Pharma 19 Veterinary Pharmacology PDF

V. Pharma 181: Basic Veterinary Pharmacology LECTURE 19: General Anesthetics FIRST SEMESTER | SY. 2024 - 2025 by: CORDERO GENERAL ANESTHETICS...

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Pharma 181: Basic Veterinary Pharmacology LECTURE 19: General Anesthetics FIRST SEMESTER | SY. 2024 - 2025 by: CORDERO GENERAL ANESTHETICS Stage III: Surgical Anesthesia Plane 1 Irregular automatic breathing Anesthesiology is the art and science of administration of Limb movement stops anesthesia Side to side movement of the eyeballs Anesthesia is the production of reversible loss of sensibility and Disappearance of palpebral, conjunctival and corneal reflexes in some cases consciousness Brisk pedal reflex may still be present Objectives: May be adequate for minor surgery To minimize or eliminate pain Relax muscle and facilitate patient restraint during surgical, Plane 2 obstetrical and other medical, diagnostic and therapeutic Laryngeal reflex persist until the middle of plane 2 procedures Eyeballs fixed in the center in the horse, cats, sheep and pigs, downward in dogs Balanced Anesthesia Pedal reflex becomes sluggish Progressive muscle relaxation - It is the used of multiple drugs in low dosage to take advantage Adequate for all surgical procedure except abdominal surgery of desirable features of selected drugs while minimizing the potential for harmful depression of homeostatic mechanism Plane 3 Components of Balance Anesthesia Breathing still automatic but the respiratory rate increases while Sensory blocking – loss of sensitivity to pain (analgesia) the depth decreases Example of agents: Nitrous oxide, Morphine, Noticeable pause between inspiration and expiration Meperidine, Fentanyl, Xylazine, Enflurane , Ketamine Motor blocking- muscle relaxation diminish motor response to Stage IV: Overdose noxious stimulation. Complete paralysis of the thoracic muscles, only the diaphragm relaxation – Xylazine functions Slight relaxation – Ethyl chloride Jerky diaphragmatic movement Medium – Chloral hydrate, Isoflurane, Enflurane, Respiratory movement gasping in nature d. Wide papillary Halothane, Barbiturate dilatation Mental blocking – loss of awareness (unconsciousness) and no recall of events at the conscious level (amnesia) Ataraxia – Phenothiazine derivatives; Ketamine Stages of anesthesia is best recognized when anesthesia in Light sleep – Fentanyl-droperidol induced by a relatively slow-acting drugs such as diethyl ether Delirium – all that produces deep sleep ketamine, nitrous oxide, and enflurane do not induce stage III. Reflex blocking – minimize autonomic nervous system response Either they induce stage II only to noxious stimuli advance to an increased level of CNS excitation, rather Blocking undesirable reflexes – Atropine than depression, resulting in myoclonic jerking followed Respiratory circulatory and digestive reflexes - by convulsive seizures. Barbiturate Useful Signs in Assessing Anesthetic Depth STAGES OF ANESTHESIA Cardiovascular system : heart rate, arterial blood pressure, color Stage I: Induction or Stage of Voluntary Excitement of mucus membrane, capillary refill time Consciousness still present Respiratory system: rate, ventilatory volumes, character of Forcible efforts to avoid being anesthetized breathing, PCO2 Breath-holding, but may not be observed in all cases Eye: position and movement, Pupil size and response to light, Fear and apprehension leading to increased respiratory rate and palpebral reflex, corneal reflex pulse rate Muscle: jaw and limb tone, presence or absence of gross Pupillary dilatation (mydriasis) movement, shivering or trembling Urination and defecation Others: body temperature, swallowing, coughing, vocalization, urine flow, salivation Stage II: Stage of Involuntary Excitement Loss of consciousness PRE-ANESTHETIC MEDICATION Reflex response to stimuli such as exaggerated limb movement Objectives may become violent necessitating restraint Mitigate fear and apprehension Pronounced vocalization Minimize salivation that may cause aspiration pneumonia (induce Unpredictable degree of violence which bears no relationship with by cholinergic blocking agents) the normal temperament of the animal, some may pass quietly Reduce pain and discomfort specially during stages I an II through this stage Improve the response to and recovery from general anesthesia. Irregular respiration; sometimes breath holding Persistent pharyngeal reflex which becomes progressively depressed  V. Pharma 181: Basic Veterinary Pharmacology LECTURE 19: General Anesthetics FIRST SEMESTER | SY. 2024 - 2025 by: CORDERO Pre-anesthetic agents Mechanism of action: Tranquilizers – acepromazine, promazine Enhances GABA-mediated inhibition of synaptic transmission by Analgesics – morphine, meperidine opening membrane chloride channels, causes cellular Anesthetics - Xylazine, ketamine hyperpolarization. Anticholinergic – atropine Adverse effects: ∙ CNS: dose-dependent CNS depression Injectable Anesthetics ∙ Cardiovascular: increased heart rate, decrease stroke volume; transient fall in cardiac output and arterial blood pressure; Examples: thiopental, alphaxolone, propofol, etomidate, ketamine, perivascular injection may occasionally cause local irritation and tiletamine-zolazepam, methohexital, pentobarbital. necrosis. Thiopental, methohexital and pentobarbital belong to the ∙ Respiratory: respiratory depression barbituric acid group, which are classified according to either ∙ Other: As anesthesia deepens, the pupil constricts rather than duration of action of chemical substitution on the parent molecule. dilates and in dangerously deep anesthesia the pupil is tiny Thiopental and methohexital are ulta-short-acting agents Pentobarbital is classified as a short-acting barbiturat Contraindications: Ketamine and tiletamine are dissociative anesthetic agents Cesarean section Alphaxolene is steroidal anesthetic ∙ Brachycephalic breeds propofol an alkylphenol ∙ Uremic patients etomidate an imidazole anesthetic agent ∙ Any patient in which prolonged anesthesia or recovery is contraindicated THIOPENTAL ALPHAXOLONE given for induction before gaseous anesthesia; may be administered as the sole agent for short-term anesthesia in may be administered as sole agent for short procedures that are cats. minimally painful. Contraindicated in dogs because of severe histamine release. If an inadequate dose is given to an unsedated or poorly sedated Induction is rapid and smooth retching and vomiting if the animal there is excitement, hypertonous and hyperalgia may be induction dose is too slow. seen Facial and peripheral muscle twitching may occur followed by relaxation. Mechanism of action: There is rapid return to consciousness Enhances GABA-mediated inhibition of synaptic transmission by opening membrane chloride channels, causes cellular Mechanism of action: hyperpolarization Believed to be via binding to or near the GABA receptor and enhancing chloride conductance; may stimulate chloride channels Adverse effects: independently. ∙ CNS: decrease in cerebral oxygen requirement, cerebral blood flow and intracranial pressure. Adverse effects: ∙ Cardiovascular: reduced blood pressure, ventricular dysrhythmias ∙ CNS: cerebral depression is similar to thiopental ∙ Respiratory: dose-dependent respiratory depression ∙ Cardiovascular:decrease in arterial blood pressure. Most ∙ Liver: hepatic dysfunction cardiovascular effect is due to vehicle rather than the active ∙ Kidneys: impaired renal function ingredients ∙ depress neonates during cesarean section ∙ Respiratory: Minimal respiratory depression. METHOHEXITAL Contraindications: hypotension, cardiac disease. induction before gaseous anesthesia; sole agent for short procedures that are minimally painful Mechanism of action: PROPOFOL Enhances GABA-mediated inhibition of synaptic transmission by Clinical applications: opening membrane chloride channels, causes cellular A very short-acting for induction before inhalational anesthesia or hyperpolarization as the sole agent for short procedures Induction of anesthesia is rapid and generally smooth Adverse effects: It produces a rapid emergence from anesthesia ▪ CNS: Can produce excitatory CNS effects and seizures have been fetal depression is minimal reported; not to be administered to patients with epilepsy and Mechanism of action: those undergoing myelography. GABA receptor binding to a different site from thiopental but ▪ Respiratory: transient dose-dependent respiratory depression resulting in the same opening of the chloride channels, causing cellular hyperpolarization PENTOBARBITAL infrequently used for this purpose sole agent for procedures struggling may be seen at early stages of anesthesia Inadequate dose may cause hyperesthesia  V. Pharma 181: Basic Veterinary Pharmacology LECTURE 19: General Anesthetics FIRST SEMESTER | SY. 2024 - 2025 by: CORDERO ETOMIDATE The tension of an agent dissolved in a liquid refers to the pressure of the agent in gas. At any given temperature the mass of gas Clinical applications: dissolved in a solution varies directly with its tension. The ratio of sole agent for non-painful procedures gas dissolved in solution to its tension is called its solubility induction prior to gaseous anesthesia coefficient. with rapid induction unconsciousness solubility of anesthetics varies widely, and the quantities of Fetal transfer is poor different anesthetics in the solvent are not equal Mechanism of action: Produces dose-dependent cortical depression; activates GABA The tension of the anesthetic agent in the brain is maintained receptors to open chloride channels. when its concentration in the alveoli is kept constant Contraindications concentration in the alveoli decreases, the tension in the Hypoadrenocorticism brain also decreases unsedated or poorly sedated patient minimum alveolar concentration (MAC) of the critical patients requiring long-term sedation anesthetic must be maintained KETAMINE Clinical applications: Sequence of Flow of Anesthetics for induction before gaseous anesthesia Gas is inhaled Gas is diluted with residual air in the lungs rarely administered as the sole agent but is usually given in Gas is distributed to the alveoli Alveolar gas equilibrates almost conjunction with xylazine or diazepam. immediately with pulmonary blood Gas dissolved in the blood It does not produce a true anesthetic state but induces dissociation is distributed throughout the body: into the interstitial fluid and from the environment, amnesia and peripheral analgesia. into the brain Muscle tone is increased provide greater analgesia for somatic or peripheral pain HALOTHANE Mechanism of action: Clinical applications: It appears to cause dissociative state and analgesia by acting as an Halothane is used primarily to maintain anesthesia following NMDA (N-methyl-D-aspartate) receptor antagonist and sigma induction with an injectable anesthetic. agonist. NMDA is an excitatory amino acid mimicking the action About 75% to 80% of inspired halothane is exhaled unchanged of glutamate in the CNS. metabolized by cytochrome P450 in the hepatocytes Adverse effects: ∙ CNS: ketamine alone raises intracranial pressure, but not when Adverse effects: combined with benzodiazepine; hallucinatory behavior, delirium, ∙ CNS: dose-dependent depression of CNS without significant excitement and purposeless muscle activity. analgesia ∙ Cardiovascular: Has a direct depressant effect and indirect ∙ Cardiovascular: Reduces cardiac output and blood pressure stimulatory effect ∙ Respiratory: less respiratory depression ∙ Respiratory: respiratory depression ∙ Live: induce mild hepatic damage. ∙ Liver: no effect on hepatic function ∙ Renal: reduce renal blood flow and glomerular filtration rate. ∙ Renal effect: no effect on renal function ∙ Skeletal muscle: the most potent trigger for malignant ∙ Skeletal muscle: extreme muscle tone and spontaneous hyperthermia movements ∙ Others: hypersalivation; increased bronchial secretion; increased drug interactions: intraocular pressure. Potentiates the action of non-depolarizing neuromuscular drugs. TILETAMINE-ZOLAZEPAM Clinical applications: ISOFLURANE administered as the sole agent for short to moderate duration sedation or for induction before gaseous anesthesia Clinical applications Separately, do not have ideal sedative or anesthetic properties most prevalent inhalation anesthetics together they produce dissociative anesthesia, muscle relaxation It is the inhalation agent of choice in critically ill patients. and some analgesia. use in most animals including dogs, cats and horses, certain exotic pets Inhalation Anesthetics Adverse effects: ∙ CNS: produces less cerebral vasodilation, while still reducing halogenated organic substances metabolic oxygen consumption hydrocarbon or ethers ∙ Cardiovascular: does depress myocardial contractility; lower halogenation has been shown to increase anesthetic potency while incidence of arrhythmias improving stability ∙ Respiratory: depresses ventilation to an equal extent than require special breathing device for delivery into the alveoli halothane. quantifying the amount of anesthetic vapor or gas in a mixture: ∙ Liver: hepatic blood flow is better (a) concentration (volume %) ∙ Renal: slight reduction of the renal blood flow and GFR (b) partial pressure (mm Hg) ∙ Skeletal muscle: can trigger malignant hyperthermia in (c) mass (mm or g). susceptible individuals; produces good muscle relaxation.  V. Pharma 181: Basic Veterinary Pharmacology LECTURE 19: General Anesthetics FIRST SEMESTER | SY. 2024 - 2025 by: CORDERO DESFLURANE extremely expensive Adverse effects: ∙ CNS: reduces cerebral metabolic rate; increases cerebral blood flow and intracranial pressure. ∙ Cardiovascular: increases heart rate and arterial blood pressure; does not sensitize heart to catecholamines ∙ Respiratory: dose-dependent respiratory depression ∙ Liver and renal: minimal depression of hepatic and renal blood flow. SERVOFLURANE Clinical applications: Many feature common to desflurane but is more potent and does not cause airway irritation; more suitable for mask induction. Contraindications: raised intracranial pressure; pneumothorax, gastric dilation and volvulus, intestinal obstruction, lung pathology, anemia DIETHYL ETHER transparent colorless liquid possibility of explosion is great may cause death if liquid is aspirated into the nasal passages. Clinical use: for induction and maintenance of anesthesia specially in small laboratory animals. Pharmacological effects: ∙ Nervous effects: Initial excitement; delirium during induction; then; brain depression ∙ Cardiac effect: Failure of respiration always precedes cardiac failure ∙ Respiratory effects: Irritation to mouth, pharynx, and respiratory tract; Stimulation of salivation; dangerous if saliva is aspirated into the respiratory tract; Coughing and breath holding ∙ Cardiosvascular effects: Depression of the cardiovascular system ∙ Neuromuscular effects: Relaxes skeletal muscles; Curare-like effect at the neuromuscular junction; Depresses impulse transmission in the spinal cord motor neuron CHLOROFORM It is a heavy sweet smelling liquid neither inflammable nor explosive Pharmacological effects ∙ Respiratory effects: Direct and indirect effects; Depressed sensitivity to carbon dioxide; Breath slow and shallow; Respiratory failure may occur during anesthesia. ∙ Cardiovascular effects: Effects are complex because the heart, medullary centers and peripheral blood vessels are all affected. Cardiac failure may occur during induction.