Analgesics Flashcards
Order of pain transmission
- Injury occurs (tissue damage, inflammation, infection, etc.(
- Release of arachidonic acid OR autocoids (bradykinin, histamine)
- (if arachidonic acid) Arachidonic acid creates prostaglandins under the action of COX
- Either autocoids OR prostaglandins activate nociceptors
- Neurotransmission through spinal cord (synapse with opioid receptors)
- Neurotransmission to brain (cerebral cortex –> perception of pain and emotional reaction to pain)
Examples of autocloids
histamine and bradykinin
examples of excitatory neurotransmitters released from the pre-synaptic neuron in the gray matter
glutamate and substance P
Endogenous opioids
endorphins
enkephalins
dynorphins
How do presynaptic opioid receptors inhibit pain neurotransmission?
They block voltage dependent calcium channels, which blocks exocytosis of excitatory neurotransmitters
How do postsynaptic opioid receptors block pain neurotransmission?
They open potassium channels which hyperpolarize membranes and block the formation of action potentials, essential for transmitting pain sensation
Examples of opioid receptors
Mu (u1)
Mu (u2)
delta
kappa
What do u1 receptors induce?
analgesia, euphoria and physical dependence
what do u2 receptors induce?
sedation, bradycardia, and resp. depression
what do delta receptors induce
spinal anesthesia and development of tolerance to opioids
what do kappa receptors induce
spinal anesthesia, miosis, and sedation
Non-opioid analgesics
NSAIDs:
ibuprofen
naproxen
aspirin
acetaminophen
MOA of NSAIDs
COX inhibitors that prevent the production of prostaglandins
Pharmacotoxicology of NSAIDs
Gastric irritation, spontaneous hemorrhaging, tinnitus; acetaminophen can cause liver failure in overdoses
MOA of fentanyl
full opioid receptor agonist; 100x more potent than morphine and 50x more potent than heroin
What is hydrocodone
the most widely prescribed drugs on the market and yet when given for the relief of pain, its dose and potential for addiction can be reduced when given with other medications
MOA of methadone
a full opioid receptor agonist that is used in the treatment of opioid addiction because it is a long-acting opioid agonist that reduces the daily cycles of craving and withdrawals.
MOA of codeine
a moderate to strong opioid receptor agonist that is used as an antitussive medication
BOA of buprenorphine
A partial opioid receptor agonist that is used in the treatment of moderate to severe opioid use disorder and as an analgesic
What is suboxone
A combination of buprenorphine and the opioid antagonist naloxone used in the treatment of opioid addiction
What is naloxegol?
a medication used to treat constipation in pts on long-term opioid therapy; a mu receptor antagonist that does not pass the BBB
Examples of opioid receptor antagonists
naltrexone (naloxone) and vivitrol
what is vivitrol
a opioid receptor antagonist that is an injectable formula of naltrexone
What is lofexidine
an alpha2 adrenergic receptor agonist, a non-opioid, that is used to alleviate the physical symptoms of heroin and other types of opioid withdrawal
MOA of gabapentin
increases GABA levels in the CNS which inhibits the subunit in the voltage-dependent calcium channel, thus suppressing the release of glutamate
Therapeutic use of gabapentin
treatment of diabetic peripheral neuropathy, trigeminal neuropathy, fibromyalgia, and “phantom limb pain”
What type of anesthetic is procaine?
ester-type anesthetic
what type of anesthetic is lidocaine?
amide-type anesthetic
What is the difference between ester-type and amide-type anesthetics?
the half life; amide-type anesthetic half life is typically 10 min and ester-type anesthetic is typically 1 minute. Amide anesthetics are metabolized by CYP enzymes and ester anesthetics are metabolized by plasma pseudocholinesterase
MOA of lidocaine and procaine
both are sodium channel blockers that inhibit formation of action potentials and thus block nerve impulse conduction by nociceptors
MOA of propofol
enhancing the release of GABA; inhibiting sodium channels, or activating the endocannabinoid system through the CNS
What is propofol?
General IV anesthetic w/ rapid onset of action, ultra-short duration of action. Used for induction and maintenance of general anesthesia; may induce resp. depression
MOA of isoflurane and etomidate
activating GABA receptors (inhibitory neurotransmitter)
What is isoflurane?
a general, inhalation anesthetic w/ global CNS depressant effects. LOC, analgesic, amnesia, suppression of peripheral sensations, and depression of resp. Control centers
what is etomidate?
a short acting IV anesthetic medication used for the induction of general anesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, and cardioversion.
MOA of ketamine
N-methyl-d-aspartate (NMDA) antagonist (subtype of an excitatory receptor for glutamate)
Ketamine usages?
short-acting IV medication that is used mainly for starting and maintaining anesthesia. Uses include sedation in ICU, analgesia, and treatment of bronchospasms.
prophylactic treatment for migraines include…
Propranolol (non selective beta antagonist)
amitriptyline (tricyclic antidepressant that elevates serotonin levels)
Divalproex (anti-seizure medication)
treatment of ongoing migraine
NSAIDs
Ergotamine: alpha 1 adrenergic agonist—cause vasoconstriction
Sumatriptan: selective serotonin receptor agonist
Telcagepant: oral CGRP receptor antagonist
MOA of nabilone
CB1 and CB2 receptor agonist that has been used in the treatment of chemotherapy-induced nausa/vomiting; treatment of chronic pain (fibromyalgia), and anorexia associated with HIV infections
What is the most common endocannabinoid that we produce?
Anandamide
MOA of Anandamide
the primary psychoactive component of cannabis, delta 9 THC, produces its effects through weak partial activation of the endocannabinoid system that contains cannabinoid 1&2 receptors
