![Page 1: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/1.jpg)
Pain ,opiate analgesics and antagonists
![Page 2: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/2.jpg)
Mechanism of pain and nociception
• Polymodal nociceptors are the main type of peripheral sensory neuron that responds to noxious stimuli; the majority are non-myelinated C fibers whose endings respond to thermal, mechanical and chemical stimuli.
• Chemical stimuli causing pain includes bradykinin, protons, ATP and vanilloids(e.g. Capsaicin)
![Page 3: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/3.jpg)
• Stimuli to these receptors (agonist) open cation channel s and causing membrane depolarization and AP initiation .
• Theses receptors are sensitized by prostaglandins which explain the analgesic effect of NSAIDs.
• Nociceptive fibers terminate in the superficial fibers of the dorsal horn, forming synaptic connection with transmission neurons running to the thalamus
![Page 4: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/4.jpg)
• Transmission in the dorsal horn in subjective to various modulatory influence, constituting the “gate control mechanism”
• Descending pathways from the midbrain and brain stem exert strong inhibitory effect on dorsal horn transmission.
• The descending inhibition is mediated mainly by enkephalin, 5-HT from NRM(neuclus raphi magnus) and noradrenaline which is released from the locus coeruleus .
![Page 5: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/5.jpg)
• Opioids analgesics causes analgesia partly by inhibiting transmission in the dorsal horn, partly by activating the descending pathways, partly by inhibiting excitation of the sensory nerve terminals in the periphery
• C-fiber activity facilitates transmission through the dorsal horn through substance P receptors and NMDA receptors.
![Page 6: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/6.jpg)
![Page 7: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/7.jpg)
![Page 8: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/8.jpg)
OPIOID ANALGESICS (NARCOTIC ANALGESICS)
• Analgesia: Relief of pain without loss of consciousness.
• Opium: Natural extract from Poppy plant used for social and medicinal purpose for thousands of years to produce euphoria, analgesia, sleep and to prevent diarrhea
• Opioid drugs: natural + synthetic morphine-like drugs.
![Page 9: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/9.jpg)
Opioids analgesics and antagonists Strong agonists includes:
AlfentanilFentanyl HeroinMepridineMethadone MorphineOxycodone Remifentanil Sufentanil.Moderate agonists includes:Codeine Propoxyphene.
![Page 10: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/10.jpg)
• Mixed Agonists and Antagonists• Pentazocine• Nalbuphine• Butorphanol• Buprenorphine
• Opioid Antagonists• Naloxone• Naltrexone• Nalmephine
![Page 11: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/11.jpg)
Opioid receptors
• The opioid agonists act at specific receptor sites to produce their pharmacological effects.
• Opioid Receptors are: μ (μ1, μ 2) қ (қ1, қ2, қ3) δ • They are for endogenous opioid-like substances:(which
also stimulate opioid receptors) • [Met]enkephalin: Tyr-Gly-Gly-Phe-Met • [Leu]enkephalin: Tyr-Gly-Gly-Phe-Leu • Beta Endorphin: a 31 amino acid peptide with
[Met]enkephalin at N-terminal sequence • Dynorphin: a 17 amino acid peptide with
[Leu]enkephalin at N-terminal sequence
![Page 12: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/12.jpg)
• Three genes have been identified which code for opioid peptides
• Beta endorphin and ACTH • Enkephalins • Dynorphins• These neuropeptides are released by stress
and appear to modulate the release of other neurotransmitters.
![Page 13: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/13.jpg)
Opioid Genes
![Page 14: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/14.jpg)
Mechanism of Action of Opioids
![Page 15: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/15.jpg)
Mechanism of ActionMorphine binds opioid receptors and thus impairs the normal sensory pathways through: - Blockade of calcium channels which leads to decreased release of substance P and glutamate from the 1st neuron of the sensory pathway (in substantia gelatinosa in spinal cord and medulla). - Decreased c-AMP which leads to opening of K-channels and hyperpolarization of the 2nd neuron of the
sensory pathway .
![Page 16: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/16.jpg)
• Effects due to μ-receptor stimulation: Supraspinal, spinal and peripheral analgesia,
euphoria, respiratory depression, miosis, decreased GIT motility, sedation, physical dependence.
• Effects due to қ-receptor stimulation: Spinal and peripheral analgesia, dysphoria,
sedation, respiratory depression (less), miosis (less), decrease GIT motility and physical dependence .
![Page 17: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/17.jpg)
• Effects due to δ-receptor stimulation: Spinal analgesia, respiratory depression , and
decrease GIT motility .They are not true opioid receptors only some
opioids react with them .
![Page 18: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/18.jpg)
Morphine - Effective orally, but is much less effective than
when given parenterally due to first-pass metabolism in the liver.
- Metabolism involves glucuronide formation, the product of which is excreted in the urine.
• 1. Central Nervous System Effects • Morphine has mixed depressant and stimulatory
actions on the CNS. - depressant effects predominate in man. - excitatory effects predominate in cats and
horses.
![Page 19: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/19.jpg)
a) Analgesia:• drowsiness is common• continuous dull pain relieved more effectively than
sharp intermittent pain• most patients indicate that they can still feel the
pain, but that it no longer bothers them• morphine is an agonist at μ and қ opioid receptors.
![Page 20: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/20.jpg)
b) Euphoria and sedation it is mainly due to activation of μ-receptor c) Emesis - morphine directly stimulates the chemoreceptor trigger
zone, usually transient and disappear with repeated administration .
d) Antianxietye) Miosis (pinpoint pupil). - it is due to stimulation of the Edenger- Westphal
nucleus of the oculomotor nerve .
![Page 21: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/21.jpg)
f) Cough reflex is inhibited: This action ,surprisingly, does not correlate closely
with analgesic and respiratory depressant effect of opiates, and its mechanism of action at receptor level is unclear of Morphine ,with chemical modification (Codiene and Pholcodiene the antitussive effect can occur at sub- analgesic dose.
![Page 22: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/22.jpg)
g) Respiration is depressed: Due to a direct effect on the brain stem
respiratory center. Death from narcotic overdose is nearly always
due to respiratory arrest. It occur at therapeutic doses but not
accompanied with cardiac center depression in contrast to other CNS depressant like general anesthetic agents.
![Page 23: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/23.jpg)
h) Other effects:• Morphine is a basic drug causes the release of
histamine causes the body to feel warm and the face, nose to itch ,bronchoconstriction and hypotension .
• It also abolishes hunger • It dilate the cerebral vessels and increase
intracranial pressure
![Page 24: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/24.jpg)
2. Cardiovascular Effects • Postural orthostatic hypotension. - due primarily to decreased V.M.C. activity
leading to peripheral vasodilation, which may be due in part to histamine release.
• In congestive heart failure, morphine decreases the left ventricular workload and myocardial oxygen demand.
![Page 25: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/25.jpg)
3. Endocrine Effects • Increases prolactin secretion • Increases vasopressin (ADH) secretion
(oliguria). • Decreases pituitary gonadotropin (LH & FSH)
secretion. • Decreases stress induced ACTH secretion.
![Page 26: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/26.jpg)
4. Gastrointestinal Effects it decrease the motility and increase the tone of the intestinal circular muscle and the tone of the anal sphincter , it also causes contraction of the gallbladder and constriction of the biliary sphincter
• Constipation (tolerance does not develop to this effect).
• Diphenoxylate and Loperamide can be used in the treatment of diarrhea.
They decrease GIT motility and peristalsis
![Page 27: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/27.jpg)
• 5. Genitourinary Effects morphine prolong the second stage of labor by decreasing the strength, duration and frequency of uterine contraction
• Inhibit urinary bladder voiding reflex (sometimes catheterization may be required in some cases )
![Page 28: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/28.jpg)
• B. Adverse Reactions• Generally direct extensions of their
pharmacological actions.• 1. respiratory depression, apnea• 2. nausea and vomiting• 3. dizziness, orthostatic hypotension, edema• 4. mental clouding, drowsiness
![Page 29: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/29.jpg)
• 5. constipation, ileus• 6. biliary spasm (colic)• 7. dry mouth• 8. urine retention, urinary hesitancy• 9. hypersensitivity reactions (contact
dermatitis, urticaria)• 10. immunosuppression (recurrent infections)
![Page 30: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/30.jpg)
• C. Precautions• 1. respiratory depression, particularly in the
newborn and patients with COPD• 3. orthostatic hypotension• 4. histamine release (asthma)• 5. drug interactions (with other CNS
depressants)• 6. tolerance and cross tolerance to other
opioids• 7.benign prostatic hyperplasia(may precipitate
urine retention
![Page 31: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/31.jpg)
• 8. dependence (psychological & physical)• 9.liver disease(accumulation of the drug) • 10.increase intracranial pressure and head
injury(it enhances cerebral ischemia)
![Page 32: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/32.jpg)
• Therapeutic uses: - Analgesia: myocardial infarction, terminal
cancer, surgery, obstetrical procedures - Dyspnea due to pulmonary edema - Severe diarrhea.
![Page 33: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/33.jpg)
II. Other Opioid (Narcotic) Analgesics
• A. Heroin (diacetyl morphine)• 1. μ- agonist• 2. Heroin is more lipid soluble than morphine
and about 2½ times more potent• 3. It enters the CNS more readily• 4. It is a schedule I drug and is not used
clinically, but it is a drug of abuse.
![Page 34: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/34.jpg)
• B. Codeine• 1. From opium or synthesized by methylation
of morphine• 2. Has a much better oral /parenteral
absorption ratio than morphine.• 3. Effective for mild to moderate pain, cough,
diarrhea.• 4. Metabolized in part to morphine by O-
demethylation.
![Page 35: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/35.jpg)
• 5. μ- receptor agonist.• 6. Has a more potent histamine-releasing
action than morphine.• 7. Dependence liability of codeine is less than
that of morphine, .• 8. It is 1/12 as potent as morphine
![Page 36: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/36.jpg)
• C. Dextromethorphan:• 1. Excellent oral antitussive• 2. No analgesic effect• 3. No GI effects• 4. No respiratory depression
![Page 37: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/37.jpg)
• D. Meperidine (Pethidine)• 1. Produces analgesia, sedation, euphoria and
respiratory depression.• 2. Less potent than morphine, 80-100 mg
meperidine equals 10 mg morphine.• 3. Shorter duration of action than morphine
(2-4 hrs).• 4. Meperidine has greater excitatory activity
than does morphine and toxicity may lead to convulsions.
• 5. Meperidine appears to have weak atropine-like activity.
![Page 38: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/38.jpg)
• 6.It does not constrict the pupils to the same extent as morphine.
• 7. Does not cause as much constipation as morphine.
8. Purely synthetic μ- agonist• 9. Not an effective antitussive agent.• 10. less effect in uterine contraction
commonly employed in obstetrics also causes less urine retention
![Page 39: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/39.jpg)
• Adverse reactions to Meperidine - respiratory depression - tremors - delirium and possible convulsions - dry mouth -severe reaction if given with MAOI, consists
of excitement, hyperthermia and convulsions; it is due to accumulation of pethidine(norpethidine) metabolite but the details are still unclear.
![Page 40: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/40.jpg)
• E. Fentanyl • 1. μ- agonist, related chemically to meperidine.• 2. Approximately 80 times more potent than
morphine, main use in anesthesia .• 3. Duration of action very short (t1/2 = 20 min).• 4. Can be given IM, IV, transdemally or via patient
controlled infusion system may be given intrathecally .
• 5.Often used during cardiac surgery because of its negligible effect on the myocardial contractility
![Page 41: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/41.jpg)
F. Sufentanil • 1. A synthetic opioid related to fentanyl.• 2. About 7 times more potent than fentanyl.• 3. Has a slightly more rapid onset of action
than fentanyl.
![Page 42: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/42.jpg)
• G. Methadone • 1. Pharmacology and analgesic potency similar to
morphine; μ- receptor agonist.• 2. Very effective following oral administration.• 3. Longer duration of action than morphine due to
plasma protein binding (t1/2 approximately 25 hrs).• 4. Used in methadone maintenance programs for
treatment of opioid addicts and for opiate withdrawal syndrome(it reduces the physical abstinence syndrome)make it possible to wean the addict from opioids.
![Page 43: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/43.jpg)
• H. Propoxyphene • 1. A methadone analog.• 2. Used orally to relieve mild to moderate
pain, it is weak analgesic ;often combined with Paracetamol .
• 3. Has a low addiction potential • 4. The most common adverse side effects are:
dizziness, drowsiness, and nausea and vomiting.
• 5. CNS depression is additive with other CNS depressants (alcohol and sedatives).
• 6. can cause cardio- toxicity and pulmonary edema which can not reversed by naloxone
![Page 44: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/44.jpg)
III. Mixed Narcotic Agonists/AntagonistsThese drugs produce analgesia, but have a lower potential for abuse
and do not produce as much respiratory depression.A. Pentazocine
1. қ- agonist (analgesia) and μ-antagonist (less respiratory depression).
2. Orally, it has about the same analgesic potency as codeine.
3. Adverse reactions to Pentazocine
• Nausea, vomiting, dizziness, dysphoria, nightmares and visual hallucinations.
Rarely used nowadays
![Page 45: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/45.jpg)
• B. Nalbuphine • 1. Resembles pentazocine pharmacologically.• 2. Like morphine, nalbuphine reduces
myocardial oxygen demand. May be of value following acute myocardial infarction due to both its analgesic properties and reduced myocardial oxygen demand.
• 3. Most frequent side effect is sedation.• 4.less propensity to produce psychotomimetic
side effects
![Page 46: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/46.jpg)
• C. Butorphanol 1. Resembles pentazocine
pharmacologically. 2. 3.5 to 7 times more potent than
morphine. 3.Not available for oral administration 4.They exhibit ceiling of respiratory
depression effect
![Page 47: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/47.jpg)
D. Buprenorphine• A partial agonist at μ-receptor.• 2. 200 times more potent than morphine.• 3. Low potential abuse, but can precipitate
withdrawal in addicts• 4.In naive persons it acts like morphine • 5.Major use is office-based detoxification of
opioids • 6.Causes less sedation, respiratory depression
and hypotension even in high doses.
![Page 48: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/48.jpg)
IV. Opiate Antagonists Opiate antagonists have no agonist properties. They
are utilized to reverse opiate induced respiratory depression and to prevent drug abuse.
• A. Naloxone (Narcan) 1. Pure opiate antagonist at all opioid receptors 2. Given parenterally -Short duration of action (1-4 h) 3. Can precipitate withdrawal in addicts.• B. Naltrexone 1. Oral pure opioid antagonist 2. Long duration of action 3. Contraindicated in liver disease 4. Used in late stages of opioid addiction treatment
( also in treatment of alcoholism).
![Page 49: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/49.jpg)
• Nalmephine: Long-acting parenteral opioid antagonist.
![Page 50: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/50.jpg)
Antitussives• Antitussives: against cough• Coughing is a protective reflex
Chemical & mechanical Afferents EFFerentsStimuli
Respiratory muscles
Sensory receptors in upper respiratory tract
Cough Center medulla
![Page 51: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/51.jpg)
• Antitussives depress cough center, therefore depress the cough reflex.
• Antitussives include: 1. Opioids: Codeine, dextromethorphan, hydrocodone,
hydromorphone. They are opioid agonists against dry cough. They are of low abuse potential. Side effects include: drowsiness and constipatiopn.
![Page 52: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/52.jpg)
• Non-opioids: e.g. butamirate citrate which depress the cough center.
• Peripherally acting antitussives: These prevent irritation of sensory receptors in the upper respiratory tract. Local anesthetics also depress the cough center. They include:
a) demulcents: liquorice, honey b) local anesthetics: benzonatate
N.B.: Antitussives should not be used in productive cough.
![Page 53: Pain,opiate analgesics and antagonists. Mechanism of pain and nociception Polymodal nociceptors are the main type of peripheral sensory neuron that responds](https://reader036.vdocuments.us/reader036/viewer/2022062408/56649ec05503460f94bcac2e/html5/thumbnails/53.jpg)
THANK YOU•REFRENCES:•RANG AND DALE•LIPPINCOTTOS•LANGE