Narcotic Analgesics

It describes Narcotic Analgesics mechanism how it acts.

1. NARCOTIC ANALGESICS Prepared by, Ms. KOTE R. B. Lecturer PRES’s Institute of Pharmacy Loni.

2. Analgesics Definition- These are pharmacological agents which when administered externally relieve mild or moderate pains without affecting degree of consciousness . Classification- 1. Narcotic Analgesics / opioid analgesics Phenanthrene Derivatives- E.g. Morphine Benzyl isoquinoline series- E.g. Papaverine 2. Non-Narcotic Analgesics / Non- opioid analgesics/ Antipyretics E.g. Salicylates & its derivatives

3. A substance used to treat moderate to severe pain. Narcotics are like opiates such as morphine and codeine, but are not made from opium. They bind to opioid receptors in the central nervous system. Narcotics are now called opioids. These are pharmacological agents which when administered externally relieve severe degree of pain associated with burns, fractures , tumors, malignancy etc Phenanthrene Derivatives- E.g. Morphine, Codeine, Thebaine Benzyl isoquinoline series- E.g. Papaverine , Noscapine , Narcine Narcotic Analgesics

4. Non-narcotic analgesics are medications used to control pain and inflammation. They are available at drugstores without a prescription or by prescription when given at higher doses. Some types of these medications can be given during surgery to reduce post-surgical pain and lessen the need for narcotics. These are pharmacological agents which when administered externally relieve mild, dull aching type of pain associated with myalgia, arthralgia Neuralgia ,toothache, body aches ,headache etc without depressing central nervous system (without narcosis) hence referred as non- narcotics Non- Narcotic Analgesics

5. A) Pharmacology of Narcotic Analgesics:- ( E.g.. Morphine) MOA - All narcotic analgesics acts on opiate receptors. Pharmacological action – Analgesia -Pain consists of both sensory and affective (emotional) components. Opioids can change both aspects of the pain experience. In most cases, these drugs have a relatively greater effect on the affective component. Euphoria- After a dose of morphine, a typical patient in pain experiences a pleasant floating sensation and freedom from anxiety and distress. Dysphoria is a state characterized by restlessness and a feeling of unease. Narcotic Analgesics

6. Sedation -Drowsiness and clouding of mentation are frequent concomitants of opioid action. Respiratory depression- All of the opioid analgesics can produce significant respiratory depression by inhibiting brain stem respiratory mechanisms. Cough suppression- Suppression of the cough reflex is a well-recognized action of opioids . However, cough suppression by opioids may allow accumulation of secretions and thus lead to airway obstruction e.g. codeine

7. Miosis- Constriction of the pupil is seen with virtually all opioid agonists. Nausea and vomiting- The opioid analgesics can activate the brain stem chemoreceptor trigger zone to produce nausea and vomiting. On GIT- Morphine reduce tone, motility, peristalsis of smooth muscles of GIT, reduces all digestive enzymes and leads to constipation.

8. ADME- When administered orally absorption is slow & incomplete. Absorption from subcutaneous route site is even and quick. Metabolism- Liver Excretion – In urine. Adverse Effect- Euphoria followed by dysphoria. Constipation Nausea, vomiting Headache, fatigue Miosis.

9. Therapeutic Uses-  Morphine is used as a good analgesic to relieve severe types of pain associated with myocardial infraction, burns , terminal stages of malignancy, pulmonary embolism. It is used as preanaesthetic medication It is a valuable agent in left ventricular failure  Tincture opium is used to produce constipation Preparations-  Tincture opium IP – 0.3 to 2.0 ml orally Morphine sulphate injection, I.P. –10mg ampoule, 10 to 20 mg subcutaneou sly

10. Contraindications- Morphine should not be used in following condition:  Head / brain injury. Undiagnosed abdominal pain . with phenothiazines monoamine oxidase inhibitors. In old patient and infants. Hypovolemic shock

11. Causes- clinical over dosage. accidental or intentional over dosing during addiction and by addicts. Symptoms- Pin-point miosis Respiratory depression - cyanosis Nausea and vomiting Clammy, pale skin. Morphine poisoning

12. Treatment- S ymptomatic If intoxication is by mouth, gastric lavage is advised If respiration is badly hampered, artificial respiration is advised. Drug treatment Pure antagonist- Naloxon Trade Name- Narcan Dose- 0.4 mg I/V Partial antagonist- Nalorphine Trade Name- Lethidrone Dose- 10 mg I/V

13. Non-Narcotic Analgesics / Non- opioid analgesics/ Antipyretics/ Anti-inflammatory Agents These are pharmacological agents which when administered externally relieve mild, dull aching type of pain associated with myalgia, arthralgia Neuralgia ,toothache, body aches ,headache etc without depressing central nervous system (without narcosis) hence referred as non- narcotics Classification- Salicylic acid derivatives: e.g . Acetyl salicylic acid Para amino phenol derivatives: e. g . Paracetamol

14. Pyrazolon derivatives: e g . Oxyphenbutazone, Indole derivatives: e g .Indomethacine Propionic acid derivatives: e g . Ibuprofen, Pharmacological action Analgesia : Relieves dull pains related to joints, muscles, nerves , bodyache , headache, toothache by acting on thalamus and hypothalamus

15. 2. Anti- Pyrexia- Pyrexia means rise in body temperature due to: High prostaglandin levels Setting of thermostat at high levels Salicylates and its derivatives reduces body temp. by following mechanism- These agent reduces prostaglandin levels There by reset the thermostat to normal Promote heat loss by vasodilatation of small skin blood vessels as well as increasing sweating thus acts as a antipyretic.

16. 3. On Respiration – Stimulates respiration by Direct action on medullary respiratory centre. Indirect action by increasing plasma carbon- dioxide concentration. 4. On GIT- salicylate ingestion causes dyspepsia, high incidences of nausea & vomiting , epigastric distress, belching, frank gastric bleeding & ulcers. 5. On blood system- Reduce platelet aggregation, promotes fibrinolysis, prolongs bleeding time .

17. 6. Anti- inflammatory action- Salicylates and its derivatives have potent Anti- inflammatory action & produce following effect- Decrease capillary permeability Reduce exudation of fluid. 7. Uricosuric effect- Salicylates in small doses (1-2mg/day) increase plasma urate level by interfering urate secretion by distal tubule. Salicylates in large doses (5 mg/day) inhibit reabsorption of urate level by proximal tubule. This results in Uricosuria

18. ADME- Well absorbed in stomach & intact skin. It remains bound to plasma proteins. Metabolized by Liver Excreted in urine in the form of conjugates with glycine & glucouronic acid. Side Effects- Dyspepsia, nausea, vomiting, epigastric distress, frank gastric bleeding ulcers. Renal / Hepatic damage.

19. Therapeutic uses- Local application as keratolytic, fungistatic, antiseptic. As analgesic to relative dull type pain like arthralgia . As an Antipyretics Anti- inflammatory Preparations- Acetyl salicylic acid I.P. Aspirin : 0.3-1gm orally Soluble Aspirin tablet I.P. : 300mg orally

20. SALICYLISM Causes- Prolonged administration of salicylates in treatment of rheumatic fever or rheumatoid arthritis. Symptoms- Headache Dizziness Vertigo Tinnitus Nausea & vomiting

21. Treatment Prompt hospitalization. Rehydration therapy to treat dehydration hyperthermia and acid base imbalance by administration of IV fluids. Gastric lavage- to remove unabsorbed drug from stomach To reduce body temp. external sponging with cold water or alcohol Vitamin K & blood transfusion is advised to prevent/treat hemorrhagic complications

22. Hypokalemia can be prevented by IV administration of potassium Ketosis can be treated by IV administration of dextrose Metabolic acidosis can be corrected by administration of sodium bicarbonate Salicylate excretion can be enhanced by alkalinization of urine by 2% dextrose & 2% sodium bicarbonate

23. Rheumatism , Antirheumatic Definition - It is inflammatory disorder that affects musculoskeleletal system i.e. joints muscles, ligaments, tendons. Anti-Rheumatic agents- No. Drug Trade name Dose 1 Phenylbutazone Butazolidine 300-600 mg/day, oral 2 Oxyphenbutazone Suganril 300-600 mg/day, oral 3 Indomethacine Indicin 25-50 mg t.i.d., oral 4 Ibuprofen Brufen 200-400 mg 5 Penicillamine - 125-250 mg 6 Chloroquin - 150-300 mg

24. Gout, anti-gout agents Definition - Gout is a disorder of purine metabolism and characterized by hyperuricaemia with severe acute arthritis . Anti-gout agents- No Drug Mechanism Preparatio n 1 Colchicine It reduces inflammation & pain. Inhibits the migration of granulocytes to inflamed tissue. It reduces urate crystal deposition 0.5 to 0.6 mg 2 Probenecid Blocks renal tubular reabsorption of uric acid & increases excretion in urine 250 mg b.i.d. orally