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.

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. 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.

 The important alkaloid isolated from opium is morphine.  Other alkaloids isolated from opium are codeine and papaverine.

Examples of Opioid Drugs Natural  morphine  codeine semisynthetic heroin synthetic  Pethidine or meperidine  methadone  fentanyl

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. Mechanism of action

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

Action 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. Analgesia Morphine produces a powerful sense of contentment and well being. Euphoria Morphine depresses respiration by reducing of the sensitivity of respiratory centre to carbon dioxide. (most common cause of death in opioid overdose) Respiration 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 Gastrointestinal tract

Therapeutic uses Morphine is strong analgesic Opioids induce sleep Analgesia Morphine suppress the cough reflex Relief of cough Treatment of diarrhoea Morphine decreases the motility and increase the tone of intestinal circular smooth muscle.

Adverse effects SedationConstipationN&V Urinary retention Potential for addiction Respiratory depression

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.

Productive cough cough that brings up sputum or mucus during expulsion Dry cough cough that does not bring up any sputum during expulsion Two Basic Types of Cough 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

MoA of Antitussives 1) Depression of medullary center 2) Increases threshold of the cough center 3) Interruption of impulses peripherally in the respiratory tract 4) Inhibition of conduction along the motor pathways

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

2- Peripheral Antitussives Inhibition of the cough receptors of Pharynx: Larynx 1Demulcents Linctus Lozenges Liquorice 2Inhalation Benzoin Menthol 3Local 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.

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.

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

Non Narcotic Antitussives Dextromethorphan Hydrobromide A synthetic compound. Strong and partial µ agonist. As effective antitussive as codeine. MOA: 1. Controls cough spasm by depressing cough center in medulla 2. 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.

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. 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.