Intravenous Anesthetic Agents PDF

Intravenous Anesthetic Agents AWAD MOHAMMED ALQAHTANI BSc of Anesthesia Technology King Khalid University, Muhayil Asir  Introduction General anesthesia began with inhaled agents but now can be induced and maintained with drugs that enter the patient through a wide range of ro...

Intravenous Anesthetic Agents AWAD MOHAMMED ALQAHTANI BSc of Anesthesia Technology King Khalid University, Muhayil Asir  Introduction General anesthesia began with inhaled agents but now can be induced and maintained with drugs that enter the patient through a wide range of routes.  Drug administration can be oral, rectal, transdermal, transmucosal, intramuscular, or intravenous for the purpose of producing or enhancing an anesthetic state. Intravenous anesthetic agents include: Barbiturates Benzodiazepines Ketamine Etomidate Propofol Barbiturates Benzodiazepines Ketamine Propofol Etomidate  Barbiturates Mechanisms of Action Barbiturates are a class of drugs that depress the central nervous system (CNS) and primarily work to calm the body and mind. Effect on the Central Nervous System (CNS): Barbiturates suppress the reticular activating system (RAS) in the brainstem, a part of the brain responsible for regulating consciousness, alertness, and wakefulness. When this system is inhibited, the person feels drowsy and relaxed, and, at higher doses, may lose consciousness. Effect on GABA-A Receptors: Barbiturates bind to GABA-A receptors, which respond to GABA, a natural inhibitory neurotransmitter that calms neural signals in the brain. These receptors open channels allowing chloride ions to enter nerve cells, making the cells more negatively charged than usual. This hyperpolarization reduces neuron activity, making it harder for neurons to send signals, producing sedative effects. Clinical Concentrations and Effect on Synaptic Transmission: At clinical concentrations (therapeutic doses), barbiturates primarily affect synaptic functions—the points where neurons communicate with each other—rather than directly altering the excitability of neurons. In other words, barbiturates decrease neurotransmitter release and reduce synaptic transmission, which limits communication between neurons. This decreases brain and body activity, causing a calming effect. Clinical Effects: Because of this mechanism, barbiturates are used in medicine as sedatives, hypnotics, and, in higher doses, anesthetics. However, their use requires great caution, as excessive doses can lead to respiratory depression, loss of consciousness, and even death in cases of overdose. In summary, barbiturates reduce neural activity in the brain by enhancing the inhibitory action of GABA, which leads to sedation and relaxation. Hemodynamic responses to barbiturates are reduced by slower rates of induction. Cardiac output is often maintained by an increased heart rate and increased myocardial contractility from compensatory baroreceptor reflexes. When barbiturates, are used in anesthesia or other treatments, they can cause a drop in blood pressure due to peripheral vasodilation. This vasodilation means blood doesn’t return to the heart as efficiently, leading to lower blood pressure. If barbiturates are administered quickly (at a fast induction rate), the body might not have enough time to respond to this sudden drop in blood pressure, which could lead to a significant hemodynamic downturn. However, when barbiturates are given slowly, the body has the chance to gradually adapt through a compensatory mechanism known as the baroreceptor reflex. How Does the Baroreceptor Reflex Work? Baroreceptors are sensory receptors located in the walls of major blood vessels, such as the aorta and carotid arteries. Their role is to monitor blood pressure. When they sense a drop in pressure, they send signals to the central nervous system to trigger compensatory responses that help raise blood pressure. These compensatory responses include: 1. Increasing heart rate: This increases the amount of blood the heart pumps per minute (cardiac output). 2.Enhancing myocardial contractility: This allows the heart to pump blood more forcefully. When barbiturates are given slowly, these compensatory mechanisms can respond effectively, helping maintain cardiac output and reduce the drug’s impact on the circulatory system. Apnea (a temporary stop in breathing)often follows an induction dose. During awakening, tidal volume (the amont of air moves per breath) and respiratory rate(the number of breaths takes per minute) are decreased following barbiturate induction BENZODIAZEPINES Mechanisms of Action Benzodiazepines bind the same set of receptors in the central nervous system as barbiturates but bind to a different site on the receptors (GABAA) Midazolam is water soluble at low pH. Diazepam and lorazepam are insoluble in water so parenteral preparations contain propylene glycol, which can produce venous irritation. Coadministeration with opioids produce myocardial depression and arterial hypotension Ventilation must be monitored in all patients receiving intravenous benzodiazepines, and resuscitation equipment must be immediately available Benzodiazepines have no direct analgesic properties. The antianxiety, amnestic, and sedative effects seen at lower doses progress to stupor and unconsciousness at induction doses.  Ketamine Ketamine produces a unique form of dissociative anesthesia. In this state, patients may seem conscious, showing signs like eye opening, swallowing, or muscle movements. However, they are unable to process or respond meaningfully to sensory input. This effect results from ketamine’s action on NMDA receptors in the brain, leading to a disconnect between sensory perception and conscious awareness, making patients appear awake but unaware or unresponsive to their surroundings. Mechanisms of Action Ketamine has multiple effects throughout the central nervous system, inhibiting polysynaptic reflexes in the spinal cord as well as excitatory neurotransmitter effects in selected areas of the brain ketamine functionally “dissociates” the thalamus (which relays sensory impulses from the reticular activating system to the cerebral cortex) from the limbic cortex (which is involved with the awareness of sensation(  Effects on Organ Systems In contrast to other anesthetic agents, ketamine increases arterial blood pressure, heart rate, and cardiac output Accompanying these changes are increases in pulmonary artery pressure and myocardial work. large bolus injections of ketamine should be administered cautiously in patients with coronary artery disease, uncontrolled hypertension, congestive heart failure, or arterial aneurysms.  ETOMIDATE Mechanisms of Action Etomidate depresses the reticular activating system and mimics the inhibitory effects of GABA. There is 30–60% incidence of myoclonus with etomidate induction of anesthesia.  Structure–Activity Relationships Etomidate contains a carboxylated imidazole. The imidazole ring provides water solubility in acidic solutions and lipid solubility at physiological pH.  Therefore etomidate is dissolved in propylene glycol for injection. This solution often causes pain on injection that can be lessened by a prior intravenous injection of lidocaine Endocrine Induction doses of etomidate transiently inhibit enzymes involved in cortisol and aldosterone synthesis. Long-term infusion and adrenocortical suppression were associated with an increased mortality rate in critically ill (particularly septicemia) patients. PROPOFOL Mechanisms of Action Propofol induction of general anesthesia may involve facilitation of inhibitory neurotransmission mediated by GABA A receptor binding Propofol is not water soluble, but a 1% aqueous solution (10 mg/mL) is available for intravenous administration as an oil-in-water emulsion containing soybean oil, glycerol, and egg lecithin. A history of egg allergy does not necessarily contraindicate the use of propofol This formulation will often cause pain during injection that can be decreased by prior injection of lidocaine or less effectively by mixing lidocaine with propofol prior to injection (2 mL of 1% lidocaine in 18 mL propofol). Propofol formulations can support the growth of bacteria, so sterile technique must be observed in preparation and handling. Propofol should be administered within 6 h of opening the ampule. Sepsis and death have been linked to contaminated propofol preparations. Factors associated with propofol-induced hypotension include large doses, rapid injection, and old age. Propofol-induced depression of upper airway reflexes exceeds that of thiopental, allowing intubation, endoscopy, or laryngeal mask placement in the absence of neuromuscular blockade. Its antiemetic effects (requiring a blood propofol concentration of 200 ng/mL) provide yet another reason for it to be a preferred drug for outpatient anesthesia. Induction is occasionally accompanied by excitatory phenomena such as muscle twitching, spontaneous movement, opisthotonus, or hiccupping Questions are welcome Thank You  Reference Clinical Anesthesiology 6th edition 2018 the Author ; G.Morgan. Maged Mikhail and Michael Murray, chapter 9, page : 175 – 189.