Module E-1 Opiod/non-opioid Flashcards
Functions of GPCR after opioid binding
Outward K flow
Inhibits influx of calcium
Inhibits adenylyl cyclase (conversion of atp to cAMP)
Location of opioid receptors in Brain
Periaqueductal gray
Limbic system
Area postrema (medulla)
Locus ceruleus (pons)
Thalamus
Cerebral cortex
Location of opioid receptors in spinal cord
Dorsal horn (substantia gelatinosa)
Mu actions/subtypes and endogenous agonists
B-Endorphin
Mu-1 supraspinal analgesia and euphoria
Mu-2 respiratory depression and miosis
Pruritis
Kappa Endogenous agoinst and actions
Dynorphin A
Spinal analgesia, sedation, dysphoria, hallucinations, antishivering
Implicated in neurobiology of addiction
Delta Endogenous agoinst and actions
Enkephalins
Supraspinal and spinal analgesia
Sedation, potentially antidepressant/anxiolytic
Respiration depression
Clinically relevant effects of opioid agents on body systems
Cough suppression
Nausea and vomiting
Vasodilation
Bradycardia
Pruritus
Delayed gastric emptying
Ileus and constipation
Urinary retention
Increased biliary pressure
Muscle rigidity
Depressed cellular immunity
Why can’t we use mu-agonists as sole agent for anesthesia?
Don’t produce amnesia
Explain Dextromethorphan
Dextrorotatory isomer that does not have analgesic activity but still produces anti-tussive effect
Common additive in OTC cough syrup
Explain dose dependent offset of opioids
Action of small doses are terminated due to redistribution
Large doses/infusions are dependent on metabolism
Metabolism of opioids
Hepatic cytochrome enzymes
Remifentanil- tissue/plasma esterases
Renal excretion of metabolites- this is why we are careful with active metabolites in renal failure
Which opioids have active metabolites?
Morphine-
Morphine-6-glucuronide
Meperidine-
Normeperidine is neurotoxic-accumulates in hepatic or renal insufficiency and can precipitate seizures
Opioids-CNS Adverse effects
Increased ICP
Sedation
Euphoria
Dysphoria
Hallucinations
Tolerance/dependence
Explain Respiratory response to opioids
Central response
Hypoventilation due to altered response to PaCO2 by the brain stem
-loss of hockey-stick shape in curve=apneic/severe hypoventilation at lower PaCO2
May see synergism with other CNS depressants
Explain cardiovascular effects of opioids
Venodilation via depression of brain stem vasomotor nuclei
Sympatholytic effects cause:
Arteriolar vasodilation, decreased BP & HR
No direct effect on myocardial contractility
Fentanyl-associated with profound bradycardia due to parasympathomimetic (increased vagal tone)
Gastric effects- opioids
Decreased peristalsis
Delayed gastric emptying
Opioid Clinical implications during cholangiography
Gall bladder and sphincter of Oddi spasm
PONV in opioids
Stimulation of chemoreceptor trigger zone in the medulla
Multi factorial- CNS/GI/vestibular system
Musculoskeletal and opioids
Muscle rigidity
-impact on ventilation/chest wall rigidity
-administer muscle relaxants
Pruritis and opioids
Transient, not drug allergy,
Antihistamines administration of antagonists or agonists-antagonists (nalbuphine)
Outline prostaglandin formation
Tissue injury
Phospholipids
Arachidonic acid
Produces Cox1 and Cox2
COX-1 effects
Cytoprotective prostaglandins
Protect gastric mucosa
Aid platelet aggregation
What does COX stand for
cyclooxygenase enzyme
COX-2 Effects
Inflammatory prostaglandins
Recruit inflammatory cells
Sensitize skin pain receptors
Regulate hypothalamic temp control
Chronic Adverse effects of NSAIDs
Increase risk of stroke/MI-imbalance of clotting pathway
Inhibit bone healing-controversial
Gastric/colonic mucosal damage and GI bleeding
Hemostatic-increased bleeding
Renal toxicity- decrease function
Phenanthrenes
Morphine backbone
Chiral center-Levo enantiomer is active
Hydromorphone
Hydrocodone
Oxycodone
Codeine
Nalbuphine
Naloxone
Phenylpiperidines
Meperidine-first synthetic
Fentanyl series
Sufentanil
Remifentanil
Alfentanil
NO chiral form-not racemic
Euphoria receptor
MU
Dysphoria receptor
Kappa
Q
Miosis in opiate use mechanism
Opiate depression of inhibitory gamma-aminobutyric acid (GABA) interneurons leads to stimulation of the Edinger Westphal nucleus, which sends a parasympathetic signal via the ciliary ganglion to the oculomotor nerve to constrict the pupil
Impact of opioids on CO2 curve
Right shift, loss of hockey stick
Describe sensitizing soup
Tissue injury causes release of many different pain mediators from the damaged tissue
H, K
Serotonin
Prostaglandins**, leukotrienes
Bradykinin
Histamine
Afferent signal
Peripheral to central
What GI symptom do we look for in chronic opioid consumption
Delayed gastric emptying/GERD
What to give for ercp spasm with opioid admin
Glucagon
Smooth muscle dilator
Meperidine contraindications
Hx seizures
MAOI
Elderly-renal?
Neuro cases (high risk seizures)
Which class of opioids has a chiral center and describe its orientation
Phenantrenes
Levo-enantionmer
