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Opioid (Narcotic) Analgesics, Opioid Antagonists, and Nonopioid Centrally Acting Analgesics : 

Opioid (Narcotic) Analgesics, Opioid Antagonists, and Nonopioid Centrally Acting Analgesics

Objectives : 

Objectives State the roles of the kappa and mu opioid receptors as they are involved in causing analgesia, respiratory depression, and euphoria. Give precise definition(s) of “narcotic” (as applied legally to classes of drugs), and compare them with the way the typical layperson uses the term. Distinguish among pure opioid agonists, agonist-antagonists, and antagonists in terms of their mechanism of action; place various named drugs in the appropriate category. Discuss the therapeutic use for opioid agonists, agonist-antagonists, and antagonists.

Objectives : 

Objectives Discuss the adverse effects of opioids and both their pharmacologic and nondrug management. The discussion should include a typical opioid agonist such as morphine, mixed opioid agonist-antagonists, and pure opioid antagonists. State how meperidine differs from morphine in terms of adverse effects and proper clinical use(s). Describe opioid drug-related factors that contribute to the development of physical and psychologic dependence. Identify drug- and administration-related factors that affect the severity of physical dependence as well as the severity and duration of withdrawal signs and symptoms when administration of that drug is stopped suddenly. Compare and contrast acute withdrawal from an opioid (assume physical dependency has occurred) with the withdrawal signs, symptoms, and likely outcomes of unsupervised withdrawal from barbiturates, alcohol, and benzodiazepines.

Opioid (Narcotic) Analgesics, Opioid Antagonists, and Nonopioid Centrally Acting Analgesics : 

Opioid (Narcotic) Analgesics, Opioid Antagonists, and Nonopioid Centrally Acting Analgesics Introduction to the opioids Basic pharmacology of the opioids Clinical use of opioids Opioid antagonists Nonopioid centrally acting analgesics

Introduction to the Opioids : 

Introduction to the Opioids Terminology Endogenous opioid peptides Opioid receptors Classification of drugs that act as opioid receptors

Terminology : 

Terminology A general term defined as any drug, natural or synthetic, that has actions similar to those of morphine

Endogenous Opioid Peptides : 

Endogenous Opioid Peptides Three families of peptides Enkephalins Endorphins Dynorphins

Opioid Receptors : 

Opioid Receptors Three main classes of opioid receptors Mu receptors Kappa receptors Delta receptors

Classification of Drugs That Act as Opioid Receptors : 

Classification of Drugs That Act as Opioid Receptors Pure opioid agonists Activate mu receptors and kappa receptors Agonist-antagonist opioids Pentazocine Nalbuphine Butorphanol Buprenorphine Pure opioid antagonists Act as antagonists at mu and kappa receptors

Basic Pharmacology of the Opioids : 

Basic Pharmacology of the Opioids Morphine Other strong opioid agonists Moderate to strong opioid agonists Agonist-antagonist opioids

Morphine : 

Morphine Source Seedpod of the poppy plant Overview of pharmacologic actions Pain relief Drowsiness Mental clouding Anxiety reduction Sense of well-being Therapeutic use: relief of pain Mechanism of analgesic action

Morphine : 

Morphine Adverse effects Respiratory depression Constipation Orthostatic hypotension Urinary retention Cough suppression Biliary colic

Morphine : 

Morphine Adverse effects (cont’d) Emesis Elevation of intracranial pressure Euphoria/dysphoria Sedation Miosis Neurotoxicity Adverse effects from prolonged use

Morphine : 

Morphine Pharmacokinetics Administered by several routes: oral, IM, IV, subcutaneous, epidural, and intrathecal Tolerance and physical dependence Tolerance Increasing doses to obtain same response Develops with analgesia, euphoria, sedation, respiratory depression Cross-tolerance to other opioid agonists Physical dependence Abstinence syndrome occurs if drug abruptly stopped

Morphine : 

Morphine Abuse liability Precautions Decreased respiratory reserve Pregnancy Labor and delivery Head injury Other precautions

Morphine : 

Morphine Drug interactions CNS depressants Anticholinergic drugs Hypotensive drugs Monoamine oxidase inhibitors Agonist-antagonist opioids Opioid antagonists Other interactions Toxicity Clinical manifestations Treatment

Morphine : 

Morphine Preparations, dosage, and administration General guidelines on dosage and administration Preparations Dosage and routes of administration Oral Intramuscular and subcutaneous Intravenous Epidural and intrathecal

Other Strong Opioid Agonists : 

Other Strong Opioid Agonists Fentanyl Parenteral Transdermal Transmucosal Alfentanil and sufentanil Remifentanil Meperidine Methadone Heroin Hydromorphone, oxymorphone, and levorphanol Basic pharmacology Preparations, dosage, and administration

Moderate to Strong Opioid Agonists : 

Moderate to Strong Opioid Agonists Codeine Actions and uses Preparations, dosage, and administration Oxycodone Analgesic actions equivalent to codeine A long-acting analgesic Hydrocodone Propoxyphene

Agonist-Antagonist Opioids : 

Agonist-Antagonist Opioids Pentazocine Actions and uses Preparations, dosage, and administration Nalbuphine Butorphanol Buprenorphine

Clinical Use of Opioids : 

Clinical Use of Opioids Dosing guidelines Physical dependence, abuse, and addiction as clinical concerns Patient-controlled analgesia Using opioids in specific settings

Dosing Guidelines : 

Dosing Guidelines Assessment of pain Pain status should be evaluated prior to opioid administration and about 1 hour after. Dosage determination Opioid analgesics must be adjusted to accommodate individual variation. Dosing schedule As a rule, opioids should be administered on a fixed schedule. Avoiding withdrawal

Figure 28-3 Fluctuations in opioid blood levels seen with three dosing procedures. : 

Figure 28-3 Fluctuations in opioid blood levels seen with three dosing procedures.

Physical Dependence, Abuse, and Addiction as Clinical Concerns : 

Physical Dependence, Abuse, and Addiction as Clinical Concerns Definitions Physical dependence Abuse Addiction Minimizing fears about physical dependence Minimizing fears about addiction Balancing the need to provide pain relief with the desire to minimize abuse

Patient-Controlled Analgesia : 

Patient-Controlled Analgesia PCA devices Drug selection and dosage regulation Comparison of PCA with traditional intramuscular therapy Patient education

Using Opioids for Specific Kinds of Pain : 

Using Opioids for Specific Kinds of Pain Postoperative pain Obstetric analgesia Myocardial infarction Head injury Cancer-related pain Chronic noncancer pain

Opioid Antagonists : 

Opioid Antagonists Naloxone Other opioid antagonists

Naloxone : 

Naloxone Mechanism of action Pharmacologic effects Pharmacokinetics Therapeutic uses Reversal of opioid overdose Reversal of postoperative opioid effects Reversal of neonatal respiratory depression Preparations, dosage, and administration Preparations and routes Opioid overdose Postoperative opioid effects Neonatal respiratory depression

Nonopioid Centrally Acting Analgesics : 

Nonopioid Centrally Acting Analgesics Tramadol Clonidine Ziconotide

Tramadol : 

Tramadol Mechanism of action Therapeutic use Pharmacokinetics Adverse effects and interactions Drug interactions Abuse liability Preparations, dosage, and administration

Clonidine : 

Clonidine Mechanism of pain relief Analgesic use Pharmacokinetics Adverse effects Contraindications Preparations, dosage, and administration

Ziconotide : 

Ziconotide Mechanism of action Clinical trials Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration

ChapteCyclooxygenase Inhibitors:NonsteroidalAnti-Inflammatory Drugs and Acetaminophen : 

ChapteCyclooxygenase Inhibitors:NonsteroidalAnti-Inflammatory Drugs and Acetaminophen

Objectives : 

Objectives Describe the similarities or differences between the cyclooxygenase-1 and -2 pathways, and state which (patho) physiologic process is mainly responsible for. Discuss the beneficial and adverse actions of nonsteroidal anti-inflammatory drugs (NSAIDs), and the basic mechanism(s) by which they arise. Identify situations (whether the presence of comorbid conditions or use of interacting drugs) in which aspirin should not be used, even for relief of mild or episodic headache or fever. State which of the alternative over-the-counter (OTC) analgesic/antipyretic drugs would be a more acceptable alternative to aspirin, and explain why. Compare and contrast the signs and symptoms of acute poisoning with aspirin and with acetaminophen; the time course of the signs/symptoms and underlying causes; and management.

Classification of Cyclooxygenase Inhibitors : 

Classification of Cyclooxygenase Inhibitors Drugs with anti-inflammatory properties NSAIDs—nonsteroidal anti-inflammatory drugs First generation—aspirin Second generation—celecoxib Drugs without anti-inflammatory properties Acetaminophen

Cyclooxygenase Inhibitors : 

Cyclooxygenase Inhibitors Uses Suppress inflammation Relieve pain Reduce fever Adverse effects Gastric ulceration Bleeding Renal impairment

Aspirin : 

Aspirin Nonselective inhibitor of cyclooxygenase Analgesic, antipyretic, anti-inflammatory Suppression of platelet aggregation Dysmenorrhea Cancer prevention Prevention of Alzheimer’s disease

Aspirin (cont’d) : 

Aspirin (cont’d) Adverse effects Gastrointestinal Bleeding Renal impairment Salicylism Reye’s syndrome Hypersensitivity reaction

Celecoxib [Celebrex] : 

Celecoxib [Celebrex] Second generation COX-2 inhibitor—fewer adverse effects than first generation Uses Osteoarthritis Rheumatoid arthritis Acute pain Dysmenorrhea Familial adenomatous polyposis

Celecoxib [Celebrex] (cont’d) : 

Celecoxib [Celebrex] (cont’d) Adverse effects Dyspepsia Abdominal pain Renal toxicity Sulfonamide allergy

Acetaminophen [Tylenol] : 

Acetaminophen [Tylenol] Analgesic, antipyretic Action Inhibits prostaglandin synthesis in central nervous system Adverse effects Hepatotoxicity Overdose—hepatic necrosis

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