PHRM845-FINAL EXAM Flashcards
Pharmacology of opiate drugs
What two types of alkaloids does opium contain?
Phenanthrenes and Benzylisoquinolines
What drugs contain phenanthrenes?
Morphine
Codeine
Thebaine
What drugs contain benzylisoquinolines?
Noscapine
Papaverine
Opioids are (synthetic/non-synthetic)
Synthetic
___ are only those opioids that are naturally occurring.
Opiates; plant-derived compounds like morphine
Structure activity relationships (SAR) of phenanthrenes
-3 position substitutions ether or ester produces decreased potency (codeine)
-6 position increases activity (hydromorphone or hydrocodone from codeine)
-14 position OH has increased potency (oxycodone)
-N-allyl give antagonists (or mixed antagonists)–naloxone or naltrexone
What gives partial agonist or antagonist activity on mu opioid receptors?
Substitutions on N
Which drugs are non-phenanthrenes?
Tramadol, Meperidine, Fentanyl, Methadone
The human genome contains several genes encoding (endogenous/exogenous) opioids.
Endogenous; Found in our body to help modulate pain
Large precursor proteins are cleaved into more ____
Opioid subtype selective peptides
Degree of redundancy in peptides
- Pro-opiomelanocortin (POMC) is cleaved to:
~Beta-endorphin targets Mu opioid - Preproenkephalin is cleaved to:
~Leu-enkaphalin targets delta opioid
~Met-enkaphalin targets mu and delta receptors - Preprodynorphin is cleaved to:
~Dynorphin targets kappa opioid - Nociceptin/Orphanin FQ
Types of opioid receptors
-GPCR
-Mu (M-morphine)
-Kappa (K-ketocyclazocine)
-Delta (D-Deferens–>where identified)
-Nociceptin, orphanin FQ receptor
-Sigma receptors (once they were cloned, it was determined they were not an opioid receptor)
GPCR opioid receptor
-Family A: peptide receptors
-Gi/o coupled: inhibit cAMP production
-Open GIRK potassium channels: inwardly rectifying K+ channels to maintain membrane potential (makes K+ flow out–>interior to be more negative–>hyperpolarized and hard to conduct an action potential–>reduces firing of pain signals)
-Close calcium channels
Endogenous opioid for mu receptors
Endorphin
Endogenous opioid for kappa receptors
Dynorphin
Endogenous opioid for delta receptors
Enkephalin
Endogenous opioid for nociceptin receptors
Nociceptin
Mu agonists work (pre/post/both) synaptically
Pre and post-synaptically
Presynaptic signaling for mu agonists
Inhibit calcium channel (Gi) which decreases neurotransmitter release and blocks conduction
Post-synaptic signaling for mu agonists
Activate the GIRK channel (G-beta/gamma); efflux of K+ leading to hyperpolarization
Beta-endorphins for the mu opioid receptor
-Endogenous morphine
-Pro-opiomelanocortin (POMC)
-Component of runners high
Therapeutic use for mu opioid receptor
-Analgesia: Not as effective for chronic pain
~Cancer pain, palliative (relief from end of life pain), patient-controlled analgesia, helpful for acute pain
-Sedation
-Antitussive: suppression of cough center in the medulla oblongata
Opioid induced side effects from mu activation
(mostly on-target effects)
-Respiratory depression
~Brian stem
~pre-Botzinger complex in the ventrolateral medulla
-Constipation
~GI tract
-Pruritus (itch)
~Side effect from opioid-induced histamine release; NOT AN ALLERGIC RESPONSE
-Addiction
-Urinary retention
~Opioid induced ADH release
-Nausea and vomiting
~Chemoreceptor trigger zone–medulla
-Miosis
~Oculomotor nerve (PAG)
~Not mepiridine (has anticholinergic effects)
Can an opioid be used as an anti-diarrheal?
Yes, some are designed to stay out of the CNS and slow motility