Pharmacology RHPT-365 Chapter 5: Analgesic Drugs By Majid Ahmad Ganaie M. Pharm., Ph.D. Assistant Professor Department of Pharmacology E mail: majidsays@gmail.com

Peripheral Analgesics Definitions Analgesic: A drug given to reduce pain without resulting in loss of consciousness. Antipyretic: A drug given to reduce or stop fever. Inflammation: A basic way in which the body reacts to infection, irritation or other injury, the key feature being redness, warmth, swelling and pain. Peripheral Analgesics Non-causal - Not treat the cause Examples: 1- Local anaesthetics (for superficial tumor) 2- Counter-irritant (apply pain that counteract or mask the original one e.g. acupuncture) Causal -Treat the cause Example: Atropine (antispasmodic)

Analgesics Narcotics Non-narcotic The class - Opioids (morphine & morphine like drugs) Examples 1- Natural (as codeine) 2- Semi synthetic e.g. di-hydromorphine & diacetylmorphine (heroin) 3- Synthetic e.g. pethidine 4- Endogenous opiates as endorphins & encephalins Non-narcotic - NSAID 1- Aspirin 2- Paracetamol 3- Diclofenac 4- Piroxicam 5- Ibuprofin 6- Ketoprofin

Opioids or narcotic analgesics Opioids or narcotic analgesics: classified based on their pharmacology action at various receptor subtypes: Pure agonists (bind and stimulate receptors), e.g. morphine, methadone, fentanyl Pure antagonists (bind and block or inhibit activity), e.g. naltrexone Partial agonists (bind and stimulate, but with less than full activity at certain receptor subtypes), e.g. Buprenex (buprenorphine) – does produce some analgesic effects, but does not depress respiration as much…a good thing Mixed agonist/antagonists (stimulating some receptors while blocking others). e.g. Talwin (pentazocine) which is a weak, less efficacious analgesic (agonist at kappa, blocks mu)

Endogenous Opioids Produced naturally in body Naturally increased when one feels pain or experiences pleasure Act on opioid receptors Produce euphoria and pain relief Examples: endorphins, enkephalins, dynorphins, endomorphins

Morphine Codeine A pure opioid agonist The most potent & efficacious analgesic we have today still Routes: oral, IM, IV, rectal (avoids nausea/ vomiting) Sustained release preparations: MS Contin, Oramorph, Kadian, Avinza Codeine A most commonly prescribed opioid analgesic in the world (often combined with aspirin or acetaminophen) Low potency Pain relief via 10% conversion to morphine

NSAID’s NSAID’s: Non-Steroidal Anti-inflammatory Drugs. Have antipyretic, analgesic and anti-inflammatory activities. Not as effective as narcotic analgesics.

inflammation, pain & fever Primarily protect GI mucosa How do they work? Arachidonic acid Maintenance Induced COX-1 COX-2 NSAIDs thromboxane / prostaglandins prostaglandins Primarily mediate inflammation, pain & fever Primarily support platelet function Primarily protect GI mucosa

Acetaminophen: Paracetamol Acetaminophen (Paracetamol) is the most commonly used over-the-counter (OTC), non-narcotic analgesic. Used as an analgesic and antipyretic. Paracetamol is found in more than 600 over-the-counter drugs. It can be found in combination with other active ingredients in many cold, sinus, and cough medications It exerts little or no pharmacologic effect on the cardiovascular, respiratory, or gastrointestinal systems, on acid-base regulation, or on platelet function. With large doses (>4g/day), an intermediate metabolite is produced that is thought to be hepatotoxic and possibly nephrotoxic.

The Salicylates: Aspirin Has antipyretic, analgesic and anti-inflamatory activities. It is useful as analgesics for certain categories of pain, such as headache and arthritis. It remains the standard, first-line drug in the therapy of rheumatoid arthritis, and can provide relief of symptoms in acute rheumatic fever. Some clinicians recommend small daily doses of aspirin for stroke or myocardial infarction because of its antiplatelet activity.

Uses of Aspirin As analgesic (300 to 600 mg during 6 to 8 h) for headache, backache, pulled muscle, toothache, neuralgias. As antipyretic in fever of any origin in the same doses as for analglesia. However, paracetamol is safer, and generally preferred. Acute rheumatic fever. Aspirin is the drug of choice. Antirheumatic doses are 75 to 100 mg/kg/day. Rheumatoid arthritis. 3-5 g/day after meal is effective in most cases. Since large doses of Aspirin are poorly tolerated for a long time.

Coxibs Coxibs are selective COX-2 inhibitors. They exert Anti-inflammatory, analgesic, and antipyretic action with low ulcerogenic potential. Celecoxib is as effective as other NSAIDs in the treatment of rheumatoid arthritis and osteoarthritis. Rofecoxib and valdecoxib have been removed from the market due to a doubling in the incidence of heart attack and stroke Celecoxib remains on the market and is approved for: Osteoarthritis and rheumatoid arthritis Pain including bone pain, dental pain, and headache

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