Drugs acting on the cns


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Drugs acting on the cns

  1. 1. Drugs Acting on The Central Nervous System By; Seyoum Gizachew (B.Pharm., MSc.)
  2. 2. Definitions • CNS pharmacology -- how drugs alter brain activity and offset pathology. • Neuropharmacology -- how drugs act on neurons at cellular/molecular level. • Psychopharmacology -- how drugs modify behavior, perception, affect and thought. 2
  3. 3. Cells forming CNS • Neuron • Neuroglia – Astrocytes – Microglia – Ependymal cells – Oligodendrocytes 3
  4. 4. Neuroglia Figure 4
  5. 5. Neurotransmission Systems • Neurons function through communication networks that may be called neurotransmission systems, • The major elements of neurotransmission systems; – neurotransmitters, synapses, and receptors. • Neurotransmitters, Synapses, and Receptors; – their interaction promotes order or disorder in the body’s physical and mental processes. • Neurotransmitter, – A chemical released by one neuron that affects another neuron or an effector organ (e.g., muscle, gland, blood vessel). 5
  6. 6. Neurotransmission Systems cont… Identifying Neurotransmitter – four criteria • Synthesis and storage in presynaptic neuron • Released by presynaptic axon terminal upon stimulation • When experimentally applied, produces response in postsynaptic cell that mimics response produced by release of neurotransmitter from the presynaptic neuron • Inactivation -a specific mechanism exists to remove the molecule from the synaptic cleft or to degrade it. 6
  7. 7. Major Neurotransmitters Excitatory Mixed • Aspartate -Acetylcholine • Glutamate - Norepinephrine -Epinephrine - Dopamine -Serotonin Inhibitory • GABA • Glycine 7
  8. 8. Neurotransmission Systems cont… • Excitatory: – create Excitatory postsynaptic potentials: EPSP – stimulate or push neuron towards an action potential (figure below) • Inhibitory: – Create Inhibitory postsynaptic potentials: IPSP – Reduce probability that neuron will show an action potential (figure below) • Some neurotransmitters are both inhibitory and excitatory, depending upon situation and location – NE, Ach, Dopamine, 5-HT. 8
  9. 9. Junctional Transmission 9
  10. 10. Neurotransmission Systems cont… • Major neurotransmission systems are the; – Cholinergic, – Dopaminergic, – GABA-ergic, – Noradrenergic, and – Serotonergic networks. 10
  11. 11. Neurotransmission Systems cont… The cholinergic system: • Uses acetylcholine (Ach) as its NT. • Ach, – the first substance to be designated as a NT in the CNS. • Located in many areas of the brain, – especially high concentrations in the motor cortex and basal ganglia. • Exerts excitatory effects at synapses and NMJs and inhibitory effects at some sites. • In the CNS, acetylcholine is associated with, – arousal, learning, memory, motor conditioning, and speech. • Dementia and Parkinsonism is associated with abnormalities in 11 cholinergic pathways.
  12. 12. Neurotransmission Systems cont… The dopaminergic system: • Uses dopamine as its NT. • Originate primarily from substantia nigra, ventral tegmental area (VTA) and hypothalamus. • Projects to different areas of brain including striatum, limbic areas (e.g. amygdala, hippocampus, nucleus accumbens), frontal and prefrontal lobe cortex, pituitary gland. • Dopamine is important in; − motor control (Parkinsonism is due to dopamine deficiency), − behavioural effects (excessive dopamine activity is implicated in schizophrenia), − hormone release (inhibits prolactin secretion) and − chemoreceptor trigger zone causes nausea and vomiting. 12
  13. 13. The dopaminergic system cont… • Two groups of dopamine receptors have been identified. • One group includes D1 and D5 receptors, – activate adenyl cyclase to produce cAMP. • The other group includes D2, D3, and D4 receptors. – inhibit activation of adenyl cyclase, – suppress calcium ion currents, and – activate potassium ion currents. 13
  14. 14. Neurotransmission Systems cont… • The GABA-ergic system – uses GABA as its neurotransmitter. • GABA – Major inhibitory NT of CNS – Found in virtually every region of the brain. • GABA receptors- two main types, A and B. • GABAA receptor: – a chloride ion channel that opens when GABA is released from presynaptic neurons. – Activation causes hyperpolarization. • GABAB receptor: – has not been delineated. – Leads to increased efflux of K+ and hyperpolarization – Also leads to decreased presynaptic Ca2+ influx. 14
  15. 15. Neurotransmission Systems cont… The Noradrenergic system: • uses norepinephrine as its NT • Originate primarily in locus coeruleus (in the pons). • Projects diffusely to cortex and brainstem. • extends to virtually every area of the brain. • Noradrenergic system is associated with; – mood, wakefulness and alertness, reward, Arousal, Attention, • Control mood – Functional deficiency contribute to depression. • Function of reward system. – Cocaine / amphetamine • Inhibit reuptake • Blood pressure regulation. 15
  16. 16. The noradrenergic system cont… • Norepinephrine receptors in the CNS, as in the sympathetic nervous system, – divided into alpha- and beta-adrenergic receptors and their subtypes. • Activation of α1, β1, and β2 receptors: – thought to stimulate activity of intracellular adenyl cyclase and the production of cAMP. • Activation of α2 receptors: – associated with inhibition of adenyl cyclase activity and decreased production of cAMP. • However, the effects of α2 receptor are thought to stem mainly from; – activation of receptor-operated potassium ion channels and – suppression of voltage-operated calcium ion channels. 16
  17. 17. The noradrenergic system cont… • These effects of α2 receptor on ion channels – may increase membrane resistance to stimuli and inhibit the firing of CNS neurons. • α2 receptors on the presynaptic nerve ending – regulate norepinephrine release. 17
  18. 18. Neurotransmission Systems cont… The serotonergic system: • uses serotonin (5-hydroxytryptamine or 5-HT) as its NT. • Serotonin-synthesizing neurons – widely distributed in the CNS, beginning in the midbrain (raphe nuclei) and projecting into the thalamus, hypothalamus, cerebral cortex, and spinal cord. – synthesized from the amino acid tryptophan. • Serotonin in CNS is associated with, – Mood, Arousal (sleep–wake cycle), emotional behavior, temperature regulation, inhibition of pain pathways in the spinal cord. – Migraine 18
  19. 19. The serotonergic system cont… Serotonin receptors • Many types and subtypes – 5-HT1-7 • Mostly metabotropic – Except 5-HT3, ionotropic • 5-HT1B/D – Presynaptic autoreceptors – Inhibitory 19
  20. 20. Neurotransmission Systems cont… The amino acid system • Includes several amino acids that may serve as both structural components for protein synthesis and NTs. • Amino acids were recognized as NTs relatively recently, – their roles and functions in this regard have not been completely elucidated. • Aspartate: – an excitatory NT found in high concentrations in the brain. • Aspartate and glutamate are considered the major fastacting, excitatory NTs in the brain. • Glycine: – an inhibitory NT found in the brain stem and spinal cord. 20
  21. 21. The amino acid system cont… • Glutamate – considered the most important excitatory NT in the CNS. – It occurs in high concentrations in virtually every area of the CNS, including the cerebral cortex, basal ganglia, limbic structures, and hippocampus. • Several subtypes of glutamate receptors have been identified. • The functions of these receptor subtypes have not been fully established. • NMDA glutamate receptor subtype; – plays a role in memory. – Overstimulation causes excitotoxicity that may result in cell death. 21
  22. 22. Drugs Affecting CNS • CNS Depressants (alcohol, Benzodiazepines) – Mild CNS depressant: decreased interest in surroundings, inability to focus. – Moderate CNS depressant: drowsiness or sleep, decreased perception of heat or cold – Severe CNS depressant: unconsciousness or coma, loss of reflexes, respiratory failure and death. • CNS Stimulants (Theophylline, Caffeine) – Mild stimulation = wakefulness, mental alertness, and decreased fatigue. – Moderate stimulation = hyperactivity, excessive talking, nervousness, and insomnia. – Excessive stimulation: confusion, seizures, cardiac dysrhythmias, death. 22
  23. 23. General Anaesthetics (GAs) Definition: General Anesthesia is Reversible, drug-induced loss of consciousness. – Depresses the nervous system. • Is a reversible and controlable state of: – Analgesia, – Amnesia, – Loss of consciousness, – Inhibition of sensory and autonomic reflexes, and – Variable degree of skeletal muscle relaxation. • Low therapeutic indices (2 to 4) – require great care in administration. 23
  24. 24. General Anaesthetics cont... • While all GAs produce a relatively similar anesthetic state, they are quite dissimilar in their secondary actions (side effects) on other organ systems. – selection of specific drugs and routes of administration is based on: • pharmacokinetic properties • Secondary (side) effects • proposed diagnostic or surgical procedure and • individual patient's age, associated medical condition, and medication use. – Thiopental sodium is not well tolerated in elderly patients. 24
  25. 25. Historical Perspectives Anesthesiology Original in the Royal College of Surgeons of England, London. 25
  26. 26. Historical Perspectives cont… • General anesthesia was absent until the mid-1800’s – surgeons relied on being able to operate at lightning speed, and most operations were amputations. • Original discoverer of general anesthetics: – Crawford Long: 1842, ether anesthesia • Ether no longer used in modern practice, yet considered to be the first “ideal” anesthetic. • Halothane: 1956 – Team effort between the British Research Council and chemists at Imperial Chemical Industries. – Preferred anesthetic of choice. • Thiopental: Intravenous anesthetic – John Lundy and Ralph Waters: 1934 26
  27. 27. General Anesthetics cont… Contemporary anesthetic management requires: • Rapid loss of consciousness, – eliminates awareness, memory of pain, anxiety, and stress • A level of analgesia sufficient to abolish the reflex reactions to pain, • Minimal and reversible influence on vital physiological functions (cardiovascular and respiratory systems) • Relaxation of skeletal muscle, • Lack of operating room safety hazards, such as flammability and explosiveness, and • Prompt patient recovery to psychomotor competence. 27
  28. 28. General Anesthetics cont… • While none of the anesthetic drugs possesses all of the features required for ideal anesthetic management. – Requires the use of anesthetic drugs and/or adjunctive agents, such as neuromuscular blocking drugs, opioids, etc. Balanced anesthesia: • is a term used to describe the multidrug approach to managing the patient’s anesthetic needs. • GAs are administered by inhalation or by intravenous routes. – Classified into two: inhalation and intravenous anesthetics. 28
  29. 29. Phases of Anesthesia 29
  30. 30. Stages of Anesthesia First Stage: Stage of Analgesia • From beginning of induction to Loss of consciousness • Analgesia: Loss or obtundation of the sense of pain w/o Loss of consciousness or the sense of touch. Second Stage: Stage of Delirium/Excitement • “Dream stage” • The patient often appears to be delirious and may vocalize but is definitely amnesic. • Respiration is irregular both in volume and rate, and retching and vomiting may occur if the patient is stimulated. – duration and severity of this stage should be limited by rapidly increasing the concentration of the agent. • This stage ends with the reestablishment of regular breathing. 30
  31. 31. Stages of Anesthesia cont… Third Stage: Surgical Stage. • Most reliable indicator of surgical stage: – loss of responsiveness to noxious stimuli, and – reestablishment of regular respiratory pattern Fourth Stage: Respiratory Paralysis (overdose). • Begins with central respiratory paralysis, ends with cardiac failure and death. • Anoxia of the vital centers • 2 to 4 or 5 min: metabolic rate will be continuous and oxygen reserves will be depleted. 31
  32. 32. Pharmacokinetic characteristics of GAs • IV anesthetics; generally employed to: – induce anesthesia, – provide supplemental anesthesia, or – permit anesthesia for short operative procedures. • Inhalational anesthetics most often used for: – longer term maintenance of the anesthetic state. • IV agents: – produce anesthesia rapidly, most are metabolized slowly, • recovery may be prolonged when used as the primary drug during a long surgical procedure. • Inhalational agents: – anesthetic partial pressure is achieved slowly, the patient recovers at a clinically acceptable rate (fast recovery). 32
  33. 33. Distribution of Intravenous Agents • Generally induce anesthesia within one or two circulation times after their administration. – rapidly achieve initial high concentration in the CNS. • Enter the brain, cross BBB: – quite lipid soluble • Brain receives a large proportion of the cardiac output, a large proportion of an IV administered agent will be distributed to the CNS. – All IV anesthetic drugs in use show this early pattern of distribution. • The initial unequal tissue–drug distribution cannot persist; – physicochemical forces tend to establish concentration equilibria with other less well perfused organs. • Called Redistribution. 33
  34. 34. Distribution of Intravenous Agents cont… Figure; The distribution of Thiopental in tissues and organs following IV injection. Note the redistribution of the drug, with time, to tissues with lower rates of blood flow. 34
  35. 35. Intravenous Anesthetic Agents 1. Ultra–Short-Acting Barbiturates • Barbiturates (derivatives of barbituric acid), thiopental sodium, thiamylal sodium, and methohexital sodium. • Thiopental sodium: – widely-used agent – rapid and pleasant induction – Produce unconsciousness rapidly – Produce amnesia – poor analgesic property. – No skeletal muscle relaxation – very short duration of action. • due to rapid redistribution to peripheral tissues. – Slow rate of metabolism, t1/2β = 12h 35
  36. 36. Thiopental sodium cont… • Induction dose 3-5 mg/Kg Adverse Effects • Cardiovascular depression: – not well tolerated in elderly patients or those with poorly compensated myocardial function. • Respiratory depression. • There are no antagonists!!! 36
  37. 37. Intravenous Anesthetic Agents cont… 2. Benzodiazepines (BZDs) – Midazolam, diazepam, and lorazepam. • cause unconsciousness without analgesia, inadequate skeletal muscle relaxation. • High amnesic potential. • Midazolam – Most popular of these agents for the induction of anesthesia, because of its aqueous solubility and short duration of action (t1/2 = 1.3–2.2h). • Lorazepam and diazepam: – not water soluble and must be formulated in propylene glycol; • propylene glycol is irritating to the vasculature on parenteral administration. • Diazepam (t1/2 = 30h) or lorazepam (t1/2 = 10-20h) 37
  38. 38. Benzodiazepine Antagonist • Flumazenil – BZDs antagonist that specifically reverses the respiratory depression and hypnosis produced by the BZD receptor agonists. – Useful when an overdose of BZD has occurred. – Also employed when a BZD has been used to produce conscious sedation and rapid recovery of psychomotor competency is desirable. 38
  39. 39. Intravenous Anesthetic Agents cont… 3. Etomidate • Similar pharmacologic properties to those of barbiturates. • But, greater margin of safety. – limited effects on the cardiovascular and respiratory systems. • Relatively short elimination half life (t1/2 = 2.9 h). • Rapidly hydrolyzed in the liver. • Induction dose = 0.2 to 0.4 mg/kg Adverse Effects • May cause pain on injection. • Can suppress the adrenocortical response to stress (decrease in cortisol and aldosterone levels), an effect that may last up to 10 hours. • There are no antagonists! 39
  40. 40. Intravenous Anesthetic Agents cont… 4. Propofol • is an IV sedative/hypnotic used in the induction or maintenance of anesthesia. • widely used and has replaced thiopental as the first choice for anesthesia induction and sedation, because it; – produces a euphoric feeling in the patient and – does not cause postanesthetic nausea and vomiting. • Onset: induction is smooth and occurs within about 30–40 seconds of administration. • Short recovery time (4 to 8 minutes) – Redistribution and rapid metabolism to glucuronide and sulfate conjugates. • No skeletal muscle relaxation 40
  41. 41. Propofol cont… • Lacks analgesic properties – lower doses of opioids. • facilitates depression in the CNS, but; – occasionally accompanied by excitatory phenomena, such as muscle twitching, spontaneous movement, and hiccups. • Induction dose = 1.5 to 2.5 mg/kg Adverse Effects • Cardiorespiratory depression. • Reduction in blood pressure: – associated with vasodilation and myocardial depression. • There are no antagonists! 41
  42. 42. Intravenous Anesthetic Agents cont… 5. Ketamine • Pharmacological actions are quite different from those of the other IV anesthetics. • Produce trancelike unconsciousness (eyes may remain open until deep anesthesia is obtained) and cataleptic; • Patient may appear awake and reactive but does not respond to sensory stimuli. • patient initially feels consciously detached from the environment before becoming unconscious. – Called Dissociative anesthesia • This dissociative anesthesia provides sedation, analgesia, amnesia, and immobility. 42
  43. 43. Ketamine cont… • Cause profound analgesia – without a deep level of anesthesia. • Can be given by an IM route: – The most important advantage – Useful in pediatrics • It stimulates the central sympathetic outflow, which in turn, – causes stimulation of the heart with increased blood pressure and Cardiac Output. – especially beneficial in patients with either hypovolemic or cardiogenic shock as well as in patients with asthma (bronchodilator). • used when circulatory depression is undesirable. • Contraindicated in in hypertensive or stroke patients. 43
  44. 44. Ketamine cont… • is lipophilic and enters the brain circulation very quickly. • it redistributes to other organs and tissues. • Metabolized in the liver by CYP3A4 (major), CYP2B6, and CYP2C9, but small amounts can be excreted unchanged. • T1/2β= 2.5-3hrs. • Induction doses: 0.5 to 1.5 mg/kg IV, 4 to 6 mg/kg IM Adverse Effects • Evoke excitatory and hallucinatory phenomena as the patient emerges from anesthesia. – The most serious disadvantage • Vomiting, salivation, lacrimation, shivering, skin rash, and an interaction with thyroid preparations that may lead to 44 hypertension and tachycardia.
  45. 45. Inhalational Anesthetics (IAs) • Can be divided into two classes based on their physical properties. – N2O and cyclopropane are gases at room T0 and – Liquids that are volatile following the application of low heat. • Most are halogenated hydrocarbons. 45
  46. 46. Pharmacokinetic Characteristics • Use generally reserved for maintenance of anesthesia. • Development of an anesthetic concentration in the brain occurs more slowly with IA than with IV drugs. • Once an anesthetic level has been achieved, however, it is easily adjusted by controlling the rate or concentration of gas delivery from the anesthesia machine. • Rapid rate of recovery from a lengthy procedure; – since IAs are eliminated by the lungs and do not depend on a slow rate of metabolism for their tissue clearance. • Partial pressure gradients control the equilibration of gases between various tissue compartments. 46
  47. 47. Pharmacokinetic Characteristics cont… • The main factors that determine the speed of induction and recovery: A. properties of the anaesthetic – blood:gas partition coefficient (i.e. solubility in blood) – oil:gas partition coefficient (i.e. solubility in fat) B. Physiological factors – alveolar ventilation rate. – cardiac output. 47
  48. 48. The Solubility of Anaesthetics • IAs can be regarded physicochemically as ideal gases: – their solubility in different media is expressed as partition coefficients. • Partition coefficient: the ratio of the concentration of the agent in two phases at equilibrium. • Blood:gas partition coefficient: – determines the rate of induction and recovery of an inhalation anaesthetic. – the lower the blood:gas partition coefficient the faster the induction and recovery. • Oil:gas partition coefficient: – determines the potency of an anaesthetic – influences the kinetics of its distribution in the body – high lipid solubility tends to delay recovery. 48
  49. 49. Partial Pressure of Gas Molecules in a Liquid • When a liquid is exposed to a gas, a partial pressure equilibrium will be achieved between the gas and liquid phases. – molecules of the gas that are physically dissolved in the liquid will exert tension that is equal to the partial pressure of the gas above the liquid. • Gas molecules will move across the alveolar membrane until those in the blood, through random molecular motion, exert pressure equal to their counterparts in the lung. • Similar gas tension equilibria also will be established between the blood and other tissues such as the brain. 49
  50. 50. Minimum Alveolar Concentration (MAC) • Anesthetic dose is usually expressed in terms of the alveolar tension required at equilibrium to produce a defined depth of anesthesia. • The dose is determined experimentally as the partial pressure needed to eliminate movement in 50% of patients challenged with a standardized skin incision. • The tension required is defined as the minimum alveolar concentration (MAC) and is usually expressed as the percentage of inhaled gases that is represented by anesthetic gas at 1 atm. • Example, methoxyflurane MAC = 0.16%, only 0.16% of the molecules of inspired gas need be methoxyflurane. 50
  51. 51. Table: Pharmacologic characteristics of IAs 51
  52. 52. Figure: Rate of Entry into the Brain: Influence of Blood and Lipid Solubility 52
  53. 53. Halogenated Hydrocarbon Anesthetics Include: Sevoflurane, desflurane, enflurane, isoflurane, halothane, and methoxyflurane. 1. Halothane: CF3-CHClBr • widely used agent, but its use is now declining in favour of isoflurane and other drugs. • Potent, and can easily produce respiratory and cardiovascular failure. • Non-explosive and non-irritant. • hypotensive because of: – myocardial depression and vasodilatation. • Hangover likely. – because of high lipid solubility. • Not analgesic. 53
  54. 54. Halothane cont… Adverse effects: • Sensitizes the heart to adrenaline, and it tends to cause cardiac dysrhythmias • Hepatotoxic 1:100,000 after repeated dose – Metabolite, trifluoroacetic acid, react with hepatic proteins and induce immune response. • Malignant hyperthermia. – excessive metabolic heat production in skeletal muscle, as a result of excessive release of Ca2+ from the sarcoplasmic reticulum. 54
  55. 55. 2. Enflurane: CHF2-O-CF2CHFCl • Halogenated anaesthetic similar to halothane. • Introduced as an alternative to methoxyflurane • Less metabolism than halothane – less risk of toxicity • faster induction and recovery than halothane (less accumulation in fat) • some risk of epilepsy-like seizures. • Can induce malignant hyperthermia. 55
  56. 56. 3. Methoxyflurane • The most potent inhalational agent available. • High solubility in tissues limits its use as an induction anesthetic. • Similar pharmacologic properties with halothane with some notable exceptions. – methoxyflurane does not depress cardiovascular reflexes • Its oxidative metabolism results in the production of oxalic acid and fluoride; – cause renal tubular dysfunction (nephrotoxic) • greatly restricted the use of methoxyflurane. 56
  57. 57. 4. Sevoflurane: CH2F-O-CH(CF3)2 • The most recently introduced inhalation anesthetic. • Has low tissue and blood solubility: – rapid induction and recovery • Hypotension: – Because of systemic vasodilation & cardiac output decrease. 57
  58. 58. 5. Isoflurane: CF3CHCl-O-CHF2 • A structural isomer of enflurane: • Now the most widely used IA – Low incidence of untoward effects (esp. preserves cardiovascular stability) • Some analgesia. • Some neuromuscular blockade and depressed respiration. • Maintain cardiac output; – Safe in patients with ischemic heart disease. • Does not sensitize myocardium to catecholamines. • Hypotension – as a result of vasodilation. • Unlike enflurane, does not produce a seizure like EEG pattern. 58
  59. 59. 6. Desflurane: CF3-CHF-O-CF2H • Shares most of the pharmacological properties of isoflurane. • Has low tissue and blood solubility compared with other halogenated hydrocarbons: – Rapid induction and recovery • Irritates the respiratory tract: – not preferred for induction • Hypotension: – Because of decreased vascular resistance • Maintain cardiac output. 59
  60. 60. Mechanism of Anesthetic Action Unitary theory (Lipid theory): • Is among the earliest proposals of mechanism of action • Proposed by Overton & Meyer, at the turn of the 20thC. – anesthetic agents interact physically rather than chemically with lipophilic membrane components to cause neuronal failure. – “Narcosis commences when any chemically indifferent substance has attained a certain molar concentration in the lipids of the cell”. Meyer 1937. 60
  61. 61. Mechanism of Anesthetic cont… • Though, this concept proposes that all anesthetics interact in a common way (the unitary theory): – Challenged by more recent work demonstrating that specific anesthetics exhibit selective and distinct interactions with neuronal processes and that those interactions are not easily explained by a common physical association with membrane components. • For example, enantiomers of newer agents have selective and unique actions, even though they have identical physical properties; – Stereoisomers of isoflurane are differentially potent but have identical oil–gas partition coefficients. 61
  62. 62. Mechanism of Anesthetic cont… 1. Facilitate GABA-mediated inhibition at GABA-A receptor sites A. Direct activation: Inhaled anesthetics, barbiturates, etomidate, propofol B. Enhance GABA action: benzodiazepines, barbiturates, etomidate, Inhaled anesthetics, propofol 2. Antagonist at NMDA receptor (N-methyl-D-aspartate glutamate receptor): Ketamine, nitrous oxide 3. Hyperpolarization by activation of K+ channels. – Inhaled anesthetics 4. Agonist action at Glycine receptor – direct action: inhaled anesthetics 62
  63. 63. Mechanism of Anesthetic cont… • The cellular and molecular mechanisms of GAs are not yet fully understood. – Clearly much must be explained (by researches) of the complex changes in the CNS that eventually produce unconsciousness. 63
  64. 64. Anesthetic adjuncts / Preanesthetic medications • The main objective of using these drugs, prior to the administration of the anaesthetic agent is to make anaesthesia safer and more agreable to the patient, or to attain the called Balanced anesthesia. • The drugs commonly used are: – Analgesics (opioids). – Benzodiazepines (for anxiolysis, amnesia, and sedation) – Anticholinergics. – Neuromuscular Blocking Agents, and – Anti-emetics. 64