Pharmacology of Opiod Analgesics Flashcards by Ayden Zarkhah

Analgesia meaning

> to block pain neurotransmission

> antinociception

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Anesthesia meaning

> to block sensory neurotransmission

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Nociception

> pain sensation

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Allodynia meaning

> the difference in pain sensation of a hyperalgesia and a normal pain response

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Functions of pain

> pain required for survival
pain dominates other systems; demands action/attention
requires proper threshold; threshold is adaptive

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Functions of pain in terms of tissue damage

> cytokines and chemical mediators
increase vascularization
sensitize somatosensory nervous system
promote recovery

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Functions of pain in terms of spontaneous and exaggerated pain

> no protective or reparative role
pain becomes the pathology
maladaptive

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Descriptive terms of pain

> type, temporal features, intensity, location, quality, exacerbating/alleviating factors

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Comorbidity of chronic pain

> anxiety
> depression
> insomnia/disrupted sleep
> activation of glia
> hyperalgesia/allodynia

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Pain transmission

> Periphery to spinal cord DRG/Posterior columns to central

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Pain processing centers in the brain

> Go to the slide in the packet…NOW

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Supraspinal opioid circuit

> PAG and RVM modifying factors to suppress the sensation of pain

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Two types of alkaloids in opium

> Phenanthrenes: Morphine, Codeine, Thebaine

> Benzylisoquinolines: Noscapine, Papaverine

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Mu opioid receptor Phenanthrenes

> Morphine, Hydrocodone, Buprenorphine, Naloxone

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Mu opioid receptor non-phenanthrenes

> Tramadol, Meperidine, Fentanyl, Methadone

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Metabolism of Phenanthrenes

> Glucuronidation at 3’ and 6’ position

> Morphine-6-glucuronide still active

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Liver metabolism of Phenanthrenes

> CYP2D6
alcohol co-ingestion can increase serum levels
elimination T1/2 increased with liver disease

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Excretion of Phenanthrenes

> glomerular filtration

> 90% excreted in 24hr

Opioid receptors type

> G protein coupled receptor - inhibition of cAMP
Mu
Kappa
Delta
Orphanin FQ receptor
Sigma receptor - not an opioid receptor

Mu opioid receptor agonists

> Beta endorphins endogenous morphine: POMC
Therapeutic target: Analgesia due to cancer, peripheral, PCA
sedation
antitussive

Side effects of mu opioid receptor agonists

> respiratory depression
> constipation
> pruritis
> tolerance/dependance
> urinary retention via ADH
> nausea/vomiting
> muscle rigidity
> miosis
> contraction of biliary tract SMC

Kappa opioid receptor agonists

> Dynorphins endogenous
potential use for treatment of addiction
counterbalance mu opioid receptor effects
salvia contains KOR agonist, salivinorin A

Delta opioid receptor agonists

> enkephalins endogenous
dynamic expressions
role in hypoxia/ischemia/stroke/hibernation
anxiety/depression/alcoholism/hyperalgesia

Action of opioid receptor signal transduction

> G-protein inhibiting Adenylyl cyclase: cAMP(D), intracellular Ca2+(D), release of NT(D)
Adenylyl cyclase activates K+ channel: hyperpolarization due to K efflux

Synaptic action of opioid receptors

> presynaptic: inhibit calcium channel(Gi) decreasing in NT release > postsynaptic: activate GIRK channel increasing K efflux resulting in hyperpolarization

Opioid agonists

``` > sufentanil > remifentanyl > fentanyl > hydromorphone(Dilaudid) > morphine > hydrocodone > oxycodone ```

clinical use of meperidine/demerol

> treat rigors | > neurotoxic: nervousness, tremors, fasciculations, seizure

clinical use of tramadol/ultram

> painkiller used when stronger not preferred | > schedule IV

clinical use of loperamide/imodium

> used as antidiarrheal > PgP substrate so low BBB penetration > schedule V

clinical use of propoxyphene/darvon

> withdrawn due to heart rhythm abnormalities

tramadol/ultram & tapentadol/nucynta

> non phenanthrene > mild opiate analgesic > SNRI properties - stimulate serotonin release > mild neuropathic pain

meperidine/demerol

> normeperidine - active metabolite - accumulate and cause CNS irritability and myoclonic seizures > renally excreted; dangerous in D renal function

methadone

``` > non phenanthrene > opioid dependence > t1/2 15-60hrs and fat soluble > NMDA antagonist > chronic pain ```

levorphanol/phenanthrene

``` > t1/2 16hr > analgesic half life is shorter than serum half life > accumulate > NMDA antagonist > neuropathic pain ```

two drugs with NMDA action

methadone and levorphanol

partial mu agonists

> buprenorphine > partial mu ag, weak k ag, delta antag > long acting, low tolerance/dependence/addiction

partial mu antagonist

naloxone and naltrexone

Opioid for surgery

> fentanyl, sufentanil, remifentanil | > fast onset and short duration

Opioid for postop, epidural

> hydromorphone, morphine | > potent, longer half life than fentanyl

opioid for management

> oxycodone, hydrocodone, oxycontin, zohydro | > oral bioavailability, longer half life than fentanyl

opioid for terminal cancer pain

> morphine | > cost, history

opioid for intolerance

> meperidine | > constipation less, risk of seizure and delirium

pharmacokinetic profile of opioids

> IV, SC/IM, oral increasing Plasma concentration but decreasing half life

Time course of opioids via IV

> hydromorphone, methadone, meperidine, morphine, sufentanil, fentanyl, alfentanil, remifentanil