This document provides an overview of opioids, including terminology, opioid receptors, pharmacological effects, classification, and details on specific opioids like morphine. It defines terms like opiates, endorphins, tolerance, dependence, withdrawal, and addiction. It describes the three main endogenous opioid peptides and the three opioid receptor types. It outlines various pharmacological effects of opioids including analgesia, respiratory depression, miosis, and immune/neuroendocrine impacts. It classifies opioids and provides details on morphine and its uses, adverse effects, and contraindications.
This document discusses neuromuscular blocking agents (NMBAs), including their history, mechanism of action, and types. It begins by defining NMBAs and explaining they are used to facilitate muscle relaxation during surgery and mechanical ventilation. It then describes the neuromuscular junction where acetylcholine binds nicotinic receptors, causing depolarization. The document categorizes NMBAs as depolarizing (e.g. succinylcholine) or non-depolarizing (e.g. atracurium, cisatracurium, vecuronium) and explains their mechanisms of action and properties like metabolism and side effects. It provides details on specific NMBAs and newer agents in development while emphas
The document discusses opioids, including their definition, sources, receptors, history of use, classifications, mechanisms of action, pharmacological effects, adverse effects, toxicity, and therapeutic uses. It describes the three main opioid receptors (mu, kappa, delta), the effects of receptor activation, and different classifications of opioids based on their receptor actions (agonists, partial agonists, antagonists, mixed). It covers the absorption, distribution, metabolism and excretion of opioids. The major pharmacological actions discussed are analgesia, sedation, respiratory depression, nausea, constipation, and dependence/withdrawal. Therapeutic uses include management of severe pain and obstetrical labor pain. Risks/cautions with impaired organ function and certain patient populations
Dr. zikrullah discusses propofol, an intravenous anesthetic agent. Key points include:
- Propofol was developed in the 1970s and first used clinically in 1977. It acts by binding to GABA receptors in the brain.
- It has rapid onset and short duration. Propofol is highly lipid soluble, rapidly redistributing and metabolizing in the liver to inactive compounds excreted by the kidneys.
- Propofol is used for induction and maintenance of general anesthesia. It provides sedation, hypnosis, amnesia and reduces intracranial pressure. Common side effects include pain on injection and hypotension.
This document provides an introduction to opioids. It discusses the history of opioid use dating back to ancient Egypt and Greece. It describes the isolation of morphine from opium in 1806 and the subsequent development of other semi-synthetic and synthetic opioids. The document outlines the four main opioid receptor types and their locations in the body. It examines the pharmacological effects of opioids including analgesia, respiratory depression, miosis, gastrointestinal effects, and others. It also covers tolerance development and cross-tolerance between opioids.
This document discusses opioid receptors and opioid analgesics. It begins by introducing opioids and their interaction with opioid receptors in the central nervous system and gastrointestinal tract. It then describes the three main types of opioid receptors - mu, kappa, and delta - and their locations in the brain and spinal cord. The document outlines various classes of opioid analgesics and antagonists based on their receptor interactions. It explains the mechanisms of action of opioids like morphine at opioid receptors, including their analgesic, sedative, and other effects. The pharmacokinetics, uses, and adverse effects of representative opioids like morphine and semi-synthetic derivatives are summarized. Finally, the mechanisms and applications of opioid antagonists such as naloxone and naltrexone
This document discusses neuromuscular blocking agents (NMBAs), including their history, mechanism of action, and types. It begins by defining NMBAs and explaining they are used to facilitate muscle relaxation during surgery and mechanical ventilation. It then describes the neuromuscular junction where acetylcholine binds nicotinic receptors, causing depolarization. The document categorizes NMBAs as depolarizing (e.g. succinylcholine) or non-depolarizing (e.g. atracurium, cisatracurium, vecuronium) and explains their mechanisms of action and properties like metabolism and side effects. It provides details on specific NMBAs and newer agents in development while emphas
The document discusses opioids, including their definition, sources, receptors, history of use, classifications, mechanisms of action, pharmacological effects, adverse effects, toxicity, and therapeutic uses. It describes the three main opioid receptors (mu, kappa, delta), the effects of receptor activation, and different classifications of opioids based on their receptor actions (agonists, partial agonists, antagonists, mixed). It covers the absorption, distribution, metabolism and excretion of opioids. The major pharmacological actions discussed are analgesia, sedation, respiratory depression, nausea, constipation, and dependence/withdrawal. Therapeutic uses include management of severe pain and obstetrical labor pain. Risks/cautions with impaired organ function and certain patient populations
Dr. zikrullah discusses propofol, an intravenous anesthetic agent. Key points include:
- Propofol was developed in the 1970s and first used clinically in 1977. It acts by binding to GABA receptors in the brain.
- It has rapid onset and short duration. Propofol is highly lipid soluble, rapidly redistributing and metabolizing in the liver to inactive compounds excreted by the kidneys.
- Propofol is used for induction and maintenance of general anesthesia. It provides sedation, hypnosis, amnesia and reduces intracranial pressure. Common side effects include pain on injection and hypotension.
This document provides an introduction to opioids. It discusses the history of opioid use dating back to ancient Egypt and Greece. It describes the isolation of morphine from opium in 1806 and the subsequent development of other semi-synthetic and synthetic opioids. The document outlines the four main opioid receptor types and their locations in the body. It examines the pharmacological effects of opioids including analgesia, respiratory depression, miosis, gastrointestinal effects, and others. It also covers tolerance development and cross-tolerance between opioids.
This document discusses opioid receptors and opioid analgesics. It begins by introducing opioids and their interaction with opioid receptors in the central nervous system and gastrointestinal tract. It then describes the three main types of opioid receptors - mu, kappa, and delta - and their locations in the brain and spinal cord. The document outlines various classes of opioid analgesics and antagonists based on their receptor interactions. It explains the mechanisms of action of opioids like morphine at opioid receptors, including their analgesic, sedative, and other effects. The pharmacokinetics, uses, and adverse effects of representative opioids like morphine and semi-synthetic derivatives are summarized. Finally, the mechanisms and applications of opioid antagonists such as naloxone and naltrexone
Myasthenia gravis is an autoimmune disorder characterized by fatigable weakness of skeletal muscles due to antibodies attacking acetylcholine receptors at the neuromuscular junction. It commonly presents with weakness of ocular, bulbar, and limb muscles that worsens with exertion and improves with rest. Diagnosis involves electrophysiological tests demonstrating decremental response to repetitive nerve stimulation and a positive response to edrophonium (Tensilon) testing. Treatment focuses on acetylcholinesterase inhibitors, immunosuppressants, thymectomy, and managing exacerbations or myasthenic crisis which can involve respiratory muscle weakness requiring intubation. Anesthesia management aims to prevent worsening of weakness through careful choice and
1. The document discusses the history, pharmacological properties, advantages, and unfavorable conditions of sevoflurane.
2. It provides details on the development of sevoflurane from the 1960s onward and its approval for use in humans in the 1990s.
3. The document also examines sevoflurane's effects on various body systems and compares it to other inhalational anesthetics like isoflurane, noting sevoflurane's favorable properties like rapid induction/recovery and brain protective effects.
This document discusses opioid analgesics, including their classification, mechanisms of action, and effects. It begins by defining analgesics, opioids, opiates, and narcotics. It then discusses the opioid morphine in depth, including its pharmacological effects in the central nervous system and peripherally. Other opioids discussed include pethidine, methadone, tramadol, endogenous opioid peptides, and opioid receptor antagonists such as naloxone. The document provides an overview of the classification, properties, uses, and adverse effects of various opioid analgesics.
Opioid pharmacology - A comprehensive subject seminar on OpioidsRohan Kolla
This document provides an outline and overview of opioid pharmacology. It begins with definitions of terms like opioids and opiates. It then discusses the history of opioid use from ancient times through modern drug development. The endogenous opioid system and opioid receptors are described. The pharmacokinetics, pharmacological effects, and clinical uses of various opioids like morphine, fentanyl, methadone, and antagonists are summarized. The document covers both central and peripheral effects of opioids on systems like the nervous, cardiovascular, immune, and gastrointestinal systems. Classification and guidelines for use of opioids in pain management are also mentioned.
This document provides an overview of the pharmacology of dopamine. It discusses dopamine synthesis, receptors, pathways in the brain, and the role of dopamine in conditions like Parkinson's disease, schizophrenia, and addiction. Dopamine is synthesized from phenylalanine and tyrosine and acts on D1-like and D2-like receptors in the mesolimbic, mesocortical, and nigrostriatal pathways. Imbalances in dopaminergic signaling are implicated in disorders such as Parkinson's, schizophrenia, and ADHD. Drugs that modify dopamine transmission are used to treat these conditions.
Opioids are medications prescribed to treat severe pain. They work in the brain to reduce pain signals and include drugs derived from opium poppy plants like morphine and heroin. This document discusses the classification, mechanisms of action, indications, and side effects of various opioids and opioid antagonists. It provides details on how different opioid drugs target receptor types in the brain and body to produce analgesic and other effects. The document also summarizes guidelines for using opioids to treat acute and chronic pain conditions.
Opioid receptors are G-protein coupled receptors located in the central nervous system and peripheral tissues that interact with opioid drugs like morphine. There are three main types of opioid receptors: mu, kappa, and delta. Mu receptors have a high affinity for morphine and are responsible for respiratory depression, euphoria, and physical dependence. Kappa receptors are activated by compounds like ethylketocyclazocine and are involved in analgesia and diuresis. Delta receptors have a lower risk of side effects compared to mu receptors and are activated by ligands like levorphanol. Opioid receptors act through G-proteins to inhibit adenyl cyclase, open potassium channels, close calcium channels, and decrease neuronal
Dexmedetomidine is a selective alpha-2 adrenoceptor agonist approved by the FDA for short-term sedation. It has sedative, anxiolytic, and analgesic properties. Dexmedetomidine has advantages over other sedatives in the ICU as it causes less respiratory depression, easier arousability, and lower incidence of delirium. Its pharmacokinetics are nonlinear and it undergoes extensive hepatic metabolism. Dexmedetomidine is also used for sedation during procedures, as an adjuvant for anesthesia and analgesia, and for neurological protection during surgery.
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.
The document discusses the history and pharmacodynamics of inhalational anesthetics. It summarizes that no single individual discovered anesthesia, but rather discoveries were made across scientific disciplines by curious individuals. It then discusses several landmark discoveries and uses of anesthetic agents from the 18th century onward. The document also summarizes some of the leading theories about how anesthetic agents produce their effects, including lipid solubility theories and theories related to their interactions with lipid bilayers and proteins like ion channels. Finally, it briefly discusses sites of anesthetic action in the body and factors that can influence their potency.
This document summarizes the pharmacology of various opioid analgesics. It discusses classical opioid effects like analgesia, sedation, respiratory depression. It then profiles specific opioids like fentanyl, sufentanil, morphine, hydromorphone, remifentanil and others. It also discusses evidence for different mu opioid receptor subtypes and the potential for mu-1 selective agonists.
Desflurane was developed in the 1990s and has the lowest blood-gas solubility of all inhalational anesthetic agents, allowing for the fastest induction and recovery. It is prepared through a multistep chemical process and requires a specialized vaporizer due to its low boiling point. Desflurane causes dose-dependent cardiovascular and respiratory depression as well as muscle relaxation. While it has rapid onset and offset, it is also highly irritating to the airway and its use requires careful monitoring due to potential for sympathetic stimulation.
Opioids are natural, semi-synthetic, and synthetic compounds that mimic the action of morphine. They act on opioid receptors both endogenously and exogenously. The physiological effects of opioids include analgesia through raising pain threshold and tolerance, respiratory depression by decreasing sensitivity to carbon dioxide, and euphoria producing a relaxed state. Opioids also cause sedation, gastrointestinal effects like nausea and constipation, and cardiovascular effects such as mild bradycardia and hypotension.
The document discusses various opioids including morphine, fentanyl, sufentanyl, meperidine, remifentanil, tramadol and pentazocine, outlining their history, classification, mechanisms of action, pharmacokinetics, clinical uses, and adverse effects. It provides details on the endogenous opioid peptides and opioid receptors in the body, as well as the therapeutic uses and pharmacology of morphine as the prototype opioid analgesic.
This document discusses adrenergic receptors and modulators. It describes the sympathetic nervous system and neurotransmitters like norepinephrine, epinephrine, and dopamine. Norepinephrine is stored in synaptic vesicles and released via calcium-dependent fusion. Release can be modulated by prejunctional autoreceptors and heteroreceptors. There are alpha and beta adrenergic receptors which are G-protein coupled and have various effects. Drugs can affect receptors as agonists or antagonists and are used to treat conditions like hypertension and heart failure.
This document discusses neuromuscular monitoring during surgery using muscle relaxants. It provides 3 key points:
1) Neuromuscular monitoring is used to assess the level of muscle relaxation during surgery, determine the onset and recovery from muscle blockade, and minimize the risk of residual paralysis.
2) Several techniques are used for monitoring including single twitch stimulation, train-of-four stimulation, tetanic stimulation, and post-tetanic count stimulation.
3) Monitoring is important for patients at risk of residual paralysis, to determine the appropriate time for reversal of muscle relaxants, and to assess adequate recovery before extubation. However, monitoring has some limitations and may not always exclude residual weakness.
Narcotics and Non-Narcotics Analgesics.pptxFarazaJaved
This document summarizes narcotic and non-narcotic analgesics. It describes major classes of analgesics including opioids, NSAIDs, acetaminophen, flupirtine, and ziconotide. Specific drugs are discussed including morphine, methadone, fentanyl, codeine, tramadol, acetaminophen, NSAIDs, flupirtine and ziconotide. Their mechanisms of action, uses, adverse effects, and classification as pure agonists, partial agonists, antagonists are summarized.
This document summarizes key information about opioid analgesics including:
1. It classifies opioids based on their strength from strong to weak and lists examples in each category.
2. It outlines several clinical uses of opioids such as for analgesia, cough suppression, and treatment of opioid dependence.
3. It describes the pharmacokinetics of opioids including absorption, metabolism, and ability to cross the placental barrier and affect fetuses.
4. It explains the mechanism of action of opioids including their binding to μ, δ, and κ receptors in the brain and spinal cord to produce effects like analgesia and respiratory depression.
General anaesthetics (GAs) are drugs which produce reversible loss of all sensation and consciousness.
The cardinal features of general anaesthesia are:
• Loss of all sensation, especially pain.
• Sleep (unconsciousness) and amnesia
• Immobility and muscle relaxation
• Abolition of somatic and autonomic reflexes.
GA was absent until the mid 1800’s
Original discoverer of GA
-Crawford long, physician from Gerogia(1842),
ETHER ANESTHESIA
. NITROUS OXIDE
- Horace wells(1844)
. GASEOUS ETHER by William T.G. Morton(1846)
. CHLOROFORM introduced by
- James simpson (1847)
METHODS OF ADMINISTRATION OF INHALATIONAL GENERAL ANAESTHETICS
OPEN METHOD: This is a simple method of administering a volatile anaesthetic.
A simple mask covered with six to ten layers of gauze, which does not fit the contour of the face is held on the face and an anaesthetic like ether, or ethyl chloride is poured on it in drops. The anaesthetic vapour, diluted with air, is inhaled through the gap between the mask and the face.
SEMI-OPEN METHOD: This method is similar to open method but the dilution with air is prevented by using either a well-fitting mask like Ogston’s mask or layers of gauze between face and the mask. A small carbon dioxide build-up occurs with this method.
SEMI-CLOSED METHOD: This method allows some rebreathing of the anaesthetic drug with the help of a reservoir but in addition, part of the volume of each succeeding inspiration is a new portion from an anaesthetic mixture. This method involves accumulation and rebreathing of carbon dioxide.
• CLOSED METHOD: This method employs the chemical agent soda lime to absorb the carbon dioxide present in the expired air. It requires the use of a special apparatus but is particularly useful when the anaesthetic agent is potentially explosive
STAGES OF ANAESTHESIA
Guedel, in 1920 outlined the four stages of general anaesthesia :
• Stage I: Stage of analgesia
• Stage II: Stage of delirium
• Stage III: Stage of surgical anaesthesia
• Stage IV: Stage of respiratory paralysis
Inadequate anaesthesia is indicated by:
Signs of ANS overactivity, such as tachycardia, rise of BP, sweating and lacrimation.
Grimacing;
Other muscle activity.
Surgical anaesthesia is indicated by:
Loss of eyelash (lid) reflex
Development of rhythmic respiration.
Deep anaesthesia is suggested by :
Depression of respiration.
Hypotension
Asystole
The document discusses several key points about opioids:
1. It describes the endogenous opioid systems and receptors in the body, including proenkephalin, prodynorphin, pro-opiomelanocortin, and the mu, kappa, delta, and other receptors.
2. It summarizes the pharmacokinetics and pharmacodynamics of opioids like morphine and meperidine, how they work in the body to produce analgesia and other effects.
3. The main effects of opioids discussed are analgesia, respiratory depression, nausea/vomiting, and other central nervous system effects. Their use in anesthesia is also covered.
This document summarizes opioids and their mechanisms of action. It discusses that opioids act on mu, kappa, and delta opioid receptors in the central nervous system and gastrointestinal tract to produce analgesia, euphoria, sedation and other effects. The document outlines the classification, agonists, antagonists and effects of different opioid receptors. It provides details on commonly used opioid analgesics like morphine, codeine, methadone, tramadol and their indications, pharmacological actions, and adverse effects. Peripheral opioid antagonists are discussed for treating opioid-induced constipation.
Myasthenia gravis is an autoimmune disorder characterized by fatigable weakness of skeletal muscles due to antibodies attacking acetylcholine receptors at the neuromuscular junction. It commonly presents with weakness of ocular, bulbar, and limb muscles that worsens with exertion and improves with rest. Diagnosis involves electrophysiological tests demonstrating decremental response to repetitive nerve stimulation and a positive response to edrophonium (Tensilon) testing. Treatment focuses on acetylcholinesterase inhibitors, immunosuppressants, thymectomy, and managing exacerbations or myasthenic crisis which can involve respiratory muscle weakness requiring intubation. Anesthesia management aims to prevent worsening of weakness through careful choice and
1. The document discusses the history, pharmacological properties, advantages, and unfavorable conditions of sevoflurane.
2. It provides details on the development of sevoflurane from the 1960s onward and its approval for use in humans in the 1990s.
3. The document also examines sevoflurane's effects on various body systems and compares it to other inhalational anesthetics like isoflurane, noting sevoflurane's favorable properties like rapid induction/recovery and brain protective effects.
This document discusses opioid analgesics, including their classification, mechanisms of action, and effects. It begins by defining analgesics, opioids, opiates, and narcotics. It then discusses the opioid morphine in depth, including its pharmacological effects in the central nervous system and peripherally. Other opioids discussed include pethidine, methadone, tramadol, endogenous opioid peptides, and opioid receptor antagonists such as naloxone. The document provides an overview of the classification, properties, uses, and adverse effects of various opioid analgesics.
Opioid pharmacology - A comprehensive subject seminar on OpioidsRohan Kolla
This document provides an outline and overview of opioid pharmacology. It begins with definitions of terms like opioids and opiates. It then discusses the history of opioid use from ancient times through modern drug development. The endogenous opioid system and opioid receptors are described. The pharmacokinetics, pharmacological effects, and clinical uses of various opioids like morphine, fentanyl, methadone, and antagonists are summarized. The document covers both central and peripheral effects of opioids on systems like the nervous, cardiovascular, immune, and gastrointestinal systems. Classification and guidelines for use of opioids in pain management are also mentioned.
This document provides an overview of the pharmacology of dopamine. It discusses dopamine synthesis, receptors, pathways in the brain, and the role of dopamine in conditions like Parkinson's disease, schizophrenia, and addiction. Dopamine is synthesized from phenylalanine and tyrosine and acts on D1-like and D2-like receptors in the mesolimbic, mesocortical, and nigrostriatal pathways. Imbalances in dopaminergic signaling are implicated in disorders such as Parkinson's, schizophrenia, and ADHD. Drugs that modify dopamine transmission are used to treat these conditions.
Opioids are medications prescribed to treat severe pain. They work in the brain to reduce pain signals and include drugs derived from opium poppy plants like morphine and heroin. This document discusses the classification, mechanisms of action, indications, and side effects of various opioids and opioid antagonists. It provides details on how different opioid drugs target receptor types in the brain and body to produce analgesic and other effects. The document also summarizes guidelines for using opioids to treat acute and chronic pain conditions.
Opioid receptors are G-protein coupled receptors located in the central nervous system and peripheral tissues that interact with opioid drugs like morphine. There are three main types of opioid receptors: mu, kappa, and delta. Mu receptors have a high affinity for morphine and are responsible for respiratory depression, euphoria, and physical dependence. Kappa receptors are activated by compounds like ethylketocyclazocine and are involved in analgesia and diuresis. Delta receptors have a lower risk of side effects compared to mu receptors and are activated by ligands like levorphanol. Opioid receptors act through G-proteins to inhibit adenyl cyclase, open potassium channels, close calcium channels, and decrease neuronal
Dexmedetomidine is a selective alpha-2 adrenoceptor agonist approved by the FDA for short-term sedation. It has sedative, anxiolytic, and analgesic properties. Dexmedetomidine has advantages over other sedatives in the ICU as it causes less respiratory depression, easier arousability, and lower incidence of delirium. Its pharmacokinetics are nonlinear and it undergoes extensive hepatic metabolism. Dexmedetomidine is also used for sedation during procedures, as an adjuvant for anesthesia and analgesia, and for neurological protection during surgery.
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.
The document discusses the history and pharmacodynamics of inhalational anesthetics. It summarizes that no single individual discovered anesthesia, but rather discoveries were made across scientific disciplines by curious individuals. It then discusses several landmark discoveries and uses of anesthetic agents from the 18th century onward. The document also summarizes some of the leading theories about how anesthetic agents produce their effects, including lipid solubility theories and theories related to their interactions with lipid bilayers and proteins like ion channels. Finally, it briefly discusses sites of anesthetic action in the body and factors that can influence their potency.
This document summarizes the pharmacology of various opioid analgesics. It discusses classical opioid effects like analgesia, sedation, respiratory depression. It then profiles specific opioids like fentanyl, sufentanil, morphine, hydromorphone, remifentanil and others. It also discusses evidence for different mu opioid receptor subtypes and the potential for mu-1 selective agonists.
Desflurane was developed in the 1990s and has the lowest blood-gas solubility of all inhalational anesthetic agents, allowing for the fastest induction and recovery. It is prepared through a multistep chemical process and requires a specialized vaporizer due to its low boiling point. Desflurane causes dose-dependent cardiovascular and respiratory depression as well as muscle relaxation. While it has rapid onset and offset, it is also highly irritating to the airway and its use requires careful monitoring due to potential for sympathetic stimulation.
Opioids are natural, semi-synthetic, and synthetic compounds that mimic the action of morphine. They act on opioid receptors both endogenously and exogenously. The physiological effects of opioids include analgesia through raising pain threshold and tolerance, respiratory depression by decreasing sensitivity to carbon dioxide, and euphoria producing a relaxed state. Opioids also cause sedation, gastrointestinal effects like nausea and constipation, and cardiovascular effects such as mild bradycardia and hypotension.
The document discusses various opioids including morphine, fentanyl, sufentanyl, meperidine, remifentanil, tramadol and pentazocine, outlining their history, classification, mechanisms of action, pharmacokinetics, clinical uses, and adverse effects. It provides details on the endogenous opioid peptides and opioid receptors in the body, as well as the therapeutic uses and pharmacology of morphine as the prototype opioid analgesic.
This document discusses adrenergic receptors and modulators. It describes the sympathetic nervous system and neurotransmitters like norepinephrine, epinephrine, and dopamine. Norepinephrine is stored in synaptic vesicles and released via calcium-dependent fusion. Release can be modulated by prejunctional autoreceptors and heteroreceptors. There are alpha and beta adrenergic receptors which are G-protein coupled and have various effects. Drugs can affect receptors as agonists or antagonists and are used to treat conditions like hypertension and heart failure.
This document discusses neuromuscular monitoring during surgery using muscle relaxants. It provides 3 key points:
1) Neuromuscular monitoring is used to assess the level of muscle relaxation during surgery, determine the onset and recovery from muscle blockade, and minimize the risk of residual paralysis.
2) Several techniques are used for monitoring including single twitch stimulation, train-of-four stimulation, tetanic stimulation, and post-tetanic count stimulation.
3) Monitoring is important for patients at risk of residual paralysis, to determine the appropriate time for reversal of muscle relaxants, and to assess adequate recovery before extubation. However, monitoring has some limitations and may not always exclude residual weakness.
Narcotics and Non-Narcotics Analgesics.pptxFarazaJaved
This document summarizes narcotic and non-narcotic analgesics. It describes major classes of analgesics including opioids, NSAIDs, acetaminophen, flupirtine, and ziconotide. Specific drugs are discussed including morphine, methadone, fentanyl, codeine, tramadol, acetaminophen, NSAIDs, flupirtine and ziconotide. Their mechanisms of action, uses, adverse effects, and classification as pure agonists, partial agonists, antagonists are summarized.
This document summarizes key information about opioid analgesics including:
1. It classifies opioids based on their strength from strong to weak and lists examples in each category.
2. It outlines several clinical uses of opioids such as for analgesia, cough suppression, and treatment of opioid dependence.
3. It describes the pharmacokinetics of opioids including absorption, metabolism, and ability to cross the placental barrier and affect fetuses.
4. It explains the mechanism of action of opioids including their binding to μ, δ, and κ receptors in the brain and spinal cord to produce effects like analgesia and respiratory depression.
General anaesthetics (GAs) are drugs which produce reversible loss of all sensation and consciousness.
The cardinal features of general anaesthesia are:
• Loss of all sensation, especially pain.
• Sleep (unconsciousness) and amnesia
• Immobility and muscle relaxation
• Abolition of somatic and autonomic reflexes.
GA was absent until the mid 1800’s
Original discoverer of GA
-Crawford long, physician from Gerogia(1842),
ETHER ANESTHESIA
. NITROUS OXIDE
- Horace wells(1844)
. GASEOUS ETHER by William T.G. Morton(1846)
. CHLOROFORM introduced by
- James simpson (1847)
METHODS OF ADMINISTRATION OF INHALATIONAL GENERAL ANAESTHETICS
OPEN METHOD: This is a simple method of administering a volatile anaesthetic.
A simple mask covered with six to ten layers of gauze, which does not fit the contour of the face is held on the face and an anaesthetic like ether, or ethyl chloride is poured on it in drops. The anaesthetic vapour, diluted with air, is inhaled through the gap between the mask and the face.
SEMI-OPEN METHOD: This method is similar to open method but the dilution with air is prevented by using either a well-fitting mask like Ogston’s mask or layers of gauze between face and the mask. A small carbon dioxide build-up occurs with this method.
SEMI-CLOSED METHOD: This method allows some rebreathing of the anaesthetic drug with the help of a reservoir but in addition, part of the volume of each succeeding inspiration is a new portion from an anaesthetic mixture. This method involves accumulation and rebreathing of carbon dioxide.
• CLOSED METHOD: This method employs the chemical agent soda lime to absorb the carbon dioxide present in the expired air. It requires the use of a special apparatus but is particularly useful when the anaesthetic agent is potentially explosive
STAGES OF ANAESTHESIA
Guedel, in 1920 outlined the four stages of general anaesthesia :
• Stage I: Stage of analgesia
• Stage II: Stage of delirium
• Stage III: Stage of surgical anaesthesia
• Stage IV: Stage of respiratory paralysis
Inadequate anaesthesia is indicated by:
Signs of ANS overactivity, such as tachycardia, rise of BP, sweating and lacrimation.
Grimacing;
Other muscle activity.
Surgical anaesthesia is indicated by:
Loss of eyelash (lid) reflex
Development of rhythmic respiration.
Deep anaesthesia is suggested by :
Depression of respiration.
Hypotension
Asystole
The document discusses several key points about opioids:
1. It describes the endogenous opioid systems and receptors in the body, including proenkephalin, prodynorphin, pro-opiomelanocortin, and the mu, kappa, delta, and other receptors.
2. It summarizes the pharmacokinetics and pharmacodynamics of opioids like morphine and meperidine, how they work in the body to produce analgesia and other effects.
3. The main effects of opioids discussed are analgesia, respiratory depression, nausea/vomiting, and other central nervous system effects. Their use in anesthesia is also covered.
This document summarizes opioids and their mechanisms of action. It discusses that opioids act on mu, kappa, and delta opioid receptors in the central nervous system and gastrointestinal tract to produce analgesia, euphoria, sedation and other effects. The document outlines the classification, agonists, antagonists and effects of different opioid receptors. It provides details on commonly used opioid analgesics like morphine, codeine, methadone, tramadol and their indications, pharmacological actions, and adverse effects. Peripheral opioid antagonists are discussed for treating opioid-induced constipation.
This document discusses various opioid analgesics and antagonists used for pain management. It describes how opioids work by binding to receptors in the central nervous system and periphery to reduce pain transmission. The major opioid receptor types are μ, κ, and δ, with μ receptors mainly responsible for analgesia. Common opioid agonists discussed include morphine, codeine, meperidine, methadone, fentanyl, and heroin. Their mechanisms of action, therapeutic uses, pharmacokinetics, and adverse effects are summarized.
This document summarizes opioids and their classification, mechanisms of action, and effects. Opioids are compounds that bind to opioid receptors in the central nervous system to produce morphine-like analgesic effects. The three main opioid receptor types are mu, kappa, and delta, which have different selectivities for opioids. Opioids relieve pain by altering pain perception in the brain and spinal cord. Common side effects include respiratory depression, constipation, and euphoria. Opioid antagonists like naloxone can reverse the effects of opioid overdose.
Opioid analgesics work by binding to opioid receptors in the brain and spinal cord to reduce pain. There are several types of opioid receptors that endogenous opioid peptides and exogenous opioids can bind to, including mu, delta, and kappa receptors. Opioids are well absorbed orally or parenterally and distributed widely throughout the body. They are metabolized in the liver mainly by conjugation with glucuronic acid and excreted in urine. Opioids produce analgesia, sedation, respiratory depression, nausea, vomiting, and constipation by acting on central and peripheral opioid receptors. Tolerance and physical dependence may develop with repeated use.
The document discusses opioids and their use in pain management. It provides an overview of opioids, describing them as natural, semisynthetic, or synthetic drugs that bind to opioid receptors in the central nervous system. It then discusses several specific opioids like morphine, codeine, oxycodone, fentanyl, and methadone, outlining their classifications, mechanisms of action, indications, and side effects. The document also covers topics like opioid receptors, partial agonists and mixed agonist-antagonists, and the physiological effects of stimulating opioid receptors.
Morphine is a potent opioid analgesic derived from opium. It acts directly on the central nervous system to relieve pain. Morphine can be administered parenterally via injection or orally, but oral bioavailability is low. Common side effects include respiratory depression, nausea, vomiting, sedation, constipation, and dependence/addiction. Several semi-synthetic opioids like hydromorphone and oxycodone were developed with improved potency and reduced side effects compared to morphine. Opioid antagonists like naloxone and naltrexone were also developed to counter the effects of opioid overdose and dependence.
The document discusses opioid autocoids, which are endogenous substances that act as neurotransmitters and neuromodulators. It begins by defining autacoids and opioids, and describing the classification of opioid receptors in the central nervous system, peripheral nervous system, and gastrointestinal tract. The physiological and pathological roles of opioid autocoids are then examined, including their effects on analgesia, mood, respiration, the gastrointestinal system, and the endocrine and immune systems. The document also covers the organ system effects of opioids, their uses for pain relief and other purposes, and potential adverse effects such as sedation, nausea, constipation, and respiratory depression.
This document summarizes opioids and their classification, mechanisms of action, pharmacokinetics and effects. It discusses both natural and synthetic opioids like morphine, codeine, heroin, fentanyl, hydromorphone, meperidine and methadone. It also covers opioid receptors, endogenous opioid peptides, and antagonists such as naloxone and naltrexone which are used to reverse opioid overdose and effects.
This document discusses analgesic and anti-inflammatory agents. It covers topics such as the types of pain, pain receptors and their stimulation, the transmission and modulation of pain, classifications of opioids and NSAIDs, and the mechanisms of action and effects of morphine, codeine, endogenous opioids, prostaglandins, and various NSAIDs. It provides an overview of the pharmacology of commonly used analgesic and anti-inflammatory medications.
This document summarizes various opioid agonists and antagonists. It discusses natural and synthetic opioids like morphine, codeine, heroin, hydromorphone, fentanyl, meperidine, methadone, and diphenoxylate. It also covers opioid receptors, endogenous opioid peptides, pharmacokinetics, effects, tolerance, toxicity, and antagonists like naloxone and naltrexone. Non-steroidal anti-inflammatory drugs are also briefly mentioned.
This document summarizes key aspects of opioid agonists and antagonists:
1. It classifies opioids as natural, semisynthetic, or synthetic, and describes the chemical structure of morphine. Morphine binds to mu, kappa, and sigma receptors in the central nervous system.
2. Endogenous opioid peptides like enkephalins and endorphins are derived from precursor proteins and act as neuromodulators or neurohormones.
3. Morphine is readily absorbed and distributed in the body, metabolized in the liver, and excreted by the kidneys. It provides analgesia and sedation by acting on the CNS but also causes respiratory depression, constipation
This document discusses analgesic drugs used in anesthesia, focusing on opioids. It describes how opioids act in the central and peripheral nervous systems to reduce the perception and reaction to pain. Various opioids are classified and their mechanisms of action, pharmacokinetics, clinical uses, and adverse effects are outlined. Morphine, meperidine, and fentanyl are discussed as examples to illustrate differences between opioids commonly used for analgesia.
This document provides an overview of opioids and opioid analgesics. It discusses how opioids act in the central nervous system and peripheral tissues to relieve pain. It describes the endogenous opioid system and three families of opioid peptides: endorphins, enkephalins, and dynorphins. It also discusses the three main types of opioid receptors: mu, kappa, and delta. The rest of the document details specific opioid analgesics including natural alkaloids like morphine and codeine, semi-synthetic opioids like heroin and oxycodone, and synthetic opioids like methadone and tramadol. It provides information on their mechanisms of action, therapeutic uses, and adverse effects.
Opioids and opiates act on mu, kappa, and delta opioid receptors throughout the body and brain. Mu receptors are responsible for analgesia, respiratory depression, and euphoria, making overdose dangerous. Chronic use can increase tolerance and risk of overdose. While prescription opioids started the current crisis, many users transition to highly dangerous illegal opioids like fentanyl and fentanyl analogs. Naloxone is used to treat overdoses but very potent synthetic opioids require high doses or continuous infusion.
This document provides an overview of opioid agonists and antagonists. It discusses the classification, chemistry, receptors, endogenous peptides, central nervous system effects, pharmacokinetics, tolerance, therapeutic uses, drug interactions, and antagonism of opioids like morphine, codeine, heroin, hydromorphone, fentanyl, meperidine, methadone, and diphenoxylate. It also covers opioid receptor antagonists naloxone and naltrexone, which are used to reverse the effects of opioid agonists and treat opioid overdose and addiction.
This document provides an overview of analgesics (painkillers) including their classification, mechanisms of action, adverse effects, uses, and addiction potential. It focuses on opioid analgesics such as morphine, codeine, heroin, pethidine, and tramadol which are derived from the opium poppy. It discusses the history of opioid use and trade dating back thousands of years. It also covers non-opioid options like NSAIDs, acetaminophen, and various opioid antagonists used to treat overdose and addiction. The document aims to educate on the appropriate use and risks of different analgesic drugs.
Clinical Symptoms and Management of Morphine ,Organophosphorus and Mercury ...Drx Piyush Lodhi
The document provides information on morphine, organophosphorus, and mercury poisoning. It discusses the symptoms, diagnosis, and treatment of each type of poisoning. For morphine poisoning, it outlines the three stages of symptoms from excitement to coma. Treatment involves gastric lavage and administration of the antidote naloxone. For organophosphorus poisoning, it describes how the chemicals inhibit acetylcholinesterase leading to excess acetylcholine and lists atropine and oxime compounds as antidotes. Mercury poisoning can be elemental, inorganic, or organic with each having different toxic profiles. Diagnosis involves blood and urine mercury levels while chelation therapy with DMPS is the treatment of choice.
This document discusses opioids, including their endogenous peptides, receptors, mechanisms of action, effects, uses, and classifications. Some key points:
- Opioids act on mu, kappa, and delta opioid receptors and produce analgesia, sedation, respiratory depression and other effects.
- Common opioids discussed include morphine, fentanyl, remifentanil and meperidine. Their pharmacokinetics, uses, and differences are outlined.
- Opioids are widely used for pain management, especially in cancer, and can decrease anesthetic requirements. However, tolerance and dependence may develop upon prolonged use.
This document discusses puerperal sepsis/infections, providing definitions and guidelines for prevention and treatment. Puerperal sepsis is defined as a genital tract infection occurring between membrane rupture or labor onset through 42 days postpartum, accompanied by at least two symptoms like fever or abnormal discharge. Puerperal infections are a broader term including infections of the genitourinary system or uterus related to labor/delivery. Prevention focuses on identifying/treating infections antenatally, adhering to sterile procedures during labor and delivery, and treating promptly with antibiotics like ampicillin, amoxicillin or gentamycin postpartum.
This document discusses the chemotherapy of amoebiasis, giardiasis, and trichomoniasis. It outlines the symptoms, diagnosis, and treatment for each infection. For amoebiasis, metronidazole is the drug of choice for colitis and liver abscesses. For giardiasis, metronidazole is the first-line treatment over 5-10 days. Common symptoms include diarrhea and stomach cramps. For trichomoniasis, the causative agent resides in the urogenital tract. Metronidazole treatment over 7 days is recommended for both men and women who are symptomatic.
The drug development process involves 5 main steps: 1) discovery and preclinical research to test safety and efficacy in animals, 2) clinical trials in 4 phases with an increasing number of participants to further evaluate safety and efficacy in humans, 3) FDA review of the new drug application and clinical trial data, 4) potential FDA approval and post-market safety monitoring, and 5) reasons for drug failure can include toxicity, inadequate performance, lack of efficacy, or low bioavailability.
Typhoid fever is caused by the bacteria Salmonella Typhi. It spreads through contaminated food or water. Symptoms include sustained fever, abdominal pain, constipation or diarrhea. Complications can include intestinal perforation, bleeding or neurological issues. Diagnosis involves blood, stool or bone marrow cultures. Treatment is with antibiotics like chloramphenicol or ciprofloxacin. Prevention involves good hygiene, protected water and vaccination.
Shigellosis is caused by Shigella bacteria and spreads through poor hygiene. It causes bloody diarrhea, fever and abdominal cramps. Treatment is supportive care and antibiotics like ampicillin or ciprofloxacin. Prevention requires proper hygiene and disposal of feces.
The document discusses the nervous system and synapses. It describes how synapses allow neurons to communicate via either electrical or chemical transmission. At chemical synapses, neurotransmitters are released from the presynaptic neuron and bind to receptors on the postsynaptic neuron, causing changes in its membrane potential. Excitatory synapses cause depolarization via EPSPs, while inhibitory synapses cause hyperpolarization or stabilization via IPSPs. Spatial and temporal summation of EPSPs at synapses can bring the postsynaptic neuron to threshold to fire an action potential. Neurotransmitters are removed from synapses via reuptake or degradation to terminate signals. Drugs can modify synaptic transmission by affecting neurotransmitter synthesis, storage, release, receptor activation, or reupt
This document discusses the various processes and routes by which drugs are excreted from the body. The major routes of excretion are renal excretion through glomerular filtration, tubular secretion, and reabsorption in the kidneys; hepatobiliary excretion through bile secretion and enterohepatic recycling in the liver; and pulmonary excretion through expiration from the lungs. Other minor routes include excretion in sweat, saliva, breast milk, and feces. The rate of excretion influences the duration of a drug's effects in the body.
This document provides an overview of the physiology of pregnancy. It discusses changes in maternal organ systems including cardiovascular, hematologic, urinary, respiratory, gastrointestinal, endocrine, and dermatologic systems. It describes signs and symptoms of pregnancy such as missed menstrual period, nausea, breast changes, and fetal movement. Diagnosis of pregnancy is confirmed through urine or blood tests to detect human chorionic gonadotropin and ultrasound to visualize the gestational sac and fetal heart.
NSAIDs work by inhibiting the COX enzymes that produce prostaglandins, which mediate inflammation and pain. They are effective for relieving inflammatory pain but do not strongly affect central pain processing like opioids. NSAIDs can have gastrointestinal, renal, cardiovascular, and bleeding side effects due to their mechanism of reducing prostaglandins, which protect gastric mucosa and regulate kidney function. Their use requires consideration of risks in patients with conditions like peptic ulcer disease, kidney impairment, or bleeding disorders.
Cushing's syndrome and Addison's disease are both endocrine disorders caused by issues with cortisol production and regulation. Cushing's syndrome results from excessive cortisol levels due to conditions like pituitary or adrenal tumors. Its symptoms are treated through surgical removal of the tumor or medical therapy to control cortisol levels. Addison's disease is caused by inadequate cortisol production, often due to autoimmune destruction of the adrenal glands. Its treatment involves lifelong glucocorticoid and mineralocorticoid hormone replacement therapy. Both conditions require monitoring and medication adjustments in response to stress or illness to prevent adrenal insufficiency or crisis.
This document provides an overview of central nervous system (CNS) drugs. It discusses how drugs can modify neurotransmitter synthesis, ion fluxes, and act as receptor antagonists. CNS drugs are classified as general depressants, general stimulants, or drugs that selectively modify function. Selective drugs include analgesics, anticonvulsants, and drugs for Parkinson's disease, appetite suppression, anesthesia, and psychiatric conditions. The document outlines characteristics of CNS drugs such as additivity, antagonism, concentration-dependent effects, and potential for drug interactions.
(1) The document discusses the use of opioids in pain management, noting their long history dating back to the 1800s and their increased use to treat wartime injuries. (2) It describes how opioids work by attaching to receptors in the brain and spinal cord to block pain messages, and notes the risk of addiction with long-term chronic pain treatment. (3) The document outlines various considerations for appropriate opioid use based on factors like age, pain severity, and risk of drug interactions or substance abuse issues.
1. The document provides an overview of body cavity development in embryology. It discusses the three main body cavities: pericardial, pleural, and peritoneal cavities.
2. The cavities develop from the intra-embryonic coelom and are partitioned by the paired pleuro-pericardial membranes and diaphragm. Serous membranes also form from the parietal and visceral layers of the lateral plate mesoderm.
3. Congenital defects that can occur due to abnormalities in body cavity development are discussed, including diaphragmatic hernias, omphalocele, and gastroschisis.
The document discusses antimycobacterial drugs used to treat tuberculosis and leprosy. It begins by outlining the challenges of treating infections caused by slow-growing mycobacteria, including their intrinsic resistance. It then describes the goals and principles of TB therapy, including using multi-drug regimens to prevent resistance. The first-line drugs for TB, including isoniazid, rifampin, pyrazinamide, and ethambutol are discussed in detail. Treatment regimens for both adults and children are provided. The document also covers definitions and treatment approaches for drug-resistant TB. Finally, it concludes with an overview of drugs used to treat leprosy such as dapsone, rifamp
This document discusses puberty, the menstrual cycle, and abnormal uterine bleeding. It begins by defining puberty and explaining the physiological changes and hormonal control of puberty onset. It then discusses the menstrual cycle in detail, explaining the ovarian, endometrial, and hormonal regulation of the cycle. Finally, it defines abnormal uterine bleeding and discusses various causes and treatments of menstrual disorders.
Thyrotoxicosis is a clinical state caused by inappropriately high levels of thyroid hormones in the body. It can be caused by Graves' disease, toxic multinodular goiter, toxic adenoma, thyroiditis, or excess thyroid hormone replacement. The excess thyroid hormones increase the basal metabolic rate and tissue thermogenesis, leading to symptoms like weight loss, heat intolerance, palpitations, tremors, and anxiety. Diagnosis involves testing thyroid hormone levels which will be high and TSH levels which will be low. Treatment options include anti-thyroid medications, radioactive iodine therapy, or surgery to reduce thyroid hormone production. Complications can include heart and bone issues if left untreated.
The document discusses drugs used for pain and inflammation management. It begins by defining inflammation, analgesics, NSAIDs, and antipyretics. NSAIDs like aspirin, ibuprofen, and paracetamol are described in more detail, including their mechanisms of action, pharmacokinetics, therapeutic uses, and adverse effects. Specific concerns for NSAID use in pregnancy and risks of overdose like Reye's syndrome and hepatitis are also summarized. The document provides an overview of pharmacotherapy options for pain and fever treatment.
This document summarizes several classes of antimicrobial drugs, including sulfonamides, chloramphenicol, azoles, oxazolidinones, glycopeptides, and carbapenems. It describes the mechanisms of action, pharmacokinetics, clinical uses, and adverse effects of specific drugs within these classes like sulfamethoxazole-trimethoprim, metronidazole, linezolid, vancomycin, and imipenem. The document provides detailed information on the properties and use of these antimicrobial agents in treating various bacterial, fungal, and protozoal infections.
This document discusses anaemia and haemoglobinopathies. It defines anaemia and classifies it based on haemoglobin levels. The physiology of haemopoiesis is explained. Different types of haemoglobin are described. Causes of anaemia are outlined for newborns, children and adults, including haemolytic, haemorrhagic and diminished red blood cell production causes. Clinical features and complications of iron deficiency anaemia are highlighted. Investigations for identifying the cause of anaemia are mentioned.
Bone is continuously remodeled by the actions of osteoclasts which resorb bone and osteoblasts which form new bone. This remodeling is regulated by parathyroid hormone (PTH) and vitamin D. PTH increases calcium levels in the blood by acting on bones, kidneys and intestines. It stimulates bone resorption and renal calcium reabsorption. PTH levels are regulated by a negative feedback loop with calcium. Diseases are associated with abnormal PTH levels and bone remodeling.
This document discusses antimicrobial therapy and antibiotics. It provides an overview of general principles of antimicrobial use and resistance. It then focuses on different classes of antibiotics including beta-lactam antibiotics such as penicillins. Several penicillin derivatives are examined in depth, including their mechanisms of action, pharmacokinetics, indications, dosages and side effects. The document emphasizes prudent antibiotic use to prevent further development of resistance.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
2. OVERVIEW
Introduction
Terminologies and Opioid receptors
Pharmacological Effects of Opioids
Classification of Opioids analgesics
MORPHINE AND RELATED OPIOID AGONISTS
MIXED OPIOID AGONIST–ANTAGONISTS OR PARTIALAGONISTS
OPIODS USED AS ANTITUSSIVE AGENTS
Pharmacokinetic and Pharmacodynamic of Opioid analgesics and
Antagonists
3. INTRODUCTION TO OPIOD TERMINOLOGIES
Opioids: Chemicals that bind to opioid receptors which are found principally in the central nervous s
gastrointestinal tract.
Opiates: are drugs derived from opium and include the natural products morphine, codeine, and theba
semisynthetic derivatives.
Endogenous opioid peptides (endorphins): Naturally occurring ligands for opioid receptors. Opia
effects by mimicking these peptides.
Narcotic: Derived from the Greek word “stupor” and it originally referred to any drug that induced sl
associated with opioids.
Tolerance refers to a decrease in effectiveness of a drug with its repeated administration and an inc
required to produce the same physiological response.
4. INTRODUCTION TO OPIOD TERMINOLOGIES
Dependence refers to a complex set of changes in the homeostasis of an organism t
disturbance of the homeostatic set point of the organism if the drug is stopped. This disturb
seen when administration of an opioid is stopped abruptly, resulting in withdrawal.
Withdrawal is the unpleasant, sometimes life-threatening physiological changes that occ
discontinuation of use of some drugs after prolonged regular use.
In the case of opioids signs of withdrawal include chills, fever, sweating, yawnin
diarrhea, nausea, dizziness and hypertension.
In general the effects observed upon withdrawal are the opposite of those observed when the
taking the drug.
5. INTRODUCTION TO OPIOD TERMINOLOGIES
Addiction refers to dependence on a habit forming substance or behavi
person is powerless to stop. This term has been partially replaced by
dependence for substance abuse.
There are two types of addictions:
Substance addictions e.g. alcoholism, drug abuse, smoking.
Process addiction e.g. gambling, spending,shopping, eating e.t.c
6. ENDOGENOUS OPIOID PEPTIDES
They are three families of endogenous opioids namely:
Enkephalins
Endomorphins
Dynorphins
Each family is derived from a disntinct precursor protein:
Endomorphins are derived from prepro-opiomelanocortin (POMC). The major opioid peptide derived from
POMC is β-endorphin. In addition to the β-endorphin, the POMC precursor is processed into the nonopioid
peptides adrenocorticotropic hormone (ACTH), melanocyte stimulating hormone (α-MSH), and β-lipotropin (β-
LPH).
Enkephalins are derived from preproenkephalin.
Dynorphins are derived from preprodynorphin.
7.
8. CELLULAR MECHANISMS OF OPIOID RECEPTORS
Opioid receptors are members of the G protein super-family of receptors.
Drug-induced interaction with these receptors is associated with a decrease in activation of the enzyme adenylyl cyclase and a
subsequent decrease in cyclic adenosine monophosphate (cAMP) levels in the cell.
Binding of opioids to their receptors produces a decrease in calcium entry to cells by decreasing the phosphorylation of the
voltage gated calcium channels and allows for increased time for the channels to remain closed.
In addition, activation of opioid receptors leads to potassium efflux, and the resultant hyperpolarization limits the entry of
calcium to the cell by increasing the negative charge of the membrane to levels at which these calcium channels fail to activate.
The net result of the cellular decrease in calcium is a decrease in the release of dopamine, serotonin, and nociceptive peptides,
such as substance P, resulting in blockage of nociceptive transmission.
9. OPIOID RECEPTORS
Three classical opioid receptor types µ (mu), δ (delta) and κ (kappa)
There are several subtypes of opioid receptors all of which belong to the G protein-coupled family of
receptors:
µ1 receptors: mediate the analgesic and euphoric effects and physical dependence on opioids.
µ2 receptors: mediate the bradycardiac and respiratory depressant effects
δ receptors: mediate spinal analgesic effects and also play a role in the modulation of tolerance to µ-
opioids.
κ opioid receptors: mediate spinal analgesia, miosis, sedation and diuresis.
10. PHARMACOLOGICAL EFFECTS OF OPIODS
i. ANALGESIA
Morphine the prototype of opioid agonists interact with receptors in the brain and in the spinal cord.
The initial binding of opioids in the brain causes the release of the inhibitory neurotransmitter serotonin. Serotonin
induces inhibition of the dorsal horn neurons.
In the spinal cord, morphine inhibits the release of most nociceptive peptides.
Opioids also have profound effects upon the cerebrocortical regions that control the somatosensory and discriminative
aspects of pain.
Therefore opioids suppress the perception of pain by eliminating or altering the emotional aspects of pain and inducing
euphoria and sleep with higher doses.
Due to this patients become inattentive to the painful stimuli, less anxious, and more relaxed.
11. PHARMACOLOGICAL EFFECTS OF OPIODS
II. MEDULLARY EFFECTS
Respiration: Morphine-like opioids depress respiration via the µ2-receptor at the level of the medulla and thereby
increase PCO2. Opioids reduce respiration which can be fatal in the case of overdose.
This effect occurs due to a decrease in both the sensitivity of the medulla to carbon dioxide concentrations and the
respiratory rate.
Nausea and emetic effects: Nausea and vomiting produced by morphine-like drugs are caused by direct
stimulation of the chemoreceptor trigger zone in the area postrema of the medulla.
All clinically useful µ-agonists produce some degree of nausea and vomiting.
Antagonists to the 5HT3 receptor are the drugs of choice in the treatment of opioid induced nausea and vomiting.
Gastric prokinetic agents e.g. metoclopramide are also useful in this type of nausea and vomiting.
12. PHARMACOLOGICAL EFFECTS OF OPIODS
III. Miosis
Morphine and most µ and k agonists cause constriction of the pupil by an excitatory action on the
parasympathetic nerve innervating the pupil. Miosis or pinpoint pupils is diagnostic of the use and abuse of the
opioids.
IV. Hypothalamic Effects
Morphine also alters the equilibrium point of the hypothalamic heat regulatory mechanisms such that body
temperature usually falls slightly.
V. Immune Function and Histamine
Opioids induce the release of histamine, which leads to the itching sensation associated with use and abuse of
opioids. Bronchioconstriction can also occur in response to histamine release. Opioids also have effects on the T-
helper and T-suppressor cells and may therefore cause immunosuppression.
13. PHARMACOLOGICAL EFFECTS OF OPIODS
VI. NEUROENDOCRINE EFFECTS
Morphine acts in the hypothalamus to inhibit the release of gonadotropin-releasing hormone (GnRH) and
corticotropin-releasing hormone (CRH), thus decreasing circulating concentrations of luteinizing hormone (LH),
follicle-stimulating hormone (FSH), and ACTH.
As a result of the decreased concentrations of pituitary trophic hormones, plasma concentrations of sex steroids
and cortisol decline but thyrotropin secretion is relatively unaffected.
The administration of µ agonists increases the concentration of prolactin in plasma by reducing the dopaminergic
inhibition of its secretion.
With chronic administration, tolerance develops to the effects of morphine on hypothalamic releasing factors.
14. PHARMACOLOGICAL EFFECTS OF OPIODS
VII. CONVULSIONS
Morphine-like drugs excite certain groups of neurons especially the hippocampal pyramidal cells.
These excitatory effects result from inhibition of the release of GABA by interneurons.
Selective δ-agonists produce similar effects.
These actions may contribute to the seizures that are produced by some agents at doses only moderately higher than those required for
analgesia, especially in children.
With most opioids, however, convulsions usually occur at doses far in excess of those required to produce profound analgesia
seizures are not seen when potent µ agonists are used to produce anesthesia.
Naloxone is more potent in antagonizing convulsions produced by some opioids (e.g. morphine, methadone, and propoxyphene) than those
produced by others (e.g. meperidine).
The production of convulsant metabolites of meperidine may be partially responsible for the convulsions.
15. PHARMACOLOGICAL EFFECTS OF OPIODS
VIII. GI EFFECTS
Morphine and most other opioids produce some degree of constipation by increasing sphincter tone
and decreasing gastric motility.
Such an effect is uncomfortable for patients required to take opioids chronically.
Tolerance to the constipative effects of the opioids does not generally occur.
Decrease in gastric motility increases gastric emptying time and reduces absorption of other drugs.
The constriction of sphincters, especially the bile duct, may result in increased pain in certain patients
with biliary colic or other GI distress.
Constriction of the urinary sphincter can lead to painful urine retention in some patients.
The effects of opioids on the GI tract are largely mediated by the parasympathetic release of
acetylcholine.
All the opioid receptors have been shown to mediate such GI effects.
16. PHARMACOLOGICAL EFFECTS OF OPIODS
IX. BILIARY TRACT EFFECTS
After the subcutaneous injection of 10 mg morphine sulfate, the sphincter of Oddi
constricts, and the pressure in the common bile duct may rise more than tenfold
within 15 minutes and this effect may persist for 2 hours or more.
Fluid pressure also may increase in the gallbladder, producing symptoms that
vary from epigastric distress to typical biliary colic.
All opioids can cause biliary spasm. Atropine only partially prevents morphine-
induced biliary spasm, but opioid antagonists prevent or relieve it. Nitroglycerin
(0.6–1.2 mg) administered sublingually also decreases the elevated intrabiliary
pressure.
17. PHARMACOLOGICAL EFFECTS OF OPIODS
X. EFFECTS ON THE SKIN
Therapeutic doses of morphine cause dilation of cutaneous blood vessels.
The skin of the face, neck, and upper thorax frequently becomes flushed.
These changes may be due in part to the release of histamine and may be responsible for the sweating and pruritus
that occasionally follow the systemic administration of morphine.
Histamine release also accounts for the urticaria commonly seen at the site of injection, which is not mediated by opioid
receptors and is not blocked by naloxone.
It is seen with morphine and meperidine but not with oxymorphone, methadone, fentanyl, or sufentanil.
Pruritus is a common and potentially disabling complication of opioid use. It can be caused by intraspinal or systemic
injections of opioids, but it appears to be more intense after intraspinal administration. The effect is reversed by naloxone.
18. PHARMACOLOGICAL EFFECTS OF OPIODS
XI. CARDIOVASCULAR EFFECTS
Therapeutic doses of morphine produce peripheral vasodilation, reduced peripheral resistance, and an
inhibition of baroreceptor reflexes but these effects do not alter blood pressure or cardiac rate and rhythm in the
supine patient.
However when supine patients assume the upright position, orthostatic hypotension and fainting may occur.
The peripheral arteriolar and venous dilation produced by morphine may be due to release of histamine, which
sometimes plays a large role in the hypotension.
In patients with coronary artery disease, 8–15 mg morphine administered intravenously produces a decrease in
oxygen consumption, left ventricular end-diastolic pressure and cardiac work.
Morphine has an effect in the treatment of angina pectoris and acute myocardial infarction by decreasing
preload, inotropy, and chronotropy, thus decreasing myocardial O2 consumption and helping to relieve ischemia.
19. PHARMACOLOGICAL EFFECTS OF OPIODS
XII. ANTITUSSIVE EFFECTS
Morphine and related opioids also depress the cough reflex by a direct action on a cough
center in the medulla.
There is no obligatory relationship between depression of respiration and depression of
coughing, and antitussive agents are available that do not depress respiration.
Suppression of cough by such agents involves receptors in the medulla that are less sensitive
to naloxone than those responsible for analgesia.
20. PHARMACOLOGICAL EFFECTS OF OPIODS
XIII. TOLERANCE AND PHYSICAL DEPENDENCE
The development of tolerance and physical dependence with repeated use is a
characteristic feature of all the opioid drugs.
All the opioid agonists produce some degree of tolerance and physical
dependence.
Intracellular mechanisms of tolerance include increases in calcium levels in cells,
increased production of cAMP and decreased potassium efflux, alterations in the
phosphorylation of intracellular and intranuclear proteins, and the resultant return
to normal levels of the release of neurotransmitters and neuromodulators.
21. CLASSIFICATION OF OPIODS ANALGESICS
1. MORPHINE AND RELATED OPIOID AGONISTS
Morphine
Codeine And Other Phenanthrene Derivatives
Meperidine And Related Phenylpiperidine Derivatives
Fentanyl, Sufentanil, And Alfentanil
Levorphanol
Methadone
Propoxyphene
Heroin
2. MIXED OPIOID AGONIST-ANTAGONIST/PARTIAL AGONIST
Pentazocine
Butorphanol
Nalbuphine
Buprenorphine
23. I. MORPHINE AND RELATED OPIOID AGONISTS
MORPHINE
Morphine remains the standard by which other opioid analgesics are compared.
The predominant effects at the µ-opioid receptor, although it interacts with other opioid receptors as well.
Pharmacological Uses of Morphine :
Treatment of moderate to severe and chronic pain.
It is used preoperatively for sedation, anxiolytic effects and to reduce the dose of anesthetics.
Drug of choice for the treatment of myocardial infarction because of its bradycardiac and vasodilatory effects.
Treatment of dyspnoea- associated pulmonary edema by reducing the anxiety associated with shortness of breath, decreases
cardiac preload and afterload.
DOC in cancer patient
24. ADVERSE EFFECTS AND CONTRAINDICATIONS OF MORPHINE
Morphine and other opioids are contraindicated in patients with hypersensitivity reactions to the opioids.
In patients with acute bronchial asthma and should not be given as the drug of first choice
In patients with pulmonary disease, because it has antitussive effects that prevent the patient from clearing any buildup of
mucus in the lungs. Opioids with less antitussive effects, such as meperidine, are better for such situations.
Corticosteroids by the patient should be halted for at least 2 weeks prior to the insertion of the catheter to prevent infection,
since morphine increases the immunosuppressive effects of the steroids.
In head trauma because of the risk of a rise in intracranial pressure from the resultant vasodilation and increased cerebrospinal
fluid volume. In such patients the onset of miosis following opioid administration can mask the pupillary responses used
diagnostically for determination of concussion.
25. ADVERSE EFFECTS AND CONTRAINDICATIONS OF MORPHINE
In patients with severe liver disease and Renal disease. The clearance of morphine and its active
metabolite, morphine-6-glucuronide may be prolonged in patients with impaired renal function leading
to accumulation of morphine and its metabolite. The dose of these drugs should be reduced in such
patients.
Morphine, like all opioids, passes through the placenta rapidly and has been associated with
prolongation of labor in pregnant women and respiratory depression in the newborn.
Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when
combined with other sedatives, such as alcohol or barbiturates.
Increased sedation and toxicity are observed when morphine is administered in combination with the
psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such
as diazepam.
26. Drug interactions with Morphine
Drug group Effects of Interaction
Sedative-hypnotics Increased central nervous system
depression, particularly respiratory
depression.
Antipsychotic tranquilizers Increased sedation and respiratory
depression.
MAO inhibitors Relative contraindication to all
opioid analgesics because of the
high incidence of hyperpyrexic
coma.
27. II. CODEINE AND OTHER PHENANTHRENE DERIVATIVES
Naturally occurring opioid found in the poppy plant.
Codeine is indicated for the treatment of mild to moderate pain and for its antitussive effects. It is widely used as an opioid
antitussive because at antitussive doses it has few side effects and has excellent oral bioavailability.
Codeine is metabolized in part to morphine, which is believed to account for its analgesic effect. IWhen given alone, orally
administered codeine has about one-tenth to one-fifth the potency of morphine for the relief of pain.
IV codeine has a greater tendency to release histamine and produce vasodilation and hypotension than morphine and thus the
use of IV codeine is rare. Codeine is rarely addictive and produces little euphoria.
Adverse effects and drug interactions with codeine are similar to those of morphine, although they are less intense. Overdose
in children results in the same effects as overdose of morphine, such as respiratory depression, miosis, and coma. These
symptoms are treated with naloxone administration.
28. OTHER PHENANTHRENE DERIVATIVES
Cont..
Hydrocodone,oxycodone, dihydrocodeine, hydromorphone, and oxymorphone are derivatives of codeine and morphine. All
are indicated for the relief of mild to severe pain and used in combination with nonopioid analgesics. The drugs vary in potency,
but their pharmacological effects do not differ significantly from those of codeine or morphine.
Hydromorphone is eight times as potent as morphine but has less bioavailability following oral administration. Its side effects
are similar to those of morphine but are more intense. Hydromorphone is indicated for use in severe pain.
Oxycodone is nearly 10 times as strong as codeine, with absorption equal to that of orally administered morphine. Neither
hydromorphone nor oxycodone is approved for use in children, and hydromorphone is contraindicated in obstetrical analgesia and
in asthmatics.
Oxymorphone is 10 times as potent as morphine, with actions similar to those of hydromorphone. Oxymorphone, however,
has little antitussive activity, and as such is a useful analgesic in patients with pulmonary disease who need to retain the ability to
cough.
29. III. MEPERIDINE AND RELATED PHENYLPIPERIDINE DERIVATIVES
Meperidine is a phenylpiperidine derivative of morphine that was developed in the late 1930s as a potential anticholinergic agent. It has some
anticholinergic side effects that lead to tachycardia, blurred vision, and dry mouth. Meperidine is approximately one fifth as potent as morphine and is
absorbed only half as well when administered orally as parenterally. It has a rapid onset and short duration of action (2 hours) which is approximately one-
fourth that of morphine.
Like morphine, meperidine has an active metabolite, normeperidine, formed by N- demethylation of meperidine. Normeperidine is not analgesic but is a
proconvulsant and a hallucinogenic agent. For this reason, meperidine use in patients with renal or liver insufficiency is contraindicated because of the
decreased clearance of the drug and its metabolite.
Meperidine differs from morphine in that it has far less antitussive effect and little constipative effect.
Particularly useful in cancer patients and in pulmonary patients, in whom the cough reflex must remain intact. However, it has more seizure-inducing
activity than morphine. Although meperidine produces spasms of the biliary tract and colon, such spasms are of shorter duration than those produced by
morphine.
Meperidine readily passes the placenta into the fetus. However, respiratory depression in the newborn has not been observed, and meperidine clearance
in the newborn is rapid because it does not rely upon conjugation to glucuronides. Meperidine, unlike morphine, has not been associated with prolongation of
labor; conversely, it increases uterine contractions.
Symptoms of overdose with meperidine are qualitatively different from those of morphine in that seizures rather than sedation are common. Respiratory
depression and miosis are also present.
30. MEPERIDINE AND RELATED PHENYLPIPERIDINE
DERIVATIVES Cont..
Diphenoxylate is a meperidine derivative used as an antidiarrheal. It exhibits no morphine like
effects at low doses, but it produces mild opioid effects, such as sedation, euphoria, and
dependence, at higher doses. Its salts are highly insoluble in water, which reduces recreational
use. Preparations often include atropine to discourage abuse.
Difenoxin is a metabolite of diphenoxylate with antidiarrheal effects similar to the parent drug.
Loperamide (Imodium) is a piperidine derivative of diphenoxylate, which acts both at the level
of the gut and also in the CNS to reduce GI motility. Its use as an antidiarrheal and its potency are
similar to those of diphenoxylate.
31. CONTRAINDICATIONS OF MEPERIDINE AND RELATED
PHENYLPIPERIDINE DERIVATIVES
Similar to those of morphine. In addition:
Because normeperidine accumulates in renal dysfunction and meperidine accumulates in
hepatic dysfunction, meperidine is contraindicated in such patients because of convulsant
effects.
In patients who have a history of seizures or who are taking medication to prevent seizures.
Phenytoin administered for seizures may reduce the effectiveness of meperidine by increasing
the metabolism of the drug in the liver.
Meperidine is not generally used in patients with cardiac dysfunction, since its anticholinergic
effects can increase both heart rate and ectopic beats.
32. IV. FENTANY AND SUFENTANIL,
Fentanyl extremely potent drugs. Used as adjuncts to anaesthesia, and fentanyl may be given transdermally as an analgesic
and as an oral lozenge for the induction of anesthesia, especially in children who may become anxious if given IV anesthesia.
Fentanyl is 80 to 100 times as potent as morphine.
Sufentanil is 500- to 1,000-fold more potent than morphine, while alfentanil is approximately 20 times more potent than
morphine. Their onset of action is usually less than 20 minutes after administration.
Dosage is determined by the lean body mass of the patient, since the drugs are lipophilic and tend to get trapped in body fat,
which acts as a reservoir, prolonging their half-life. In addition, redistribution of the drugs from the brain to fat stores leads to a
rapid offset of action.
However, all the adverse side effects associated with morphine are produced with far greater intensity, but shorter duration, by
fentanyl in the patch, the lozenge, or IV administration.
33. FENTANYLAND SUFENTANIL, Cont…
Sufentanil is much more potent than fentanyl and is indicated specifically for long neurosurgical procedures.In
such patients, sufentanil maintains anaesthesia over a long period when myocardial and cerebral oxygen balances are
critical.
Fentanyl commonly used to relieve pain from intubation of premature infants. Tolerance and physical dependence
have been demonstrated after prolonged use of fentanyl in the newborn.
Adverse Effects and Contraindications
In addition to all the adverse effects and contraindications described for morphine, the following contraindications
apply specifically to these drugs:
They are contraindicated in pregnant women because of their potential teratogenic effects. They also can cause
respiratory depression in the mother, which reduces oxygenation of fetal blood. The incidence of sudden infant
death syndrome (SIDS) in the newborn is also increased.
Cardiac patients need to be monitored closely when receiving these drugs because of their bradycardiac and
hypotensive effects resulting from prolonged vasodilation.
In addition, these drugs stiffen the chest wall musculature but this effect can be reversed by naloxone.
34. V. LEVORPHANOL
Levorphanol is an L-isomer morphinan derivative of morphine that is five to seven times more potent than morphine.
It produces all the side effects associated with morphine but less nausea and vomiting.
It is indicated for moderate to severe pain as a preoperative anxiolytic.
It is often used in combination with thiopental to reduce the latter drug’s anaesthetic dose and to decrease postoperative
recovery time.
The D-isomer of levorphanol, dextromethorphan, does not possess opioid analgesic activity but is a useful antitussive.
35. VI. METHADONE
Methadone has an analgesic profile and potency similar to that of morphine but a longer duration of action and better oral
bioavailability.
Methadone and its derivative, L-α-acetyl- methadol (LAAM) have been shown to be useful in the treatment of opioid
addiction.
Methadone is a useful analgesic drug for the treatment of moderate to severe pain.
Unlike morphine, it is generally not used epidurally because of its long duration of action.
The side effects and signs of overdose following methadone administration are similar to those observed with morphine.
Overdose is treated with naloxone.
Clearance of methadone is via the urine and bile as the cyclic N-demethylated drug. The ability to N-demethylate the drug
decreases in elderly patients, prolonging the action of methadone. In such patients, dosing intervals should be longer than in
younger patients. In addition, the pH of the urine has a major effect on clearance of the drug.Alkalinization of the urine or renal
insufficiency decreases excretion of the drug.
36. METHADONE Cont..
Drug interactions and precautions for the use of methadone: similar to those of morphine.
In addition, rifampicin and hydantoins markedly increase the metabolism of methadone and can
precipitate withdrawal from methadone.
Conversely, the tricyclic antidepressants and certain benzodiazepines can inhibit metabolism of
methadone, thereby increasing accumulation of the drug, prolonging its half-life, and intensifying its side
effects.
Continuous dosing with methadone may lead to drug accumulation and to an increased incidence of
side effects.
In pregnant heroin-addicted women, substitution of methadone for heroin has been shown to be
associated with fewer low-birth-weight newborns and fewer learning and cognition problems later in the
life of the child.
37. VII. PROPOXYPHENE
Propoxyphene (dextropropoxyphene) structurally related to methadone but is much less potent as an analgesic.
Compared with codeine, propoxyphene is approximately half as potent and is indicated for the treatment of mild pain.
Toxicity from propoxyphene, especially in combination with other sedatives, such as alcohol, has led to a decrease in its use.
Death following ingestion of alcohol in combination with propoxyphene can occur rapidly (within 20 minutes to 1 hour).
The drug is not indicated for those with histories of suicide or depressive illnesses.
Like meperidine, propoxyphene has an active metabolite, norpropoxyphene, that is not analgesic but has excitatory and local
anesthetic effects on the heart similar to those of quinidine.
38. PROPOXYPHENE Cont..
Use of the drug during pregnancy is not safe. Teratogenic effects and withdrawal signs have been observed in
newborns.
As with morphine, propoxyphene requires adequate hepatic and renal clearance to prevent toxicity and drug
accumulation. It is thus contraindicated in the elderly patient and those with renal or liver disease.
Propoxyphene interacts with several drugs. The use of sedatives in combination with propoxyphene can be fatal.
Metabolism of the drug is increased in smokers due to induction of liver enzymes.Thus, smokers may require a higher
dose of the drug for pain relief.
Propoxyphene enhances the effects of both warfarin and carbamazepine and may increase the toxicity
associated with both drugs, such as bleeding and sedation, respectively.
The abuse liability of propoxyphene is low because of the extreme irritation it causes at the site of injection. Oral
use is the preferred route of administration for this reason.
39. VIII. HEROIN
Heroin is the diacetyl derivative of morphine.
It is either injected or snorted (taken intranasally).
Injection of the drug leads to the eventual collapse of the vessels into which it is injected, leading to the
appearance of track marks under the skin.
Heroin passes rapidly into the brain and thus has a rapid onset of action.
It is then metabolized to morphine. The rapid onset contributes to the abuse liability of the drug.
Heroin use in pregnant women can lead to low-birth-weight babies, babies born addicted to heroin,
immunosuppression, and an increased incidence of infections in both the mother and newborn.
40. ACUTE OPIOID TOXICITY
Acute opioid toxicity may result from clinical overdosage, accidental overdosage in addicts, or suicide
attempts.
Symptoms and Diagnosis
The triad of coma, pinpoint pupils, and depressed respiration strongly suggests opioid poisoning.
Coma: A patient who has taken an overdose of an opioid usually is stuporous or, if a large overdose has
been taken, may be in a coma.
Depressed respiration: The respiratory rate will be very low, or the patient may be apneic and
cyanotic.
Pinpoint pupils: The pupils will be symmetrical and pinpoint in size.
Frank convulsions occasionally occur in infants and children.
41. Treatment Of Acute Opioid Toxicity
Establish a patent airway and ventilate the patient.
Opioid antagonists can produce dramatic reversal of the severe respiratory depression, with
naloxone being the treatment of choice.
Tonic-clonic seizures, occasionally seen as part of the toxic syndrome with meperidine and
propoxyphene, are also ameliorated by treatment with naloxone
42. 2. MIXED OPIOID AGONIST–ANTAGONISTS /PARTIALAGONISTS
They are potent analgesics in opioid-naive patients but precipitate withdrawal in patients who are physically
dependent on opioids.
Useful for the treatment of mild to moderate pain.
Developed to reduce the addiction potential of the opioids while retaining the analgesic potency of the drugs.
Their analgesic effects due to an interaction at the κ-receptor and to a lesser extent the µ-opioid receptor.
Interaction at the κ-receptor increases the sedative effects of the drugs.
The dysphoric (unpleasant state characterized by restlessness and malaise) and psychotomimetic side effects -
attributed to interaction at the δ -receptor.
43. 2. MIXED OPIOID AGONIST–ANTAGONISTS /PARTIAL AGONISTS
Cont..
The mixed agonist–antagonists and partial agonists differ from morphine in that they:
(1) Produce excitatory and hallucinogenic effects,
(2) Produce a low degree of physical dependence,
(3) Produce excitatory effects related to the sympathetic discharge of norepinephrine and
therefore, are positive inotropic agents in the heart.
45. PENTAZOCINE
A potent analgesic with antagonistic activity in opioid-addicted patients.
Incompletely blocks the effects of morphine in such patients but will precipitate withdrawal.
To eliminate abuse of the drug via IV administration, pentazocine is combined with naloxone
(IV Talwin-NX®).
Talwin-NX admnistration produces no analgesic or euphoric effects because naloxone blocks
the pentazocine moiety.
However, the drug will retain its analgesic potency when administered orally, since naloxone is
not active orally.
46. PENTAZOCINE CONT..
Pentazocine produces as much respiratory depression as morphine but does not
produce the same degree of constipation or the biliary constriction observed with
morphine.
Pentazocine may increase GI motility if used in high doses.
Unlike morphine, pentazocine increases heart rate and blood pressure by
releasing norepinephrine.
Pentazocine also may increase uterine contractions in pregnancy.
47. CLINICAL USES OF PENTAZOCINE
Indicated for relief of moderate pain in patients not receiving large doses of opioids.
Also used as premedication for anesthesia and as a supplement to surgical anesthesia.
48. ADVERSE EFFECTS OF PENTAZOCINE
Sedation resulting from an interaction with the κ-receptor.
Sweating, dizziness, psychotomimetic effects, anxiety, nightmares, and headache.
Nausea and vomiting are less frequent than with morphine.
Respiratory depression and increased heart rate, body temperature, and blood pressure
accompany overdose.
Naloxone is effective in reducing the respiratory depression induced by pentazocine.
49. CONTRA-INDICATIONS OF PENTAZOCINE
Most of the contraindications specific to pentazocine stem from its excitatory effects.
Other contraindications are similar to those for morphine.
Pentazocine is contraindicated in patients with myocardial infarction because it increases heart rate
and cardiac load.
It is contraindicated in epileptic patients because it decreases seizure threshold.
It is contra-indicated in head trauma patients because it can increase intracranial pressure.
Pentazocine use in patients with psychoses is contraindicated because of its psychotomimetic side
effects.
50. DRUG INTERACTIONS OF PENTAZOCINE
Pentazocine with the antihistamine tripelennamine results in a combination known to drug
abusers as T’s and Blues. This combination produces heroin like subjective effects, and heroin
addicts use it in the absence of heroin.
Alcohol or barbiturates greatly enhances its sedative and respiratory depressant effects.
51. TOLERANCE AND DEPENDENCE OF PENTAZOCINE
Tolerance to the analgesic effects of pentazocine develops.
Withdrawal signs are milder than those seen with morphine, and they produce
more excitatory effects.
52. BUTORPHANOL
Butorphanol is chemically related to levorphanol but pharmacologically similar in
action to pentazocine.
As an opioid antagonist it is nearly 30 times as potent as pentazocine and has one-
fortieth the potency of naloxone.
It is a potent opioid analgesic indicated for the relief of moderate to severe pain.
Its potency is 7 times that of morphine and 20 times that of pentazocine as an analgesic.
53. BUTORPHANOL Cont..
Its onset of action is similar to that of morphine.
The side effects and signs of toxicity are similar to those produced by pentazocine.
It produces excitatory effects and sedation and precipitates withdrawal in opioid-
dependent patients.
Adverse effects, contraindications, and drug interactions are similar to those for
pentazocine and morphine.
54. NALBUPHINE
A mixedd agonist–antagonist that is similar in structure to both the antagonist naloxone
and the agonist oxymorphone.
Administered parenterally and is equipotent to morphine and 5 times as potent as
pentazocine.
Although the pharmacological effects are similar to those produced by pentazocine,
nalbuphine produces fewer psychotomimetic effects.
It differs from pentazocine in that it has far greater antagonist than agonist effect.
55. NALBUPHINE Cont..
Thus, its use is likely to precipitate severe withdrawal in opioid-dependent patients.
It is used for moderate to severe pain, surgical anesthesia and obstetrical analgesia.
Nalbuphine’s abuse potential is less than that of codeine and propoxyphene, although
tolerance and dependence have been shown following chronic administration.
Drug interactions and contraindications are similar to those for pentazocine and
morphine.
56. BUPRENORPHINE
Buprenorphine is a mixed agonist–antagonist and a derivative of the naturally occurring
opioid thebaine.
Buprenorphine is highly lipophilic and is 25 to 50 times more potent than morphine as
an analgesic.
The sedation and respiratory depression it causes are more intense and longer lasting
than those produced by morphine.
Its respiratory depressant effects are not readily reversed by naloxone.
57. BUPRENORPHINE Cont..
It binds to the µ-receptor with high affinity and only slowly dissociates from the receptor, this
explain the lack of naloxone reversal of respiratory depression.
Has more agonist than antagonist effects and is often considered a partial agonist rather
than a mixed agonist–antagonist, although it precipitates withdrawal in opioid-dependent
patients.
Its pharmacological effects are similar to those produced by both morphine and pentazocine
and is used in moderate to severe pain.
58. BUPRENORPHINE Cont…
The abuse potential of buprenorphine is low.
While high doses of the drug are perceived by addicts as being morphine-like.
It reduces the craving for morphine and for the stimulant cocaine.
Thus, buprenorphine is a potential new therapy for the treatment of addiction to both
classes of drugs.
Drug interactions and contraindications are similar to those described for pentazocine
and morphine.
59. B. OPIOID ANTAGONISTS
Naloxone and Naltrexone are pure opioid antagonists synthesized by
relatively minor changes in the morphine structure.
Opioid antagonists bind to the opioid receptors with high affinity.
The pure antagonists block the effects of opioids at all opioid receptors.
All opioid antagonists will precipitate withdrawal in opioid-dependent
patients.
60. NALOXONE
Naloxone is a pure antagonist and its major application is in the
treatment of acute opioid overdose.
Because of its fast onset (minutes), naloxone administered IV is used most
frequently for the reversal of opioid overdose.
However, it fails to block some side effects of the opioids that are mediated
by the δ- receptor, such as hallucinations.
The half-life of naloxone in plasma is 1-2 hours.
61. NALOXONE Cont..
It is rapidly metabolized via glucuronidation in the liver and cleared by the kidney.
Due to the relatively short duration of action of naloxone , frequent administration is
required because a severely depressed patient may recover after a single dose of naloxone and
appear normal, only to relapse into coma after 1–2 hours.
This rapid offset of naloxone makes it necessary to administer the drug repeatedly until the
opioid agonist has cleared the system to prevent relapse into overdose.
62. NALOXONE Cont..
When given orally has a large first-pass effect, which reduces its potency significantly.
Approved for use in neonates to reverse respiratory depression induced by maternal
opioid use.
In addition, naloxone has been used to improve circulation in patients in shock, an
effect related to blockade of endogenous opioids.
63. NALTREXONE
Naltrexone is three to five times as potent as naloxone.
Has duration of action of 24 to 72 hours, depending on the dose.
Used orally in the treatment of opioid abstinence.
Naltrexone exhibits a large first-pass effect in the liver.
64. NALTREXONE Cont..
The major metabolite, 6-naltrexol, is also a pure opioid antagonist and
contributes to the potency and duration of action of naltrexone.
Administration of naltrexone orally blocks the effects of abused opioids and is
used to decrease the craving for opioids in highly motivated recovering addicts.
65. SIDE EFFECTS OF NALTREXONE
High doses of the opioids can overcome the naltrexone blockade and lead to seizures or respiratory
depression and death.
Naltrexone can induce hepatotoxicity at doses only five times the therapeutic dose.
Should be used with care in patients with poor hepatic function or liver damage.
Side effects are more common with use of naltrexone than with naloxone administration.
Such side effects include headache, difficulty sleeping, lethargy, increased blood pressure, nausea,
sneezing, blurred vision, and increased appetite.
66. NALMEFENE
Nalmefene is a long-acting injectable pure opioid antagonist that binds all opioid receptors and reverses
the effects of opioid agonists at those receptors.
The onset of action is 2 minutes after IV administration.
Hepatic metabolism is slow and occurs via glucuronide conjugation to inactive metabolites.
Its half-life of 11 hours is about 5 times that of naloxone.
Indications include use in postoperative settings to reverse respiratory depression and in opioid
overdose.
67. NARCOTIC ANTITUSSIVE AGENTS
Certain opioids are used mainly for their antitussive effects.
Such drugs generally are those with substituents on the phenolic hydroxyl group
of the morphine structure.
The larger the substituent, the greater the antitussive versus analgesic selectively
of the drugs.
68. NARCOTIC ANTITUSSIVE AGENTS
i. DEXTROMETHORPHAN
Dextromethorphan hydrobromide is the D-isomer of levorphanol.
It lacks CNS activity but acts at the cough center in the medulla to produce an antitussive effect.
It is half as potent as codeine as an antitussive.
It has few side effects but potentiates the activity of monoamine oxidase inhibitors, leading to hypotension and
infrequently coma.
Dextromethorphan is often combined in lozenges with the local anesthetic benzocaine, which blocks pain from
throat irritation due to coughing.
69. NARCOTIC ANTITUSSIVE AGENTS
II. LEVOPROPOXYPHENE
Levopropoxyphene is the L-isomer of the analgesic agonist dextropropoxyphene.
Levopropoxyphene is only mildly antitussive and is rarely used.
It has no CNS effects. Side effects include dizziness and nausea.
70. NARCOTIC ANTITUSSIVE AGENTS
III. NOSCAPINE
Noscapine is a naturally occurring product of the opium poppy.
It is a benzylisoquinoline with no analgesic or other CNS effects.
Its antitussive effects are weak, but it is used in combination with other agents in
mixtures for cough relief.
71. NARCOTIC ANTITUSSIVE AGENTS
IV. BENZONATATE
Benzonatate is related to the local anesthetic tetracaine.
It anesthetizes the stretch receptors in the lungs, thereby reducing coughing.
Adverse reactions include hypersensitivity, sedation, dizziness, and nausea.