This document discusses the pharmacology of commonly used drugs for conscious sedation, including barbiturates, benzodiazepines, and other sedatives. It describes how barbiturates like pentobarbital, methohexital, and thiopental act as central nervous system depressants and can cause respiratory depression. It also explains that benzodiazepines like diazepam and midazolam produce sedation, anxiolysis, and amnesia by enhancing the effect of the neurotransmitter GABA at brain receptors, but can also depress respiration especially when combined with other CNS depressants. The document provides details on dosages, routes of administration, onset of action, and side effects
Stage III: Stage of Surgical Anaesthesia
- Begins after excitement stage ends and lasts until anaesthetic is stopped
- Patient is unconscious and has regular breathing
- Pupils are dilated and fixed
- Reflexes like eyelash, swallowing are lost
- Surgery can be safely performed during this stage
The document discusses post-extubation stridor, which is upper airway obstruction that can occur after a patient is extubated from a ventilator. It defines post-extubation stridor and reviews risk factors such as duration of intubation and cuff pressures. The cuff leak test is presented as a way to identify patients at risk. Studies are reviewed showing steroids given before extubation can reduce the risk of stridor. Clinically, it recommends identifying at-risk patients, performing the cuff leak test, and considering steroid treatment for high-risk patients before extubation.
Intravenous induction agents are drugs given intravenously to induce anesthesia rapidly. Ideal properties include water solubility, stability, rapid onset within one arm-brain circulation time, rapid redistribution and clearance with no active metabolites, minimal effects on vital organs, and a high therapeutic ratio. Common IV induction agents discussed are barbiturates, propofol, ketamine, etomidate, benzodiazepines, and opioids. Each drug has different effects on the cardiovascular, respiratory, and central nervous systems and potential complications.
Pharmaceutical Quality Management of Dexamethasone tablets BP
Dexamethasone tablets USP
DEXAMETHSONE OPTHALMIC SUSPENSION BP
DEXAMETHSONE OPTHALMIC SUSPENSION USP
Dexamethasone is a synthetic (man-made) corticosteroid.
Corticosteroids are naturally-occurring chemicals produced by the adrenal glands located above the kidneys.
- Local anesthetics are drugs that cause reversible loss of sensation, especially pain, in a localized area of the body when applied topically or injected locally. They block the generation and conduction of nerve impulses at the site of contact without damaging neurons.
- Common uses include dentistry, excision procedures, dermatology, and spinal or regional anesthesia. Local anesthetics work by inhibiting sodium influx through voltage-gated sodium channels in neurons, interrupting action potential generation and signal conduction.
- Examples of side effects include central nervous system stimulation or depression in high doses, cardiovascular effects like arrhythmias and hypotension, and hypersensitivity reactions.
Ondansetron
Class
• Seratonin ( 5-HT3) antagonist.
Uses
1. The management of nausea and vomiting induced by chemotherapy and
radiotherapy .
2. In the prevention and treatment of PONV
Main action
• Antiemetic.
Lecture slides for undergraduates medical (MBBS) Students. Source material for this presentation is Essentials of Pharmacology, KD Tripathi, Katzung and Goodman and Gillman. It deals with Local anaesthetics with their mechanism of action, pharmacokinetics , adverse effects and therapeutic uses.
Stage III: Stage of Surgical Anaesthesia
- Begins after excitement stage ends and lasts until anaesthetic is stopped
- Patient is unconscious and has regular breathing
- Pupils are dilated and fixed
- Reflexes like eyelash, swallowing are lost
- Surgery can be safely performed during this stage
The document discusses post-extubation stridor, which is upper airway obstruction that can occur after a patient is extubated from a ventilator. It defines post-extubation stridor and reviews risk factors such as duration of intubation and cuff pressures. The cuff leak test is presented as a way to identify patients at risk. Studies are reviewed showing steroids given before extubation can reduce the risk of stridor. Clinically, it recommends identifying at-risk patients, performing the cuff leak test, and considering steroid treatment for high-risk patients before extubation.
Intravenous induction agents are drugs given intravenously to induce anesthesia rapidly. Ideal properties include water solubility, stability, rapid onset within one arm-brain circulation time, rapid redistribution and clearance with no active metabolites, minimal effects on vital organs, and a high therapeutic ratio. Common IV induction agents discussed are barbiturates, propofol, ketamine, etomidate, benzodiazepines, and opioids. Each drug has different effects on the cardiovascular, respiratory, and central nervous systems and potential complications.
Pharmaceutical Quality Management of Dexamethasone tablets BP
Dexamethasone tablets USP
DEXAMETHSONE OPTHALMIC SUSPENSION BP
DEXAMETHSONE OPTHALMIC SUSPENSION USP
Dexamethasone is a synthetic (man-made) corticosteroid.
Corticosteroids are naturally-occurring chemicals produced by the adrenal glands located above the kidneys.
- Local anesthetics are drugs that cause reversible loss of sensation, especially pain, in a localized area of the body when applied topically or injected locally. They block the generation and conduction of nerve impulses at the site of contact without damaging neurons.
- Common uses include dentistry, excision procedures, dermatology, and spinal or regional anesthesia. Local anesthetics work by inhibiting sodium influx through voltage-gated sodium channels in neurons, interrupting action potential generation and signal conduction.
- Examples of side effects include central nervous system stimulation or depression in high doses, cardiovascular effects like arrhythmias and hypotension, and hypersensitivity reactions.
Ondansetron
Class
• Seratonin ( 5-HT3) antagonist.
Uses
1. The management of nausea and vomiting induced by chemotherapy and
radiotherapy .
2. In the prevention and treatment of PONV
Main action
• Antiemetic.
Lecture slides for undergraduates medical (MBBS) Students. Source material for this presentation is Essentials of Pharmacology, KD Tripathi, Katzung and Goodman and Gillman. It deals with Local anaesthetics with their mechanism of action, pharmacokinetics , adverse effects and therapeutic uses.
Anticoagulation and Regional AnesthesiaRajnish Gupta
Discussing the ASRA Guidelines for Anticoagulation and Antithrombotics during Regional Anesthesia including the considerations for neuraxial anesthesia and deep blocks. We also discuss the use of the ASRA Coags app. Question and Answer included.
The patient has received an excessive dose of ketamine for her body weight. Ketamine has a long duration of action and she is still experiencing its effects 12 hours later when she should have recovered much sooner. A lower and more appropriate dose of ketamine should have been used.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
A powerpoint explaining in detail about all the intravenous induction agents and their clinical uses, pharmacokinetics & pharmacodynamics, adverse effects and complications.
Lidocaine is a rapid-acting local anesthetic first synthesized in 1943 that was approved by the FDA in 1948. It is widely used for local anesthesia and pain management. Lidocaine works by blocking sodium channels in neurons, preventing action potentials and nerve conduction. It has a short half-life of 1.6 hours and is metabolized in the liver. Lidocaine is commonly administered via local injection but is also available in topical forms and as an intravenous antiarrhythmic. When combined with a vasoconstrictor like epinephrine, lidocaine has an increased duration of anesthesia. Lidocaine remains the gold standard for local anesthesia due to its fast onset and short duration of action.
Vortioxetine was approved by the FDA in 2013 under the brand name Brintellix for the treatment of major depressive disorder. However, it was later renamed Trintellix due to brand name confusion with the antiplatelet drug Brilinta. Trintellix is a multimodal antidepressant that works by inhibiting the serotonin transporter, antagonizing various serotonin receptors, and indirectly increasing release of other neurotransmitters. Clinical trials showed Trintellix to be effective at reducing depressive symptoms and may have benefits for cognitive function compared to placebo. It has a favorable side effect and safety profile, making it a treatment option when other antidepressants cannot be tolerated or are ineffective.
This document discusses the development and properties of various atypical antipsychotic drugs. It provides chemical structures and names for common atypical antipsychotics like clozapine, risperidone, olanzapine, quetiapine and ziprasidone. It summarizes the pharmacokinetics, therapeutic indications, side effects and dosing for these drugs. The document also discusses differences between first and second generation antipsychotics and adverse effects of antipsychotic treatment.
General Anesthetics
General anesthesia is a reversible state of central nervous system depression that provides five important benefits during surgery or medical procedures: sedation, lack of awareness and amnesia, muscle relaxation, suppression of reflexes, and analgesia. It is produced through a combination of intravenous and inhaled agents to safely induce, maintain, and recover the patient from anesthesia. The selection of specific anesthetic drugs is based on the procedure, patient characteristics, and status of organ systems. Careful monitoring at each stage ensures optimal anesthesia and recovery.
Acetylcholine and succinylcholine are important neurotransmitters. Acetylcholine is the most abundant neurotransmitter in the body and acts as a chemical messenger between neurons and muscles. It is synthesized from choline and acetyl-CoA and works by binding to nicotinic and muscarinic receptors. Succinylcholine is a neuromuscular blocking drug that causes paralysis by binding to acetylcholine receptors and depolarizing muscle cells. Both acetylcholine and succinylcholine act at the neuromuscular junction to either stimulate or block muscle contraction. Their effects are location-dependent, with risks including hyperkalemia and malignant hyperthermia.
- Thoracic paravertebral block (TPVB) involves injecting local anesthetic alongside thoracic vertebrae to block spinal and sympathetic nerves, providing anesthesia for chest and abdominal procedures.
- Hugo Sellheim pioneered TPVB in 1905, though it fell out of favor mid-20th century before renewed interest in 1979.
- TPVB is now used for surgical anesthesia and analgesia in children and is effective for procedures like breast surgery, thoracotomy, and herniorrhaphy.
- Ultrasound guidance can help identify relevant anatomy like ribs and pleura to safely perform TPVB, reducing risks like pneumothorax.
Propofol is an intravenous sedative used for inducing and maintaining general anesthesia. It works by enhancing the effect of the inhibitory neurotransmitter GABA in the brain. Propofol is formulated as a 1% aqueous solution containing soybean oil, glycerol, and egg lecithin. It has a rapid onset of 15-30 seconds, short duration of 5-10 minutes, and is metabolized in the liver. Common uses include anesthesia induction, sedation, and ventilation in ICU patients. Side effects include nausea, cough, and confusion.
This document discusses the history and development of antipsychotic drugs. It notes that early antipsychotics like chlorpromazine were discovered serendipitously for their anesthetic or antihistamine properties in the 1930s-1950s. Between 1954 and 1975, about 15 antipsychotics were introduced in the US. Clozapine in 1990 marked the beginning of atypical or second-generation antipsychotics. The document also discusses theories around the role of dopamine and glutamate in schizophrenia, and how different drug classes target various receptors to treat symptoms.
Skeletal muscle relaxants work by blocking acetylcholine receptors at the neuromuscular junction, relaxing muscles. There are two main types - depolarizing and non-depolarizing. Succinylcholine is the only depolarizing drug used clinically. It causes initial fasciculations before prolonged muscle relaxation. Non-depolarizing drugs like tubocurarine and vecuronium are competitive antagonists that do not activate acetylcholine receptors, preventing muscle contraction. They have short, intermediate, or long durations of action and differ in side effects and metabolism. Dantrolene works via a different mechanism by preventing calcium release in muscles.
This document discusses depression, mania, and various antidepressant medications. It covers the symptoms of depression and mania. It then discusses various classes of antidepressants including SSRIs, SNRIs, TCAs, MAOIs, and atypical antidepressants. For each class, it describes the mechanisms of action, therapeutic uses, adverse effects, and examples of medications within the class.
Anaesthesia International Certificates FRCA, MCAI & EDAIC -OrientationSCORE Training Centre
Anesthesia International Certificates FRCA, MCAI & EDAIC -Orientation
Session surmise most of the reputable Postgraduate international certificates in the Anesthesia specialty. Which are:
FRCA, Fellowship of the Royal College of Anesthetists
MCAI, Membership of College of Anesthesia of Ireland.
EDAIC, European Diploma in Anesthesia and Intensive Care Medicine.
Drug Abuse & Misuse, Sedative-Hypnotics “Benzodiazepines”Asra Hameed
Benzodiazepine abuse is a growing problem and carries serious risks to health and society.
Benzodiazepines are commonly used by polydrug abusers, alcoholics and sometimes as primary recreational drugs.
People who abuse benzodiazepines often take very large doses orally, by injection or by snorting.
Benzodiazepine use leads to dependence and a withdrawal syndrome which may include convulsions and psychosis.
Further research is needed on the optimal short-term and long-term management of benzodiazepine abuse.
The primary source of illicit benzodiazepines is from doctors' prescriptions.
This document discusses premedication, which is the administration of drugs before anesthesia induction. It has psychological and pharmacological components. Pharmacological premedication aims to provide anxiolysis, analgesia, amnesia and other effects. Common drugs used include benzodiazepines, barbiturates, opioids, NSAIDs, antacids and anticholinergics. Factors like a patient's physical status, surgery type and risk of aspiration are considered. The goals of premedication are to minimize anxiety and discomfort from surgery and anesthesia, while facilitating recovery.
This document discusses various drugs used for anesthesia induction and maintenance. It describes common inducing agents like thiopentone sodium, methohexitone sodium, propofol, and etomidate. Slower acting drugs include benzodiazepines and ketamine. These drugs work by targeting GABA or NMDA receptors. Complications during and after anesthesia can include respiratory depression, arrhythmias, awareness, and organ toxicity.
sedation in neuro icu requires frequent interruptions for serial neurological examination. incorporation of inhalational agents in icu improves sedation practices.
The document summarizes the properties and clinical uses of dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist. It was first synthesized in the 1980s and approved by the FDA in 1999 for sedation in intensive care units. Dexmedetomidine has sedative, anxiolytic, and analgesic effects. It provides a unique sedation state resembling natural sleep and reduces opioid requirements. Clinical trials demonstrate dexmedetomidine results in shorter ICU and ventilator times compared to midazolam. Adverse effects include hypotension and bradycardia. The document reviews the pharmacokinetics, mechanisms of action, clinical effects, indications and trials of dexmedetomidine
This document lists various common medical conditions and the drugs that are commonly used to treat them. It includes conditions such as acid indigestion, acne, allergies, arthritis, asthma, attention deficit hyperactivity disorder, bacterial infections, cancer, colds, diabetes, ear infections, eczema, emphysema, eye conditions, fever, fungal infections, heartburn, high cholesterol, and many others. For each condition it provides a list of drug classes and examples of drugs within those classes that are often prescribed.
Anticoagulation and Regional AnesthesiaRajnish Gupta
Discussing the ASRA Guidelines for Anticoagulation and Antithrombotics during Regional Anesthesia including the considerations for neuraxial anesthesia and deep blocks. We also discuss the use of the ASRA Coags app. Question and Answer included.
The patient has received an excessive dose of ketamine for her body weight. Ketamine has a long duration of action and she is still experiencing its effects 12 hours later when she should have recovered much sooner. A lower and more appropriate dose of ketamine should have been used.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
A powerpoint explaining in detail about all the intravenous induction agents and their clinical uses, pharmacokinetics & pharmacodynamics, adverse effects and complications.
Lidocaine is a rapid-acting local anesthetic first synthesized in 1943 that was approved by the FDA in 1948. It is widely used for local anesthesia and pain management. Lidocaine works by blocking sodium channels in neurons, preventing action potentials and nerve conduction. It has a short half-life of 1.6 hours and is metabolized in the liver. Lidocaine is commonly administered via local injection but is also available in topical forms and as an intravenous antiarrhythmic. When combined with a vasoconstrictor like epinephrine, lidocaine has an increased duration of anesthesia. Lidocaine remains the gold standard for local anesthesia due to its fast onset and short duration of action.
Vortioxetine was approved by the FDA in 2013 under the brand name Brintellix for the treatment of major depressive disorder. However, it was later renamed Trintellix due to brand name confusion with the antiplatelet drug Brilinta. Trintellix is a multimodal antidepressant that works by inhibiting the serotonin transporter, antagonizing various serotonin receptors, and indirectly increasing release of other neurotransmitters. Clinical trials showed Trintellix to be effective at reducing depressive symptoms and may have benefits for cognitive function compared to placebo. It has a favorable side effect and safety profile, making it a treatment option when other antidepressants cannot be tolerated or are ineffective.
This document discusses the development and properties of various atypical antipsychotic drugs. It provides chemical structures and names for common atypical antipsychotics like clozapine, risperidone, olanzapine, quetiapine and ziprasidone. It summarizes the pharmacokinetics, therapeutic indications, side effects and dosing for these drugs. The document also discusses differences between first and second generation antipsychotics and adverse effects of antipsychotic treatment.
General Anesthetics
General anesthesia is a reversible state of central nervous system depression that provides five important benefits during surgery or medical procedures: sedation, lack of awareness and amnesia, muscle relaxation, suppression of reflexes, and analgesia. It is produced through a combination of intravenous and inhaled agents to safely induce, maintain, and recover the patient from anesthesia. The selection of specific anesthetic drugs is based on the procedure, patient characteristics, and status of organ systems. Careful monitoring at each stage ensures optimal anesthesia and recovery.
Acetylcholine and succinylcholine are important neurotransmitters. Acetylcholine is the most abundant neurotransmitter in the body and acts as a chemical messenger between neurons and muscles. It is synthesized from choline and acetyl-CoA and works by binding to nicotinic and muscarinic receptors. Succinylcholine is a neuromuscular blocking drug that causes paralysis by binding to acetylcholine receptors and depolarizing muscle cells. Both acetylcholine and succinylcholine act at the neuromuscular junction to either stimulate or block muscle contraction. Their effects are location-dependent, with risks including hyperkalemia and malignant hyperthermia.
- Thoracic paravertebral block (TPVB) involves injecting local anesthetic alongside thoracic vertebrae to block spinal and sympathetic nerves, providing anesthesia for chest and abdominal procedures.
- Hugo Sellheim pioneered TPVB in 1905, though it fell out of favor mid-20th century before renewed interest in 1979.
- TPVB is now used for surgical anesthesia and analgesia in children and is effective for procedures like breast surgery, thoracotomy, and herniorrhaphy.
- Ultrasound guidance can help identify relevant anatomy like ribs and pleura to safely perform TPVB, reducing risks like pneumothorax.
Propofol is an intravenous sedative used for inducing and maintaining general anesthesia. It works by enhancing the effect of the inhibitory neurotransmitter GABA in the brain. Propofol is formulated as a 1% aqueous solution containing soybean oil, glycerol, and egg lecithin. It has a rapid onset of 15-30 seconds, short duration of 5-10 minutes, and is metabolized in the liver. Common uses include anesthesia induction, sedation, and ventilation in ICU patients. Side effects include nausea, cough, and confusion.
This document discusses the history and development of antipsychotic drugs. It notes that early antipsychotics like chlorpromazine were discovered serendipitously for their anesthetic or antihistamine properties in the 1930s-1950s. Between 1954 and 1975, about 15 antipsychotics were introduced in the US. Clozapine in 1990 marked the beginning of atypical or second-generation antipsychotics. The document also discusses theories around the role of dopamine and glutamate in schizophrenia, and how different drug classes target various receptors to treat symptoms.
Skeletal muscle relaxants work by blocking acetylcholine receptors at the neuromuscular junction, relaxing muscles. There are two main types - depolarizing and non-depolarizing. Succinylcholine is the only depolarizing drug used clinically. It causes initial fasciculations before prolonged muscle relaxation. Non-depolarizing drugs like tubocurarine and vecuronium are competitive antagonists that do not activate acetylcholine receptors, preventing muscle contraction. They have short, intermediate, or long durations of action and differ in side effects and metabolism. Dantrolene works via a different mechanism by preventing calcium release in muscles.
This document discusses depression, mania, and various antidepressant medications. It covers the symptoms of depression and mania. It then discusses various classes of antidepressants including SSRIs, SNRIs, TCAs, MAOIs, and atypical antidepressants. For each class, it describes the mechanisms of action, therapeutic uses, adverse effects, and examples of medications within the class.
Anaesthesia International Certificates FRCA, MCAI & EDAIC -OrientationSCORE Training Centre
Anesthesia International Certificates FRCA, MCAI & EDAIC -Orientation
Session surmise most of the reputable Postgraduate international certificates in the Anesthesia specialty. Which are:
FRCA, Fellowship of the Royal College of Anesthetists
MCAI, Membership of College of Anesthesia of Ireland.
EDAIC, European Diploma in Anesthesia and Intensive Care Medicine.
Drug Abuse & Misuse, Sedative-Hypnotics “Benzodiazepines”Asra Hameed
Benzodiazepine abuse is a growing problem and carries serious risks to health and society.
Benzodiazepines are commonly used by polydrug abusers, alcoholics and sometimes as primary recreational drugs.
People who abuse benzodiazepines often take very large doses orally, by injection or by snorting.
Benzodiazepine use leads to dependence and a withdrawal syndrome which may include convulsions and psychosis.
Further research is needed on the optimal short-term and long-term management of benzodiazepine abuse.
The primary source of illicit benzodiazepines is from doctors' prescriptions.
This document discusses premedication, which is the administration of drugs before anesthesia induction. It has psychological and pharmacological components. Pharmacological premedication aims to provide anxiolysis, analgesia, amnesia and other effects. Common drugs used include benzodiazepines, barbiturates, opioids, NSAIDs, antacids and anticholinergics. Factors like a patient's physical status, surgery type and risk of aspiration are considered. The goals of premedication are to minimize anxiety and discomfort from surgery and anesthesia, while facilitating recovery.
This document discusses various drugs used for anesthesia induction and maintenance. It describes common inducing agents like thiopentone sodium, methohexitone sodium, propofol, and etomidate. Slower acting drugs include benzodiazepines and ketamine. These drugs work by targeting GABA or NMDA receptors. Complications during and after anesthesia can include respiratory depression, arrhythmias, awareness, and organ toxicity.
sedation in neuro icu requires frequent interruptions for serial neurological examination. incorporation of inhalational agents in icu improves sedation practices.
The document summarizes the properties and clinical uses of dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist. It was first synthesized in the 1980s and approved by the FDA in 1999 for sedation in intensive care units. Dexmedetomidine has sedative, anxiolytic, and analgesic effects. It provides a unique sedation state resembling natural sleep and reduces opioid requirements. Clinical trials demonstrate dexmedetomidine results in shorter ICU and ventilator times compared to midazolam. Adverse effects include hypotension and bradycardia. The document reviews the pharmacokinetics, mechanisms of action, clinical effects, indications and trials of dexmedetomidine
This document lists various common medical conditions and the drugs that are commonly used to treat them. It includes conditions such as acid indigestion, acne, allergies, arthritis, asthma, attention deficit hyperactivity disorder, bacterial infections, cancer, colds, diabetes, ear infections, eczema, emphysema, eye conditions, fever, fungal infections, heartburn, high cholesterol, and many others. For each condition it provides a list of drug classes and examples of drugs within those classes that are often prescribed.
Procedural sedation and analgesia (conscious sedation)Venkat Nag
if you are anxious about getting your teeth treated, or if your threshold to pain isn't quite high, conscious sedation is an option for you. here sedatives are given that completely relaxes you and you wont feel a thing while the procedure is going on.
This document discusses patient monitoring during anesthesia. It describes monitoring as collecting data on physiologic and safety parameters using clinical skills and equipment to evaluate patients and make treatment decisions. Key aspects of monitoring include consciousness level, respiration, oxygenation, blood pressure, heart rate, and temperature. Complications of inadequate monitoring can include respiratory and cardiovascular issues. Monitoring equipment may include pulse oximetry, capnography, EKG, and blood pressure cuffs. The person monitoring must not have other assignments and must immediately report any changes to the physician.
Dr. Minnu Panditrao's Dexmedetomidine for intraoperative sedation & analgesiaMinnu Panditrao
Prof. Minnu Panditrao shares her own ideas about the use dexmedetomidine for various indications i.e. for sedation, intra and post operative analgesia.
Sedation & Paralysis in ICU- DR.RAGHUNATH ALADAKATTIapollobgslibrary
This document discusses analgesia, sedation, and neuromuscular blockade in the ICU. It covers the reasons these drugs are used, including relieving pain, anxiety, and stress from mechanical ventilation. Opioids, benzodiazepines, propofol and ketamine are some of the classes of drugs discussed for providing analgesia and sedation. Monitoring sedation levels and protocols like daily sedation interruptions are recommended. Neuromuscular blockade drugs are also briefly covered, noting their uses for intubation and mechanical ventilation.
This document provides an overview of procedural sedation and analgesia (PSA). It discusses the general approach, including contraindications, prerequisites, monitoring, and medications used. Common sedative medications like propofol, etomidate, ketamine, midazolam, and fentanyl are described in terms of their pharmacodynamics, pharmacokinetics, dosing, and side effects. The document provides guidance on selecting appropriate medications based on the type of procedure and patient characteristics or comorbidities.
This document discusses procedural sedation and analgesia (PSA). It defines PSA as the administration of sedatives or dissociative anesthetics to induce a depressed level of consciousness while maintaining cardiorespiratory function and little to no patient reaction or memory. It describes different levels of sedation from minimal to deep and lists example procedures and agents used for each level. It provides guidance on patient evaluation, risks, monitoring, step-by-step technique, sedation agents and their risks, and follow up instructions.
Pharmacology of sedative drugs (30 08-15)wgalal1971
The document discusses drugs used for conscious sedation in adults and pediatrics. It provides dosing guidelines for midazolam, diazepam, fentanyl, morphine, meperidine, thiopental, ketamine, and propofol. Key points include:
- Midazolam, diazepam and fentanyl are commonly used options that provide anxiolysis, sedation and analgesia.
- Drug selection depends on the required effects and patient characteristics. Lower doses are recommended for the elderly, debilitated, or when multiple CNS depressants are used.
- All sedatives can cause respiratory depression, so monitoring
This document discusses procedural sedation and analgesia (PSA) in the emergency department. It outlines reasons why pain is sometimes inadequately treated, including fear of over-sedation and lack of knowledge. It then discusses indications, standards of care, preprocedural fasting, contraindications, risk reduction strategies, commonly used drugs and their dosages for both adults and pediatrics, special considerations for the elderly/comorbid patients and pregnancy, complications, and details specific drugs including propofol, etomidate, and benzodiazepines like midazolam. Monitoring, aspiration risk, and various levels of sedation are also covered.
Decreasing risks of conscious sedation (7 12-14)wgalal1971
The document discusses the risks associated with conscious sedation during medical procedures. It notes that while the overall complication rate is low at 13.5 events per 1,000 procedures, certain factors can increase risk such as the use of multiple sedating agents, opioids, advanced sedation techniques, and patient-related factors like obesity or underlying medical conditions. It emphasizes the importance of careful patient selection, monitoring, and preparedness to manage complications in order to minimize risks and prevent serious adverse events during conscious sedation.
This document provides guidelines for sedation, analgesia, and neuromuscular blockade in the adult intensive care unit (ICU). It describes the benefits of daily awakening and sedation titration programs. It discusses assessing and treating pain, and the consequences of untreated pain. It reviews sedation and analgesia options like opioids, benzodiazepines, propofol, and neuromuscular blocking agents. It also addresses delirium screening, risk factors, and treatment options. The optimal level of sedation allows for patient interaction while maintaining comfort. Daily awakening and titrating sedation to the minimum required level can reduce ICU and ventilation times.
Staff nurses' perception of medication errors, perceived causes, and reportin...Reynel Dan
The document discusses a research paper on staff nurses' perceptions of medication errors. Specifically, it examines their perception of errors, perceived causes, and reporting behaviors. The paper provides background on medication errors being a major cause of preventable deaths. It discusses theories that guide the study and defines key terms. Overall, the paper aims to understand nurses' views and behaviors regarding medication errors to improve policies and reduce errors and associated costs and deaths.
This document discusses principles of conscious sedation for pediatric patients. It begins by introducing conscious sedation and its increasing use for painful procedures in non-traditional settings. The purpose is to familiarize providers with standards for safe and effective pediatric moderate sedation. Key points discussed include: the procedural sedation continuum; increased risks for children requiring deeper sedation than adults; importance of patient evaluation, monitoring, and rescue skills; and guidance on supervision, staffing, equipment and disposition for safe sedation. Specific considerations are outlined for sedation agents, levels of practitioner training, and factors to consider for each sedation case.
Conscious sedation is a minimally depressed level of consciousness using drugs like nitrous oxide and oxygen mixtures, fentanyl, diazepam or midazolam to relieve anxiety while maintaining the patient's ability to independently maintain their airway and respond to verbal commands. It has objectives of keeping vital signs stable, making the patient cooperative while conscious, increasing their pain threshold, and providing amnesia. It is commonly used for uncooperative or anxious patients and can be delivered enterally, parenterally, transdermally or via inhalation with monitoring of oxygen levels, ventilation and vital signs. Nitrous oxide is often used due to its rapid onset and recovery through 4 phases.
1) Intravenous sedation involves using sedatives and analgesics in small doses to depress consciousness while maintaining breathing and response to commands.
2) Nurses must be competent in administering sedation, including assessing patients before, during, and after procedures while monitoring vitals like breathing and oxygen levels.
3) The proper equipment and medications must be available in case issues arise during conscious sedation.
Sedation and general anesthesia in dentistryAkram Nasher
The document discusses sedation and general anesthesia techniques used in dentistry. It describes four levels of anesthesia from local anesthesia to general anesthesia. For sedation techniques, it covers oral, inhalational and intravenous sedation. For oral sedation it discusses drugs, factors influencing absorption and advantages and disadvantages. For inhalational sedation it focuses on nitrous oxide use and equipment. Intravenous sedation outlines commonly used drug combinations. Risks, indications and administration techniques are also outlined. The document provides a detailed overview of sedation and anesthesia in dentistry.
Sedation monitoring and post sedation recovery and dischargetaem
This document outlines guidelines for procedural sedation and analgesia. It recommends having appropriate monitoring equipment and administering analgesics before sedatives. Patients should be monitored until recovery to their baseline mental status. At minimum, procedural sedation requires one clinician to perform the procedure while another continuously monitors the patient. Regular monitoring of vital signs, oxygen saturation, and ventilation is important. The use of capnography may help detect respiratory complications earlier than pulse oximetry alone. Patients must meet discharge criteria related to symptoms, vital signs, and orientation before being discharged.
This document provides an introduction to conscious sedation, including the objectives, responsibilities, equipment, medications, and patient risk factors involved. The key points are:
1) Conscious sedation requires careful monitoring as patients can easily slip into deeper sedation, so providers must be prepared to rescue patients and understand sedation levels.
2) Responsibilities include proper patient assessment, monitoring, documentation, discharge criteria and patient education.
3) A hospital policy is needed to outline privileged providers, areas, equipment, monitoring requirements and discharge standards.
4) Patient safety is the top priority, requiring policy, screening, monitoring during and after procedures, and prudent sedation administration combined with vigilant monitoring.
The document discusses several classes of sedative-hypnotic drugs including benzodiazepines, barbiturates, and other nonbarbiturate sedative-hypnotics. Benzodiazepines act by enhancing the effects of the inhibitory neurotransmitter GABA at GABA-A receptors and have a wide margin of safety. Barbiturates also enhance GABA effects but are no longer recommended due to their narrow therapeutic range and potential for abuse and dependence. Chloral hydrate is a relatively safe nonbarbiturate hypnotic used in some patient populations.
Sedatives and hypnotics drugs ppt by kashikant yadavKashikant Yadav
Sedatives and hypnotics are central nervous system depressants that are used to induce sleep or reduce anxiety. Barbiturates were previously commonly used but have largely been replaced by benzodiazepines due to lower risks of dependence and overdose. Both classes of drugs work by enhancing the effects of the inhibitory neurotransmitter GABA. Sedatives primarily reduce anxiety and excitement while hypnotics are used to induce sleep. Common side effects include drowsiness, dizziness, and impaired coordination. Tolerance can develop with repeated use of both barbiturates and benzodiazepines.
Briefly describe sedative hypnotic drug with their classification and mechanism , therapeutic effect , adverse effect and dose preparation . this presentation is useful for pharma student .
This document discusses sedatives and hypnotics, including their mechanisms of action, classifications, and examples. It focuses on barbiturates and benzodiazepines. Barbiturates act by enhancing GABA activity in the brain, leading to CNS depression. They are classified based on duration of action and therapeutic use. Common side effects include dependence and withdrawal. Benzodiazepines also enhance GABA activity and are used as anxiolytics, for seizures, and to treat sleep disorders. They are classified based on duration of action from long to short acting.
This document discusses anxiolytics and hypnotics, specifically focusing on barbiturates and benzodiazepines. It covers their history, classifications, mechanisms of action, pharmacokinetics, therapeutic uses, adverse effects, and treatment of overdoses. Barbiturates were originally used as sedatives but were replaced by benzodiazepines in the 1990s due to benzodiazepines having a better safety profile with less dependence and abuse potential. Both classes of drugs work by enhancing the effects of the neurotransmitter GABA.
The central nervous system directs bodily functions and processes sensory information. Sedative-hypnotic drugs like benzodiazepines and barbiturates depress nervous system activity by enhancing the effects of the inhibitory neurotransmitter GABA. Benzodiazepines are generally safer with less severe side effects than barbiturates. Both can cause tolerance, dependence, and dangerous respiratory depression in overdose.
The document discusses psychoactive drugs and the synthesis of barbiturates and phenobarbital. It defines psychoactive drugs as chemicals that alter mood, behavior, and perceptions. It describes the four main types - stimulants, depressants, narcotics, and hallucinogens. It then focuses on barbiturates, describing their synthesis, mechanism of action by enhancing the GABA neurotransmitter, and uses including epilepsy treatment. Finally, it discusses phenobarbital as a long-acting barbiturate used for seizures, its synthesis, mechanism of action, uses, and disadvantages like withdrawal risks.
torture drugs introductory and example.pptxSonuThorve
Pentobarbital is a barbiturate drug that is used as a preanesthetic, sedative, and to control seizures. It works by enhancing the effects of the inhibitory neurotransmitter GABA in the brain, which decreases neuronal activity and causes sedation, hypnosis, and amnesia. Pentobarbital can be administered intramuscularly, intravenously, or orally. While it has medical uses, it is also used in lethal injections for capital punishment in some countries. Side effects include respiratory depression, low heart rate, dizziness, and nausea.
This document discusses different classes of sedative and hypnotic drugs, including their mechanisms of action, pharmacokinetics and therapeutic uses. It covers barbiturates, benzodiazepines, zolpidem, and buspirone. Barbiturates and benzodiazepines enhance the effects of the inhibitory neurotransmitter GABA, whereas zolpidem selectively binds to GABA receptors. These drugs have varying onset and duration of action and are used to treat conditions like anxiety, insomnia and seizures. Adverse effects include respiratory depression, dependence and withdrawal symptoms.
Sedatives & Hypnotics
Sedatives
➢ It is a drug that reduces excitement and calms the person
➢ A drug that reduces excitement, calms the patient (without inducing sleep)
➢ Sedatives in therapeutic doses are anxiolytic agents
➢ Most sedatives in larger doses produce hypnosis (trans like state in which
subject becomes passive and highly suggestible)
Pharmacodynamics of benzodiazepines, barbiturates and newer hypnoticsDomina Petric
The document discusses the pharmacology of benzodiazepines, barbiturates, and newer hypnotics. It describes how these drugs bind to GABAA receptors in the central nervous system to potentiate the effects of the neurotransmitter GABA. This leads to sedation, hypnosis, anesthesia, anticonvulsant effects, muscle relaxation and other actions by enhancing chloride channel opening. Tolerance and dependence can develop with long-term use of these sedative-hypnotic drugs.
This document summarizes several newer narcotics and drugs of abuse, including their mechanisms of action, uses, and health effects. It discusses dextropropoxyphene (Darvon), an opioid pain reliever that is addictive and causes dependence. It also covers buprenorphine, used to treat opioid addiction, ketamine and PCP which are dissociative anesthetics, and LSD, mescaline and psilocybin which are hallucinogenic. Finally, it provides information on cannabinoids like THC, GHB, and several opioid antagonists such as nalbuphine, dezocine, naltrexone, and nalmefene.
This document discusses different types of general anesthetics. It begins by defining general anesthesia and describing its stages. It then covers various classes of general anesthetics including inhalation anesthetics like nitrous oxide and halothane, ultra short-acting barbiturates like thiopental sodium, dissociative anesthetics like ketamine, and narcotic and non-narcotic analgesics. For each type, it provides details on properties, mechanisms of action, advantages, and synthesis when applicable. The document aims to provide an overview of common general anesthetics used in medical practice.
Sedative-hypnotic drugs reduce anxiety and induce sleep by depressing activity in the central nervous system. The main classes are benzodiazepines, barbiturates, and newer non-benzodiazepine agents. Benzodiazepines have largely replaced barbiturates due to their wider therapeutic index, lower risk of interactions and dependence, and the availability of antagonists. Both benzodiazepines and barbiturates work by enhancing the effects of the inhibitory neurotransmitter GABA.
General anesthetics provide amnesia, analgesia, muscle relaxation and sedation, placing the patient in a reversible state of unconsciousness. There are inhalational agents like nitrous oxide, halothane, enflurane and isoflurane, and intravenous agents like propofol, ketamine and thiopental. They work mainly by enhancing the effect of the inhibitory neurotransmitter GABA at GABAA receptors. Different agents have advantages and disadvantages related to their potency, metabolism, effects on vital organs and side effects. Careful selection of agents and monitoring is required for safe anesthesia.
Quazi Istiaque Bari presented on sedative and hypnotic drugs. The presentation covered the differences between sedatives and hypnotics, including their sites of action and effects. It also discussed dose response curves, the structures of benzodiazepines and barbiturates, and the pharmacokinetics of sedative hypnotic drugs. The presentation provided an overview of sedative and hypnotic drugs for a pharmacology course.
This document summarizes information about sedatives and hypnotics. It defines sedatives as drugs that reduce excitement and calm patients without inducing sleep, while hypnotics produce sleep resembling natural sleep. Both act by facilitating GABAergic transmission. Common classes discussed are benzodiazepines, barbiturates, antihistamines, and other sedative-hypnotics. Their mechanisms, clinical uses, and side effects are compared. Sedatives are used to relieve anxiety, while hypnotics induce sleep. Toxic doses can depress respiration and blood pressure, potentially causing death.
This document provides information about sedatives and hypnotics. It defines sedatives as drugs that reduce excitement and calm patients without inducing sleep, while hypnotics produce sleep resembling natural sleep. Both act through facilitating GABA neurotransmission. Common classes discussed are benzodiazepines, barbiturates, antihistamines, and other newer non-benzodiazepine drugs. Their mechanisms, clinical uses, and side effects are explained. Sedatives are used to relieve anxiety and cause sedation, while hypnotics are used for sleep initiation or maintenance.
5th LF Energy Power Grid Model Meet-up SlidesDanBrown980551
5th Power Grid Model Meet-up
It is with great pleasure that we extend to you an invitation to the 5th Power Grid Model Meet-up, scheduled for 6th June 2024. This event will adopt a hybrid format, allowing participants to join us either through an online Mircosoft Teams session or in person at TU/e located at Den Dolech 2, Eindhoven, Netherlands. The meet-up will be hosted by Eindhoven University of Technology (TU/e), a research university specializing in engineering science & technology.
Power Grid Model
The global energy transition is placing new and unprecedented demands on Distribution System Operators (DSOs). Alongside upgrades to grid capacity, processes such as digitization, capacity optimization, and congestion management are becoming vital for delivering reliable services.
Power Grid Model is an open source project from Linux Foundation Energy and provides a calculation engine that is increasingly essential for DSOs. It offers a standards-based foundation enabling real-time power systems analysis, simulations of electrical power grids, and sophisticated what-if analysis. In addition, it enables in-depth studies and analysis of the electrical power grid’s behavior and performance. This comprehensive model incorporates essential factors such as power generation capacity, electrical losses, voltage levels, power flows, and system stability.
Power Grid Model is currently being applied in a wide variety of use cases, including grid planning, expansion, reliability, and congestion studies. It can also help in analyzing the impact of renewable energy integration, assessing the effects of disturbances or faults, and developing strategies for grid control and optimization.
What to expect
For the upcoming meetup we are organizing, we have an exciting lineup of activities planned:
-Insightful presentations covering two practical applications of the Power Grid Model.
-An update on the latest advancements in Power Grid -Model technology during the first and second quarters of 2024.
-An interactive brainstorming session to discuss and propose new feature requests.
-An opportunity to connect with fellow Power Grid Model enthusiasts and users.
Monitoring and Managing Anomaly Detection on OpenShift.pdfTosin Akinosho
Monitoring and Managing Anomaly Detection on OpenShift
Overview
Dive into the world of anomaly detection on edge devices with our comprehensive hands-on tutorial. This SlideShare presentation will guide you through the entire process, from data collection and model training to edge deployment and real-time monitoring. Perfect for those looking to implement robust anomaly detection systems on resource-constrained IoT/edge devices.
Key Topics Covered
1. Introduction to Anomaly Detection
- Understand the fundamentals of anomaly detection and its importance in identifying unusual behavior or failures in systems.
2. Understanding Edge (IoT)
- Learn about edge computing and IoT, and how they enable real-time data processing and decision-making at the source.
3. What is ArgoCD?
- Discover ArgoCD, a declarative, GitOps continuous delivery tool for Kubernetes, and its role in deploying applications on edge devices.
4. Deployment Using ArgoCD for Edge Devices
- Step-by-step guide on deploying anomaly detection models on edge devices using ArgoCD.
5. Introduction to Apache Kafka and S3
- Explore Apache Kafka for real-time data streaming and Amazon S3 for scalable storage solutions.
6. Viewing Kafka Messages in the Data Lake
- Learn how to view and analyze Kafka messages stored in a data lake for better insights.
7. What is Prometheus?
- Get to know Prometheus, an open-source monitoring and alerting toolkit, and its application in monitoring edge devices.
8. Monitoring Application Metrics with Prometheus
- Detailed instructions on setting up Prometheus to monitor the performance and health of your anomaly detection system.
9. What is Camel K?
- Introduction to Camel K, a lightweight integration framework built on Apache Camel, designed for Kubernetes.
10. Configuring Camel K Integrations for Data Pipelines
- Learn how to configure Camel K for seamless data pipeline integrations in your anomaly detection workflow.
11. What is a Jupyter Notebook?
- Overview of Jupyter Notebooks, an open-source web application for creating and sharing documents with live code, equations, visualizations, and narrative text.
12. Jupyter Notebooks with Code Examples
- Hands-on examples and code snippets in Jupyter Notebooks to help you implement and test anomaly detection models.
Generating privacy-protected synthetic data using Secludy and MilvusZilliz
During this demo, the founders of Secludy will demonstrate how their system utilizes Milvus to store and manipulate embeddings for generating privacy-protected synthetic data. Their approach not only maintains the confidentiality of the original data but also enhances the utility and scalability of LLMs under privacy constraints. Attendees, including machine learning engineers, data scientists, and data managers, will witness first-hand how Secludy's integration with Milvus empowers organizations to harness the power of LLMs securely and efficiently.
Driving Business Innovation: Latest Generative AI Advancements & Success StorySafe Software
Are you ready to revolutionize how you handle data? Join us for a webinar where we’ll bring you up to speed with the latest advancements in Generative AI technology and discover how leveraging FME with tools from giants like Google Gemini, Amazon, and Microsoft OpenAI can supercharge your workflow efficiency.
During the hour, we’ll take you through:
Guest Speaker Segment with Hannah Barrington: Dive into the world of dynamic real estate marketing with Hannah, the Marketing Manager at Workspace Group. Hear firsthand how their team generates engaging descriptions for thousands of office units by integrating diverse data sources—from PDF floorplans to web pages—using FME transformers, like OpenAIVisionConnector and AnthropicVisionConnector. This use case will show you how GenAI can streamline content creation for marketing across the board.
Ollama Use Case: Learn how Scenario Specialist Dmitri Bagh has utilized Ollama within FME to input data, create custom models, and enhance security protocols. This segment will include demos to illustrate the full capabilities of FME in AI-driven processes.
Custom AI Models: Discover how to leverage FME to build personalized AI models using your data. Whether it’s populating a model with local data for added security or integrating public AI tools, find out how FME facilitates a versatile and secure approach to AI.
We’ll wrap up with a live Q&A session where you can engage with our experts on your specific use cases, and learn more about optimizing your data workflows with AI.
This webinar is ideal for professionals seeking to harness the power of AI within their data management systems while ensuring high levels of customization and security. Whether you're a novice or an expert, gain actionable insights and strategies to elevate your data processes. Join us to see how FME and AI can revolutionize how you work with data!
Fueling AI with Great Data with Airbyte WebinarZilliz
This talk will focus on how to collect data from a variety of sources, leveraging this data for RAG and other GenAI use cases, and finally charting your course to productionalization.
HCL Notes and Domino License Cost Reduction in the World of DLAUpanagenda
Webinar Recording: https://www.panagenda.com/webinars/hcl-notes-and-domino-license-cost-reduction-in-the-world-of-dlau/
The introduction of DLAU and the CCB & CCX licensing model caused quite a stir in the HCL community. As a Notes and Domino customer, you may have faced challenges with unexpected user counts and license costs. You probably have questions on how this new licensing approach works and how to benefit from it. Most importantly, you likely have budget constraints and want to save money where possible. Don’t worry, we can help with all of this!
We’ll show you how to fix common misconfigurations that cause higher-than-expected user counts, and how to identify accounts which you can deactivate to save money. There are also frequent patterns that can cause unnecessary cost, like using a person document instead of a mail-in for shared mailboxes. We’ll provide examples and solutions for those as well. And naturally we’ll explain the new licensing model.
Join HCL Ambassador Marc Thomas in this webinar with a special guest appearance from Franz Walder. It will give you the tools and know-how to stay on top of what is going on with Domino licensing. You will be able lower your cost through an optimized configuration and keep it low going forward.
These topics will be covered
- Reducing license cost by finding and fixing misconfigurations and superfluous accounts
- How do CCB and CCX licenses really work?
- Understanding the DLAU tool and how to best utilize it
- Tips for common problem areas, like team mailboxes, functional/test users, etc
- Practical examples and best practices to implement right away
How information systems are built or acquired puts information, which is what they should be about, in a secondary place. Our language adapted accordingly, and we no longer talk about information systems but applications. Applications evolved in a way to break data into diverse fragments, tightly coupled with applications and expensive to integrate. The result is technical debt, which is re-paid by taking even bigger "loans", resulting in an ever-increasing technical debt. Software engineering and procurement practices work in sync with market forces to maintain this trend. This talk demonstrates how natural this situation is. The question is: can something be done to reverse the trend?
Main news related to the CCS TSI 2023 (2023/1695)Jakub Marek
An English 🇬🇧 translation of a presentation to the speech I gave about the main changes brought by CCS TSI 2023 at the biggest Czech conference on Communications and signalling systems on Railways, which was held in Clarion Hotel Olomouc from 7th to 9th November 2023 (konferenceszt.cz). Attended by around 500 participants and 200 on-line followers.
The original Czech 🇨🇿 version of the presentation can be found here: https://www.slideshare.net/slideshow/hlavni-novinky-souvisejici-s-ccs-tsi-2023-2023-1695/269688092 .
The videorecording (in Czech) from the presentation is available here: https://youtu.be/WzjJWm4IyPk?si=SImb06tuXGb30BEH .
Introduction of Cybersecurity with OSS at Code Europe 2024Hiroshi SHIBATA
I develop the Ruby programming language, RubyGems, and Bundler, which are package managers for Ruby. Today, I will introduce how to enhance the security of your application using open-source software (OSS) examples from Ruby and RubyGems.
The first topic is CVE (Common Vulnerabilities and Exposures). I have published CVEs many times. But what exactly is a CVE? I'll provide a basic understanding of CVEs and explain how to detect and handle vulnerabilities in OSS.
Next, let's discuss package managers. Package managers play a critical role in the OSS ecosystem. I'll explain how to manage library dependencies in your application.
I'll share insights into how the Ruby and RubyGems core team works to keep our ecosystem safe. By the end of this talk, you'll have a better understanding of how to safeguard your code.
Digital Banking in the Cloud: How Citizens Bank Unlocked Their MainframePrecisely
Inconsistent user experience and siloed data, high costs, and changing customer expectations – Citizens Bank was experiencing these challenges while it was attempting to deliver a superior digital banking experience for its clients. Its core banking applications run on the mainframe and Citizens was using legacy utilities to get the critical mainframe data to feed customer-facing channels, like call centers, web, and mobile. Ultimately, this led to higher operating costs (MIPS), delayed response times, and longer time to market.
Ever-changing customer expectations demand more modern digital experiences, and the bank needed to find a solution that could provide real-time data to its customer channels with low latency and operating costs. Join this session to learn how Citizens is leveraging Precisely to replicate mainframe data to its customer channels and deliver on their “modern digital bank” experiences.
"Choosing proper type of scaling", Olena SyrotaFwdays
Imagine an IoT processing system that is already quite mature and production-ready and for which client coverage is growing and scaling and performance aspects are life and death questions. The system has Redis, MongoDB, and stream processing based on ksqldb. In this talk, firstly, we will analyze scaling approaches and then select the proper ones for our system.
Dandelion Hashtable: beyond billion requests per second on a commodity serverAntonios Katsarakis
This slide deck presents DLHT, a concurrent in-memory hashtable. Despite efforts to optimize hashtables, that go as far as sacrificing core functionality, state-of-the-art designs still incur multiple memory accesses per request and block request processing in three cases. First, most hashtables block while waiting for data to be retrieved from memory. Second, open-addressing designs, which represent the current state-of-the-art, either cannot free index slots on deletes or must block all requests to do so. Third, index resizes block every request until all objects are copied to the new index. Defying folklore wisdom, DLHT forgoes open-addressing and adopts a fully-featured and memory-aware closed-addressing design based on bounded cache-line-chaining. This design offers lock-free index operations and deletes that free slots instantly, (2) completes most requests with a single memory access, (3) utilizes software prefetching to hide memory latencies, and (4) employs a novel non-blocking and parallel resizing. In a commodity server and a memory-resident workload, DLHT surpasses 1.6B requests per second and provides 3.5x (12x) the throughput of the state-of-the-art closed-addressing (open-addressing) resizable hashtable on Gets (Deletes).
Discover top-tier mobile app development services, offering innovative solutions for iOS and Android. Enhance your business with custom, user-friendly mobile applications.
Crafting Excellence: A Comprehensive Guide to iOS Mobile App Development Serv...
11. pharmacology (autosaved)
1. Pharmacology of Commonly Used Drugs in Conscious Sedation
PHARMACOLOGY OF COMMONLY
USED DRUGS IN CONSCIOUS
SEDATION
Conscious Sedation 67
2. Pharmacology of Commonly Used Drugs in Conscious Sedation
BARBITURATES
Barbiturates are those agents that may pharmacologically be described as “sedative-
hypnotics”. Chemically, they are derivatives of barbituric acid or malonyl urea, which is a
combination of malonic acid and urea. Barbituric acid itself has no hypnotic properties, but
replacement of hydrogen by various radicals produces many different drugs processing hypnotic
characteristics. The new compounds are varied in their actions, both the potency and duration of
action being markedly affected by the different substitutions.
The barbiturates may be divided into two categories based on the chemical structure.
Those compounds having oxygen attached to the carbon of the urea component are properly
termed barbiturates. They are frequently referred to as oxybarbiturates to distinguish them from
those of the second category, the thiobarbiturates - which have a sulfur atom in place of the
oxygen. Although the pharmacology of all barbiturates is essentially similar they differ in
potency, duration, and intensity of effect. Thiobarbiturates possess a greater degree of fat
solubility, and are more rapid in onset, have shorter duration of action, and are somewhat more
toxic than the oxybarbiturates. 93
The barbiturates are general depressants; they depress the activity of nerve, skeletal
muscle, smooth muscle, cardiac muscle, and the central nervous system. However, it must be
emphasized that the central nervous system is exquisitely sensitive to depression by barbiturates;
as a result, when these drugs are administered in therapeutic doses, the effects on other structures
are absent or negligible. All degrees of depression of the central nervous system are possible,
ranging from mild sedation to general anesthesia or to coma.
Conscious Sedation 68
3. Pharmacology of Commonly Used Drugs in Conscious Sedation
Drugs in this category appear to act at all levels of neuraxis. There is a complex,
interrelated group of pathways coursing through the reticular formation of the midbrain and
medulla and extending anteriorly into the thalamus and hypothalamus – the “reticular activating
system.” This system is very sensitive to the depressant effects of sedative hypnotic drugs. It is
their effect on the reticular system that seems to be responsible for the inability to maintain
wakefulness under the influence of these compounds. The cerebral cortex is among structures
most sensitive to these drugs, since they do depress cerebral function as evidenced by release of
inhibitions and the production of amnesia in the conscious patient. 93
Barbiturates can be classified based on the time of onset and duration of action into
four groups: 93
1. Ultra short acting: The ultra short acting barbiturates most commonly used are thiopental
sodium, thiamylal sodium, and methohexital sodium. With the exception of thiopental
these drugs are administered exclusively by the intravenous route for the production of
conscious sedation. They possess the shortest duration of action and are also the most
potent barbiturates available. With all drugs in this group the peak effect after intravenous
administration will be realized in 30 to 60 seconds. Sedative effect will be present for 5 to
7 minutes for methohexital, the shortest acting and most potent barbiturate, and for 10 to
15 minutes with thiopental and thiamylal.
Thiopental is the only agent in this group that may be administered by any
route other than the intravenous. A rectal suspension is available that when instilled
rectally in doses of no more than 10 to 14mg. per pound will produce sedation in 8 to 10
minutes. This method is particularly useful in apprehensive children. Duration will be
about 30 to 60 minutes.
Conscious Sedation 69
4. Pharmacology of Commonly Used Drugs in Conscious Sedation
2. Short acting barbiturates: The short acting barbiturates most commonly used are
pentobarbital and secobarbital. They may be administered orally, intramuscularly, or
intravenously. These drugs are particularly useful via the intravenous route for the
production of conscious sedation, either as a sole agent or in combination with other
central nervous system depressants. When used alone intravenous dose range usually is
from 50 to 100 mg. lower doses must be employed when used these drugs are used in
conjugation with psycho sedatives and / or narcotic analgesics. Duration of sedation via
the intravenous route will range from 2 to 3 hours.
Short acting barbiturates are also of value when administered via the
oral route to provide the patient with a restful sleep the night before his dental
appointment. Depending on the individual, the oral dose will range from 50 to 200 mg.
the drug will require 30 to 45 minutes for its maximum effectiveness and will have
duration of 4 to 6 hours. Providing the patient with a restful sleep the night before his
appointment will allow him to arrive at the office well rested and thus with an elevated
pain reaction threshold.
3. Intermediate acting barbiturates: The intermediate acting barbiturates most commonly
used are amobarbital, aprobarbital, and butabarbital. They are administered via the oral
route only and effective in 45minutes to one hour. Duration will range from 6 to 8 hours.
They may be used to best advantage on the night before the appointment to aid the patient
in obtaining a good night‟s rest.
4. Long acting barbiturates: The long acting barbiturates most commonly used are barbital
sodium and Phenobarbital. These agents are indicated for oral administration only and,
Conscious Sedation 70
5. Pharmacology of Commonly Used Drugs in Conscious Sedation
because of their long duration of 8 to 10 hours, are seldom if ever indicated in dental
practice.
PENTOBARBITAL
Pentobarbital is an oxybarbiturate and is one of the most frequently used barbiturates for
pediatric sedation. Pentobarbital is a barbiturate with no inherent analgesic properties that
produces profound sedation, hypnosis, amnesia, and anticonvulsant activity in a dose dependent
fashion. With intravenous titration, sedation is evident in 3–5 min with duration of roughly 30–
40 min. Like other barbiturates, pentobarbital can lead to respiratory depression and hypotension.
In many centers, pentobarbital is the intravenous sedative of choice for diagnostic imaging in
children, and is regarded as better than midazolam or chloral hydrate for this indication. 95
METHOHEXITAL AND THIOPENTAL
When given intravenously, both methohexital and thiopental produce effective sedation within 1
min and induce potent respiratory depression in the same manner as propofol and intimidate.
Clinical recovery is rapid (about 15 min). The depth of sedation achieved in existing small series
is not well described, but seems to be at or beyond levels consistent with deep sedation.
Barbiturates are rapidly absorbed rectally and methohexital or thiopental given by this route can
reliably produce anxiolysis and sedation suitable for CT or MRI scanning. Although respiratory
depression is unusual with typical doses, it can occur.
When transporting patients who have received pentobarbital, methohexital, or thiopental
from a more controlled location such as the emergency department to a radiology suite, vigilance
is required to maintain adequate monitoring and to ensure that skilled personnel remain available
Conscious Sedation 71
6. Pharmacology of Commonly Used Drugs in Conscious Sedation
to manage airway complications. Barbiturates are rapidly absorbed rectally and methohexital or
thiopental given by this route can reliably produce anxiolysis and sedation suitable for CT or
MRI scanning. Although respiratory depression is unusual with typical doses, it can occur.95
BENZODIAZEPENES
Mode of action:
Binding of gamma – aminobutyric acid (GABA) to its receptor on the cell membrane triggers an
opening of a chloride channel, which leads to an increase in chloride conductance. The influx of
chloride ions causes a small hyper polarization that moves the post- synaptic potential away from
its firing threshold and thus inhibits the formation of action potential away from its firing
threshold and thus inhibits the formation of action potentials. Benzodiazepines bind to specific,
high affinity sites on the cell membrane, which are separate from but adjacent to the receptor for
GABA.93
The benzodiazepine receptors are found only in the central nervous system, and their
location parallels that of the GABA neurons. The binding of benzodiazepines enhances the
Conscious Sedation 72
7. Pharmacology of Commonly Used Drugs in Conscious Sedation
affinity of GABA receptors for this neurotransmitter, resulting in a more frequent opening of
adjacent chloride channel. This in turn results in hyper polarization and further inhibition of
neuronal firing. Benzodiazepines and GABA mutually increase the affinity of their binding sites
without actually changing the total number of sites. The clinical effects of the various
benzodiazepines correlate well with each drug‟s binding affinity for the GABA receptor-
chloride ion channel complex.93
At low doses, the benzodiazepines are anxiolytic. They are thought to reduce anxiety
by selectively inhibiting neuronal circuits in the limbic system of the brain. All of the
benzodiazepines used to treat anxiety have some sedative properties. At higher doses, certain
benzodiazepines produce hypnosis.
Uses:
Primary therapeutic effects of benzodiazepines include sedation, anxiolysis, and anterograde
amnesia – all beneficial for the treatment of the fearful pediatric dental patient. These drugs
possess muscle relaxant and anti-convulsant properties as well. 93
Conscious Sedation 73
8. Pharmacology of Commonly Used Drugs in Conscious Sedation
Adverse Effects:
Benzodiazepines demonstrate a wide margin of safety and a wide therapeutic index which
represents the dosage difference between an effective dose and a lethal dose. Its onset and
duration of action are relatively short when compared with other orally administered sedatives.
Minimal adverse reactions are associated with these drugs, and a reversible agent is available.
Benzodiazepines administered alone can cause respiratory depression, an effect that is amplified
when given in combination with opioids. Moreover, this synergistic effect causing significant
respiratory depression can also occur when benzodiazepines are administered in the presence of
other CNS depressants such as a patient‟s own medications.
Physiological effects may include nausea, vomiting and/or unsteady movements
(ataxia). This latter condition can manifest as a loss of head control, leading to a compromise of
the patient‟s airway. Other undesirable responses may include a paradoxical or angry response,
whereby the patient appears irritable, agitated and/or combative. Benzodiazepines should be
avoided in patients with acute narrow angle glaucoma, and are contraindicated for patients with a
known allergy or hypersensitivity to them or any of their components. 93
DIAZEPAM
Diazepam is a benzodiazepine derivative. The chemical name of diazepam is 7-chloro-1, 3-
dihydro-1-methyl-5-phenyl-2H-1, 4-benzodiazepin-2-one. It is a colorless to light yellow
crystalline compound. The empirical formula is C16H13ClN2O and the molecular weight is
284.75. The structural formula is as follows:96
Conscious Sedation 74
9. Pharmacology of Commonly Used Drugs in Conscious Sedation
A benzodiazepine that is lipid soluble and water insoluble. It is readily absorbed from the
gastro intestinal tract, reaching peak levels at 2 hours. Biotransformation of the drug occurs quite
slowly and it has a half life of 20 to 50 hours. The drug has three active metabolites, one of
which is also very lipophilic and has a half life of 96 hours. These metabolites are anxiolytic than
sedative.
After intravenous administration, diazepam is redistributed within 30 to 45 minutes,
and the patient seems not to be sedated although free from anxiety. The patient should not be
considered recovered from the drug. It has simply been redistributed. In fact stored drug can be
redistributed to the CNS by a fatty meal consumed sometime later and the patient will suddenly
feel resedated. This is referred to as rebound effect.
Diazepam has strong anticonvulsant activity and provides some prophylaxis against this
adverse reaction of other drugs during the operative procedure. Diazepam can be administered
orally, rectally, or parenterally. If the intravenous route is selected, use of a large vein and slow
administration is recommended because the drug‟s propensity to cause irritation of the vein, with
resultant thrombophlebitis. In addition rapid administration may result in apnea. Ataxia and
prolonged CNS effects are the only common adverse reactions that can be anticipated when
diazepam is used for conscious sedation. 97
Conscious Sedation 75
10. Pharmacology of Commonly Used Drugs in Conscious Sedation
Dosage:
Oral or rectal – 0.2to 0.5 mg/kg to a maximum single dose of 10mg
Intravenous – 0.25mg/kg
Supplied as:
Tablets – 2, 5, and 10 mg
Suspension- 5mg/ml
MIDAZOLAM
Midazolam HCL first was synthesized by Fryer and Walser in 1976. Midazolam is a short-
acting, water-soluble benzodiazepine. It has anxiolytic, sedative, hypnotic, anticonvulsant,
muscle-relaxant, and anterograde amnesic effects. The drug has been used as a preanesthetic
sedative in adults, and more recently in children. Chemically, midazolam HCl is 8-chloro-6-(2-
fluorophenyl)-1-methyl-4 H -imidazo [1, 5-a] [1, 4] benzodiazepine hydrochloride. Midazolam
hydrochloride has the molecular formula C18H13ClFN3•HCl, a calculated molecular weight of
362.25 and the following structural formula: 96
Midazolam is imidazo benzene with unique properties when compared with other
benzodiazepines. It is water soluble in its acid formulation but is highly lipid soluble in vivo.
Midazolam also has a relatively rapid onset of action and high metabolic clearance when
Conscious Sedation 76
11. Pharmacology of Commonly Used Drugs in Conscious Sedation
compared with other benzodiazepines. The drug produces reliable hypnosis, amnesia, and anti
anxiety effects when administered orally, intramuscularly, or intravenously. There are many uses
for midazolam in the peri operative period including premedication, anesthesia induction and
maintenance, and sedation for diagnostic and therapeutic procedures. Clinical advantages of
midazolam are: 98
1. Water soluble
2. Rapid onset
3. Short acting
4. Anticonvulsant, muscle relaxant
5. Anterograde amnesia
6. Clinically inactive metabolites
7. Relatively high margin of safety
8. Reversal agent available
9. May be administered intra nasally
Like most drugs, its onset of action varies greatly depending upon its route of
administration. Intravenous administration will result in the most rapid onset of action due to its
immediate deposit into a patient‟s circulation. However, when administered orally, the drug is
exposed to metabolic clearance mechanisms in the intestine and liver, and will take longer to
produce its pharmacological effects pending its eventual deposit into the circulatory system and
action at receptors.
For pediatric dental patients, it is commonly administered orally, in doses of 0.25 –
0.75 mg/kg, with an upper limit of up to 1.0 mg/kg. An effective dose is usually 0.5 mg/kg and
should not exceed the maximally recommended dose of mg. In obese children, the dose should
Conscious Sedation 77
12. Pharmacology of Commonly Used Drugs in Conscious Sedation
be calculated based on ideal body weight. When supplied as an oral formulation, the bitter taste
often requires an accompanying flavoring agent, (i.e. apple juice) for patient acceptance. In order
to enhance analgesia, the sedative can be mixed with an acetaminophen elixir, at a dosage of 15
mg/kg. The oral form of midazolam has a cherry flavored vehicle that can be mixed with
children‟s flavored aspirin or acetaminophen to increase the palatability.84
Intravenous midazolam is highly lipid soluble and redistributes rapidly.
Consequently intravenous midazolam can be titrated to effect with fractionated doses of 0.05-0.1
mg/kg that may be repeated at intervals of 3 to 4 minutes. As opposed to the oral route of
administration, intravenous midazolam reaches peak effect in 2 to 3 minutes. Slow intravenous
administration is recommended with close observation for respiratory depression. When
combined with intravenous opioids for painful procedures, midazolam has potent sedative effects
and the use of cardio-respiratory monitoring is imperative. A maximum intravenous dose of 0.05
88
mg/kg has been recommended when combining the drug with narcotics.
Anterograde amnesia is even more prominent than when the drug is used orally.
Slurred speech has been shown to coincide with the onset of anterograde amnesia. Certain
underlying conditions or medications may prolong the effects of midazolam. Heparin decreases
protein binding and increases the free fraction. Hepatic metabolism is inhibited by cimetidine,
which prolongs the elimination half-life. Intravenous midazolam is an excellent agent for
sedation and anxiolysis in patients for minor procedures when an intravenous line is in place. It
provides complementary sedation for patients receiving opioids for very painful procedures due
to synergy but extreme caution is warranted when combining the drugs due to respiratory
depression.
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13. Pharmacology of Commonly Used Drugs in Conscious Sedation
Midazolam may be given as an intramuscular bolus of 0.08-0.1 mg/kg. Good
sedation and cooperation scores were recorded at 15 minutes after this dose in one study.
Persistent sedation is minimal 60 minutes after the dose. Midazolam gives reliable sedation after
intramuscular dosing - a useful alternative for children who will not accept oral medications,
particularly where residual sedation is a concern.84
Midazolam may be given by the intranasal route at doses of 0.2-0.4mg/kg. Onset
time is intermediate between the oral and intravenous routes of administration (10-15 minutes).
The effectiveness of this route of administration is well established as a pre - medicant for
anesthesia but its use is limited by burning on application to the nasal mucosa which most
children find very objectionable, as well as the bitter taste of midazolam reaching the
oropharynx. Adverse effects including respiratory depression and synergy with opioids are
similar to those mentioned above. For sedation and anxiolysis in young children who either
refuse or cannot take an oral dose of midazolam. Onset is reliable but most children will only
accept this route of administration once.97
Midazolam may be administered rectally at doses of 0.3-0.75 mg/kg. A dose of 0.3
mg/kg has been shown to give reliable levels of sedation with a mean time of 16 minutes to
maximal blood level. Rectal administration is generally not as well tolerated in children > 3 years
of age. After thirty minutes, blood levels were generally low but sedation and anxiolysis effects
remain.84
Dosage: Oral – 0.25 to 1.0 mg/kg to a maximum single dose of 20mg;
Intramuscular – 0.1 to 0.15 mg/kg to a maximum dose of 10 mg;
Intravenous – slow titration;
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14. Pharmacology of Commonly Used Drugs in Conscious Sedation
Supplied as: Syrup-2mg/ml;
Injectable – 1- and 5mg/ml vials
BENZODIAZEPINE ANTAGONIST: FLUMAZENIL
One of the benefits of using benzodiazepines is the ability to reverse possible undesirable effects
such as oversedation. Flumazenil is a benzodiazepine antagonist, acting competitively at the
benzodiazepine site of the GABA receptor, but without altering its morphology. Chemically,
flumazenil is ethyl 8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo [1, 5-a] (1, 4)
benzodiazepine-3-carboxylate. Flumazenil has an imidazobenzodiazepine structure, a calculated
molecular weight of 303.3, and the following structural formula: 96
Flumazenil is a white to off-white crystalline compound with an octanol: buffer partition
coefficient of 14 to 1 at pH 7.4. It is insoluble in water but slightly soluble in acidic aqueous
solutions.
This reversal agent is typically administered intravenously and its onset of action is
usually within 1 minute. The first dose administered is 0.01 mg/kg with a maximum dose of 0.2
mg. Doses should be administered slowly over 15-30 seconds, and may be repeated every minute
at 0.01 mg/kg for up to 5 doses or a maximum cumulative dose of 1.0 mg. The duration of action
of flumazenil is about 30 minutes, less than the half life of the benzodiazepine being reversed.
Therefore, the patient should be carefully monitored after its administration for any signs of
Conscious Sedation 80
15. Pharmacology of Commonly Used Drugs in Conscious Sedation
resedation and hypoventilation. If such undesirable signs occur, another dose may be required or
an infusion may need to be initiated.97
For reversal of sedation, the initial dose should be 0.01 mg/kg (up to 0.2 mg) given over
15 seconds. If the desired level of consciousness does not occur after waiting an additional 45
seconds, another dose of 0.01 mg/kg (up to 0.2 mg) should be administered and dosing repeated
at 60-second intervals to a maximum total dose of 0.05 mg/kg or 1 mg, whichever is lower. Most
patients respond to doses in the range of 0.6 to 1.0 mg. A series of injections is preferable to a
single bolus to titrate to a desired end point and thus manage the problem with the minimally
effective amount of drug. Onset of reversal is usually seen within 1 to 2 minutes. 88
The duration and degree of reversal are related to dose and plasma concentration of
the sedating benzodiazepine, as well as that of the antagonist given. This coupled with the fact
that the duration of effect is shorter for flumazenil than for most benzodiazepines, means that
resedation can occur. Patients should be carefully monitored for re-sedation and respiratory
depression throughout that period of reversal. The longer the period of sedation, the longer that
period required for monitoring and surveillance for re-sedation. If re-sedation occurs, repeated
doses of flumazenil at no less than 20-minute intervals may be used.
Dosage: intravenous – as described above
Supplied as: 5-and 10ml multiple-use vials containing 0.1 mg/ml in boxes of 10
CHLORAL HYDRATE
Chloral hydrate, the oldest member of the hypnotic group of drugs, was discovered by Liebig in
1832.It is produced by the hydration of chloral (trichloroacetalydhyde -CC, CHO). The chloral
hydrate produced is a crystalline substance readily soluble in oil or water. Chloral Hydrate is
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16. Pharmacology of Commonly Used Drugs in Conscious Sedation
classified as a non-barbiturate, a hypnotic that has been widely used as a sedative in pediatric
dentistry for decades.96
Its mechanism of action is unknown, yet its depressant effects on the C.N.S. are
primarily due to its active metabolite, trichloro ethanol (TCE), a carcinogen in mice. Following
oral administration, chloral hydrate is absorbed into the bloodstream and the major portion of
this drug is reduced by liver alcohol dehydrogenase to trichoroethanol. The trichloroethanol may
then be conjugated to glucoronides of urochloralic acid and excreted in the urine and bile. A
small portion of the chloral hydrate as well as a small portion of trichloroethanol is oxidized in
the kidney and liver by a DPNH-dependent enzyme system to the inactive metabolite,
trichloroacetic acid.
It may be administered orally at a dose of 25-50 mg/kg, with a maximal total dose of
1,000 mg. Its onset of action is 30-60 minutes and duration of up to 5 hours. A major
disadvantage of this medication is that of all the orally administered sedative medications, it may
have the worst taste. Moreover, its liquid concentration is a mucosal irritant that can cause
nausea, vomiting or even laryngospasm. 84
Compared with other agents, other notable side effects include its delayed onset, prolonged
recovery, possible cardio-irregularity at higher doses, and no analgesic properties. Chloral
hydrate depresses genioglossus activity causing hypotonicity of the tongue which can lead to it
falling backward against oropharyngeal structures, depressing respiration and compromising the
patient‟s airway. Moreover, it has no reversal agent.88
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17. Pharmacology of Commonly Used Drugs in Conscious Sedation
Nordenberg, et al., reported that the recommended hypnotic dose of chloral hydrate
depresses the cerebral hemispheres and induces sleep without significant changes in respiration,
blood pressure or heart rate. With higher doses the respiratory rate may be depressed and the
blood pressure reduced due to medullary depression and peripheral cutaneous vasodilation.
However, because of its therapeutic ratio, these and other known untoward effects are not seen
following the ingestion of sedative quantities.
It is particularly effective for non-painful procedures requiring sedation or sleep in
children younger than 2 years of age who do not require an intravenous catheter. Some
practitioners recommend sleep deprivation for children prior to giving chloral hydrate. Chloral
hydrate should be given in a quiet, calm and dimly lit environment to be most effective.
Chloral hydrate is well established as a sedative for painless procedures such as for
radiographs, CT and MRI scans. Usefulness in painful procedures is limited by patient
movement and agitation that occurs during a painful procedure even when the child may appear
to be much sedated. The long elimination half-life of chloral hydrate (trichloroethanol) often is
an indication for prolonged supervision prior to discharge.84
PROPOFOL
Propofol is 2, 6 diisopropylphenol, a phenol derivative with sedative, hypnotic and anesthetic
properties. 96
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18. Pharmacology of Commonly Used Drugs in Conscious Sedation
Propofol is a clear colourless insoluble phenolic compound supplied in an isotonic, oil-in-
water, Intra-lipid emulsion that came into use as a useful, short acting, IV anaesthetic in 1984. It
is unrelated, chemically, to any other anaesthetic agent, but behaves rather like ketamine (q.v.).
Recovery from propofol is, however, rather more rapid, and „hangovers‟ are less common. The
drug is rapidly redistributed into fat and other body tissues and more than half leaves the
circulation within 10 minutes even after neonatal IV administration. It is then conjugated and
metabolized in the liver, the elimination half life being 5–10 hours although, with sustained use,
elimination from deep stores may take 2–3 days.96
Propofol‟s primary mechanism of action is through the GABAA receptor. Through
this mechanism propofol results in neuronal cell membrane hyper polarization, inhibition of the
action potential and a reduction in cell activity. Propofol is not teratogenic or fetotoxic in
animals but crosses the placenta readily, and the manufacturers do not recommend use during
pregnancy or delivery, although no problems have been encountered with use for Caesarean
delivery.97
Propofol can be administered by either bolus dosing or bolus dosing followed by a
continuous infusion. Because of propofol‟s short duration, procedures exceeding 15 to 20
minutes are often best managed by a bolus dose followed by continuous infusion to maintain the
desired plasma concentration and clinical effect. As noted above onset of action is extremely
rapid and induction of sedation or anesthesia may be achieved with 2-3 mg/kg in 95% of patients
within 60-90 seconds. Typical induction doses for sedation include infusing propofol at 0.5-2
mg/kg/min until the child is asleep. Infusion of 100-150 mcg/kg/min maintain sleep in close to
100% of patients. Doses of propofol following induction can be used at 0.5-1 mg/kg if the patient
84
awakens.
Conscious Sedation 84
19. Pharmacology of Commonly Used Drugs in Conscious Sedation
The three properties of propofol that make it such a useful sedative-hypnotic are high
lipid solubility, large volume of distribution and high metabolic clearance. In fact clearance of
propofol exceeds hepatic blood flow. Propofol is metabolized by the liver through
glucuronidation pathways to inactive conjugated metabolites. It is highly protein bound. Its
pharmacokinetics is summarized best by a 3-compartment model. Infants have a larger volume
of distribution and a greater metabolic clearance than older children. Consequently bolus doses
required to achieve clinical effect is higher in infants. Similarly because the metabolic clearance
is higher in infants, continuous infusions rates are greater.
Propofol is particularly effective as a sole agent for noninvasive radiologic procedures. For
MRI and CT scans infusions of 100-150 mcg/kg results in a very high success rate. Propofol is
also very effective either as a sole agent or combined with opioids/ketamine for brief painful
procedures. As a single agent propofol is effective for invasive oncology procedures89,90 and
gastrointestinal procedures84
KETAMINE
Ketamine is chemically related to phencyclidine (PCP) and cyclohexamine; it has a molecular
weight of 238 and a pKa of 7.5. Although ketamine hydrochloride is water soluble, ketamine's
lipid solubility is ten times that of thiopentone. The molecular structure (2-(O-chloropheny l)-2-
methylamino cyclohexanone) contains a chiral centre at the C-2 carbon of the cyclohexanone
ring so that two enantiomers of the ketamine molecule exist: s (+) ketamine and r (-) ketamine.96
Conscious Sedation 85
20. Pharmacology of Commonly Used Drugs in Conscious Sedation
The mechanism of action of Ketamine includes:99
1. Noncompetitive antagonist of the central nervous system NMDA receptors
a. NMDA receptor is a calcium-gated channel receptor
b. NMDA receptor agonists are excitatory amino acids: glutamic acid, aspartic
Acid and glycine
c. Agonist binding to receptor results in opening of ion channel and depolarization
Of the neuron
d. NMDA receptor is involved in sensory input at the spinal, thalamic, limbic, and
Cortical levels
e. Ketamine blocks sensory input and impairs limbic functions
2. Agonist at α- and β-adrenergic receptors
3. Antagonist at muscarinic receptors of the central nervous system
4. Blocks reuptake of catecholamines
5. Agonist at opioid sigma receptor
Ketamine is one of the most versatile sedative-analgesic agents and results in a
number of desired clinical effects that are dose-dependent.At the lowest of doses anxiolysis and
Conscious Sedation 86
21. Pharmacology of Commonly Used Drugs in Conscious Sedation
analgesia occur. Antegrade amnesia occurs at slightly higher doses and is often accompanied by
perceptual changes. Higher doses result in a sedated state that is described as a “dissociative
sedation”. Typically spontaneous respirations and airway reflexes are maintained although may
not be totally normal. Ketamine generally causes an increase in heart rate, blood pressure and
cardiac output. 100
Because of concerns of potentially increasing intracranial pressure, ketamine should be
used with caution in patients with suspected increased intracranial pressure as well as open globe
injuries. Ketamine‟s neuropsychiatric effects include visual hallucinations that may be
accompanied by emergence phenomena and agitation. Oral secretions are typically only mildly
increased but may require antisialogogues. The single most severe adverse effect with ketamine
sedation is laryngospasm. Ketamine is clinically effective by a number of different routes.
Oral/Rectal Ketamine:
Oral and rectal doses of ketamine are 4-10 mg/kg. Onset of sedation occurs in 15-30 minutes and
effects may be prolonged by the oral or rectal route lasting 3 to 4 hours. Ketamine‟s active
metabolite norketamine predominates with oral/rectal administration typically in a ratio of
norketamine to ketamine of 5 to 1 and 3 to 1 respectively. Norketamine is approximately one-
third as potent as ketamine. Following oral administration (10 mg/kg), peak effects occurred in
30 to 40 minutes in children undergoing painful cancer procedures. Typically, higher doses of
oral ketamine (8-10 mg/kg) are more effective as a premedication than lower doses (3-6
mg/kg).84
Intramuscular (IM) Ketamine:
Intramuscular ketamine reaches peak blood levels and clinical effect in five minutes after 3 to 10
mg/kg. Recovery from dissociation occurs within 15 to 30 minutes with coherence and
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22. Pharmacology of Commonly Used Drugs in Conscious Sedation
purposeful neuromuscular activity returning in 30-120 minutes. A smaller dose of 3 mg/kg has
been employed to facilitate intravenous catheter placement or acceptance of a mask for
anesthesia induction, with no delay in discharge compared to control patients after 60 minutes.
The 100 mg/ml formulation of ketamine is preferred for IM administration in older
children to minimize volume related injection site discomfort. Experience with intramuscular
ketamine is extensive. Sedation is accompanied by the excellent analgesia. Intramuscular
administration of ketamine is an excellent means of sedating the “out of control” patient for IV
placement or mildly painful procedures. Deep sedation may occur. 84
Intravenous Ketamine:
Ketamine is typically given in doses of 0.5 to 1 mg/kg although doses of 2 mg/kg can be used.
Peak concentrations occur within 1 to 2 minutes and rapid absorption by the highly perfused
cerebral tissues allows almost immediate induction of clinical effects. Ketamine then slowly
redistributes into the peripheral tissues; thus decreasing central nervous system levels that
correlate with return of coherence, generally 10-15 minutes if no additional doses are given.
Deep levels of sedation may be achieved. Remarkably painful procedures are tolerated well
following administration of ketamine because of its profound analgesic effects as well as the
dissociative sedation it affords.
Intravenous ketamine is well established as a safe and efficacious agent in pediatric
patients. Because of higher blood levels with intravenous use, ketamine administered by this
route may have more problems than oral or intramuscular administration. Oral secretions may be
avoided by the administration of an antisialogogue (atropine 0.01-0.02 mg/kg or glycopyrrolate
0.005 mg/kg intravenous). 84
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23. Pharmacology of Commonly Used Drugs in Conscious Sedation
Although patients will continue to breath and maintain airway tone, silent pulmonary
aspiration of oral contents has been reported with deep levels of sedation. Patients may continue
to move during sedation and eyes remain open. Emergence delirium is much less common in
children than adults and may be prevented or treated by the administration of a small dose of a
benzodiazepine or preparing the patient by discussing the clinical effects of ketamine prior to
administration.
Ketamine alone is particularly effective for procedures with moderate to severe
discomfort and pain. Initial doses of 0.5 mg/kg followed by repeat doses of 0.25-0.5 mg/kg were
effective for 97% of pediatric patients undergoing invasive emergency department procedures. In
combination with midazolam, ketamine doses of 0.5-1.5 mg/kg was superior in efficacy and
safety to an opioid-midazolam combination in children undergoing painful pediatric oncology
procedures.
Similarly the combination of propofol and ketamine 1 mg/kg resulted in less restlessness
during burn dressing changes compared to a propofol-fentanyl combination. Ketamine should be
used cautiously if at all in individuals with intracranial hypertension, systemic hypertension or
neuropsychiatric disorders and/or any child with visual or auditory. 84
NARCOTICS
Narcotics are the “heavy artillery” of pediatric sedation. They are not employed with any
great consideration for their analgesic properties. They do produce sedation and euphoria to a
greater degree in children than in adults. Local anesthesia is still required for intra-operative pain
control. Local anesthetics are also CNS depressants.
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24. Pharmacology of Commonly Used Drugs in Conscious Sedation
A significant drug-drug and drug-physiologic interaction can occur when narcotics or
other drugs that depress respiration are combined with local anesthetics. In usual doses, local
anesthetics are CNS depressants and will provide additive depression when combined with other
CNS depressants. In addition, when drugs that depress respiration are used (particularly
narcotics), varying degrees of hypercarbia can occur, with a resultant decrease in serum pH. As
the respiratory depression continues to deepen, respiratory and metabolic acidosis results in an
increase in the availability of lidocaine to the CNS. This occurs as a result of less serum protein
binding of lidocaine along with central vasodilation and an increase in blood flow to the CNS inn
an acidotic state. 97
Consequently the threshold for CNS lidocaine toxicity is lowered. Lidocaine toxicity
results in CNS excitation and seizures and ultimately coma and death. As a result, the maximum
dosage of local anesthetic must be reduced when used in combination with a CNS and/or
respiratory depressant. This very important and significant interaction is often overlooked and is
the cause of many of the adverse incidents reported in pediatric sedation. The maximum local
anesthetic does in children may allow for the use of only one or two dental cartridges, which is
quite different than for adult patients.
Combination with other sedative drugs, including nitrous oxide-oxygen, reduces the need
for larger doses of narcotics and thus reduces the potential for unwanted effects from these
potent drugs. A practitioner employing narcotics should be thoroughly familiar with their actions
and interactions and should have had some supervised experience in their use as well as in
management of the airway and patient resuscitation procedures.88
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25. Pharmacology of Commonly Used Drugs in Conscious Sedation
FENTANYL
Fentanyl is a synthetic opiate agonist in the same chemical class as meperidine. It is a potent
narcotic analgesic. A dose of 0.1 mg is approximately equivalent to 10 mg of morphine or 75 mg
of meperidine. Fentanyl has a rapid action, and after a submucosal or intramuscular injection the
onset occurs in 7 to 15 minutes; duration of effects is 1 to 2 hours. The drug is metabolized by
the liver and is excreted in the urine.97
Fentanyl produces little histamine release and has much less emetic effect than morphine
or meperidine. Fentanyl can be administered by the intramuscular, intravenous, or submucosal
route. When it is used with other CNS depressants, the dose should be reduced. The drug works
well with orally administered diazepam and nitrous oxide-oxygen. It is not recommended for use
in children younger than 2 years of age.
The oral transmucosal preparation of fentanyl has never become popular for procedural
sedation and analgesia because titration is difficult, effectiveness is variable, and the incidence of
emesis is high (31–45%).89 Like all opioids, fentanyl can cause respiratory depression. Because
of the lack of histamine release with fentanyl, nausea and vomiting are less common than with
morphine or meperidine. In the absence of substantial ethanol intoxication, hypovolaemia, or
concomitant drug ingestion, hypotension is rare, even with very large doses of fentanyl (doses of
50 _g/kg are common in adult and pediatric cardiac surgery). A common reaction to fentanyl is
isolated nasal pruritus.97
A widely-described but rare adverse effect of fentanyl with potential for respiratory
compromise is chest-wall rigidity. This complication is associated with much higher doses (_5
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26. Pharmacology of Commonly Used Drugs in Conscious Sedation
_g/kg as a bolus dose) than those used for procedural sedation and analgesia; indeed, this adverse
event has not been reported in this setting.
Dosage: 0.002 to 0.004 mg/kg
Supplied: 0.05 mg/mL in 2-and 5-mL amples
MEPERIDINE
Meperidine is a synthetic opiate agonist. It is water soluble but is incompatible with many other
drugs in solution. Meperidine may be administered orally or by subcutaneous, intramuscular, or
intravenous injection. It is least effective by mouth. It is bitter and requires taste masking by a
flavoring agent. By the oral route, peak effect occurs in 1 hour and lasts about 4 hours. Parenteral
administration shortens the time of onset and duration. High doses that lead to an accumulation
of normeperidine, a primary metabolite of meperidine, have resulted in seizures. Meperidine
should be used with extreme caution in patients likely to accumulate or be sensitive to this
metabolite (e.g., patients with hepatic or renal disease, or history of seizures).
Dosage: Oral, subcutaneous, or intramuscular-1.0 to 2.2 mg/kg, not to exceed 100mg
when given alone or 50 mg when in combination with other CNS depressants 97
Supplied: Oral tablets-50 and 100 mg;
Oral syrup-50mg/5mL;
Parenteral solution-25, 50, 75, and 100 mg/mL.
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27. Pharmacology of Commonly Used Drugs in Conscious Sedation
NARCOTIC ANTAGONIST
A semi synthetic opiate antagonist used for the sole purpose of reversing the effects of narcotic
drugs. Naloxone is a pure antagonist, with no agonist activity even in large doses. It acts in 2 to 5
minutes after subcutaneous or intramuscular injection and 1 to 2 minutes intravenously. After
intravenous administration the duration of reversal about 45 minutes; it is slightly longer when
the drug is administered intramuscularly or subcutaneously. This is an important difference,
because the duration of reversal is about 45 minutes; it is slightly longer when the drug is
administered intramuscularly or subcutaneously. This is an important difference, because the
duration of effect of the opiate is in all likelihood longer than that of the antagonist.
Consequently, patients undergoing reversal of sedation with naloxone should be kept
under continual surveillance until it has been determined that the narcotic will not produce a
rebound effect. The time period will vary depending on the duration of action of the narcotic.
Repeated doses of naloxone may be necessary to establish patient stability. If the decision has
been made to administer an antagonist, other resuscitative measures must be available and must
be used as necessary. Naloxone administration should never take precedence over basic
resuscitative measures. There is no evidence to support the contention that naloxone will reverse
respiratory depression but not the sedative action of the opiate.97
Adverse reactions include nausea, vomiting, sweating, hypotension, hypertension,
ventricular tachycardia and fibrillation, and pulmonary edema. None of these effects, however,
has been reported with its use in pediatric conscious sedation.
Dosage: Intravenous, subcutaneous, intramuscular-initial dose: 0.01 mg/kg; subsequent doses:
0.1 mg /kg (2 mg maximum) every 2 to 3 minutes
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28. Pharmacology of Commonly Used Drugs in Conscious Sedation
Supplied: Parenteral solution-0.02, 0.4, 1.0 mg/kg
NITROUS OXIDE
Nitrous oxide is an inorganic inhalation agent that is colourless, odorless to sweet-smelling, and
non-irritating to the tissues. It is non-flammable but will support combustion. It is slightly
heavier than air, with a specific gravity of 1.53, and has a blood: gas partition coefficient of 0.47.
Because of its low solubility in blood, it has a very rapid onset and recovery time.
Nitrous oxide has multiple mechanisms of action. The analgesic effect of nitrous oxide
appears to be initiated by neuronal release of endogenous opioid peptides with subsequent
activation of opioid receptors and descending Gamma-amino butyric acid type A (GABAA)
receptors and noradrenergic pathways that modulate nociceptive processing at the spinal level.
The anxiolytic effect involves activation of the GABAA receptor either directly or indirectly
through the benzodiazepine binding site.
Unlike other anaesthetics, nitrous oxide produces a mild analgesic effect at subanesthetic
concentrations. The mechanism for this effect most likely involves an interaction with the
endogenous opioid system because it is abolished by administration of the opioid antagonist,
naloxone. The strongest evidence is that nitrous oxide stimulates release of enkephalins, which
bind to opioid receptors that trigger descending noradrenergic pathways.
Inhaled nitrous oxide provides anxiolysis and mild analgesia and sedation. It is commonly
dispensed at concentrations between 30% and 70% with oxygen composing the remainder of the
mixture. Nitrous oxide has rapid onset (30–60 s), maximum effect after about 5 min, and rapid
Conscious Sedation 94
29. Pharmacology of Commonly Used Drugs in Conscious Sedation
recovery upon discontinuation. At typical procedural sedation and analgesia concentrations there
is preservation of hemodynamic status, spontaneous respirations, and protective airway reflexes.
Nitrous oxide has an excellent safety profile; however as a sole agent it does not reliably produce
adequate procedural conditions, and in many cases is supplemented with an opioid or local or
regional anesthesia. Administration can also be useful for intravenous access or venipuncture in
frightened children.
The safest method of nitrous oxide administration is via a self-administered demand-valve
mask, which needs negative inspiratory pressure to activate gas flow. If the patient becomes
somnolent, the mask will fall from their face and gas delivery will cease. The main limitation of
self-administration is that it is ineffective in uncooperative patients, including most frightened
young children.
Continuous-flow nitrous oxide has been used in this population with a mask strapped over
the nose, or over the nose and mouth producing moderate or deep sedation and necessitating an
additional physician dedicated to continuous gas titration. This technique is associated with
more frequent emesis than self-administration (0% vs. 4%), posing a potential hazard when a
mask is strapped over the child‟s mouth.
Several minor adverse effects can be evident, including nausea, dizziness, voice
change, euphoria, and laughter. Because of its high diffusibility, nitrous oxide should be avoided
in patients with potential closed-space diseases such as bowel obstruction, middle ear disease,
pneumothorax, or pneumocephaly. A scavenging system must be in place to ensure compliance
with occupational safety regulations as occupational exposure to nitrous oxide has been
associated with increased rates of spontaneous abortions.
Conscious Sedation 95
30. Pharmacology of Commonly Used Drugs in Conscious Sedation
ANTIHISTAMINES
HYDROXYZINE
Hydroxyzine hydrochloride is designated chemically as 2-[2-[4-(p-Chloro-?-phenylbenzyl)-1-
piperazinyl] ethoxy] ethanol dihydrochloride. Hydroxyzine hydrochloride occurs as a white,
odorless powder which is very soluble in water 96
Hydroxyzine is an antihistamine with mild sedative and antiemetic properties. In
normal doses, it has no cardio vascular or respiratory depressant effects. It is rapidly absorbed
from the gastrointestinal tract with clinical effect seen in 15 to 30 minutes, peak levels occur at 2
hours, and mean half-life is 3 hours. Administration is preferably by the oral route. Intramuscular
injections must be deep in a large muscle mass. The drug should not be injected subcutaneously
or intravenously because of potential tissue necrosis and hemolysis. Adverse reactions include
extreme drowsiness, dry mouth and hypersensitivity.97
Dosage: Oral-1 to 2mg/kg;
Intramuscular-1.1mg/kg
Supplied as: Tablets-10, 25, 50 and 100mg;
Syrup- 10mg/5ml;
Injectable-25 or 50mg/ml;
Conscious Sedation 96
31. Pharmacology of Commonly Used Drugs in Conscious Sedation
DRUGS USED FOR PROCEDURAL SEDATION AND ANALGESIA
Conscious Sedation 97