Nonopioid+Analgesics

= Nonopioid Analgesics =

Natalie and Arlene will work together on this page (This is week #7 readings. Deadline is April 25th) 1. **__Pain controlling effect of nonopioid analgesics__**: Mechanism of action typically involves the inhibition of one or more components of the inflammatory response. 2. __**The two groups of analgesics are**__: a. Nonopioid Analgesics (Salicylates.) b. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs.) 3. **__The chemical makeup of salicylates are__**: 2400 years ago, poplar and willow bark were discovered to contain salicin, a glycoside of salicylic alcohol. The active principle of willow & poplar preparations, salicylic acid, was first extracted in 1835 from natural sources & later prepared by chemical synthesis. In 1853, Charles Rederich von Gerhardt was the first to synthesize aspirin (acetylsalicylic acid) by treating sodium salicylate with acetyl choloride and in 1899 introduced into medicine by Heinrich Dresser of the Bayer Company of Germany. Aspirin is the standard of reference against which NSAIDs are compared & evaluated. 4. **__The mechanism of action of salicylates are__**: //__Efficacy results from their ability to inhibit COX activity __//, preventing the synthesis and release of COX products, especially PGs. Review: COX is assoc. w/elevtated concentrations of PGs during inflammation, pain and fever. PGs are mediators of inflammation. Other salicylates & NSAIDs are reversible competitive inhibitors of the COX enzyme. Salicylates may inhibit cell migration & some functions of PMSs. Other mechanisms contributing to anti-inflammatory effects are reduced capillary permeability, reduced antibody production, and alterations in CT synthesis. Aspirin uniquely inactivates COX by irreversibly acetylating the enzyme, not only inhibiting PG production during inflammation, but also enables COX-2 to produce 15-hydroxyeicosatetraenoic acid; assoc.w/adverse effects. Aspirin’s analgesic effect is inhibition of PG synthesis at the site of injury or inflammation. PGs sensitize pain receptors to other mediators such as histamine & bradykinin; salicylates & other NSAIDs inhibit the synthesis of PGs induced by bradykinin but not the binding of PGs to their receptors. 5. **__The pharmacokinetics (absorption,distribution,fate) of salicylates are__**: //__Absorption __// – Factors such as the particle size and compression of the tablet greatly influence the absorption rate. //__Orally, it is rapidly absorbed in the small intestine__//. Other factors such as gastric emptying time, gastric contents, and level of autonomic activity of the patient, may also influence the rate of absorption. //__Excretion __//– The elimination half-life of sodium salicylate is 2-3 hours after a single analgesic dose. The //__liver is the main site of biotransformation__//. Free salicylate and its metabolites are //__excreted by glomerular filtration & by active proximal tubular secretion in the kidney__//, approx. 10% appears unchanged in the urine. 6. **__The pharmacologic effects of salicylates are__**: general therapeutic effects include clinically useful analgesic, antipyretic, anti-inflammatory, antiplatelet effects. Symptomatic relief of acute pain, fever, and chronic inflammatory diseases. Aspirin’s efficacy in treating inflammation & pain is closely related to its inhibition of PG synthesis. Has a ceiling effect, there is a dose-response for pain relief; increasing the dose beyond the standard dose does not enhance the analgesic effect further and does increase the likelihood for toxic effects. 7. **__The toxicity of salicylates is__**: Aspirin& NAIDs contraindicated for patients with //__active GI ulcers__//, may lead to sudden and potentially fatal GI hemorrhage. Antiplatelet effects lead to //__pronounced increases in bleeding time__//. Prolongation of bleeding time can promote intraoperative and postoperative hemorrhage in dental surgical procedures. Medical consultation needed to have the patients physician approve or disapprove the discontinuation of an antiplatelet prior to dental tx.Aspirin & NSAIDs contraindicated for patients with //__kidney/renal disorders__//. Acute renal failure is more likely to develop in patients with preexisting renal insufficiency, congestive heart failure, or dehydration because the renal arterioles are more dependent on PGs to maintain normal perfusion of the glomeruli (PGs are involved in reducing water and Na+ reabsorption at the ascending loop of Henle and maintain proper dilation of the renal vasculature.) NSAIDs are responsible for chronic renal toxicity “analgesic-associated nephropathy,” characterized by papillary necrosis and chronic interstitial nephritis.Aspirin & salicylates are contraindicated for the treatment of flulike symptoms, chickenpox, gastroenteritis, any febrile respiratory condition in children or teen agers. The //__use of aspirin in children has a strong assoc. between the development of Reye’s syndrome__// and the ingestion of aspirin in children and teen agers //__with viral infections__//.Toxicity caused by aspirin overdose is common. Symptoms & severity depend on the dose. Chronic toxicity results in a syndrome termed slicylism; characterized by tinnitus, nausea, vomiting, headache, hyperventilation, and mental confusion.Aspirin most frequently used drug for attempted suicide, commonly involved in accidental poisoning/especially in children. Occur at doses greater than 6-10 g in adults or when intake exceeds 150-200 mg/kg of body weight.Cardinal signs & symptoms of acute aspirin overdose include nausea, vomiting, tinnitus, hyperthermia, and hyperventilation. Hyperventilation eventually leads to respiratory alkalosis, followed by respiratory & metabolic acidosis accompanied by dehydration. Impaired vision, hallucinations, delirium, and CNS effects may be evident and considered life-threatening.Allergic reactions to aspirin can occur; allergic responses manifested by skin rashes, hives, angioedema or anaphylaxis.Intolerance to salicylates symptoms range from rhinitis to severe asthma, and hives and angioedema as well. Acetaminophen is the only antipyretic analgesic that may be used safely in patients with aspirin intolerance. 8. **__The drug interactions of salicylates are__**: Aspirin effects blood glucose and can //__interact adversely with insulin or oral hypoglycemic agents__//, causing unpredictable changes in blood glucose concentrations; enhancing hypoglycemic effects. Internal bleeding may occur if aspirin is used in conjunction w/anticoagulants, such as warfarin and heparin. Warfarin can be displaced from plasma proteins by aspirin. Dangerous drug combination is aspirin and alcohol because alcohol sensitizes the gastric mucosa to aspirin. Aspirin decreases the effect of certain antihypersensitives drugs, B-adrenoreceptor blockers, diuretics, ACE inhibitors. 9. **__The uses of salicylates are__**: General therapeutic effects used for acute pain, rheumatic fever (aspirin reduces acute inflammatory coomponents of the disease, such as fever, joint pain, swelling, and immobility.), rheumatoid arthritis (chief clinical & pathologic feature result from chronic inflammation of synovial membranes. The pain & inflammation controlled by salicylates produce a measurable reduction of inflammation in the joints & assoc.tissues, a lessening of symptoms & improved mobility. Reduce PMN activity inhibiting PG synthesis.), fever (inhibiting the synthesis of PGs in the hypothalamus, aspirin is thought to reduce the thermal set-point toward noraml.), prophylaxis against platelet aggregation (inhibit simultaneously platelet aggregation & production of PGs. Selective block of TXA2 synthesis in platelets provides the rationale for using long-term low-dose aspirin therapy to prevent MI & occlusive stroke iin at-risk patients.) 10. **__The dosage and preparations of salicylates are__**: Aspirin analgesic dosage 650-1000 mg q 4-6 h; maximum daily dose 4000 mg. 11. **__The chemical classification of nonsteriodal anti-inflammatory agents or drugs are__**: 12. **__The mechanism of action of NSAID's are__**: NSAID's affect the perception of pain on the peripheral, inhibit prostaglandin sythesis, anagesia, antipyretic, and anti-inflammatory. they exert their actions on damaged tissue. 13. **__The pharmacologic effects of NSAID's are__**: Treatment of pain and anti-inflammatory. 14. **__The adverse reactions of NSAID's are__**: adverse reaction on the CNS include headaches, sedation, diziness, confusion, mental depression, verigo and convultions. On the gastrointestinal tract they cause irritation, pain and bleeding. Oral adverse reactions include dry mouth, gingival ulcerations and ulcerative stomatitis. renal reactions include urinary tract infections and renal failure. Also blood clotting that may last as long as the drug is in the system. There are also adverse reactions to to other drugs in which it will increase the effect of that drug such as lithium and digoxin as well as methotrexate which can also cause bone marrow toxicity. Diuretics, bete blockers, and ACE inhibitors all reduce antihypertensive effects. 15. **__The contraindications and cautions of NSAID's are__**:Contraindicated in those with congenital heart disease, post operative coronary bypass graft, renal dysfunction, necrotizing entercolitis, thrombocytopenia, hypersensitivity and it reversibly decreases platlet aggregation. 16. **__The uses of NSAID's are__**:They aure used as an anti-inflammatory, mild or moderate pain relief and fever, also to treat rheumatoid arthritis and pain during menstration. 17. **__NSAID's uses in dentistry are:__** NSAID's are used in Dentistry for the managment of pain. 18. **__Specific NSAID's__** Ibuprofen- Antipyretic and anti-inflammatory used to lessen the severity of post operative pain and is the drug of choice used in Dentistry. Its onset of action is 30 minutes and its duration last 4-6 hours with a half life of 2 hours. The ususal dosage is 400-800mg every 4-6 hours. Naproxen- a sodium salt used for pain relief and anti-inflammatory. it is rapidly absorbed from the gastrointestinal tract and expelled most entirely from the renal. It has a half life of 2 hours and its dosage is taken every 8-12 hours. COX II- It is a sulfanomide used for arthritis. it is contraindicated in patients with allergies to other sulfanomides. It may cause serious gastrointestinal tract and renal toxicity, including sodium and water retension, hypertension and acute renal failure and it may interfere with antihypertensive effects of ACE-inhibitors, diuretics and beta-adrenergic blockers. 19. **__The pharmacokinetics of acetaminophen are__**: it is the only antipyretic analgesic of choice when asprin cannot be used because of gastric problems and other contraindications. It has analgesic and antiplyritic effects that is similar to asprin. It may be more active than asprin as an inhibitor of CNS COX and less active in the periphery. Acetaminophen has very week anti-inflammatory effects copared to asprin and may be a more selective inhibitor of neuronal PG synthesis. When peroxides from leukocytes in inflammed tissue are present, it may lead to inhibition of acetaminophen which may inhibit the effect. 20. __**The pharmacologic effects of acetaminophen are**__: Acetaminophen has little to noe effect on the cardiovascular system and respiratory system when used at theraputic doses. It doesn't inhibit platelet aggregation, cause occult bleed or gastric irritation, affect uric acid excretion, or have as many drug interactions as asprin. The liver is the organ mostly affected in an overdose and acute renal toxicity may occur. analgesic neuropathy may occure with long-term use, but is unlikely. 21. **__The absorbtion, fate and excretion of acetaminophen are:__** Acetaminophen is absorbed in the small intestine after being taken orally. It freely crosses the placenta and is distributed throughout the body. The half life is approximately 2-4 hours. Elimination is through the kidneys by glomerular filtration and active proximal tubular secretion. 22. **__The adverse reactions of acetaminophen are__**: Usually from an overdose since at theraputic doses it does not cause nausea, inhibit platelet aggregation, prolong prothrombin time, or produce any other side effects. Allergic reactions are rare and result in a skin rash and it rarely produces methemoglobinemia. 23. **__The uses of acetaminophen are__**: For those patients that asprin and NSAID's are a contraindication to.It is not used to reduce inflammation, but it is used to treat pain resulting from inflammation. Since it has a low toxicity at theraputic doses, it is considered the first-line therapy for osteoarthritis. it is the antipyretic of choice in children and teenagers because it is not associated with Reye's syndrome. 24.**__The theraputic uses in Dentistry of acetaminophen are__**: Used in the treatment of postoperative dental pain. It is used in combination with an opiod analgesic.