1. Opioids and antitussives
Dr. Yieldez Bassiouni

2. How pain is transmitted?
The injury will cause release of various pain chemical mediators like prostaglandin, histamine, serotonin, bradykinin and substance P.
These mediators will stimulate the pain receptors in the skin.

3. Pain signals are generated and transferred via the sensory nerve to the spinal cord to the thalamus
-then the massage come out of the spinal cord and travel via motor nerve to the arm muscle, causing the arm to withdraw quickly
-no sensation under the skin (subcutaneous or in muscles)

4. Analgesia means no pain
Analgesics are agents which relieve the pain without disturbing consciousness
Analgesics are divided in to two main classes:
1) Opioid analgesics
2) Non-opioid analgesics (analgesics-antipyretics)

5. Opioid Non-Opioid analgesics (analgesics-antipyretics)
Are the most powerful analgesics that can relieve any type of pain
Act mainly at the level of the cortex. CNS
Can produce addiction
Example: Morphine and codeine
Are mild analgesics that treat mild types of pain as headache…..
Act at the level of the thalamus & hypothalamus
No addiction
Example: NSAIDs e.g. salicylates, and paracetamol

6. Opioid Analgesics
Opioids are drugs acting at opioid receptors, morphine is the prototype of opioid agonists.
Opioid analgesics are potent drugs which selectively depress the CNS and relieve pain.
They are mainly obtained from unripe capsules of Opium poppy plant.

7. OPIOIDS  OPIATES derived directly from opium poppy natural or synthetic with morphin – like action
May be narcotic or non narcotic

8. The important alkaloid isolated from opium is morphine.
Other alkaloids isolated from opium are codeine and papaverine.smooth muschle relaxant

9. Examples of Opioid Drugs
Natural
morphine
codeine
semisynthetic
heroim( methymorphin
synthetic
Pethidine 1/5 morphin activity+ less addiction or meperidine
methadone for Rx of addiction
fentanyl

10. Morphine

11. Mechanism of action
Opioids exert their major effect by interacting with opioids receptors in the CNS and ANS, such as GIT and urinary bladder.
Morphine inhibits release of many excitatory transmitters from nerve terminal carrying painful stimuli.

12. Opioid Receptors
Several types of opioid receptors have been identified at various sites in the nervous system and other tissues.
These are Mu (μ), Kappa (κ) , sigma and Delta (∂) receptors .

13. Action Analgesia Euphoria Gastrointestinal tract Respiration
Raising the pain threshold at the spinal cord level
Altering the brain’s perception of pain. Patients are aware of the presence of pain, but the sensation is not unpleasant.
Euphoria
Morphine produces a powerful sense of contentment and well being.
Respiration
Morphine depresses respiration by reducing of the sensitivity of respiratory centre to carbon dioxide . (most common cause of death in opioid overdose)
Gastrointestinal tract
decreases the motility and increasing the tone of intestinal smooth muscle.
Morphine also increases the tone of GIT sphincters
Overall, morphine produces constipation, with little tolerance
Action

14. Therapeutic uses Relief of cough Analgesia Treatment of diarrhoea
Morphine is strong analgesic
Opioids induce sleep
Relief of cough
Morphine suppress the cough reflex
Treatment of diarrhoea
Morphine decreases the motility and increase the tone of intestinal circular smooth muscle.
Morphin addict charactiristic  pin point pupil (miosis)

15. Adverse effects Nausea and vomiting May lead to death Sedation
Constipation
N&V
Urinary retention
Potential for addiction
Respiratory depression
Nausea and vomiting
May lead to death

16. Antitussives

17. Why do we ?
It is a defensive mechanism to removes excessive secretions
Removes potentially harmful foreign substances (beneficial)
In some situations, coughing can be harmful, such as after hernia repair surgery

18. Cough receptors
bronchi, diaphragm, external auditory canal, larynx, nose, paranasal sinuses , pericardium, pharynx, pleura, stomach, trachea and tympanic membrane.

19. Two Basic Types of Cough
Productive cough
cough that brings up sputum or mucus during expulsion
Dry cough
cough that does not bring up any sputum during expulsion
Give antitussive
Give expectorant
Cough interferes with sleep and work

20. Antitussives = cough suppressant
Drugs used to stop or reduce coughing
Opioid and non-opioid
Used only for nonproductive cough
NB: when pnt has productive cough, give expectorant
Not antihistamine because it will dry the sputum and make it thick  harder to expel (vicid)

21. MoA of Antitussives Depression of medullary center
Increases threshold of the cough center
Interruption of impulses peripherally in the respiratory tract
Inhibition of conduction along the motor pathways
Work on stretch receptors on lungs  numb them inactive
Soothing effect (ex: lozanges)

22. 1- Centrally acting Antitussives Codeine Pholcodine Hydrocodone
Narcotic antitussives
Codeine
Pholcodine
Hydrocodone
Non narcotic antitussives
Dextromethorphan
Noscapine

23. Lignocaine (only in special circumstances)
2- Peripheral Antitussives
Inhibition of the cough receptors of Pharynx: Larynx
1 Demulcents
Linctus
Lozenges
Liquorice
2 Inhalation
Benzoin
Menthol
3 Local anaesthetics on pulmonary stretch receptors of alveoli:
Benzonatate
Lignocaine (only in special circumstances)

24. Narcotic Antitussives
Codeine
An opium alkaloid similar to morphine
less potent than morphine as analgesic and respiratory depressant.
60% effective orally.
A standard antitussive
A small fraction of administered codeine is metabolized to morphine which is responsible for analgesic effects of codeine. Euphoric effect used for sever cough of bronchogenic carcinoma
Less addictive
Used limited due to SE.

25. Directly suppresses cough centre in Medulla.
MOA of Codeine:
Directly suppresses cough centre in Medulla.
Suppresses cough for about 6 hrs.
Adverse effects of Codeine:
In therapeutic doses minimum side effects
Sedations, nausea, constipation
At higher doses respiratory depression and drowsiness can occur.
Contraindicated in asthmatic patients. Can cause tolerance and dependance.

26. Pholcodeine
Pholcodeine has similar efficacy as codeine with longer duration of action of 12hrs
It has no analgesic or addiction property
no euphoria

27. Non Narcotic Antitussives
Dextromethorphan Hydrobromide
A synthetic compound.
Strong and partial µ agonist.
As effective antitussive as codeine.
MOA:
Controls cough spasm by depressing cough center in medulla
Increase the threshold for coughing

28. Advantages of Dextromethorphan
No effect on ciliary activity
No CNS depression
No addiction potential
No constipation
Contraindicated in children below 6 yrs of age and also in patients taking Monoamine oxidase inhibitors.

29. Noscapine An opium alkaloid
No narcotic, analgesic or dependance inducing properties.
Equally effective antitussive as codeine
Useful for spasmodic cough.
Headache and nausea are usual side effects
Contraindicated in asthamatic patients.

30. Antitussive Drug Acting Peripherally

31. Inhibition of cough receptor of
Peripherally acting antitussive agent are acting through inhibition of cough receptor or pulmonary stretch receptor as
Inhibition of cough receptor of
Pharynx: demulcent and soothing pastilles, and gargles
Larynx: emollient and soothing spray of menthol and eucalyptus
Tracheobronchial airway: inhalation of hot steam medicated with tr. Benzoin co.

32. Inhibition of pulmonary stretch receptor of alveoli: benzonanatete “tesselone”
Chemically related to tetracaine.
MOA :Reduces the cough reflex by anesthetizing the stretch receptors in the respiratory passages, Lungs and Pleura.stop nerve transmission to cough center.
It has some central effects also.
Benzonatate begins to work within 15 to 20 minutes, and its effects last for approximately 3 hours.
Adverse effects:
Headache, Dizziness
Nasal Congestion, burning of eyes & tightness in chest.