!Narcotic Analgesics Flashcards
Analgesia
Relief of pain without loss of consciousness
Opium
Natural extract from poppy plant used for social and medicinal purpose for thousands of years to produce euphoria, analgesia, sleep and to prevent diarrhea
Opoid drugs
Natural+synthetic morphine-like drugs
Narcotic
Opoid analgesics
Compounds related to opium and applies to any substance whether endogenous synthetic or semisynthetic drugs that produce morphine like effects that are blocked by antagonists such as naloxone
Antagonist to narcotics
Naloxone
Opium effects
Euphoria, analgesia and sleep, and to prevent diarrhea
Opiates
Drugs derived from opium, and they clued the natural products morphine, codeine, and the wine, and may semisynthetic derivatives such as buprenorphine
Endogenous ones are naturally occurring ligand for opoid receptors
What are opoid analgesics used for
Severe pain
Moderate pain
How do opoids such as heroin and morphine work
Mimicking naturally occurring substances called endogenous opoid peptides or endorphins
Phenanthrenes
Morphine Codeine Hydrocodone Hydromorphone Levophanol Oxycodone Oxymorphone Beprenorphone Nalbuphine Butorphanol Naloxone Heroin
Benzomorphans
Pentazocine
Diphenoxylate
Loperamide
Phenylpiperidines
Meperidine
Fentanyl
Sufentanil
Remifentanil
Diphenylheptanes
Methadone
Propoxyphene
Natural opium alkaloids
Morphine, codeine
Semisynthetic opiates
Hydromorphone, oxymorphones
Synthetic opoids
Pethidine, tramadol, methadone, fentanyl, alfentanil, remifentanil
Opoid agonist-antagonists
Pentazocine
Partial mu receptor agonist
Buprenorphine
Mu receptor antagonist
Naltrexone
Analgesics
Morphine Hydromorphinemethadone Meperidine Fentanyl Codeine Oxycodone Hydrocodone Propoxyphene Dextromethorphan
Mixed receptor agonist antagonists
Pentazocine
Nalbuphine
Buprenorphine
Butorphanol
Opoid antagonists
Naloxone
Naltrexone
Indications for use of hospital narcotics to relieve pain
MI Sickle cell crisis Positive operative procedures Trauma Cancer Kidney stones Back pain
Adjunct to general anesthesia Epidural Palliative care Antitussice Antidiarrheal
MOA
Presynaptic mu receptor activation inhibits calcium influx into sensory neurons, which decreases NT release
Postsynaptic mu receptor activation increases K efflux, which decrease postsynaptic response to excitatory Neurotransmission
Postsynaptic mu receptor activation increases K effluent, which decreases postsynaptoc response to extraordinary NT
Ok
Effects of opoids
Analgesic(stimulant)
Antidiarrheal(stimulant)
Analgesic(dampen)
Antitussive(dampen)
Morphine good amount
Decrease in pain perception (nociception)
Too much morphine
Respiratory depression
Oversee
Morphine, methadone, fentanyl MOA
Strong mu receptor agonist and variable affinity delta and k receptors
Effects of morphine, methadone and fentanyl
Analgesia, relief of anxiety, sedation, slowed GI transit
Clinical applications of morphine , methadone, fentanyl
Severe pain, adjunct in anesthesia (fentanyl, morphine), pulmonary edema (morphine only) maintence in rehabilitation programs (methadone only)
Pharmacokinetics morphine , methadone, fentanyl
First pass effect
Duration 1-4 hours(except methadone which is 4-6)
Toxicity morphine , methadone, fentanyl
Respiratoy depression, severe constipation, addiction liability, convulsion
Hydromorphone, oxymorphone
Like morphine in efficacy, but higher potency
Meperdine
Strong agonist with anticholinergic effects
Oxycodone
Dose dependent analgesia
Sufentanil, alfentanil, remifentanil
Like fentanyl but shorter duration of action
Codeine , hydrocodone
Opoid agonists
Less efficacious than morphine can antagonize strong agonists
Effects of codeine and hydrocodone
Like strong agonists, and weaker effects
Clinical applications codeine, hydrocodone
Mild-moderate pain, cough(codeine)
Pharmacokinetics codeine, hydrocodone
Like strong agonists
Toxicity codeine hydrocodone
Dependent on genetic variation or metabolism
Buprenorphine
Mixed opoid agonist-antagonist
Partial mu agonist and k antagonist
Effects buprenorphine
Like strong agonists but can antagonist their effects and also reduces craving for alcohol
Clinical application buprenorphine
Moderate pain and some maintence rehabilitation programs
Pharmacokinetics buprenorphine
Long duration of action 4-8 h
May precipitate abstinence syndrome
Nalbuphine
Mixed opoid agonist antagonist
K agonist and mu antagonist
Effects of nalbuphine
Like strong agonists but can antagonize their effects also reduces craving for alcohol
Clinical application nalbuphine
Moderate pain
Nalbuphine pharmacokinetics
Long duration of action 4-8 h may precipitate abstinence syndrome
Dextromethrophan
Antitussives
Poorly understood but strong and partial mu agonists are also effective antitussives
Action dextromethorphan
Reduces cough reflex+ dextromethorphan, lecopropoxyphene not analgesic
Clinical application dextromethorphan
Acute debilitating cough
Destromethorphan pharmacokinetics
Duration 30-60 min
Toxicity dextromethorphan
Minimal when taken as directed
Naloxone
Opoid antagonists
Antagonist at mu, delta and kappa
Naloxone effects
Rapidly antagonizes all opoid effects
Clinical applications naloxone
Opoid overdose
Pharmacokinetics naloxone
Duration 1-2 hours (may have to be repeated when treating overdose) and
Toxicity naloxone
Precipitates abstinence syndrome in dependent users
Tapentadol MOA
Mu agonist strong NET inhibitor
Effects tapentadol
Analgesia
Clinical use of tapentadol
Moderate pain
Pharmacokinetics tapentadol
4-6 hours
Toxicity tapentadol
Headache, nausea, and vomiting , possible dependence
Tramadol MOA
Mixed effects, weak mu agonist, moderate SERT inhibitor, weak NET inhibitor
Effects tramadol
Analgesia
Clinical use of tramadol
Moderate pain, adjunct to opoids in chronic syndromes
Pharmacokinetics tramadol
4-6 hours
Tramadol toxicity
Seizures, risk of serotonin syndrome
Mu receptor
Supraspinal and spinal analgesia, inhibition of respiration, slowed GI transit, modulation of hormone and NT release
Delta receptor
Supraspinal and spinal analgesia, modulation of hormones and NT release
Kappa receptor
Supraspinal and spinal analgesia, psychotomimetic effects, slowed GI transit
Endogenous opoid peptide affinity mu receptors
Endorphins>enkephalins>dynorphins
Delta receptor endogenous opoid peptide affinity
Enkephalins>endorphins and dynorphins
Kappa receptor
Dynorphins» endorphins and enkephalins
Morphine receptor
Mu and kappa
Hydromorphone. Receptor
Mu
Oxymorphone receptor
Mu
Methadone receptor
Mu
Meperidine receptor
Mu
Fentanyl receptor
Mu
Sufentanil receptor
Mu, delta, kappa
Alfentanil receptor
Mu
Remifentanil receptor
Mu
Levophanol receptor
Mu
Levophanol receptor
Mu
Codeine receptor
Activate or inactive mu
Hydrocodone receptor
Plus or minus mu
Oxycodone
Mu
Pentazocine
Plus minus mu
Plus kapp
Nelbuphine
Negative mu
Plus kappa
Nelbuphine
Minus mu
Plus kappa
Beprenorphine
Plus minus mu
Minus delta
Minus kappa
Butorphanol
Plus minus mu
Plus kappa
Alll of them have high efficacy except which
Low codeine
Moderate hydrocodone and pentazoicine
Methadone
Mu opoid full agonist
Buprenorphine
Partial agonist at mu kappa and delta
Naltrexone
Partial agonist kappa and antagonist at mu
Nalmefene
Antagonist nalmefene
Partial agonist kappa
Full agonist
Methadone
Partial agonist
Buprenorphine
Antagonist
Naloxone
Adverse effects with acute use
Respiratory depression Nausea/vomiting Pruritus Urticaria Constipation Urinary retention Delirium Sedation Myoclonus Seizures
Adverse effects with chronic use
Hypogonadism Immunosuppression Increased feeding Increased growth hormone secretion Withdrawal effects Tolerance dependence Abuse addiction Hyperalgesia Impairment when driving
Methadone addiction
Opoid
Buprenorphine addiction
Opoid
Naltrexone addiction
Alcohol and opoid
Nalmefene addiction
Nalmefene
Oxycodone side effects central
Hallucination, confusion, fainting, dizziness
Oxycodone skin advers
Hives rash
Oxycodone respiratory side effects
Difficulty breathing
Slower breathing
Face side effects oxycodone
Swelling
Eyes side effect oxycodone
Swelling smaller pupil
Throat oxycodone
Hoarseness welling difficult swallowing
Heart oxycodone
Fast or slow heart beat
Muscular side effects oxycodone
Seizures
Contraindications for morphine
Acute respiratory depression
Renal failure (from accumulation of the metabolistes morphine-3-glucuronide and morphine-6-glucuronide)
-chemical toxicity
-raised intracranial pressure, including head injury (risk of worsening respiratory depression
-biliary colic
-although it has previously been thought that morphone was contraindicated in acute pancreatitis, a review of the literature shows no evidence for this
Mu receptor location
Pre and post synaptic on primary afferent neurons and peripheral sensory neurons
Endogenous ligand mu
B endorphin
Leu enkephlain
Met ankephalin
Dynorphin
Clinical effect mu
Supraspinal analgesia Sedation Spinal analgesia Respiratory depression Bradycardia Hypothermia Miosis Euphoria Pruritus Nausea and vomiting Constipation Urinary retention
Delta receptor
Olfactory bulb
Cerebral cortec
Presynaptic on primary afferent neurons , motor integrationa Nd nociceptors areas
Endogenous ligand delte
Leu enkephalin
Met enkephalins
Clinical effect delta
Supraspinal analgesia Spinal analgesia Respiratory depression Constipation Physical dependence
Kappa
Hypothalamus
Nociceptors areas
Endogenous ligand kappa
Dynorphin
Clinical effect kappa
Supraspinal analgesia Sedation Spinal analgesia Dysphagia Psychotomimetic effects Decrease vasopressin and diuretics
