Non-Narcotic Analgesics & Anti-Inflammatory Drugs PDF

Non-Narcotic Analgesics, Nonsteroidal Anti- Inflammatory Drugs Inflammation is a normal, protective response to tissue injury caused by physical trauma, noxious chemical, or microbiologic agents. Non- steroidal anti-inflammatory drugs (NSAIDs) mechanisms of action differ from anti- inflammato...

Non-Narcotic Analgesics, Nonsteroidal Anti- Inflammatory Drugs Inflammation is a normal, protective response to tissue injury caused by physical trauma, noxious chemical, or microbiologic agents. Non- steroidal anti-inflammatory drugs (NSAIDs) mechanisms of action differ from anti- inflammatory steroids or narcotic analgesics. Most NSAIDs exert their anti-inflammatory and analgesic action via inhibition of prostaglandin biosynthesis. Pain can be defined as an unpleasant sensory and emotional experience that is associated with actual or potential tissue damage. Acute pain is of short duration and lasts less than 3 to 6 months. Intensity of acute pain is from mild to severe. Causes of acute pain include postoperative pain, procedural pain, and traumatic pain. Acute pain usually subsides when the injury heals. Chronic pain lasts longer than 6 months and ranges in intensity from mild to severe. Chronic pain associated with malignancy includes the pain of cancer, acquired immunodeficiency syndrome (AIDS), multiple sclerosis, sickle cell disease, and end-stage organ system failure. The nonnarcotic analgesics are a group of drugs used to relieve pain without the possibility of causing physical dependency, which can occur with the use of the narcotic analgesics.  Acetylsalicylic Acid or Aspirin Aspirin week organic acid that has antipyretic, anti-inflammatory, analgesic effects.. Salicylates lower an elevated body temperature by dilating peripheral blood vessels, which in turn cools the body Used as analgesic for pain headache arthritis, dysmenorrhea, rheumatoid, relief of fever, rheumatoid arthritis, In addition, aspirin also prolongs the bleeding time by inhibiting the aggregation (clumping) of platelets. When the bleeding time is prolonged, it takes a longer time for the blood to clot after a cut, surgery, or other injury to the skin or mucous membranes. Aspirin used as prophylaxis of thromboebolism due to aspirin's antiplatelet activity due to inhibit thromboxane production, reduction of the risk of myocardial infarction in those with unstable angina or previous myocardial infarction; and reduction of the risk of transient ischemic attacks or strokes in men who have had transient ischemia of the brain due to fibrin platelet emboli This use has been found to be effective only in men (not women).salicylic acid is used topically to treat corns. Adverse effects: confusion, lassitude, difficulty in hearing and urination. Skin rashes diarrhea, respiratory depression, hypersensitivity, and Reye's syndrome. Due to aspirin gastric irritation there is enteric-coated preparation (Buffered). Gastric upset, heartburn, nausea, vomiting, anorexia, and gastrointestinal bleeding may occur with salicylate use.. Some individuals are allergic to aspirin and the other salicylates..  Indomethacin Indomethacin more potent anti-inflammatory than aspirin, antipyretic and analgesic, used in rheumatoid arthritis, osteoarthritis ankylosing, acute gout. Adverse effect, abdominal pain, ulcers, dizziness, diarrhea, and anorexia.  Mefenamic Acid Mefenamic acid is anti-inflammatory, analgesic and antipyretic, used analgesic in rheumatoid arthritis, soft tissue injury, dysmenorrhea. Adverse effects: G.I discomfort, diarrhea  Phenylbutazone Phenylbutazone has powerful anti- inflammatory effect but week analgesic and antipyretic activities. Phenylbutazone is prescribed chiefly in short term treatment of acute gout and acute rheumatoid arthritis when other NSAIDs agents have failed. Adverse effect include agranulocytosis and aplastic anemia.  Diclofenac Diclofenac potent anti-inflammatory, analgesic and antipyretic used in ankylosing spondylitis , musculoskeletal injury. Adverse effect nausea, ulceration.  Ibuprofen Ibuprofen an anti-inflammatory, more analgesic than aspirin and acetaminophen, used in the treatment of arthritis and osteoarthritis. Adverse effects nausia, G.I irritation.  Acetaminophen or Paracetamol Paracetamol: its an analgesic and antipyretic but has no anti- inflammatory activity. This drug is particularly useful for those with aspirin allergy and bleeding disorders,.it’s the safest analgesic, the over dose in adult about 15g and 4g in child. Adverse reactions associated with the use of acetaminophen usually occur with chronic use or when the recommended dosage is exceeded. Adverse reactions to acetaminophen include skin eruptions, urticaria (hives), hemolytic anemia, pancytopenia (a reduction in all cellular components of the blood), hypoglycemia, jaundice (yellow discoloration of the skin), hepatotoxicity (damage to the liver), and hepatic failure (seen in chronic alcoholics taking the drug).  COX II Inhibitors (Celecoxib, Refecoxib) COX II Inhibitors has anti-inflammatory and analgesic effects equal to other NSAID with less side effects. Although the exact mechanisms of actions are not known, thought to act by inhibiting prostaglandin (a group of naturally occurring fatty acids that act within the body to regulate acid secretion of the stomach, regulate body temperature and platelet aggregation, and control inflammation) synthesis by inhibiting the action of the enzyme cyclooxygenase, the enzyme responsible for prostaglandin synthesis. Act to inhibit the activity of two related enzymes: cycloo1xygenase-1 (COX-1), the enzyme that helps to maintain the stomach lining; and cyclooxygenase-2 (COX-2), the enzyme that triggers pain and inflammation. The anti-inflammatory effects carried out by inhibition of COX-2. The gastrointestinal adverse reactions are caused by inhibition of COX-1. The newer NSAIDs (celecoxib and rofecoxib) appear to work by specifically inhibiting the COX-2 enzyme, without inhibiting the COX-1 enzyme. Celecoxib and rofecoxib relieve pain and inflammation with less potential for gastrointestinal adverse reactions. The traditional NSAIDs, such as ibuprofen and naproxen, are thought to regulate the pain and inflammation by blocking COX-2. Unlike celecoxib and rofecoxib, these drugs also inhibit COX-1, the enzyme that helps maintain the lining of the stomach. This inhibition of COX-1 causes the unwanted gastrointestinal reactions, such as stomach irritation and ulcers.  Autacoids and Their Antagonists Autacoids are circulating or locally acting hormone- like substances, which originated from diffuse tissues, (e.g. Prostaglandin, histamine, Serotonin, Angiotensins, Kinins, bradykinin, Thromboxane A2, and Leukotrienes). The word autacoid comes from the Greek: autos (self) and akos (medicinal agent or remedy) the differ from hormone in that are produced by many tissues rather than in specific endocrine gland. Autacoid antagonists is compound that inhibit the synthesis of certain autacoids, or interfere with their interaction with receptors. The two main functions of the autacoids are to modulate local circulation and the influence the process of inflammation.  Prostaglandins Prostaglandins are derivatives of prostanoic acid, a 20-carbon fatty acid containing 5-carbon ring. Specifically, prostaglandins are synthesized from arachidonic acid by the enzyme cyclooxygenase (COX), which exists as two isozymes, COX I and COX II. COX I function constantly on daily synthesis of prostaglandins that contribute to normal homeostasis, including protection of the gastric mucosal through prostaglandins and homoeostasis through the synthesis of thromboxane. COX II is expressed only in response to inflammation or injury. Its role limited to the production of prostaglandins for their role in the inflammatory response. The only clinically relevant thromboxane currently identified is thromboxane A2 (TXA2), which causes platelet aggregation. Prostaglandins affect numerous body function, a fact limits the therapeutic usefulness of these agents.  Leukotrienes Leukotrienes are 20-carbon derivatives of the fatty acids that formed via the enzymatic pathway catalyzed by lipoxygenase. Leukotrienes play a role in numerous physiological function the major function is bronchoconstriction, increased mucus secretion, modify lymphocyte proliferation and differentiation, and heart negative inotropy. Leukotriene antagonist Leukotriene antagonist prevents the synthesis of leukotrienes by inhibiting the enzyme lipoxygenase, or competitively inhibit leukotrienes at their various receptor sites. Zileuton, Zafirlukast, and Montelukast Therapeutic indication of this Leukotriene antagonist is limited to the treatment of asthma. These agents reduce bronchospasm symptoms that are mediated through leukotrienes.  Histamine and their Antagonist Histamine is bioamine derived principally from dietary histidine, act as chemical messenger that mediate a wide range of cellular responses, including allergic and inflammatory reaction. Histamine is produced in response to injury. It acts on areas such as the vascular system and smooth muscle, producing dilatation of arterioles and an increased permeability of capillaries and venules. Dilatation of the arterioles results in localized redness. An increase in the permeability of small blood vessels produces an escape of fluid from these blood vessels into the surrounding tissues, which produces localized swelling. Thus, the release of histamine produces an inflammatory response. Histamine is also released in allergic reactions or hypersensitivity reactions, such as anaphylactic shock. Histamine has powerful pharmacologic actions, two classes of receptors mediate the action of histamine H1, H2. A third histamine receptor has been identified. Its function has yet to be elucidated, but it is believed to act, at least in part , as an autoreceptor. H1 receptors are responsible for the contraction of bronchial and intestinal smooth muscle, vasodilatation, increased capillary permeability, and pruritus. H2 receptors principally regulate gastric acid secretion  :Histamine Antagonists inhibit the synthesis or the receptor interactions of Histamine. Antihistamines are drugs used to counteract the effects of histamine on body organs and structures. Antihistamines block most, but not all, of the effects of histamine. They do this by competing for histamine at histamine receptor sites, thereby preventing histamine from entering these receptor sites and producing an effect on body tissues. Some antihistamines have additional effects, such as antipruritic, antiemetic, and sedative effects.  H1- receptors antagonists blocks the histamine effects on  Bronchial smooth muscle  Intestinal smooth muscle  Small blood vessels  Sensory impulses for itching  The general uses of the :antihistamines include Relief of the symptoms of seasonal and perennial allergies Allergic and vasomotor rhinitis Allergic conjunctivitis Mild and uncomplicated angioneurotic edema and urticaria Relief of allergic reactions to drugs, blood, or plasma Relief of coughs caused by colds or allergy Adjunctive therapy in anaphylactic shock Treatment of parkinsonism Relief of nausea and vomiting Relief of motion sickness Sedation Adjuncts to analgesics Each antihistamine may be used for one or more of these reasons.  Preparation 1st generation- sedating Rxs short acting Chlorpheniramine (Allerfin) Promethazine (Phenergan) Diphenhydramine (Benadryl) Dimenhydrinate (Dramamine) Hydroxyzin (Atarax} Meclizine (Bonine) Promethazine (Phenergan} 2nd generation- non-sedating Rxs long acting Terfenadine (Seldane) Astemizole (Hismanal) Foxofenadine (Telfast} Loratadin (Clritine} Cetirizine (Zyrtic}  ,Adverse effects Drowsiness, Hallucination and sedation are common adverse reactionsseen with the use of many of the antihistamines. Some antihistamines appear to cause more drowsiness and sedation than others. These drugs may also have varying degrees of anticholinergic (cholinergic blocking) effects, which may result in dryness of the mouth, nose, and throat and a thickening of bronchial secretions. Several newer preparations (eg, loratadine) cause little, if any, drowsiness and fewer anticholinergic effects than some of the other antihistamines. Photosensitivity may occur with the use of the antihistamines. Some antihistamines may cause dizziness, disturbed coordination, fatigue, lassitude, hypotension, headache, epigastric distress, and photosensitivity (exaggerated response to brief exposure to the sun, resulting in moderately severe to severe sunburn). Although these drugs are sometimes used to treat allergies, a drug allergy can occur with the use of an antihistamine. Symptoms that may indicate an allergy to these drugs include skin rash, urticaria, and anaphylactic shock.  H2-receptor antagonists inhibit gastric acid secretion. They have no significant action at H1 receptors Adverse reactions of the histamine H2 antagonists include dizziness, somnolence, headache, confusion, hallucinations, diarrhea, and impotence (that is reversible when the drug is discontinued). Adverse reactions are usually mild and transient.  Cimetidine: used in the treatment of patients with duodenal and gastric ulcers, gastric hypersecretory states. Adverse effects, confusion, a number of drug interactions.  Ranitidine: same use of cimtidne with less drugs interaction.  Famotidine same as ranitidine.