide GABAA receptor modulators Anesthetic effects Maintenance anesthesia NB! Malignant hyperthermia (genetic) - All flurans have ↑ T, tachycardia, respiratory failure, arrhythmogenic effects! acidosis, rigidity, rhabdomyolysis RSU Farmakoloģijas katedra 9 2022/2023  Anesthetics Major sites of action of the volatile anesthetics are shown schematically RSU Farmakoloģijas katedra 10 2022/2023  Anesthetics Inhalation anesthetics Gaseous substances Nitrous oxide (N2O) NMDA receptor antagonist Sedative, analgesic effect, anesthetic effects without muscle relaxation N2O causes release of endogenous opioid peptides (endorphins) in brain stem Maintenance anesthesia RSU Farmakoloģijas katedra 11 2022/2023  Anesthetics Major sites of action of the gaseous anesthetics nitrous oxide and xenon are shown schematically RSU Farmakoloģijas katedra 12 2022/2023  Anesthetics Characterization of the pharmacological profile of inhalation agents 1) Anesthetics can 2) concomitantly, anesthetics inhibit modulate inhibitory excitatory neurotransmitter receptors receptors on GABA (e.g., N cholinoreceptors, and NMDA glutamate receptors) Explanation of the color of the circles: green - positive, red - negative, light red - low effect; white - no effect Ligand-gated and voltage-gated ion channels are thought to be among the most relevant targets for general anesthetics. The activities of representative inhaled anesthetics on these targets in vitro are summarized. A dark green or pink spot indicates significant potentiation or inhibition, respectively, by the anesthetic at clinically relevant concentrations; a light pink spot indicates some inhibition, and an empty spot indicates no effect at clinically relevant concentrations. This summary represents a synthesis of major effects, but important differences exist between various receptor and channel isoforms (not indicated here). AMPA, α-Amino acid-3-hydroxy-5-methyl-4-isoxazole; CA2+ , calcium ion; GABA, gammaaminobutyric acid; K+ , potassium ion; nACh, nicotinic acetylcholine; NMDA, N-methyl-D-aspartate; Na+ , sodium ion. (Modified from Rudolph U, Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci. 2004;5:709–720.) The image is for illustrative purposes only RSU Farmakoloģijas katedra 13 2022/2023  Sedative agents Sedative agents i/v Dexmedetomidine Central ɑ2 receptor agonist Sedative, anxiolytic, analgetic and sympatholytic activity Sedation Used in intensive care units for short-term diagnostic or surgical procedures.Reduces the need for propofol, midazolam, opioids RSU Farmakoloģijas katedra 2022/2023 14  Premedication Premedication is used to prepare the patient for general anesthesia and surgical manipulation Premedication may reduce the SE of anesthetic or surgical manipulation Premedication is given before general anesthesia, for example, the night before the scheduled manipulation or just a few minutes before. Premedication uses drugs from different pharmacological groups. For example, cholinolytics, anxiolytics, sedatives, BAB, hypotensive agents, antihistamines, hypoacids Diazepam Midazolam Atropine See. lectures anxiolytics, cholinergics RSU Farmakoloģijas katedra 15 2022/2023  Miorelaxants Central action muscle relaxants BZD Peripheral action muscle relaxants N cholinoreceptor agonist Suxamethonium N cholinoreceptor antagonists Rocuronium See. lectures anxiolytics, cholinergics RSU Farmakoloģijas katedra 16 2022/2023  Local anesthetics Local anesthetics reversibly inhibit sensory (temperature, touch, taste, smell, pain) and or motor (movement) irritation of nerve fibers, as well as interrupt the conduction of the excitation pulse in the nerve fibers. Analgesia is only one of the pharmacological effects of local anesthesia RSU Farmakoloģijas katedra 17 2022/2023  Local anesthetics Types of local anesthesia 1. Surface or terminal anesthesia. The drug is applied topically to the skin or mucous membranes. As a result of its use, the sensory nerve receptors are blocked. 2. Infiltration anesthesia. The drug is injected into the tissues (skin, subcutaneous tissue, muscles) - impregnates (infiltrates) the tissue without being directly injected into the nerve, and then diffuses from the tissue into the nerve. As a result, both sensory and smaller nerve receptors are blocked, 3. Regional anesthesia Spinal (subarachnoid, intrathecal) anesthesia. The drug is injected into the subarachnoid space (lumen). A distinction is made between spinal anesthesia (with muscle relaxation) and analgesia (without muscle relaxation). The nerve roots of the spinal cord are blocked. Epidural (peridural) anesthesia. The drug is injected into the spinal canal in the epidural space. The drug substance then diffuses into the subarachnoid space. The nerve roots of the spinal cord are blocked. Wire anesthesia. The drug is administered perineural or endoneural. Nerve trunks and plexus are blocked RSU Farmakoloģijas katedra 18 2022/2023  Local anesthetics Axon (sensory neuron) membrane fragment The Na + channels, the heterotrimeric proteins, consist of three subunits α, β1, β2 Both non-ionized and ionized forms of local anesthetic are essential. Due to its lipophilic properties, the non-ionized form penetrates well through the cell membrane and thus reaches the receptor while the other form causes Na + channel blockade, since only the ionized form is capable of binding to the ion channel RSU Farmakoloģijas katedra 19 2022/2023  Local anesthetics Problems of local anesthetics 1. The degree of ionization depends on the pKa of the drug and the pH of the tissues. As tissue pH may differ from physiological 7.4 (for example, infected tissues have a more acidic environment), the degree of ionization of the drug and its ability to induce anesthesia will also be altered (this will decrease in infected tissues). 2. Most local anesthetics have vasodilatory properties, which adversely affect the safety profile of medicines, as the risk of systemic SE increases. To reduce vasodilation caused by local anesthesia, it is often combined with vasoconstrictors. This allows to reduce the dose of the medicine and localize its action. 3. Systemic side effects Cardiotoxicity (risk of AV block, risk of arrhythmias) and CNS toxicity (depression or agitation) Systemic SE risk is potentiated by liver disease. Cirrhosis or worsening of hepatic blood flow (eg, chronic heart failure) slows down amide metabolism and potentially increase the risk of systemic toxicity RSU Farmakoloģijas katedra 20 2022/2023  Local anesthetics Aminoamides or amides Amides are metabolized by hepatic microsomal enzymes P450, therefore, their duration of action may be ~ 2 times longer than that of esters * Lidocaine ** Bupivacaine Na + channel blockade (membrane stabilization), inhibition of excitation pulse conduction in sensory fibers, anesthetic effect NB! Lidocaine i / v - Class 1B antiarrhythmic * All types of anesthesia ** Infiltration, spinal, epidural and wire anesthesia (for example, obstetrics / nerve block in chronic back pain) RSU Farmakoloģijas katedra 21 2022/2023  Local anesthetics Amino esters or esters Benzocaine Main disadvantages of surface anesthetics - esters: 1.Short-term action duration (rapid hydrolytic metabolism due to esterases in tissues and plasma) 2. Allergic complications are more common (sensitization to ester hydrolysis metabolite - paraaminobenzoic acid or PABA) For local anesthetics-amides, these disadvantages are not typical Surface anesthesia RSU Farmakoloģijas katedra 22 2022/2023