Pharmacology of Analgesic Agents: Opioids Flashcards
Nociceptor
sensory receptor of the peripheral somatosensory nervous system that is capable of transducing and encoding noxious stimuli
Nociception
- The neural process of encoding noxious stimuli
- Physiologic process that underlies the conscious perception of pain. Does not require consciousness
- How that differs from pain? Our patients can have nociception, but NOT pain
Hyperalgesia
increased pain from a stimulus that normally provokes pain
Allodynia
pain due to a stimulus that does not normally provoke pain
Analgesia/hypoalgesia
absence (analgesia) or reduction of pain (hypoalgesia) in response to stimulation which would normally be painful
Pre-emptive analgesia
the admin of analgesic drugs PRIOR to the occurrence of tissue damage to achieve better, longer lasting pain control
Multi-modal analgesia
- Provision of analgesia using drugs from different classes w/ complementary analgesic activities, whilst simultaneously minimising overall side effects
- This is b/c pain pathway can be interrupted at more than one site, & the more sites that are targeted, the better will be the overall analgesia provision
Neuropathic Pain
type of pain that occurs as a result of a pathology in the CNS. It may be thru mechanical injury nerves such as that seen in diabetic neuropathy, amputation, spinal cord injury, neoplasia
Central sensitisation
- Condition of the NS assoc’d w/ dvlpmt & maintenance of chronic pain
- When it occurs, the NS goes thru a process where it becomes reset in a state of high reactivity, which lowers the threshold for which pain is perceived.
Anaesthesia without analgesia only acts on what part of the pain processing & pathway?
Perception
What is the cause, duration, and txt of acute pain?
Cause: usually known
Duration: short, well-characterised
Txt: resolution of underlying cause, self-limiting
What is the cause, duration, and treatment of chronic pain?
Cause: often unknown
duration: persists after expected healing, >3 mos
Txt: underlying cause & pain disorder, outcome is pain control, NOT cure
What medication classes are used for pain?
opioids, NSAIDs, local, NMDA antagonists, A-2 agonists, etc
When does toxicity of opioids occur?
High doses
* iatrogenic
* ingestion of patches
* police dogs
* human abuse
What are clinical signs of opioid toxicity?
- severe resp depression, cyanosis possible
- bradycardia, hypotension
- altered mental state/sedate (non-responsive)
- hypothermia
- miosis (small pupil)
- death if untreated
What schedule of drug are opioids?
Schedule 2
Explain the mechanism of action for opioids
- Presynaptically decreased Ca2+ influx leads to reduction of NTs leading to inhibition of nociceptive input
- Post-synaptically K+ enhanced efflux leads to neuronal hyperpolarisation & inhibition of ascending pathway leading to inhibition of nociceptive input
The strongest opioids act on… others act on… receptors.
Mu, kappa
What route of administration is used with opioids?
IV, IM, SQ, PO, Epidural, IA, Transdermal, Transmucosal
Supraspinal sites of action of opioids include?
brain, chemoreceptor trigger zone (CTZ)
Absorption, onset, & offset times of opioids are…
drug & species dependent
Spinal sites of action of opioids include…
dorsal horn, peripheral terminals of nociceptive afferent neurons
Opioids impact what other systems?
GIT, urinary, uterus, synovium
Transdermal use of opioids can aid in…
long-term pain mgmt
What are the main CNS effects of opioids?
- Analgesia (Gold Std)
- Sedation
- Euphoria – esp in cats
- Dysphoria – esp in dogs, vocalising confused w/ pain, must differentiate btw pain vs dysphoria
- Reduction of anaesthetic requirements – reduces side effects of anaesthesia
What main effects do opioids have on the cardiovascular system?
- Minimal effects on cardiac output, contractility & BP
- Bradycardia (except pethidine –> tachycardia)
- Reduction in BP may occur, b/c anaesthetic requirements are reduced
What are the main respiratory effects of opioids?
- Respiratory depression – conscious or unconscious, alters responsiveness of CO2 so cannot respond to breathing b/c body will not notice
- Inhibition of cough reflex (antitussive)
What are the main digestive effects of opioids?
- Emesis (morphine, hydromorphone mostly)
- Constipation
- Reduced Colon motility
- Pethidine: spasmolytic
What are the main urinary effects of opioids?
- Urinary retention – esp if given as an epidural
- Decreased urinary production (conflicting data)
- κ agonists: increase urinary production (↓ release of vasopressin)
Explain opioid activity
- full mu agonist - elicits max response at the receptor
- Partial agonist - weakly stimulates mu receptor, elicits partial response at the receptor, but a strong affinity so difficult to displace once IN the receptor
- Antagonist - no intrinsic activity, blocks the receptor
- Agonist-antagonist - mixed activities int he receptor, effect on kappa possible w/ non on mu, poor analgesia than mu agonists
Morphine has what kind of opioid activity?
Full mu agonist, mild kappa affinity
What is morphine used for?
- premedication & analgesia
- in horses
- epidural
- acute & chronic pain indications
Where is morphine metabolised? What are the main metabolites?
- hepatic & extra-hepatic metabolisation sites
- Inactive metabolite: mrophine-3-glucuronide
- active metabolite: morphine-6-glucoride
- Cats: sulfate conjugation –> morphine-6-glucoride
Morphine has poor… which causes
Poor lipid solubility
causes GI effects
What are the different routes of administration of morphine?
IV, IM, SQ, oral, epidural, intrathecal, intra-articular
What is the onset of action of morphine?
- 15-30 mins after IM injection
- Faster IV but caution of side effects (histamine release) so give slow
What is the duration of action of morphine?
- 4-6 hrs
What are the main CNS effects of morphine?
analgesia, sedation
What are the main CVS effects of morphine?
bradycardia
histamine release if given IV
What respiratory system effects occur from morphine?
hypoventilation, bronchospasm so avoid in asthmatics
What are the main GIT effects of morphine?
- nausea, V
- constipation
- contracts sphincter of Oddi
What type of activity is present in methadone?
Synthetic, pure mu agonist
What are the main uses of methadone?
- Some NMDA antagonism effect
- used for premed & analgesia
Methadone is more lipid soluble than…
morphine
What are the main routes of administration of methadone?
IV, IM, SQ
What is the onset of action of methadone?
10-20 mins IM
What is the duration of action of methadone?
approx 4 hrs, maybe 6 depending on dose
What are the main CNS effects of methadone?
- analgesia (chronic & refractory pain)
- less sedation than morphine
What are the main cardiovascular effects of methadone?
- bradycardia
- no histamine release (safe IV)
- more seen when under GA
What are the main resp system effects of methadone?
- resp depression
- panting
What are the main GIT signs of methadone?
- no V due to liposolubility
- little effect on biliary tract
Pethidine is also known as…
Meperidine
What is the main activity of Pethidine/Meperidine?
Pure mu agonist
What is the main use of Pethidine/meperidine?
Premed & sedative effects
What is the main route of administration of Pethidine/meperidine?
IM ONLY
(IV causes strong histamine release)
What is the onset of action of pethidine/meperidine?
15-20 mins
What is the duration of action of pethidine/meperidine?
lasts up to 90 mins (avg 30-60 mins)
What are the main CNS effects of pethidine/meperidine?
- mydriasis (dilated pupils)
- sedation
What are the main CV effects of pethidine/meperidine?
- increase HR
- severe hypotension if histamine release occurs
- neg inotropic effects
What GIT effects occur with Pethidine/meperidine?
- No V
- spasmolytic on GIT smooth muscle
- no bile duct spasm
What are the main urinary tract effects of pethidine/meperidine?
spasmolytic effect
What other effects occur with pethidine/meperidine?
- decreased salivary & respiratory secretions
- reduces shivering, esp post-op
Fentanyl has what type of opioid activity?
Synthetic pure mu agonist
What is the main use of fentanyl?
- Useful for rescue analgesia intraoperatively
- as a CRI
What are the main routes of admin of fentanyl?
IV, IM, SQ, transdermal
(IM/SQ rarely used b/c short-acting)
What is the onset of action of fentanyl?
<2 mins after IV bolus
What is the duration of action of fentanyl?
<20 mins after bolus
Where does metabolisation of fentanyl occur?
Liver & lungs
What are the main CNS effects of fentanyl?
- analgesia
- sedation
- excitement in cats
What are the main CVS effects of fentanyl?
bradycardia
What are the main resp system effects of fentanyl?
Hypoventilation
What type of opioid activity is present in buprenorphine?
partial mu receptor agonist
What are main uses of buprenorphine?
Analgesic & premed
What are the main routes of admin of buprenorphine?
IM, IV, SQ, OTM
What is the onset of action of buprenorphine?
20 mins IV, 40 mins IM
What is the druation of action of buprenorphine?
6-8 hours
Where is buprenorphine metabolised?
liver
What opioid activity is present in butorphanol?
Mixed agonist/antagonist
What are the main uses of butorphanol?
sedative, analgesic, anti-tussive effects
What are the main routes of admin of butorphanol?
IM, IV
What is the duration of action of butorphanol?
1.5-2 hours
Butorphanol is metabolised in the…
liver
Butorphanol is excreted…
90% renally, 10% bile
What are the CNS effects of butorphanol?
good sedation, potentiates action of acepromazine & alpha-2 agonists
What are some analgesic effects of butorphanol?
- visceral pain in horses?
- unsuitable for painful procedures
What are some GIT effects of butorphanol?
reduction in smooth muscle activity
What opioid activity is present in Tramadol?
Atypical centrally-acting opioid
What does Tramadol in the body?
inhibits serotonin & noradrenalin reuptake
What are the routes of admin of Tramadol?
IV, IM, epidural, PO
What is the half life of tramadol in dogs? cats?
dogs: 4-6 hrs
cats: longer (slower clearance)
What are side effects of Tramadol?
- sedation
- nausea
- excitement/dysphoria/euphoria (cats)
- tremor/trmbling/ataxia/muscle fasciculations (IV in horse)
- may reduce seizure threshold (pediatric P)
- resp depression at high doses in cats
What are some ultra-potent opioids used in zoo/wild animals?
- Etorphine
- Carfentanil
What are the main opioid reversal agents?
Naloxone, Naltrexone, Diprenorphine
