Analgesics

Question 1

What is analgesia?

Answer 1

• analgesia = the reduction of pain – according to the drug’s effect-more pronounced in either the viscera or the musculoskeletal system
• acute perioperative, traumatic, and disease-related pain-generally treated with one/more analgesics

Question 2

Classify the analgesics and name the active substances

Answer 2

1) Opioid (narcotic) analgesics:
• supress pain by affecting hypothalamus, thalamus and the brain cortex
− morphine and morphine-like drugs:codeine,pethidine,and
−synthetic compounds: methadone, etorphine, fentanyl and carfentanyl
- Centrally acting analgesics which selectively produce analgesia without seriously impairing other functions - consciousness and sensory modalities other than pain.
2) Anti-inflammatory antipyretic-analgesics (NSAIDs):
– acetylsalicyclic acid, phenylbutazone, ketoprofen, carprofen, flunixin, paracetamol, metamizole, meloxicam, firocoxib, tepoxalin
-Possess both peripheral and central site of action.

Question 3

Characterize opioid analgesics

Answer 3

Opioid analgesics
• the derivatives of opium (opiates): e.g., morphine, codeine, hydromorphone – differ among one another primarily in potency
• the synthetic drugs: meperidine (pethidine), etorphine, fentanyl, and carfentanil – not chemically related to opium or morphine, but act as opiate receptor agonists
• high efficacy and remarkable safety
– in life-threatening respiratory depression - reversibility with antagonist naloxone
• Most of the drugs in this group are controlled substances (abuse potential)

Question 4

Indications of opioid analgesics

Answer 4

Indications:
– to provide analgesia;
– as preanesthetics, anesthetic adjuncts,
– to provide a sedating, calming effect and euphoria,
– for immobilization and chemical restraint,
– for diarrhea treatment, for the inhibition of GIT motility,
– asantitussives,
– increased locomotor activity (used illegally in performance horses)

Question 5

Where are opioid receptors located and what are the 3 classes of receptors?

Answer 5

Opioid receptors identified within:
– the CNS and ANS,
– GIT, heart, kidney,
– vas deferens, pancreas, fat cells, Ly,
– and adrenal glands - stimulated by opioids at the cell membrane surface.

3 classes of opiate receptors:
• μ,κandδ
-Endogenous opioids – nat. chemicals (peptides) in the body that interact with opiate rec. - natural physiol. responses, incl. modulation of pain: β-endorphin, Dynorphin A, Leu- and Met-enkephalin.

Question 6

Describe the pre and post-synaptic opioid receptors.

Answer 6

Presynaptic μ,κandδ spinal receptors:
-are present in the dorsal horn of the spinal cord
- decrease the excitatory NT release by decreasing the rate of calcium influx
Postsynaptic μ receptors:
-also in the dorsal root ganglion
-hyperpolarize the neuron by increasing the potassium channel conductance which decreases the propagation of the nociceptive signal
Opioid receptors are also located in various locations in the descending pain inhibitory pathways

Question 7

Opioid analgesics mechanism of action

Answer 7

• The activation of the opioid receptor is coupled to changes in ion conductance and G-protein interaction.
• Opioid agonists with μ or δ-receptor coupling – G-protein-mediated ↓cAMP – ↑ in K+ conductance, hyperpolarization and ↓synaptic transmission.
• κ- receptors – G-protein-mediated mechanism – ↓ in Ca++ influx (inhibition of volt. gated Ca2+ channels) and neurotransmitter immobilization and release
* all 3 receptors cause decreased neurotransmitter release or impulse transmission
• Analgesia is enhanced and duration of analgesia is increased when α2- adrenergic agonists and opioids are administered simultaneously.

Question 8

Describe full and partial opioid agonists, antagonists and a combination thereof.

Answer 8

Opioids may be:
– full agonists - dose-dependent effect, which eventually plateaus with
unconsciousness and anesthesia, e.g., morphine,
– partial agonists - plateaus at a submax. response (less than full agon.; never produce anesthesia alone) despite ↑d., e.g., buprenorphine
– antagonists – competitive – displace the agonist from the opiate receptor, but do not result in receptor activation, e.g., naloxone, and
– combinations thereof e.g., nalbuphine (μ-antagonist but κ-agonist)

Question 9

Effect of opioid analgesics on the respiratory system

Answer 9

• Dose-dependent respiratory depression - activation of the μ receptor – ↓ response
to ↑PCO2
– well tolerated in healthy animals; concurrent anesthesia may ↑ the respir. depression; – may be more problematic in animals with preexisting respiratory disease
• Antitussive effect – central inhibition of the cough center:
– morphine, butorphanol, methadone, and tramadol – in dogs or cats.

Question 10

Effect of opioid analgesics on the CNS. Analgesia?

Answer 10

• ↑doses produce excitement and very high doses result in convulsions
• grand mal seizures in dogs; convulsive activity and generalized excitement in cats
• Horses– dose-dep. excitation (buprenorphine – restlessness,
excitement, head-shaking, pawing, and leg-shifting for 3-4 hr) – combin. with sedatives/tranquilizers
• analgesic effect by binding to spinal and supraspinal receptors