This document discusses the mechanisms of action and pharmacological properties of nonopioid analgesics, including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). It explains that these drugs inhibit the cyclooxygenase (COX) enzymes involved in prostaglandin synthesis, thereby reducing pain and inflammation. The document outlines the pathways involved in prostaglandin synthesis from arachidonic acid. It also describes the therapeutic effects and potential gastrointestinal, renal, platelet, and allergy-related side effects that can result from COX inhibition.
NSAIDs are the chemically diverse class of drugs that have anti-inflammatory, analgesic & antipyretic properties.
They are also called as Non Narcotic, Non Opioid, Aspirin like analgesics.
They are among the widely used therapeutic agents world wide and often taken without prescription for minor aches and pain.
They are used to suppress the symptoms of inflammation associated with rheumatic disease.
This document discusses NSAIDs (non-steroidal anti-inflammatory drugs). It provides a brief history of NSAIDs including the isolation of salicylic acid in 1836 and the development of aspirin in 1899. It also covers the common characteristics, mechanisms of action, and therapeutic uses of NSAIDs for treating pain, inflammation, and fever by inhibiting prostaglandin synthesis. The document further explains the pathophysiology of these conditions and how NSAIDs work to reduce symptoms.
This document provides an overview of analgesics, with a focus on non-steroidal anti-inflammatory drugs (NSAIDs). It defines pain and discusses the classification, mechanism of action, and history of analgesics. NSAIDs are introduced as a class of drugs that relieve pain and inflammation by inhibiting cyclooxygenase (COX) enzymes and subsequent prostaglandin synthesis. The document outlines the role of prostaglandins in inflammation and bone resorption, as well as the beneficial and harmful actions of NSAIDs through COX inhibition. Host modulation is discussed as a treatment concept in periodontics where NSAIDs may reduce tissue destruction by modulating the host inflammatory response.
analgesics and anti inflammatory drugs - Session 1Suman Mukherjee
The document provides an overview of analgesics. It defines analgesia and pain and classifies analgesics into two main groups - opioids and nonopioids. Opioids include morphine, which is the main component of opium. Morphine interacts with mu-opioid receptors in the brain and spinal cord to produce analgesia. Nonopioids include NSAIDs that work by inhibiting the COX enzymes. COX-1 helps protect the stomach lining while COX-2 contributes to inflammation. NSAIDs can be classified based on their selectivity for COX-1 vs COX-2. Common NSAIDs like aspirin, ibuprofen, and diclofenac are mentioned.
This document discusses NSAIDs (non-steroidal anti-inflammatory drugs). It begins by defining NSAIDs and describing their mechanisms of action, including inhibiting cyclooxygenase enzymes to reduce prostaglandin production. It then classifies different types of NSAIDs and describes their individual properties, mechanisms of action, effects, and potential adverse reactions. The document provides detailed information on the pharmacology of NSAIDs.
NSAIDs are a group of drugs that relieve pain, fever, and inflammation by inhibiting prostaglandin synthesis. They can be classified based on their action on COX enzymes or their chemical structure. Their mechanism of action involves blocking COX pathways to prevent the formation of prostaglandins. Common adverse effects include gastric irritation and impaired healing. NSAIDs should be used cautiously in patients with conditions like peptic ulcer or impaired kidney function.
This document summarizes analgesics used to treat pain. It describes how analgesics work on the central and peripheral nervous system. It discusses opioid analgesics like morphine which work on mu receptors in the spinal cord. It also discusses non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin and paracetamol which inhibit cyclooxygenase enzymes. The document outlines the mechanisms, effects, uses and side effects of various classes of analgesics as well as combination analgesic therapies for treating dental pain.
NSAIDs are the chemically diverse class of drugs that have anti-inflammatory, analgesic & antipyretic properties.
They are also called as Non Narcotic, Non Opioid, Aspirin like analgesics.
They are among the widely used therapeutic agents world wide and often taken without prescription for minor aches and pain.
They are used to suppress the symptoms of inflammation associated with rheumatic disease.
This document discusses NSAIDs (non-steroidal anti-inflammatory drugs). It provides a brief history of NSAIDs including the isolation of salicylic acid in 1836 and the development of aspirin in 1899. It also covers the common characteristics, mechanisms of action, and therapeutic uses of NSAIDs for treating pain, inflammation, and fever by inhibiting prostaglandin synthesis. The document further explains the pathophysiology of these conditions and how NSAIDs work to reduce symptoms.
This document provides an overview of analgesics, with a focus on non-steroidal anti-inflammatory drugs (NSAIDs). It defines pain and discusses the classification, mechanism of action, and history of analgesics. NSAIDs are introduced as a class of drugs that relieve pain and inflammation by inhibiting cyclooxygenase (COX) enzymes and subsequent prostaglandin synthesis. The document outlines the role of prostaglandins in inflammation and bone resorption, as well as the beneficial and harmful actions of NSAIDs through COX inhibition. Host modulation is discussed as a treatment concept in periodontics where NSAIDs may reduce tissue destruction by modulating the host inflammatory response.
analgesics and anti inflammatory drugs - Session 1Suman Mukherjee
The document provides an overview of analgesics. It defines analgesia and pain and classifies analgesics into two main groups - opioids and nonopioids. Opioids include morphine, which is the main component of opium. Morphine interacts with mu-opioid receptors in the brain and spinal cord to produce analgesia. Nonopioids include NSAIDs that work by inhibiting the COX enzymes. COX-1 helps protect the stomach lining while COX-2 contributes to inflammation. NSAIDs can be classified based on their selectivity for COX-1 vs COX-2. Common NSAIDs like aspirin, ibuprofen, and diclofenac are mentioned.
This document discusses NSAIDs (non-steroidal anti-inflammatory drugs). It begins by defining NSAIDs and describing their mechanisms of action, including inhibiting cyclooxygenase enzymes to reduce prostaglandin production. It then classifies different types of NSAIDs and describes their individual properties, mechanisms of action, effects, and potential adverse reactions. The document provides detailed information on the pharmacology of NSAIDs.
NSAIDs are a group of drugs that relieve pain, fever, and inflammation by inhibiting prostaglandin synthesis. They can be classified based on their action on COX enzymes or their chemical structure. Their mechanism of action involves blocking COX pathways to prevent the formation of prostaglandins. Common adverse effects include gastric irritation and impaired healing. NSAIDs should be used cautiously in patients with conditions like peptic ulcer or impaired kidney function.
This document summarizes analgesics used to treat pain. It describes how analgesics work on the central and peripheral nervous system. It discusses opioid analgesics like morphine which work on mu receptors in the spinal cord. It also discusses non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin and paracetamol which inhibit cyclooxygenase enzymes. The document outlines the mechanisms, effects, uses and side effects of various classes of analgesics as well as combination analgesic therapies for treating dental pain.
Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking cyclooxygenase (COX) enzymes, which reduces prostaglandin production and consequently decreases inflammation, pain, and fever. NSAIDs are used to treat conditions like arthritis, gout, and postoperative pain but can cause side effects like gastrointestinal ulceration and bleeding by inhibiting protective prostaglandins in the stomach. They may also increase risks of cardiovascular and renal issues. Care must be taken with NSAID combinations or when used with other drugs that impact renal function.
This document provides information on nonsteroidal anti-inflammatory drugs (NSAIDs) and antipyretic-analgesics. It discusses the classes of NSAIDs including mechanisms of action, therapeutic uses, examples of drugs, and side effects. NSAIDs work by inhibiting cyclooxygenase enzymes and thereby reducing production of prostaglandins involved in inflammation, pain, and fever. The document also reviews antirheumatic drugs for conditions like rheumatoid arthritis, as well as drugs for treating gout such as allopurinol, probenecid, and corticosteroids.
Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase (COX) enzymes and subsequent prostaglandin production. This reduces pain, fever, and inflammation. NSAIDs inhibit both COX-1 and COX-2, with COX-1 inhibition causing side effects like gastric ulceration, while selective COX-2 inhibitors have fewer side effects but higher costs. The mechanisms of analgesia, antipyresis, and anti-inflammation by NSAIDs are through inhibition of prostaglandin biosynthesis in both the central and peripheral nervous systems.
The document discusses pain and its classification, pathways, and treatment. It defines pain and describes the gate control theory of pain modulation. Pain is classified as nociceptive, neuropathic, or idiopathic. Treatment includes non-opioids like NSAIDs, opioids like morphine, and adjuvants. Morphine is a potent analgesic that acts primarily on mu opioid receptors in the CNS and PNS to reduce pain perception. Its mechanisms, effects, kinetics, uses, and adverse effects are outlined.
Aceclofenac is an NSAID that selectively inhibits COX-2 and has been shown to reduce inflammation and pain. It is well-absorbed orally and metabolized to active metabolites. Clinical trials demonstrate aceclofenac is effective for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other conditions, with fewer side effects than other NSAIDs like diclofenac. The recommended dosage is 100 mg twice daily by mouth.
This document discusses nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. It provides details on their mechanism of action as cyclooxygenase inhibitors, reducing prostaglandin synthesis and inflammation. Common uses include analgesia, antipyresis, and reducing the risk of cardiovascular events like heart attacks. Adverse effects include gastrointestinal irritation and bleeding. Aspirin is prototypical and its pharmacology and therapeutic uses are discussed in depth.
NSAIDs work by inhibiting the cyclooxygenase (COX) enzymes COX-1 and COX-2, which decreases the production of prostaglandins and leads to their anti-inflammatory, analgesic, and antipyretic effects. Aspirin irreversibly inhibits COX-1 and COX-2, while other NSAIDs reversibly inhibit the enzymes. NSAIDs are used to treat pain, fever, and inflammation conditions but can cause gastrointestinal adverse effects by reducing protective prostaglandins in the stomach. Their antiplatelet effect from COX-1 inhibition also increases bleeding risk. Acetaminophen is an effective antipyretic that is preferred in pregnancy due to safety.
Analgesics are drugs that relieve pain without causing unconsciousness. They are divided into opioid and non-opioid categories. Opioid analgesics include natural opium alkaloids like morphine and codeine, semi-synthetic opiates, and synthetic opioids. They act on opioid receptors in the brain. Non-opioid analgesics include NSAIDs like aspirin and ibuprofen, which reduce pain and inflammation by inhibiting prostaglandin synthesis. Acetaminophen is also a non-opioid analgesic. Both opioid and non-opioid analgesics can cause side effects like hypersensitivity, peptic ulcers, liver damage, and renal toxicity when taken in excess.
This document discusses nonsteroidal anti-inflammatory drugs (NSAIDs), including their classification, mechanisms of action, examples of different drug classes, and pharmacological effects. It focuses on aspirin as the prototype NSAID, describing its absorption, metabolism, uses, adverse effects, and interactions. Selective COX-2 inhibitors like celecoxib and rofecoxib are also introduced as NSAIDs with reduced gastric irritation.
NSAIDs are a class of drugs that relieve pain, fever, and inflammation by inhibiting cyclooxygenase enzymes. There are various types of NSAIDs classified by their chemical structure. All NSAIDs work by blocking prostaglandin production, but they differ in their selectivity for COX-1 vs COX-2 enzymes. Common adverse effects include gastrointestinal irritation and bleeding, as well as renal impairment. NSAIDs are commonly used to treat pain, fever, and inflammatory conditions like arthritis.
NSAIDs are a group of drugs that reduce pain, fever, and inflammation by inhibiting the COX enzymes that produce prostaglandins. COX enzymes exist in two forms, COX-1 and COX-2. NSAIDs work by blocking both forms of COX, though some are more selective for COX-2. This inhibition of COX reduces prostaglandin production and subsequent pain/fever/inflammation. However, it can also reduce platelet count and increase risk of stomach ulcers. NSAIDs are classified into several categories based on their chemical structure and mechanisms of action. The structure of individual NSAIDs influences their biological activity and side effect profiles.
A PowerPoint presentation on "NSAIDS" suitable for reading by UG and PG Medical/Paramedical students of Pharmacology and Pharmacy sciences. This Ppt. is prepared for academic purpose only and already presented to my students in one of the theory classes of mine.
This document summarizes opioids and their use as analgesics. It discusses the classification of opioids as natural, semi-synthetic, or synthetic and describes their mechanisms of action through mu, delta, and kappa receptors in the central nervous system. The document outlines the pharmacokinetics of opioid absorption, distribution, metabolism, and excretion. It also discusses the clinical uses of opioids like morphine, as well as their side effects, risks of overdose and addiction, and treatment options for opioid overuse.
Selective cox 2 inhibitors design by siddharthSiddharth Jain
The document discusses selective COX-2 inhibitors, which are a type of NSAID that selectively binds to the COX-2 enzyme responsible for inflammation and pain. It provides background on the COX-1 and COX-2 enzymes and reasons for developing selective COX-2 inhibitors to avoid the side effects of non-selective NSAIDs like ulceration and bleeding. The key structural differences between COX-1 and COX-2 that allow for selective inhibitor design are described. Examples of important selective COX-2 inhibitors developed include celecoxib and parecoxib.
The document discusses non-steroidal anti-inflammatory drugs (NSAIDs) and their role in periodontal disease treatment. It covers the definition of NSAIDs, their history of use, classification, mechanisms of action including inhibition of prostaglandin synthesis, and various types including salicylates, propionic acid derivatives, and selective COX-2 inhibitors. NSAIDs are proposed to have host modulatory properties for periodontal disease by suppressing inflammation and bone resorption mediated by prostaglandins. However, risks of adverse gastrointestinal effects must be weighed against potential benefits for periodontitis.
This document provides an overview of opioids including their pharmacology, mechanisms of action, classifications, and clinical uses. It discusses how opioids bind to receptors in the central and peripheral nervous systems to produce analgesic and other effects. Opioids are classified based on their receptor activities and include pure agonists, partial agonists, mixed agonist-antagonists, and pure antagonists. The document reviews the central and peripheral effects of opioids as well as their indications, contraindications, and interactions. It also discusses opioid tolerance, dependence, overdose, and withdrawal.
1. NSAIDs work by inhibiting prostaglandin synthesis via blocking cyclooxygenase (COX) enzymes. They are classified based on selectivity for COX-1 vs COX-2.
2. Aspirin is a non-selective, irreversible COX inhibitor. It provides analgesic, antipyretic and anti-inflammatory effects. Common adverse effects include gastric irritation and bleeding risks.
3. Paracetamol is considered a COX-3 inhibitor. It has analgesic properties but does not cause gastric irritation or bleeding like other NSAIDs. Acute overdose can cause liver damage.
This document summarizes inflammation and anti-inflammatory drugs. It describes the phases of inflammation, signs of inflammation, and mediators of the inflammatory response such as histamine, bradykinin, prostaglandins, and leukotrienes. It then discusses nonsteroidal anti-inflammatory drugs (NSAIDs) and their mechanisms of action by inhibiting cyclooxygenase enzymes and decreasing prostaglandin synthesis. Common NSAIDs are described including their pharmacological properties, mechanisms of action, therapeutic uses, and potential adverse effects such as gastrointestinal issues and bleeding risks.
This 20-slide slide set created with PowerPoint describes prostanoid synthesis and their effects on the body; mechanisms of action, beneficial and adverse effects of NSAIDS; the difference between the effects of low and high dose aspirin; and the effects and toxicity of paracetamol (acetaminophen). This is an introduction to the topic of NSAIDS which would be appropriate for beginners. Contributed by Christopher Fowler, Umeå University, Sweden.
9. NSAIDS.pptxNSAIDS inhibit the enzyme cyclooxygenase (COX) types 1 and 2, w...samiyamohammed284
Renal
Renally produced prostaglandins (PGE2 and PGI2) are essential
in maintaining adequate renal perfusion when the level of circulating vasoconstrictors Platelets
Impaired platelet function (reduced aggregation).
as a result of decreased thromboxane A2 (TXA2) production.
TXA2 is present in large amounts in activated platelets and acts locally as a chemo-attractant for other platelets, leads to the formation of a platelet plug and induces localized vasoconstric
Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking cyclooxygenase (COX) enzymes, which reduces prostaglandin production and consequently decreases inflammation, pain, and fever. NSAIDs are used to treat conditions like arthritis, gout, and postoperative pain but can cause side effects like gastrointestinal ulceration and bleeding by inhibiting protective prostaglandins in the stomach. They may also increase risks of cardiovascular and renal issues. Care must be taken with NSAID combinations or when used with other drugs that impact renal function.
This document provides information on nonsteroidal anti-inflammatory drugs (NSAIDs) and antipyretic-analgesics. It discusses the classes of NSAIDs including mechanisms of action, therapeutic uses, examples of drugs, and side effects. NSAIDs work by inhibiting cyclooxygenase enzymes and thereby reducing production of prostaglandins involved in inflammation, pain, and fever. The document also reviews antirheumatic drugs for conditions like rheumatoid arthritis, as well as drugs for treating gout such as allopurinol, probenecid, and corticosteroids.
Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase (COX) enzymes and subsequent prostaglandin production. This reduces pain, fever, and inflammation. NSAIDs inhibit both COX-1 and COX-2, with COX-1 inhibition causing side effects like gastric ulceration, while selective COX-2 inhibitors have fewer side effects but higher costs. The mechanisms of analgesia, antipyresis, and anti-inflammation by NSAIDs are through inhibition of prostaglandin biosynthesis in both the central and peripheral nervous systems.
The document discusses pain and its classification, pathways, and treatment. It defines pain and describes the gate control theory of pain modulation. Pain is classified as nociceptive, neuropathic, or idiopathic. Treatment includes non-opioids like NSAIDs, opioids like morphine, and adjuvants. Morphine is a potent analgesic that acts primarily on mu opioid receptors in the CNS and PNS to reduce pain perception. Its mechanisms, effects, kinetics, uses, and adverse effects are outlined.
Aceclofenac is an NSAID that selectively inhibits COX-2 and has been shown to reduce inflammation and pain. It is well-absorbed orally and metabolized to active metabolites. Clinical trials demonstrate aceclofenac is effective for osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other conditions, with fewer side effects than other NSAIDs like diclofenac. The recommended dosage is 100 mg twice daily by mouth.
This document discusses nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin. It provides details on their mechanism of action as cyclooxygenase inhibitors, reducing prostaglandin synthesis and inflammation. Common uses include analgesia, antipyresis, and reducing the risk of cardiovascular events like heart attacks. Adverse effects include gastrointestinal irritation and bleeding. Aspirin is prototypical and its pharmacology and therapeutic uses are discussed in depth.
NSAIDs work by inhibiting the cyclooxygenase (COX) enzymes COX-1 and COX-2, which decreases the production of prostaglandins and leads to their anti-inflammatory, analgesic, and antipyretic effects. Aspirin irreversibly inhibits COX-1 and COX-2, while other NSAIDs reversibly inhibit the enzymes. NSAIDs are used to treat pain, fever, and inflammation conditions but can cause gastrointestinal adverse effects by reducing protective prostaglandins in the stomach. Their antiplatelet effect from COX-1 inhibition also increases bleeding risk. Acetaminophen is an effective antipyretic that is preferred in pregnancy due to safety.
Analgesics are drugs that relieve pain without causing unconsciousness. They are divided into opioid and non-opioid categories. Opioid analgesics include natural opium alkaloids like morphine and codeine, semi-synthetic opiates, and synthetic opioids. They act on opioid receptors in the brain. Non-opioid analgesics include NSAIDs like aspirin and ibuprofen, which reduce pain and inflammation by inhibiting prostaglandin synthesis. Acetaminophen is also a non-opioid analgesic. Both opioid and non-opioid analgesics can cause side effects like hypersensitivity, peptic ulcers, liver damage, and renal toxicity when taken in excess.
This document discusses nonsteroidal anti-inflammatory drugs (NSAIDs), including their classification, mechanisms of action, examples of different drug classes, and pharmacological effects. It focuses on aspirin as the prototype NSAID, describing its absorption, metabolism, uses, adverse effects, and interactions. Selective COX-2 inhibitors like celecoxib and rofecoxib are also introduced as NSAIDs with reduced gastric irritation.
NSAIDs are a class of drugs that relieve pain, fever, and inflammation by inhibiting cyclooxygenase enzymes. There are various types of NSAIDs classified by their chemical structure. All NSAIDs work by blocking prostaglandin production, but they differ in their selectivity for COX-1 vs COX-2 enzymes. Common adverse effects include gastrointestinal irritation and bleeding, as well as renal impairment. NSAIDs are commonly used to treat pain, fever, and inflammatory conditions like arthritis.
NSAIDs are a group of drugs that reduce pain, fever, and inflammation by inhibiting the COX enzymes that produce prostaglandins. COX enzymes exist in two forms, COX-1 and COX-2. NSAIDs work by blocking both forms of COX, though some are more selective for COX-2. This inhibition of COX reduces prostaglandin production and subsequent pain/fever/inflammation. However, it can also reduce platelet count and increase risk of stomach ulcers. NSAIDs are classified into several categories based on their chemical structure and mechanisms of action. The structure of individual NSAIDs influences their biological activity and side effect profiles.
A PowerPoint presentation on "NSAIDS" suitable for reading by UG and PG Medical/Paramedical students of Pharmacology and Pharmacy sciences. This Ppt. is prepared for academic purpose only and already presented to my students in one of the theory classes of mine.
This document summarizes opioids and their use as analgesics. It discusses the classification of opioids as natural, semi-synthetic, or synthetic and describes their mechanisms of action through mu, delta, and kappa receptors in the central nervous system. The document outlines the pharmacokinetics of opioid absorption, distribution, metabolism, and excretion. It also discusses the clinical uses of opioids like morphine, as well as their side effects, risks of overdose and addiction, and treatment options for opioid overuse.
Selective cox 2 inhibitors design by siddharthSiddharth Jain
The document discusses selective COX-2 inhibitors, which are a type of NSAID that selectively binds to the COX-2 enzyme responsible for inflammation and pain. It provides background on the COX-1 and COX-2 enzymes and reasons for developing selective COX-2 inhibitors to avoid the side effects of non-selective NSAIDs like ulceration and bleeding. The key structural differences between COX-1 and COX-2 that allow for selective inhibitor design are described. Examples of important selective COX-2 inhibitors developed include celecoxib and parecoxib.
The document discusses non-steroidal anti-inflammatory drugs (NSAIDs) and their role in periodontal disease treatment. It covers the definition of NSAIDs, their history of use, classification, mechanisms of action including inhibition of prostaglandin synthesis, and various types including salicylates, propionic acid derivatives, and selective COX-2 inhibitors. NSAIDs are proposed to have host modulatory properties for periodontal disease by suppressing inflammation and bone resorption mediated by prostaglandins. However, risks of adverse gastrointestinal effects must be weighed against potential benefits for periodontitis.
This document provides an overview of opioids including their pharmacology, mechanisms of action, classifications, and clinical uses. It discusses how opioids bind to receptors in the central and peripheral nervous systems to produce analgesic and other effects. Opioids are classified based on their receptor activities and include pure agonists, partial agonists, mixed agonist-antagonists, and pure antagonists. The document reviews the central and peripheral effects of opioids as well as their indications, contraindications, and interactions. It also discusses opioid tolerance, dependence, overdose, and withdrawal.
1. NSAIDs work by inhibiting prostaglandin synthesis via blocking cyclooxygenase (COX) enzymes. They are classified based on selectivity for COX-1 vs COX-2.
2. Aspirin is a non-selective, irreversible COX inhibitor. It provides analgesic, antipyretic and anti-inflammatory effects. Common adverse effects include gastric irritation and bleeding risks.
3. Paracetamol is considered a COX-3 inhibitor. It has analgesic properties but does not cause gastric irritation or bleeding like other NSAIDs. Acute overdose can cause liver damage.
This document summarizes inflammation and anti-inflammatory drugs. It describes the phases of inflammation, signs of inflammation, and mediators of the inflammatory response such as histamine, bradykinin, prostaglandins, and leukotrienes. It then discusses nonsteroidal anti-inflammatory drugs (NSAIDs) and their mechanisms of action by inhibiting cyclooxygenase enzymes and decreasing prostaglandin synthesis. Common NSAIDs are described including their pharmacological properties, mechanisms of action, therapeutic uses, and potential adverse effects such as gastrointestinal issues and bleeding risks.
This 20-slide slide set created with PowerPoint describes prostanoid synthesis and their effects on the body; mechanisms of action, beneficial and adverse effects of NSAIDS; the difference between the effects of low and high dose aspirin; and the effects and toxicity of paracetamol (acetaminophen). This is an introduction to the topic of NSAIDS which would be appropriate for beginners. Contributed by Christopher Fowler, Umeå University, Sweden.
9. NSAIDS.pptxNSAIDS inhibit the enzyme cyclooxygenase (COX) types 1 and 2, w...samiyamohammed284
Renal
Renally produced prostaglandins (PGE2 and PGI2) are essential
in maintaining adequate renal perfusion when the level of circulating vasoconstrictors Platelets
Impaired platelet function (reduced aggregation).
as a result of decreased thromboxane A2 (TXA2) production.
TXA2 is present in large amounts in activated platelets and acts locally as a chemo-attractant for other platelets, leads to the formation of a platelet plug and induces localized vasoconstric
NSAIDs have an extremely safe profile when used for acute dental pain.
Within a group they tend to have similar characteristics & tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses.
Rather, differences among compounds usually relate to dosing regimens (related to compound’s elimination half –life), route of administration, & tolerability profile.
So, clinician should have a thorough knowledge of mechanism of action, pharmacokinetics, pharmacodynamics, dosage & adverse effects of each drug before prescribing the same.
Non steroidal anti inflammatory drugs (NSAIDS)Girmay Fitiwi
NonSteroidalAntiInflammatoryDrugs (NSAIDs) are a heterogeneous class of drugs that inhibit cyclooxygenase (COX) enzymes and reduce prostaglandin production, providing anti-inflammatory, analgesic, and antipyretic effects. They are used to treat mild to moderate pain, chronic inflammation, and postoperative pain. NSAIDs work by inhibiting both COX-1 and COX-2 enzymes, with COX-1 inhibition causing side effects and COX-2 inhibition providing therapeutic effects. Common NSAIDs discussed in more detail include diclofenac, ketorolac, and aspirin.
This document discusses non-steroidal anti-inflammatory drugs (NSAIDs), including their classification, mechanisms of action, therapeutic uses, and adverse effects. NSAIDs work by inhibiting the enzyme cyclooxygenase (COX) to reduce pain, fever, and inflammation. While most NSAIDs inhibit both COX-1 and COX-2, selective COX-2 inhibitors like celecoxib may have fewer gastrointestinal side effects. Common adverse effects include gastrointestinal toxicity, renal failure, and increased risk of cardiovascular and liver problems. The document also briefly discusses aspirin and paracetamol/acetaminophen.
This document discusses non-steroidal anti-inflammatory drugs (NSAIDs), including their mechanism of action, types, uses, and side effects. It explains that NSAIDs work by inhibiting cyclooxygenase enzymes and reducing inflammation. There are two types of NSAIDs - non-selective ones that inhibit both COX-1 and COX-2 enzymes, and COX-2 selective ones that have fewer gastrointestinal side effects but can increase heart risks. Common NSAIDs like aspirin, ibuprofen, and naproxen are used to treat pain, fever, and inflammatory conditions. However, NSAIDs also increase risks of ulcers, heart issues, and kidney disease.
Pain and inflammation treatment with NSID drugs Akshay Kumar
Acenofenac and acetaminophen( paracetamol) role as N.S.I.D in the treatment of pain and Inflammation with pharmacology and indication, adverse effects and contraindications
1. Arachidonic acid is released from cell membranes and metabolized via either the cyclooxygenase pathway or lipoxygenase pathway to produce prostaglandins, thromboxanes, leukotrienes, and lipoxins.
2. These metabolites are involved in various physiological and pathological processes such as inflammation, hemostasis, smooth muscle contraction, and pain sensation.
3. Nonsteroidal anti-inflammatory drugs function by inhibiting cyclooxygenase, thereby blocking prostaglandin production and reducing inflammation.
This document discusses NSAIDs (non-steroidal anti-inflammatory drugs) and their role in controlling inflammation. It begins by describing the normal inflammatory response and how chronic inflammation disrupts the off switch. It then discusses the various mediators involved in inflammation and the four classic signs. The document goes on to explain the pathways involved like eicosanoids and cyclooxygenase, the mechanism of action and types of NSAIDs, potential dietary interventions using EPA, and treatments for conditions like gouty arthritis.
ROLE OF ANTI-INFLAMMATORY DRUGS IN SURGERYDR AMEER HAMZA
Inflammation is the body's protective response to injury or infection that involves immune cells, blood vessels, and molecular mediators. It causes redness, heat, swelling, and pain. There are three phases: acute, delayed, and chronic. Mediators like prostaglandins and histamine cause vasodilation, increased permeability, and pain. Steroidal anti-inflammatory drugs and non-steroidal anti-inflammatory drugs inhibit inflammation by different mechanisms. NSAIDs inhibit the COX enzyme to prevent prostaglandin production, while steroids inhibit phospholipase A2. Both drug classes can cause side effects with long term use like gastric irritation.
The document discusses prostaglandin-endoperoxide synthase (PTGS), also known as cyclooxygenase (COX), which is responsible for the formation of prostanoids like prostaglandins. It has two isoforms, COX-1 and COX-2. COX-1 is constitutively expressed and regulates normal physiological functions, while COX-2 is induced during inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit these enzymes to reduce inflammation. Several NSAIDs are described, including their mechanisms of action, medical uses, and potential adverse effects.
The document discusses NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin. It explains that NSAIDs work by inhibiting the cyclooxygenase (COX) enzymes involved in prostaglandin synthesis, thereby reducing inflammation. NSAIDs are effective for mild to moderate pain relief but opioids are preferred for more severe pain. Common side effects of NSAIDs include gastric irritation and renal problems due to reduced prostaglandin production in the stomach and kidneys. The document provides details on the classification, mechanisms of action, and uses of various NSAIDs.
COX inhibitors have been known to cause platelet inhibition by inhibiting thromboxane A2 production. Aspirin causes irreversible inhibition of COX, and therefore, the duration of platelet inhibition lasts until 7 to 10 days after drug discontinuation.
A type of drug that is used to treat inflammation and pain, and is being studied in the prevention and treatment of cancer. COX inhibitors belong to the family of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Also called cyclooxygenase inhibitor.
The document discusses different types of NSAIDs and acetaminophen, their mechanisms of action, and adverse effects. It describes how aspirin and nonselective NSAIDs like ibuprofen inhibit both COX-1 and COX-2 isoforms, decreasing prostaglandin synthesis throughout the body. More recent COX-2 selective inhibitors like celecoxib were developed to reduce gastrointestinal toxicity. Acetaminophen is only a weak inhibitor of COX-1 and COX-2 and may inhibit COX-3 in the CNS. While NSAIDs can cause gastrointestinal ulceration and renal damage, acetaminophen is generally safe at therapeutic doses but overdose can cause hepatotoxicity.
NSAIDs have analgesic, antipyretic and anti-inflammatory properties. They work by inhibiting cyclooxygenase (COX) enzymes and reducing prostaglandin production. NSAIDs are classified as nonselective COX inhibitors like aspirin, preferential COX-2 inhibitors like nimesulide, or selective COX-2 inhibitors like celecoxib. Common adverse effects include gastrointestinal irritation. NSAIDs are used to treat pain, fever, and inflammation conditions like arthritis.
This document summarizes anti-inflammatory drugs. It discusses the inflammatory process and mediators like histamine, prostaglandins, leukotrienes and thromboxane A2. It describes the three phases of inflammation and signs like redness, heat, swelling and pain. Two major classes of anti-inflammatory drugs are discussed: steroidal anti-inflammatory drugs (SAIDs) like cortisone and hydrocortisone, and non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin, ibuprofen and naproxen. The mechanisms, common uses and potential side effects of various NSAIDs are outlined.
NSAIDs are a class of drugs that reduce pain, fever, and inflammation by blocking prostaglandin production. They include aspirin, ibuprofen, and naproxen which are available over-the-counter. NSAIDs work by inhibiting the COX enzymes involved in prostaglandin synthesis. They can cause side effects like ulcers and bleeds from their effects on COX-1. COX-2 selective NSAIDs aim to reduce inflammation while sparing the stomach lining by selectively inhibiting COX-2. Paracetamol is considered separately due to its different mechanism of action, providing analgesia and antipyresis through central COX inhibition in the brain.
Antiarrhythmic drugs work by altering the conduction of electrical signals in the heart and changing the refractory periods of cardiac cells. They are classified into four classes based on their effects. Class IA drugs like quinidine and procainamide work by slowing the rise of the action potential upstroke, decreasing conduction velocity, and prolonging the refractory period. They have moderate potassium channel blocking effects. Class IA drugs are used for supraventricular arrhythmias and ventricular tachycardia but can cause toxicity like heart block or dangerous arrhythmias.
The document discusses the biological basis of cardiac repair after myocardial infarction. It notes that massive cardiomyocyte loss due to infarction overwhelms the heart's limited regenerative capacity, resulting in scar formation. Necrotic cells trigger an intense inflammatory response through danger signals and toll-like receptor signaling that recruits leukocytes. As inflammation subsides, fibroblasts proliferate and deposit collagen, maintaining ventricular integrity. Dysregulated inflammation, impaired resolution, or excessive fibrosis can cause adverse remodeling and heart failure. Modulating the inflammatory and reparative response may prevent post-infarction heart failure.
This document discusses angina pectoris, including its causes, types, and treatment strategies. It begins by defining angina pectoris as chest pain or discomfort caused by coronary heart disease when the heart muscle does not receive enough blood, usually due to narrowed or blocked arteries. It then describes the three main types of angina - classic, unstable, and variant - and their distinguishing features. The remainder of the document focuses on drug therapies for angina, explaining how organic nitrates, beta-blockers, and calcium channel blockers work to reduce oxygen demand or increase supply to relieve anginal symptoms. It provides details on the mechanisms and effects of these major drug classes and notes some of their potential side effects.
Ototoxicity refers to damage to the auditory or vestibular system caused by drugs or chemicals. Many known ototoxins cause cellular damage through generation of reactive oxygen species rather than direct action. The inner ear has limited regenerative ability, so ototoxic injury often leads to permanent hearing or balance problems. Exposure to industrial solvents and heavy metals can also cause ototoxicity. Noise exposure may increase the risk of ototoxicity by lowering the levels of chemicals needed to cause harm. Various antioxidants have shown potential to protect against ototoxicity in animal studies.
Chlorine gas is a pulmonary irritant that causes acute damage to the upper and lower respiratory tract. It has been used as a chemical weapon and is still involved in some attacks. Exposure to chlorine gas leads to inflammation of the airways and lungs and can cause pulmonary edema. Symptoms range from irritation to death depending on concentration. Treatment involves oxygen, fluids, bronchodilators, and corticosteroids. Prolonged effects are possible but most recover without long-term issues.
This document discusses the autonomic nervous system. It describes how the autonomic nervous system is divided into the sympathetic and parasympathetic nervous systems. The sympathetic nervous system is responsible for the "fight or flight" response and increases heart rate and blood pressure. Its neurotransmitters are epinephrine and norepinephrine. The parasympathetic nervous system is responsible for "rest and digest" functions and decreases heart rate and increases digestion. Its main neurotransmitter is acetylcholine. The document outlines the receptors, effects, and roles of the sympathetic and parasympathetic nervous systems on various organs.
1. Warfarin toxicity is caused by overdose or drug interactions that inhibit vitamin K recycling, preventing production of clotting factors. Bleeding is the main risk.
2. Treatment involves stopping warfarin, administering vitamin K1 to restore clotting factors, and plasma or PCC to rapidly reverse coagulopathy based on INR.
3. Superwarfarins require weeks of vitamin K1 due to their long half-lives. Activated charcoal may be given for recent ingestions. Monitoring INR guides further treatment.
Chlorine gas is a pulmonary irritant that causes acute damage to the upper and lower respiratory tract. It has been used as a chemical weapon and is still involved in some attacks. Exposure to chlorine gas leads to inflammation of the airways and lungs and can cause pulmonary edema. Symptoms range from irritation to death depending on concentration. Treatment involves oxygen, fluids, bronchodilators, and corticosteroids. High risk patients may require hospitalization for monitoring due to risk of respiratory failure.
This document discusses adrenergic antagonists (sympatholytics) which inhibit the sympathetic nervous system by blocking adrenergic receptors or neurons. It describes various types of adrenergic blocking drugs that are selective for α and β receptors. Non-selective α-blockers like phenoxybenzamine cause irreversible blockade while phentolamine is competitive. Selective α1-blockers lower blood pressure with minimal effects on cardiac output. Orthostatic hypotension is a common side effect of α-blockers due to inhibition of venous vasoconstriction.
Toxicity of hydrocarbons can affect many organs but most commonly the lungs due to aspiration. Hydrocarbons are a diverse group of organic compounds including gasoline, oils, and solvents. Their physical properties like viscosity and volatility determine toxicity risk. Inhalation can cause pneumonitis while ingestion risks aspiration pneumonia. Symptoms include respiratory, CNS, cardiac, and GI issues. Treatment is supportive with monitoring for pulmonary or cardiac complications.
Drugs taken during pregnancy can directly harm the fetus, alter placental function, or induce preterm labor. Most drugs transfer through the placenta and reach levels in the fetus of 50-100% of maternal levels. Factors like timing and dose of exposure determine if a drug causes birth defects. While some drugs are known teratogens, effects of most are unclear due to challenges studying drugs in pregnancy. Careful risk/benefit analysis of medication needs during pregnancy is required.
This document discusses antidepressant drugs and their mechanisms of action. It begins by describing how antidepressants work by altering neurotransmitter systems like serotonin and norepinephrine in the brain. Several classes of antidepressants are then discussed, including MAOIs, TCAs, SSRIs, SNRIs, and NDRIs. Each works differently but generally aims to increase neurotransmitter activity in the brain. The document examines specific drugs in each class, their history, mechanisms, and common side effects. Mood disorders like depression and bipolar disorder are also briefly overviewed.
Lithium intoxication can cause mild symptoms like weakness and nausea or more severe symptoms like delirium, coma, and organ damage. Long term effects are also possible and include neurological issues like cerebellar dysfunction. Diagnosis involves checking the patient's history, measuring lithium levels in their blood, and conducting tests like ECG and bloodwork. Treatment focuses on hydration, electrolyte balance, gastric lavage, diuretics, and hemodialysis for moderate to severe cases to reduce lithium levels in the blood. Special care must be taken with fluid management in patients at risk for lithium-induced diabetes insipidus. Hemodialysis is the primary treatment for severe lithium toxicity due to lith
This document discusses emetics, which induce vomiting, and antiemetics, which prevent vomiting. It describes the physiology of vomiting including the vomiting center and chemoreceptor trigger zone in the brain. It explains the mechanisms and sites of action of various classes of antiemetic drugs including antihistamines, 5-HT3 receptor antagonists, dopamine antagonists, cannabinoids, glucocorticoids, and others. It provides details on specific antiemetic drugs like metoclopramide, ondansetron, dexamethasone, and their indications, mechanisms, pharmacokinetics and adverse effects.
Antifungal drugs work by targeting differences between fungal and human cell membranes and metabolism. Azoles like fluconazole inhibit ergosterol synthesis while polyenes like amphotericin B bind to ergosterol in the fungal cell membrane. Topical antifungals like nystatin and tolnaftate treat superficial infections while systemic drugs like fluconazole and itraconazole treat deep infections. Common adverse effects include nausea, liver toxicity, and drug interactions. The choice of antifungal depends on the infecting organism, infection severity, and route of administration needed.
Constipation is defined as infrequent and difficult bowel movements. It affects 2-27% of the population and has many potential causes. Treatment options include non-drug approaches like diet and exercise changes as well as various drug approaches using laxatives. There are several classes of laxatives including bulk-forming, emollient, hyperosmotic, saline, and stimulant laxatives. All laxative use requires monitoring for side effects and electrolyte disturbances.
This document provides an overview of Alzheimer's disease including its causes, symptoms, stages, diagnosis, and treatment approaches. It discusses how Alzheimer's is characterized by plaques and tangles in the brain made up of beta-amyloid and tau proteins. Current treatment aims to improve cognitive function and behaviors through cholinesterase inhibitors and memantine, though none can stop or reverse the disease. Non-pharmacological interventions like education, communication, and stimulation therapies may provide additional support.
Organophosphorous compounds work by inhibiting acetylcholinesterase, leading to overstimulation of muscarinic and nicotinic receptors. Signs and symptoms include muscarinic effects like excessive sweating, urination, and salivation ("DUMBELS") and nicotinic effects like muscle weakness. Treatment involves atropine to reverse muscarinic effects, pralidoxime to reactivate acetylcholinesterase within 48 hours, benzodiazepines for seizures, and supportive care like ventilation and fluid management. Measuring red blood cell acetylcholinesterase levels can help confirm exposure.
Drugs taken during pregnancy can affect the fetus in several ways. They may act directly on the fetus, altering the placenta's function, or causing uterine contractions. Factors like dose, timing and pharmacokinetics influence fetal effects, which range from no impact to death. While many drugs are relatively safe, careful risk-benefit assessment is needed due to variable and sometimes unknown risks. Precautions like using the lowest effective dose can help minimize harm to the developing fetus or newborn.
This document summarizes drugs used to treat blood dysfunctions related to thrombosis, bleeding, and anemia. It describes the formation of blood clots and the drugs used to regulate clotting, focusing on platelet activation and aggregation inhibitors like aspirin, clopidogrel, abciximab, eptifibatide, and tirofiban. It also discusses the coagulation cascade and anticoagulants like heparin and warfarin that inhibit coagulation factors to prevent unwanted clotting.
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfRahul Sen
Time-lapse embryo monitoring is an advanced imaging technique used in IVF to continuously observe embryo development. It captures high-resolution images at regular intervals, allowing embryologists to select the most viable embryos for transfer based on detailed growth patterns. This technology enhances embryo selection, potentially increasing pregnancy success rates.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
The skin is the largest organ and its health plays a vital role among the other sense organs. The skin concerns like acne breakout, psoriasis, or anything similar along the lines, finding a qualified and experienced dermatologist becomes paramount.
Know the difference between Endodontics and Orthodontics.Gokuldas Hospital
Your smile is beautiful.
Let’s be honest. Maintaining that beautiful smile is not an easy task. It is more than brushing and flossing. Sometimes, you might encounter dental issues that need special dental care. These issues can range anywhere from misalignment of the jaw to pain in the root of teeth.
- Video recording of this lecture in English language: https://youtu.be/Pt1nA32sdHQ
- Video recording of this lecture in Arabic language: https://youtu.be/uFdc9F0rlP0
- 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
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfrightmanforbloodline
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
2. Safe and effective management of acute
dental pain can be accomplished with
nonopioid and opioid analgesics.
To formulate regimens properly, it is
essential to appreciate basic pharmacological
principles and appropriate dosage strategies
for each of the available analgesic classes.
Conventional analgesics either
1. interrupt ascending nociceptive impulses
2. depress their interpretation within the
central nervous system (CNS).
3. Formerly, it was believed that opioids acted
only within the brain and spinal cord, but the
action of nonopioids was confined to the
periphery (ie, the site of injury).
This explanation is no longer tenable,
however; both are known to act centrally
and peripherally.
In fact, the feature that best distinguishes
these analgesic classes is their mechanism of
action.
Opioids activate specific receptors in a
manner identical to opiates, such as
morphine.
Nonopioids interrupt prostaglandin synthesis,
thereby resembling aspirin in action.
4. include acetaminophen(APAP) and the
nonsteroidal anti-inflammatory drugs(NSAIDs).
The analgesic efficacy of these agents is typically
underestimated.
However, they generally are equivalent or
superior to opioids for managing musculoskeletal
pain, and they produce a lower incidence of side
effects, including the potential for abuse.
Dental pain is included in the musculoskeletal
category, and for decades studies have
repeatedly found that NSAIDs are generally
superior to opioids at conventional dosages.
5. All of the NSAIDs and paracetamol act by inhibiting
the synthesis of prostaglandins.
Prostaglandins and related compounds are produced
in minute quantities by virtually all tissues.
They generally act locally on the tissues in which they
are synthesized, and they are rapidly metabolized to
inactive products at their sites of action.
Therefore, the prostaglandins do not circulate in the
blood in significant concentrations.
Thromboxanes, leukotrienes are related lipids,
synthesized from the same precursors as the
prostaglandins, and use interrelated pathways.
These compounds are sometimes referred to as
eicosanoids
6. Arachidonic acid,is the primary precursor of
the prostaglandins and related compounds.
Arachidonic acid is present as a component of
the phospholipids of cell membranes primarily
phosphatidylinositol and other complex lipids.
Free arachidonic acid is released from tissue
phospholipids by the action of phospholipase A2
via a process controlled by hormones and other
stimuli.
There are two major pathways in the synthesis
of the eicosanoids from arachidonic acid.
7. All eicosanoids with ring structures that is, the
prostaglandins, thromboxanes, and
prostacyclins are synthesized via the
cyclooxygenase pathway.
Two related isoforms of the cyclooxygenase
enzymes have been described.
1- Cyclooxygenase-1 (COX-1) is responsible for
the physiologic production of Prostanoids.
2- cyclooxygenase-2 (COX-2) causes the elevated
production of prostanoids that occurs in sites of
disease and inflammation.
8. COX-1 is described as a Housekeeping enzyme
that regulates normal cellular processes, such as
gastric cytoprotection, vascular homeostasis,
platelet aggregation, and kidney function.
COX-2 is constitutively expressed in tissues such
as the brain, kidney, and bone. Its expression at
other sites is increased during states of
inflammation.
two enzymes share 60 percent homology in
amino acid sequence. However, the
conformation for the substrate-binding sites and
catalytic regions are slightly different.
Another distinguishing characteristic of COX-2 is
that its expression is inhibited by
glucocorticoids.
9.
10. Alternatively, several lipoxygenases can act
on arachidonic acid to form leukotrienes or
lipoxins, depending on the tissue.
Leukotrienes cause bronchospasm.
Antileukotriene drugs, such as zileuton,
zafirlukast, and montelukast, are useful for
the treatment of moderate to severe allergic
asthma
11.
12.
13.
14. Many of the actions of prostaglandins are
mediated by their binding to a wide variety
of distinct cell membrane receptors that
operate via G proteins, which subsequently
activate or inhibit adenylyl cyclase or
stimulate phospholipase C.
Their functions vary widely, depending on
the tissue.
For example, the release of TXA2 from
platelets triggers the recruitment of new
platelets for aggregation
15. They are also responsible for protection of
gastric mucosa.
Prostaglandins are also among the chemical
mediators that are released in allergic and
inflammatory processes, increasing body
temprature, and pain sensation.
16. The NSAIDs are a group of chemically dissimilar
agents that differ in their antipyretic,
analgesic, and anti-inflammatory activities.
They act primarily by inhibiting the
cyclooxygenase enzymes that catalyze the first
step in prostanoid biosynthesis.
This leads to decreased prostaglandin synthesis
with both beneficial and unwanted effects.
17. Ibuprofen is conventionally regarded as the
prototype of this large group of synthetic
compounds known for their analgesic,
antipyretic, and anti-inflammatory efficacy.
These therapeutic effects and their most
notable side effects can be explained almost
entirely by their ability to inhibit the
cyclooxygenase (COX) required for synthesis
of various families of prostanoids
18. Analgesic (CNS and peripheral effect) may
involve non-PG related effects
Antipyretic (CNS effect)
Anti-inflammatory (except acetaminophen)
due mainly to PG inhibition.
Some shown to inhibit activation, aggregation,
adhesion of neutrophils & release of lysosomal
enzymes
Some are Uricosuric
19.
20. Clinical use of NSAIDs is predicated on their
ability to reduce the synthesis of
prostaglandins implicated in pain, fever, and
inflammation.
However, these agents are hardly selective in
this goal and also inhibit the production of
additional prostanoids that perform useful
physiological functions.
This accounts for potential side effects and
contraindications.
21. The most frequent side effects of NSAIDs are related
to their gastrointestinal (GI ) toxicity. Prostaglandins
stimulate the production of a mucous lining that
protects the stomach and small intestine. The erosive
and ulcerative side effects common to NSAIDs are
attributed to their inhibiting the synthesis of these
particular prostaglandins.
This action not only occurs locally as orally
administered drug lies in contact with gastric
mucosa but also follows absorption and systemic
distribution to the GI mucosa.
Parenteral administration does not preclude a
risk for GI erosions and ulcerations.
22. The ability of NSAIDs to inhibit
cyclooxygenases in platelets reduces the
synthesis of thromboxane A2, which normally
contributes to platelet aggregation.
This accounts for the so-called antiplatelet
effect of these agents and is a consideration
following surgical procedures.
However, aspirin is the only NSAID that has
proven effective in preventing thrombotic
events such as acute coronary syndromes or
stroke.
This is so because the antiplatelet action of
aspirin is irreversible, lasting the life span of
the platelet (up to 14 days).
23. Other NSAIDs bind weakly and reversibly to
platelet cyclooxygenases, which results in
loss of their mild antiplatelet influence after
drug elimination.
Although nonaspirin NSAIDs all prolong
bleeding times to some degree, this does not
correlate with significant clinical bleeding
following minor surgical procedures.
However, nonaspirin NSAIDs generally are
withheld before major thoracic, abdominal,
or orthopedic procedures.
If aspirin is medically necessary for patients,
such as those with endovascular stents who
are at risk for life threatening clot
formation, it should not be withdrawn.
24. NSAIDs should be avoided in patients suffer
bleeding disorders and in those taking
anticoagulants such as warfarin and powerful
antiplatelet drugs such as clopidogrel (Plavix).
Patients receiving monotherapy with low-dose
aspirin are not as great a concern but should
be considered.
The issue with NSAIDs is due not so much to
their antiplatelet action but to NSAID-induced
injury of GI mucosa that may bleed far more
profusely in this patient population.
NSAIDs increase the risk for GI bleeding
twofold to threefold in patients medicated
with clopidogrel (Plavix) and fourfold to
fivefold in those taking warfarin
25. By inhibiting cyclooxygenase, NSAIDs shunt the
arachidonic pathway toward leukotriene
synthesisre .
Leukotrienes mediate a variety of tissue
responses,including those associated with
bronchospasm and anaphylaxis.
Certain individuals may be extremely
sensitive to even subtle elevation in
leukotriene synthesis, which may result in
signs and symptoms of allergic response.
Acetaminophen is the conventional alternative
for patients reporting an allergic reaction to
any NSAID, unless the patient can identify a
particular product that he or she has tolerated
without problem in the past.
26.
27. Prostaglandins play an essential role in renal
perfusion, and diminished levels of these are
believed to account for reported cases of
nephrotoxicity after longterm NSAID use.
In the healthy patient, nephrotoxicity
attributed to NSAIDs requires high doses for
extended periods (eg, a year or longer).
However, a patient with compromised renal
function relies more heavily on prostaglandins
for adequate function, and acute renal failure
can occur within hours of NSAID administration.
NSAIDs must never be prescribed for patients
who have known or questionable renal function.
28. Decreased synthesis of prostaglandins can
result in retention of sodium and water and
may cause edema and hyperkalemia in some
patients Interstitial nephritis can also occur
with all NSAIDs except aspirin.
29. Also should be avoided during pregnancy because
prostaglandins maintain patency of the ductus
arteriosus during fetal development.
Although this concern is most relevant during the
third trimester, NSAIDs generally should be avoided
throughout pregnancy.
In all cases where NSAIDs are contraindicated,
acetaminophen is the conventional nonopioid
alternative.
30. Celecoxib (Celebrex) is representative of agents
that selectively inhibit COX-2; it reduces pain and
inflammation with little or no influence on gastric
mucosa.
However, this selective inhibition may promote
greater synthesis of prostanoids derived from COX-1,
including thromboxane-mediated effects leading to
possible thrombotic events (eg, myocardial
infarction, stroke).
Detection of serious cardiovascular events
associated with COX-2 inhibitors have led to
withdrawal of rofecoxib and valdecoxib from the
market (celecoxib is still available for use in
patients with RA).
31.
32. Additionally, the U.S. Food and Drug Administration
(FDA) has required that the labeling of the traditional
NSAIDs and celecoxib be updated to include the
following:
1) a warning of the potential risks of serious
cardiovascular thrombotic events, myocardial
infarction, and stroke, which can be fatal;
additionally, a warning that the risk may increase
with duration of use and that patients with
cardiovascular disease or risk factors may be at
greater risk; for celecoxib
2) a warning that use is contraindicated for the
treatment of perioperative pain in the setting of
coronary artery bypass graft surgery; for both.
3) a notice that there is increased risk of serious
gastrointestinal (GI) adverse events, including
bleeding, ulceration, and perforation of the
stomach or intestines, which can be fatal. For
NSAIDs; traditional
33. These events can occur at any time during use and
without warning symptoms.
Elderly patients are at greater risk for serious GI
events.
Aspirin, however, has proven to be beneficial in
patients for the primary and secondary
prevention of cardiovascular events and is most
commonly used for this purpose rather than for
pain control.
34. In summary, NSAIDs are contraindicated for
patients who have:
1. a current history of nephropathy
2. erosive or ulcerative conditions of the GI
mucosa
3. anticoagulant therapy
4. hemorrhagic disorders
5. intolerance or allergy to any NSAID;
Symptoms of true allergy include urticaria,
bronchoconstriction, or angioedema. Fatal
anaphylactic shock is rare.
35. Aspirin is the prototype of traditional NSAIDs.
Analgesic action: Prostaglandin E2 (PGE2) is
thought to sensitize nerve endings to the action of
bradykinin, histamine, and other chemical
mediators released locally by the inflammatory
process.
Thus, by decreasing PGE2 synthesis, aspirin and
other NSAIDs repress the sensation of pain.
The salicylates are used mainly for the
management of pain of low to moderate intensity
arising from musculoskeletal disorders rather than
that arising from the viscera.
36. Antipyretic action:
Fever occurs when the set-point of the anterior
hypothalamic thermoregulatory center is elevated.
This can be caused by PGE2 synthesis, which is
stimulated when an endogenous fever-producing
agent (pyrogen), such as a cytokine, is released from
white cells that are activated by infection,
hypersensitivity, malignancy, or inflammation.
The salicylates lower body temperature in patients
with fever by impeding PGE2 synthesis and release.
Aspirin resets the thermostat toward normal, and it
rapidly lowers the body temperature of febrile
patients by increasing heat dissipation as a result of
peripheral vasodilation and sweating.
Aspirin has no effect on normal body temperature.
37. Duration of action ~ 4 hr.
Orally taken.
Weak acid (pKa ~ 3.5); so, non-ionized in
stomach easily absorbed.
Hydrolyzed by esterases in tissues and blood
to salicylate (active) and acetic acid.
Most salicylate is converted in liver to H2O-sol
conjugates that are rapidly excreted by
kidneys.
38. 1. Because salicylates are excreted in breast milk,
aspirin should be avoided during pregnancy and
while breast-feeding.
39. Reye's syndrome: Aspirin and other salicylates
given during viral infections has been associated
with an increased incidence of Reye's syndrome,
which is an often fatal, fulminating hepatitis
with cerebral edema. This is especially
encountered in children, who therefore should
be given acetaminophen instead of aspirin when
such medication is required to reduce fever.
Ibuprofen is also appropriate.
Children who have received live varicella virus
vaccine should
avoid aspirin for at least 6 weeks after
vaccination to prevent Reye's syndrome.
40. Drug interactions: Concomitant administration
of salicylates with many classes of drugs may
produce undesirable side effects.
Because aspirin is found in many over-the-
counter agents, patients should be counseled to
read labels to verify aspirin content to avoid
overdose.
Salicylate is 90 to 95 percent protein bound and
can be displaced from its protein-binding sites,
resulting in increased concentration of free
salicylate; alternatively, aspirin could displace
other highly protein-bound drugs, such as
warfarin, phenytoin, or valproic acid, resulting
in higher free concentrations of the other agent.
41. Diflunisal is three- to four-fold more potent
than aspirin as an analgesic and an anti-
inflammatory agent, but it has no antipyretic
properties.
Diflunisal does not reduce fever, because it
does not cross the blood-brain barrier.
42. Ibuprofen [eye-byoo-PROE-fen] was the first in
this class of agents to become available.
It has been joined by naproxen [nah-PROX-en],
fenoprofen [fen-oh-PROE-fen], ketoprofen [key-
toe-PROE-fen], flurbiprofen [flur-bye-PROE-
fen], and oxaprozin [ox-ah-PROE-zin].
All these drugs possess anti-inflammatory,
analgesic, and antipyretic activity; additionally,
they can can alter platelet function and prolong
bleeding time.
their GI effects are generally less intense than
those of aspirin.
43. All are well absorbed on oral administration
and are almost totally bound to serum
albumin.
Oxaprozin has the longest half-life and is
administered once daily.
They undergo hepatic metabolism and are
excreted by the kidney.
The most common adverse effects are GI,
ranging from dyspepsia to bleeding.
Side effects involving the central nervous
system (CNS), such as headache, tinnitus,
and dizziness, have also been reported.
44. This group of drugs includes indomethacin [in-doe-METH-
a-sin], sulindac [sul-IN-dak], and etodolac [eh-TOEdoh-
lak].
All have anti-inflammatory, analgesic, and antipyretic
activity.
They are generally not used to lower fever.
Despite its potency as an anti-inflammatory agent, the
toxicity of indomethacin limits its use to the treatment of
acute gouty arthritis, ankylosing spondylitis, and
osteoarthritis of the hip.
Sulindac is an inactive prodrug that is closely related to
indomethacin. The adverse reactions caused by sulindac
are similar to, but less severe than, those of the other
NSAIDs, including indomethacin.
Etodolac has effects similar to those of the other NSAIDs.
GI problems are less common.
45. Piroxicam [peer-OX-i-kam] and meloxicam [mel-
OX-i-kam] are used to treat RA, ankylosing
spondylitis, and osteoarthritis.
They have long half-lives, which permit once-
daily administration.
Meloxicam inhibits both COX-1 and COX-2, with
preferential binding for COX-2, and at low to
moderate doses shows less GI irritation than
piroxicam.
However, at high doses, meloxicam is a
nonselective NSAID, inhibiting both COX-1 and
COX-2.
46. Diclofenac [dye-KLO-feh-nak] and tolmetin
[tole-MEN-tin] are approved for long-term
use in the treatment of RA, osteoarthritis,
and ankylosing spondylitis.
Diclofenac is more potent than indomethacin
or naproxen.
47. Ketorolac [key-toe-ROLE-ak] is a potent analgesic but
has moderate anti-inflammatory effects.
It is available for oral administration, for
intramuscular use in the treatment of postoperative
pain.
Ketorolac undergoes hepatic metabolism, and the
drug and its metabolites are eliminated via the urine.
Ketorolac is indicated for short-term relief of
moderate to severe pain for up to 5 days after the
first dose is administered via IV or intramuscular
dosing at the doctor's office or in a hospital.
This agent is to be avoided in pediatric patients;
patients with mild pain, and those with chronic
conditions, the dose should not exceed 40 mg/day.
Ketorolac can cause fatal peptic ulcers as well as GI
bleeding and/or perforation of the stomach or
intestines.
48. Celecoxib [sel-eh-COCKS-ib] is significantly more
selective for inhibition of COX-2 than of COX-1.
Unlike aspirin, celecoxib does not inhibit platelet
aggregation and does not increase bleeding time.
Celecoxib has similar efficacy to NSAIDs in the
treatment of pain.
Celecoxib, when used without concomitant
aspirin therapy, has been shown to be associated
with less GI bleeding and dyspepsia; however, this
benefit is lost when aspirin is added to celecoxib
therapy.
In patients at high risk for ulcers (that is, history
of peptic ulcer disease), use of PPIs with
celecoxib and aspirin may be necessary to avoid
gastric ulcers.
49. Pharmacokinetics:
Celecoxib is readily absorbed, reaching a peak
concentration in about 3 hours.
It is extensively metabolized in the liver by
cytochrome P450 (CYP2C9) and is excreted in the
feces and urine.
Its half-life is about 11 hours; thus, the drug is
usually taken once a day but can be administered
as divided doses twice daily.
The daily recommended dose should be reduced
by 50 percent in those with moderate hepatic
impairment,
celecoxib should be avoided in patients with
severe hepatic and renal disease.
Celecoxib is contraindicated in patients who are
allergic to sulfonamides.
50.
51. After prolonged use, NSAIDs may interfere with
the effectiveness of most classes of
antihypertensive medications; calcium channel
blockers are a notable exception.
The precise mechanism for this interaction is
unknown but is believed to be related to
diminished vasodilator actions attributed to
renal prostaglandins.
In the rare event that postoperative analgesics
must be continued for longer than 5 days,
hypertensive patients should return to the
office for blood pressure assessment. If pressure
has elevated more than 8% above baseline, it
would be wise to replace the NSAID with
acetaminophen.
52. serum levels of lithium and methotrexate
are elevated during concurrent consumption
of NSAIDs. To prevent toxicity, NSAIDs should
be avoided in patients medicated with these
agents, particularly those taking high-dose
regimens.
53. In general, no convincing evidence indicates that a
particular NSAID is more effective or safer than other
members of this drug class.
Selective COX-2 inhibitors such as celecoxib produce less
GI toxicity after short-term use, but this advantage wanes
as consumption continues.
Patients vary considerably in their clinical response and GI
tolerance to a particular agent. Given its efficacy and low
side effect profile and cost, ibuprofen is generally a sound
initial choice. Regardless of the agent selected, however,
an optimal dosing schedule should be maintained for 2 to3
days before an alternative agent is prescribed.
usually antiniflammtory effect requires higher dose than
that for pain relief.
54.
55. Compared with NSAIDs, the mechanism of action of
acetaminophen is less clear but is believed to involve an
inhibition of prostaglandin synthesis within the CNS.
It has little influence on peripheral prostaglandin
synthesis, especially within inflamed tissues.
This is a likely explanation for its lacking anti-
inflammatory efficacy and sharing none of the
peripheral side effects attributed to NSAIDs.
However, it is an ideal analgesic for patients who
present any contraindications to NSAIDs. As an analgesic
and antipyretic, acetaminophen is equal in potency and
efficacy to aspirin and presumably may be somewhat
inferior to ibuprofen and other NSAIDs as well.
56. Hepatotoxicity is the most significant
adverse effect of acetaminophen.
The dose may be less for patients who are
poorly nourished, who have liver
dysfunction, or who are being treated with
other hepatotoxic medications.
For example, in contrast to the 4 g/d
allowed healthy patients, those suspected of
chronic alcoholism should limit their
maximum daily intake to 2 grams.
57. Most cases of postoperative dental pain include an
inflammatory component. For this reason, NSAIDs
are the most rational first-line agents often
superior to conventional dosages of opioids.
Should a patient present a contraindication to
NSAIDs, acetaminophen is the only alternative.
Nonopioids exhibit a ceiling to their analgesic
response, but optimal doses should be established
before it is assumed that the NSAID has failed.
Furthermore, the combination of a NSAID with
acetaminophen provides greater analgesic efficacy
than does either agent alone, and this strategy
may obviate the need for opioids.
58.
59. Opioids are natural or synthetic compounds that produce
morphine-like effects. [The term opiate is reserved for
drugs, such as morphine and codeine, obtained from the
juice of the opium poppy.]
All drugs in this category act by binding to specific opioid
receptors in the CNS to produce effects that mimic the
action of endogenous peptide neurotransmitters (for
example, endorphins, enkephalins, and dynorphins).
Although the opioids have a broad range of effects, their
primary use is to relieve intense pain and the anxiety that
accompanies it, whether that pain is from surgery or a
result of injury or disease, such as cancer.
However, their widespread availability has led to abuse of
those opioids with euphoric properties. [Dependence is
seldom a problem in patients being treated for severe
pain with these agents, as in cancer or acute pain in
terminally ill patients.]
Antagonists that can reverse the actions of opioids are
also very important clinically for use in cases of overdose.
60.
61. Opioids interact stereospecifically with protein
receptors on the membranes of certain cells in the
CNS, on nerve terminals in the periphery, and on
cells of the gastrointestinal tract and other anatomic
regions.
The major effects of the opioids are mediated by
three major receptor families. μ (mu), κ(kappa), and
δ (delta). Each receptor family exhibits a different
specificity for the drug(s) it binds.
All three opioid receptors are members of the G
protein coupled receptor family and inhibit adenylyl
cyclase.
They are also associated with ion channels,
increasing postsynaptic K+ efflux (hyperpolarization)
or reducing presynaptic Ca2+ influx, thus impeding
neuronal firing and transmitter release.
62.
63. High densities of opioid receptors known to be involved in integrating
information about pain are present in five general areas of the CNS. They
have also been identified on the peripheral sensory nerve fibers and on
immune cells.
1. Brainstem: Opioid receptors influence respiration, cough, nausea and
vomiting, blood pressure, pupillary diameter, and control of stomach
secretions.
2. Medial thalamus:
3. Spinal cord: involved with the receipt and integration of incoming
sensory information, leading to the attenuation of painful afferent
stimuli.
4. Hypothalamus: Receptors here affect neuroendocrine secretion.
5. Limbic system: These receptors probably do not exert analgesic
action, but they may influence emotional behavior.
6. Periphery: Opioids also bind to peripheral sensory nerve fibers and
their terminals. As in the CNS, they inhibit Ca2+-dependent release of
excitatory, proinflammatory substances (for example, substance P)
from these nerve endings.
7. Immune cells: The role of these receptors in has not been
determined.
64. Opioids produce most of their therapeutic and adverse
effects by acting as agonists at opioid receptors.
Morphine produces its effects by acting as an agonist at
both mu and kappa receptors
The mu receptor is responsible for mediating analgesia
and 2 of the most undesirable side effects attributed to
opioids: respiratory depression and dependence. Mu
effects have unlimited intensity
Like mu receptors, the kappa receptor mediates
analgesia and respiratory depression, but efficacy at this
receptor is limited
When high doses of opioids are used, selective
kappa agonists are viewed as safer, but less
analgesic, compared with traditional mu agonists.
65. Mu
Located throughout CNS
Responsible for:
respiratory depression
analgesia
nausea and vomitting
Miosis
constipation
euphoria
66. Only modest analgesia
Little or no respiratory depression
Little or no dependence
Dysphoric effects
68. Analgesia
Euphoria may affect dompaminergic receptors and mu receptors
Sedation and anxiolysis but level not as CNS depressants
Drowsiness and lethargy
Apathy
Cognitive impairment
Depression of respiration
Reduce response of respiratory center to high level of carbon monoxide
Main cause of death from opioid overdose
Combination of opioids and alcohol is especially dangerous
Cough suppression
Opioids suppress the “cough center” in the brainstem
Pupillary constriction
pupillary constriction in the presence of analgesics is characteristic
of opioid use
69. Nausea and vomiting
Stimulation of receptors in an area of the
medulla called the chemoreceptor trigger zone
causes nausea and vomiting
Unpleasant side effect, but not life threatening
Gastrointestinal symptoms
Opioids relieve diarrhea as a result of their
direct actions on the intestines
Other effects
Opioids can release histamines causing itching
or more severe allergic reactions including
bronchoconstriction
Opioids can affect white blood cell function and
immune function
70. Pure agonists:
These opoids have high affinity for
receptor binding plus high efficacy used in
management of sever pains. They all have
high affinity for Mμ receptors and
generally lower affinity for δ and κ sites.
They always cause both physical and
psychological dependence.
Morphine
Heroin 3 times more potent than morphine
Methadone effective analgesia, orally
effective, long duration
fentanyl
Codeine 110 activity of morphine
Oxymorphone 6-8 times as morphine
Naglaa El-Orabi, Ph D
72. mixed agonist-antagonists:
These drugs may produce agonist effects
at some opiate receptors and antagonist
effects at another opiate receptors
e.g Pentazocine, Nalbuphine,
Nalorphine, and Dezocine.
Nalbuphine is agonist on -receptor
and potent anatagonist at m-receptor but
weak antagonist at -receptors.
Pentazocine is antagonist at μ-
receptors but partial agonists on - and -
receptors.
Toxicityof opiates
73. These so-called agonist-antagonists are not
constipating, produce less respiratory
depression at higher doses, and have less
potential for abuse, but their limited analgesic
efficacy diminishes their value when
postoperative pain is severe.
Higher doses are no more effective than
conventional doses. Because they act as
antagonists at mu receptors, agonist-
antagonists
may precipitate a withdrawal syndrome in
patients dependent on opioids.
75. Therapeutic uses of Opiates :
i. Pain management:
- Relief of moderate to severe acute pain (Like
postoperative pain, pain associated with
orthopedic manipulations, myocardial infarction
pain, cancer pain, renal colic)
- To induce brief tranqullizing effect with
analgesia in serious and frightening conditions
accompanied by pain (e.g. multiple traumas )
ii. Preanesthetic medication to reduce pain
sensation and anxiety ( e.g Fentany,
Pethidine)
iii. Cough Suppression (e.g. codeine,
dextromethorphan)
iv. Symptomatic treatment of sever diarrhea
and dysentery (e.g. Diphenoxylate,
Loperamide)
76. - Opiates have
many legal
medicinal uses in
addition to high
potential of
abuses.
- Members of
opiates family are
listed in different
drug schedules.
s
Narcotic Drug Most Common
Uses
Heroin Abuse
Morphine Analgesia
Methadone Treat narcotic
dependence
Meperidine Analgesia
Oxycodone Analgesia
Propoxyphene Analgesia
Codeine Analgesia,
antitussive
Loperamide Antidiarrheal
Diphenoxylate Antidiarrheal
Opium tincture Antidiarrheal
77. LATENCY TO ONSET
*oral (-30 minutes)
*intranasal (2-3 minutes)
*intravenous (30 seconds)
*pulmonary-inhalation (6-11 seconds)
DURATION OF ACTION – anywhere between 4 and 72
hours depending on the substance in question.
Metabolism –
hepatic via phase 1 and phase 2 biotransformations to
form a diverse array of metabolites ( eg., morphine to
morphine-6-glucuronide).
Opiate metabolites are excreted in the urine. Impaired
renal function can lead to toxic effects from
accumulated drug or active metabolites (eg,
normeperidine).
78. Precautions: Opiates should be avoided to
be used in patients with the following
pathologic disorders:
i. Decreased impaired respiratory functions
e.g. emphysema, asthma and CPOD.
ii. Biliary colic
iii. Head injury (increase in ICP)
iv. Reduced blood volume
v. Hepatic and renal insufficiency
vi. During pregnancy and labor.
79. Dependence occurs when the body
accommodates to the influences of a drug
and, upon sudden discontinuation,the
patient experiences a withdrawal syndrome
that generally includes reactions opposite
those produced by the particular drug. For
example, opioids produce sedation, and
constipation. A patient who is experiencing
opioid withdrawal becomes excited and
experiences diarrhea.
80. After repeated administration, patients
develop tolerance to opioids. This is to say
that greater doses are required to produce
the same intensity of effect formerly
provided by a smaller dose.
Tolerance to analgesia, sedation, and
respiratory depression occurs simultaneously,
but it is curious that no tolerance occurs to
the constipating or miotic effects of opioids.
Constipation may become severe and night
vision becomes impaired.
81. Addiction is distinct from dependence or
tolerance. It is a compulsive behavior centered on
seeking a drug and its effects for nonmedical
reasons generally for pleasure. It It is a complexp
sychiatric phenomenon, but it should not be
attributed to the drug.
Opioids produce dependence, even after as little
as 5^7 days of therapy, and this may require
institution of a tapering dosage schedule.
However, opioids do not produce addiction; they
should not be withheld on the presumption that
the patient will become ‘‘addicted.’’
Obviously, opioids must be prescribed cautiously
for patients who demonstrate addictive
personality.
82.
83. Codeine has very little affinity for the mu receptor
and may be considered a prodrug because 11% of the
parent drug is converted to morphine by cytochrome
P450 CYP2D6.The morphine metabolite accounts for
its entire analgesic effect.
Altered activity of CYP2D6 offers one explanation for
varied responses to codeine and to its derivatives
Roughly 5- 9% of the Caucasian population
metabolizes codeine poorly because these individuals
have inherited nonfunctional CYP2D6. For them,
analgesia resulting from codeine will be less than
expected with the general population.
Likewise, a variety of drugs that a patient may be
taking concurrently have the ability to inhibit or
induce CYP2D6 activity. For example, the SSRI
antidepressants are CYP2D6 inhibitors, making
codeine less effective. This is established for
fluoxetine (Prozac) and paroxetine (Paxil)
84. Hydrocodone is demethylated to hydromorphone
For this reason, hydrocodone shares the same
considerations regarding demethylation
addressed previously for codeine.
In contrast, the analgesic effect of oxycodone is
almost entirely attributedto the parent drug
because only scant amounts are demethylated
to oxymorphone.
This makes it the better choice for patients
taking medications known to inhibit CYP2D6.
Their potency allows for lower doses of these
agents and reduces the incidence of nausea
compared with codeine
85.
86. Meperidine: A significant portion of an IM dose of
meperidine is converted to normeperidine, a
metabolite that has no analgesic properties but is a
noted cardiovascular and CNS stimulant.
Furthermore, this metabolite has a 17 hours half life.
For hospitalized patients, meperidine is used for only a
day or 2; otherwise, normeperidine will accumulate. In
fact, many hospitals have deleted it from their
formularies.
Pentazocine: Pentazocine is the only oral agonist
antagonist analgesic available in the United States.
It produces its analgesic effect by acting as an agonist
at kappa receptors but is an antagonist at mu
receptors.
Therefore it reverses all effects of traditional mu
agonist opioids if taken concurrently.
Additionally, pentazocine is available compounded with
APAP.
87. Tramadol. Tramadol is a centrally acting analgesic with
binary action.
The parent drug inhibits the reuptake of norepinephrine
and serotonin. This resembles the action of tricyclic
antidepressants and potentiates descending neural
pathways that inhibit incoming nociceptive impulses. This
action has proven efficacy in the management of chronic
pain.
The principal metabolite of tramadol, O-
desmethyltramadol (M1), demonstrate agonist action on
mu receptors, providing analgesic efficacy approximating
that of codeine.
Formation of this metabolite is provided by CYP2D6
enzymes and introduces the identical risk for drug
interactions described earlier for codeine.
88. Tramadol is not recommended for patients
with a tendency toward opioid abuse or
dependence.
It is available in combination with
acetaminophen but is no more effective than
codeine-acetaminophen combinations
89. Mild to moderate pain generally can be managed by
using optimal doses of nonopioids: ibuprofen 400^
800 mg, acetaminophen 1000 mg, or a combination of
the two.
Although it is unwise to combine NSAIDs,the addition
of acetaminophen to an NSAID is reasonable.
Regardless of pain severity, one should seek to
optimize ‘‘around-the-clock’’ dosages of these agents
and then, if necessary, add an opioid to the regimen
as needed for breakthrough pain.
This practice generally will reduce the amount of
opioid required, sometimes to only a fraction of the
maximum doses .
It is irrational to prescribe opioid combinations
routinely as ‘‘first-line’’ analgesics