Pharmacology I: CNS X - Opioid Analgesics and Pain Control

…: pain not directly linked to tissue injury

neuropathic pain

pain pathway: … → … → … → … → … ( 5)

nociceptive stimuli, nociceptors, action potential in afferent neurons, dorsal horn, higher centers

Mediators and modulators of pain: … (10)

substance P, bradykinin, prostaglandins, glutamate, GABA, ATP, 5-HT, NE, adenosine, endogenous opioid peptides

2 pathways modulating pain sensations: … (2)

ascending pathway, descending pathway

Ascending pathways: Opioid receptors are located on … (2)

primary afferent pain transmission neurons, spinal cord pain transmission neurons

Primary afferent neurons: … (2)

A-delta fibers, C-fibers

…: involved in sharp and localized pain, somatic pain

A-delta fibers

…: involved in dull diffuse, aching, or burning pain, visceral pain

C-fibers

Descending pathways: opioid recepotr are located on neurons in the … (2)

midbrain, medulla

The descending pathway is involved in …

pain modulation

…: a state in which no pain is felt despite the presence of normally painful stimuli

analgesia

Major types of opioid receptors: … (3)

u, K, delta

Opioid receptors are …

g-coupled receptors

Upon activation opioid receptors: … (3)

decrease cAMP, increase K, decrease Ca conductance

u receptor activation plays a role in … (4)

analgesia, sedation, euphoria, respiratory depressant

u-receptor and delta-receptor activation plays a role in …

slow GI transit

u-receptor and k-receptor activation plays a role in …

sedative actions

k-receptor activation causes …

dysphoria

delta-receptor activation leads to development of …

tolerance

…: extracted from poppy, contains morphine, used for analgesia, sleep, prevent diarrhea, euphoria

opium

All opioids activate the u receptors, with varying activity on the … (2)

k, delta

Classification of opioids: … (3)

clinical use, analgesic strength, ratio of agonist to antagonist

Strong opioids: … (4)

Morphine, pethidine, methadone, fentanyl

The strong opioids are all …

u receptor agonists

…: strong opioid used in heroin recovery

methadone

Moderate opioids: … (2)

oxycodone, codeine

…: moderate u receptor agonist used for analgesic purposes as well as cough suppressant

codeine

…: weak opioid, partial u agonist, weak k agonist, used for analgesia and opiate addiction

Buprenorphine 

Opioids are best absorbed when administered …

orally

Morphine undergoes extensive …

first-pass metabolism

… (2) are administered parenterally in their sustained-release forms, to avoid or compensate for the first pass metabolism

morphine, oxycodone

… are used for fentanyl administration

fentanyl

most opioids are metabolized by … to inactive glucuronide conjugates

hepatic enzymes

… is a metabolite that has analgesic activity

morphine-6-glucuronide

Codeine is metabolized by … (genotypic variability)

CYP2D6

Opioids release … once they bind to the opioid receptors

endogenous opioid peptides

Upon receptor activation the presynaptic neurons close …, decreasing the release of Ach, NE, 5-HT, Glu, substance P

voltage-gated Ca channels

Upon receptor activation the post synaptic neurons … → inhibitory potential

open K channels

Acute effects of opioids: … (9)

analgesia, sedation, euphoria, antitussive actions, resp depression, nausea, GI effects, smooth muscle, miosis

sedation and euphoria occur at … than those required for analgesia, some patients may experience dysphoria due to k-receptors

lower doses

Opioid actions in the medulla → inhibition of the resp center → decreased response to … → cerebrovascular dilation → raised intracranial pressure

carbon dioxide

Nausea and vomiting are caused by opioid activation of the …

chemoreceptor trigger zone

Opioids can cause constipation due to the decreased … from receptor interaction in the enteric nervous system

peristalsis

Opioids cause contraction of: … (3)

biliary tract sm, ureteral sphincter, bladder sphincter

Opioids cause reduction in … → prolonging labor

uterine tone

… is the only opioid that does not cause miosis (pupil constricition)

meperidine

For less sever pain and in the chronic setting → moderate agonists are given in combination with …

NSAIDs

Opioids can be used as …, preoperatively and intraoperatively in combination with other agents in anesthesia protocols

anesthesia

Opioid toxicity symptoms: .. (4)

nausea, vomiting, constipation, respiratory depression

Opioid drug interactions: … (5) → cause additive CNS depression

ethanol, sedative-hypnotics, anesthetics, anti-psychotic drugs, tricyclic anti-depressants

Opioid contraindications: … (6)

head trauma, pulmonary dysfunction, hepatic dysfunction, renal dysfunction, adrenal deficiency, thyroid deficiency, pregnancy

Characterisitcs of overdose: … (3)

pupillary constricition, respiratory depression, comatose state

DIagnosis is confirmed upon adminastration and positibe response to …

antagonist

…: antagonist given in cases of overdose

naloxone

tolerance occurs after the intial dose, clinically it is evident after …

2-3 weeks

Buperonorphine is … to naloxone

resistant

…: weak opioid agonist and acts as an SNRI, used in chronic pain, simialar to opioids and serotonin when given with other anti-depressants

tramadol