Opioids and antitussives Dr. Yieldez Bassiouni

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.

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)

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)

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

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.

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

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

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

Morphine

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.

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 .

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

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)

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

Antitussives

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

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

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

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)

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)

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

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)

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.

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.

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

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

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.

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.

Antitussive Drug Acting Peripherally

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.

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.