ADVANCED P 6521 Midterm study guide

ADVANCED P 6521 Midterm study guide Pharmacokinetics  Understanding the implications of changing renal function on creatinine and drug dosing. -Drug accumulation secondary to reduced renal excretion is the most important cause of ADR’s in older adults. In older adults, the proper index for renal function is creatinine clearance, not serum creatinine levels. Creatinine levels do not adequately reflect kidney function in older adults because the source of serum creatinine- lean muscle mass- declines parallel with the decline in kidney function. Creatinine levels may be normal even though renal function is greatly reduced. Most medications use adjustments for renal problems use creatinine clearance, for a few medications the estimated glomerular filtration rate (eGFR) is used.  What is the impact of the following on drug levels and dosing: o Cirrhosis- liver disease can cause drugs to accumulate because the liver is the major site for drug metabolism. If liver function declines, metabolism declines, and to prevent toxic levels from accumulating, the dosage of drugs through the hepatic metabolism must be reduced or discontinued if the liver disease develops. (pg 43) o Protein binding- The most important protein binding is plasma albumin. This is because albumin is a large molecule that cannot leave the bloodstream. Thus anything that binds to albumin is bound to stay in the bloodstream as well, resulting in bound molecules not reaching their sites of actions unless the drug is metabolized or excreted until the drugprotein bond is broken. Then the drug is free to leave the circulation. Albumin has limited binding sites so one drug and displace another causing the displaced drug to freely circulate, rise, and increase the intensity of the drug response resulting in possible toxicity (pg17) o Drug interactions-Drugs produce their effects by interacting with other chemicals. The simple occupancy theory states the more available receptors for a drug, the higher the intensity of the drug and maximum drug response occurs when all drug receptors are occupied. The modified occupancy theory describes the affinity or strength of attraction between receptor and drugs. Higher affinity produces more effective drug responses at low doses. High affinity drugs are deemed very potent. Intrinsic activity refers to the drugs ability to activate a receptor site upon binding. Drugs with high intrinsic activity cause intense receptor activity. Drugs with high intrinsic activity have high maximal efficacy. After binding, drugs can either mimic the action of endogenous regulatory molecules or block the action of endogenous regulatory molecules; drugs that mimic are agonists, drugs that block are antagonists, and drugs that only moderate intrinsic activity are partial agonist. (pg26) o Half-life-Drug half-life is defined as the time required for the amount of drug in the body to decrease by 50%. No matter what the amount of the drug in the body be, 50% will leave during a specified time period of time. The half-life of a drug determines the dosinginterval. If a drug has a short half-life, the frequency of administration must be closer together, and in contrast a long half-life means a long time can separate doses without loss of benefits. (pg21). Routes of Administration and Dosage Forms:  The major routes of administration are: Oral (PO) (tablet, capsule, or solution)-Benefits: easy, convenient, inexpensive, ideal for selfadministration, potentially reversible. Challenges: inactivation of drug by gastric acid and digestive enzymes, nausea and vomiting, must be conscious and cooperative. Intravenous (IV) (liquid)-Benefits: rapid onset, precise control over drug levels, large volumes of fluid can be given, and can use irritant drugs. Challenges: Irreversible, expensive, inconvenient, difficult to self-administer, risk for fluid volume overload, infection, and an embolus, and the drug must be water-soluble. Intramuscular (IM) (liquid)- Benefits: permits use of poorly soluble drugs and depot drugs. Challenges: possible discomfort, inconvenient, and potential for injury. Subcutaneous (SubQ) (liquid)- same as IM Other routes include topical (cream), transdermal (medicinal skin patch), and inhaled (aerosolized) .(pg16)  Understand when it is OK to crush (or not crush) certain dosage forms and why. Extended release, slow releasing, sustained release tablets or capsules and enteric coating tablets are not to be crushed because they are formulated with a bioavailable design to release, breakdown, or withstand immediate breakdown within the body.  Which routes of administration have the fastest and slowest rates of absorption? Fastest is IV with an instantaneous absorption, then IM with a rapid absorption to water-soluble drugs only (slow for poorly soluble drugs), SubQ is the same as IM, and PO is the slowest.  Know the relative onset, monitoring, and appropriate use of various dosage forms including: o Patches (ie; fentanyl rivastigmine)-uses the transdermal system to deliver a drug slowly through a patch absorbed through the skin, reaching effective levels in 24 hours. Levels remain steady for another 48 hours, after which the patch should be replaced. If the patch is not replaced, the only absorption that will occur is whatever is left on the skin. o Suppositories (ie: acetaminophen)- absorbed slowly and blood levels are slower than with oral dosing. Pg 495o Sublingual tablets-designed to be absorbed through the oral mucosa (to avoid first-pass hepatic metabolism). This route has the additional advantage of preventing “cheeking” because doing so will simply cause the drug to be absorbed as intended. o Tablets- preferred for most patients. Slow and variable absorption through the epithelial lining of the GI tract and capillary wall. o Liquid (known common measures)- Usually concentrated and must be diluted before use. Dilution may be performed with a variety of fluids, including milk, fruit juices, and carbonated beverages. o Injectableso Nasogastric o Elixir Therapeutics: Gastrointestinal, Cardiac, Respiratory, Neurology, Musculoskeletal  Understand the mechanism of action, side effects, appropriate use and contraindications for the classes of drugs and individual drugs listed below. Also, know the key patients education points including cautions, expected effects, and appropriate use (with food, empty stomach, etc.). o Anti-diarrheals: OPIOID-Diphenoxylate HCI with atropine sulfate (Lomotil) is an opioid used only for diarrhea. It must be taken orally as it insoluble in water. The atropine is present to counter act the euphoric and possibly addictive effects of diphenoxylate and discourage abuse. If diphenoxylate is taken alone and in high doses it can mimic the effects of morphine. OPIOID-Loperamide (Imodium)- works by suppressing bowel motility, and fluid secretion into the intestinal lumen. This drug is poorly absorbed, does not cross the blood brain barrier, and can be taken in large quantities without morphine like effects so it has no potential for abuse. Bismuth subsalicylateMECHANISM- disrupts the cell wall of H. pylori causing lysis and death. USES-treat and prevent H. pylori. SIDE EFFECTS- black discoloration of the tongue and stool and is often thought to be a GI bleed at first. o Laxatives:Bulk-forming- have a similar action on the bowel function as dietary fiber. These agents are nondigestible and nonabsorbable and swell in water to form a viscious solution or gel softening the fecal mass and increasing in bulk. Should be drank with a full glass of water or esophageal obstruction can occur. Is used as a temporary treatment for constipation. Osmotics (Laxative salts, Polyethylene glycol, and lactulose)- Laxative salts (Sodium phosphates) are poorly absorbed salts whose osmotic action draws water into the intestinal lumen. Accumulation of water causes fecal mass to soften and swell, thereby stretching the intestinal wall and stimulating peristalsis. Typically used for diagnostic or surgical procedures, to purge the bowel of a poison, or evacuate a dead parasite. Side effects include substantial water loss. Contraindications include renal patients (toxic magnesium levels in renal patients), heart failure, hypertension, and edema (sodium phosphate causes fluid retention). Polyethylene glycol used primarily for chronic constipation. Common side effects include nausea, abdominal bloating, cramping, and flatulence. It can also be used to cleanse the colon before a colonoscopy and other procedures. Lactulose is composed of galactose and fructose, is more expensive than the other 2 mentioned, and has more unplaseant side effects such as flatulence and cramping. It is often used to excrete ammonia in patients with portal hypertension and hepatic encephalopathy secondary to chronic liver disease. Stimulants (bisacodyl, senna, and castor oil)-stimulate intestinal motility and increase the amount of water and electrolytes within the intestinal lumen by increasing secretion of water and ions into the intestines and reducing the amount of water and electrolytes absorbed. Most stimulant laxatives are group II agents: they act on the colon to produce a semifluid stool within 6-12 hours. Typically used for opioid induced constipation and constipation from slow intestinal transit. o Therapy for various gastrointestinal disorders including: Ulcers, Irritable Bowel Syndrome, and Crohns ulcerative colitis: Antiemetics (serotonin receptor antagonists, glucocorticoids, substance P/neurokinin-1 antagonist, benzodiazepines, and dopamine antagonists)-Serotonin receptor antagonists are the most effective antiemetics. Four serotonin receptor antagonists are available: Zofran (ondanestron), granisetron, dolasetron, and palonosetron. They work by the blockade of type 3 serotonin receptors (5-HT3 receptors) located in the chemo receptor trigger zone and on afferent vagal neurons in the upper GI tract. Possible side effects include headache, diarrhea, and dizziness and the greatest concern is it prolongs QT intervals posing a risk for torsades de pointes. Glucocorticoids such as methylprednisolone (solu-medrol) and dexamethasone (decadron) can suppress chemo induced nausea and vomiting and are administered via IV. The exact mechanism is unknown. Substance P/Neurokinin-1 antagonists (aprepitant, rolapitant, netupitant, and fosaprepitant) block neuronkinin-1type receptors for substance P in the chemo triggerzone and can enhance the response of other antiemetic drugs. Aprepitant can be taken with food, and can cause fatigue, dizziness, asthenia, hiccups, and diarrhea. Can inhibit CYP3A4 and CYP2D6, enzymes involved in the break down of warfarin and ethinyl and estradiol both of which are found in birth control. So warfarin patients needs to be monitored closely and or switched to a different medication. Benzodiazepines (lorazepam, Ativan) can suppress chemo induced nausea and vomiting. It works by sedation, suppression of anticipatory nausea, and anterograde amnesia. Dopamine antagonists (phenothiazines, prochlorperazine, promethazine, Phenergan, Haldol, haloperidol, metoclopramide, reglan) MECHANSIM-suppress emesis by blocking dopamine-2 receptors in the chemo trigger zone. USES- Typically used in surgery, cancer chemotherapy, and nausea from toxins. SIDE EFFECTS include hypotension, and sedation. CONTRAINDICATIONS-Serious respiratory depression and local tissue injury can occur from Phenergan IV use and is thus contraindicated in children under 2 years old and advised to be given IM as its risk for local injury are less. Drugs for inflammatory bowel syndrome Alosetron (lotronex) MECHANISM- works by selective blockade of 5-HT3 receptors which are found in the neurons that innervate the viscera and can increase stool firmness, decrease both fecal urgency and frequency. USES- approved for IBS in women whose symptoms (frequent and severe abdominal pain affecting daily life) have lasted longer than 6 months. It should be taken on an empty stomach. SIDE EFFECTS/CONTRAINDICATIONS- bowel obstruction, impaction, and perforation. Protein pump inhibitors (Omeprazole, Prilosec) MECHANISM- causes irreversible inhibition of proton pump enzymes that generate the gastric acids and stimulate gastric acid release. USES-approved for short-term (4-8wks) duodenal ulcers, gastric ulcers, erosive esophagitis, and GERD. Long-term use is for hypersecretory conditions (ZollingerEllison syndrome). Are given to hospitalized patient to prevent stress ulcers (ICU, ventilated more than 48 hours, spinal cord injury, and multiple traumas). SIDE EFFECTS: Pneumonia, fractures, rebound acid hypersecretion, hypomagnesemia, and diarrhea. Mesalamine (5-Aminosalicylic Acid Derivatives) MECHANISM- reduces inflammation by suppressing prostaglandin synthesis, and migration of inflammatory cells into the affected region. USES: mild to moderate ulcerative colitis episodes. Less effective against severe cases. SIDE EFFECTS: nausea, fever, rash, and arthralgia. Various forms of anemia can occur so periodic CBC’s should be collected.Ranitidine (Histamine-2 receptor antagonists) MECHANISMS-blocks histamine 2 receptors to inhibit the secretion of gastric acids. USES- gastric and duodenal ulcers and Zollinger-Ellison syndrome. SIDE EFFECTS-cancer causing when stored at high temperatures. No longer prescribed or on the market. o Cough, Cold, and Sinus therapies including: Antihistamines (dimenhydrinate, Dramamine, meclizine, antivert and cyclizine)- Histamine-1 receptor antagonists are the first line drugs for mild to moderate allergic rhinitis and are most effective when taken prophylactically and less effective when taken after symptoms. Loratadine (Claritin) MECHANISIM: is a second-generation antihistamine and works on the parietal cells of the stomach lining by releasing gastric acid. USES: is often used to prevent seasonal allergies such as itching, sneezing, and rhinorrhea. SIDE EFFECTS: It can also be given before another medication that has a lot of side effects to reduce its effects and to prevent gastric upset. Fexofenadine (allegra) MECHANISIM: is a second-generation antihistamine that is given for seasonal allergies. Minimal to no drowsiness has been found in consumers making it the most preferred. Cough suppressants- opioid antitussives such as codeine (more effective) and hydrocodone (more likely to be abused). Opioid antitussives such as codeine decreases frequency and intensity of coughing and has only 1/10 the amount needed to relieve pain reducing its risk for physical dependence. Not recommended for children due to respiratory depression side effects. Nonopioid antitussives such as dextromethorphan, is the most effective over the counter cough medicine. It is in almost all cough medicines and is a derivative of opioids so taken in large quantities can produce physical dependence. It also has pain relief effects through blockade of N-methyl-D-asparate in the brain and spinal cord. Nasal decongestants (sympathomimetics): phenylephrine (short acting) & oxymetazoline (long acting) MECHANISM: activate alpha1 adrenergic receptors within the nasal blood vessels causing vasoconstriction shrinking swollen membranes followed by nasal drainage. USES: nasal congestion brought on by sinusitis and colds. In patients with allergic rhinitis, medications only relieve nasal congestion. SIDE EFFECTS/CONTRAINDICATIONS: Rebound congestion can occur from prolonged use so topical application should be limited to 3-5 days. Other side effects include restlessness, irritability, anxiety, and insomnia, hypertension, coronary artery disease, cardiac arrhythmias and CVA’s. Pseudoephedrine is more effective than phenylephrine but is highly associated with abuse, which is why it needs a prescription in most states. o Cardiac medications:Digoxin (Lanoxin): known as cardiac glycosides and a second line drug for treating HF. It does NOT prolong life. Can shorten life in women. MECHANISM: exerts a positive inotropic action on the heart to increase the force of ventricular contraction by inhibiting sodium-potassium adenosine triphosphate, which promotes calcium accumulation within myocytes and increase cardiac output. USES: used primarily in HF to reduce symptoms, increase exercise intolerance, and decrease hospitalizations. Other uses include treating supraventricular dysrhythmias. SIDE EFFECTS/CONTRAINDICATIONS: dysrhythmias, increased urine production, renin release declines, sympathetic tone declines. Anorexia, nausea, and vomiting, fatigue, and visual disturbances (blurred vision, yellow tinge to vision, halos around objects) are the most common symptoms of THERAPEUTIC RANGE/TOXICITY: 0.5-0.8 ng/mL—digoxin levels slightly higher than normal greatly increase the risk for toxicity. Hypokalemia secondary to the use of diuretics is the most common cause of dysrhythmias with digoxin use. Statins (HMG-CoA reductase inhibitors)- MECHANISIM: increase the number of LDL receptors on hepatocytes. Cholesterol synthesis is inhibited which causes hepatocytes to increase LDL receptors and are better able to remove LDL from the blood. USES: hypercholesterolemia, primary and secondary prevention of an MI, angina, and, stroke, primary prevention, post MI therapy, and diabetes. SIDE EFFECTS/CONTRAINDICATIONS: Myopathy (muscle aches, tenderness, and weakness), myositis (muscle inflammation) that can lead to rhabdomylosis (the breakdown of muscle) which causes an elevation in creatine kinase (CK) which can cause renal impairment; hepatotoxicity, and new-onset diabetes. Colestipol is a bile acid sequestrants. Colestipol is older and less preferred. Colesevelam is the newest and preferred bile acid sequestrant due to lack of side effects. It is usually combined with diet, exercise, and a statin. MECHANISM: is a nonabsorbable resin that binds to bile acids and other substances in the GI tract to prevent their absorption and promote excretion. USES: reduce elevated LDL cholesterol. SIDE EFFECTS/CONTRAINDICATIONS: constipation, bloating, indigestion, and nausea. Older meds like colestipol decreased fat absorption and thus decreased lipid soluble vitamin absorption. Thiazide diuretics, digoxin, warfarin, and some abx may be insoluble if taken with bile sequesterants and should be taken an hour before a sequesterant or four hours after. Nitroglycerin (nitrate)- highly lipid soluble and can be delivered SL, buccal, or transdermal. MECHANISIM: causes vascular smooth muscle to promote vasodilation primarily on veins and partially on arteries. USES: angina attacks SIDE EFFECTS/CONTRAINDICATIONS: headache, orthostatic hypotension, and reflex tachycardia. Abrupt cessation can result in vasospasm.o Blood pressure medications: Calcium channel blockers (CBBs)- dihydropyridines and nondihydropyridines MECHANISM: prevent calcium ions from entering cells preventing contraction of vascular smooth muscle causing vasodilation. CCBs work primarily on peripheral arterioles and arteries and arterioles of the heart. In the heart, CCBs work on the myocardium, sinoatrial node, atrioventricular node, and beta-1 adrenergic receptors. USES: treats hypertension, angina pectoris, and cardiac dysrhythmias. Verapamil (calan) & nicardipine (cardene) are the most common dihydropyridines and nifedipine (Procardia) & diltiazem (Cardizem) are the most common nondihydropyridines used. SIDE EFFECTS/CONTRAINDICATIONS: constipation (results from blocking calcium channels of the smooth muscle within the intestines), dizziness, facial flushing, headache, edema of ankles and feet. CCBs should NEVER be used in patients with sick sinus syndrome, second degree or third degree heart blocks. Verapamil increases the risk for digoxin toxicity by 60% so patients taking both meds should be monitored closely. Betablockers and verapamil have the same effect on the heart and together can cause excessive cariosuppression and should thus be taken hours apart. Grapefruit juice should be avoided when on CCBs especially felodipine and nifedipine. ACE inhibitors (angiotension-converting enzyme inhibitors) MECHANISIM: reduce levels of angiotension II through inhibition of ACE and increase levels of bradykinin through inhibition of kinase II to dilate blood vessels, reduce blood volume, and prevent or reverse pathologic changes in the heart and blood vessels. USES: treat hypertension, heart failure (reduces cardiac afterload and increases cardiac output. Increases renal blood flow, increasing fluid loss and decreasing edema. Reduces venous return to the heart which reduces right heart workload), left ventricular dysfunction, diabetic and nondiabetic nephropathy (can prevent or slow renal failure), and MI’s. They are also used to prevent cardiovascular events. SIDE EFFECTS/CONTRAINDICATIONS: cough (caused by bradykinin accumulation), angioedema (caused by bradykinin accumulation), first-dose hypotension, hyperkalemia, fetal injury, and neutropenia. All ACE inhibitors can be given with food, EXCEPT captopril and moexipril. ACE inhibitors are excreted by the kidneys, so a dosage reduction may be needed in kidney failure patients. Diuretics- 4 classes: loop diuretics, thiazide diuretics, osmotic diuretics, and potassium sparing diuretics. MECHANISM: Loop diuretics (furosemide; Lasix) acts in the loop of Henle in the kidney to block reabsorption of sodium and chloride producing profound diuresis. Thiazide diuretics (hydrochlorothiazide; HCTZ) act on the early segment of the distal convoluted tubule to excrete sodium, chloride, potassium, and water. This occurs at a must slower rate than loop diuretics. Potassium-sparing diuretics (Aldosterone antagonists-spironolactone and nonaldosterone antagonists-triamterene and amiloride) Spironolactone indirectly works to block aldosterone in the distal nephron which promotes sodium uptake in exchange for potassium secretion. Minimal diuresis is caused and its affects take up to 48 hours to develop.USES: Loop diuretics is used for pulmonary edema with CHF, edema of hepatic, cardiac, or renal origin, and hypertension. Particularly useful in renal impairment. Thiazide diuretics is used to treat hypertension and edema. Adequate renal function is needed for optimal diuresis outcomes. SIDE EFFECTS/CONTRAINDICATIONS: Loop diuretics can cause hyponatremia, hypochloremia, dehydration, hypotension, hypokalemia, and ototoxicity (NEVER USE with gentamicin or risk for ototoxicity increases. Thiazide diuretics can cause hyponatremia, hypochloremia, dehydration, hypotension, and hypokalemia. Potassium-sparing diuretics-spironolactone can cause hyperkalemia which can cause fatal dysrhythmias and endocrine effects (hirsutism, gynecomastia, menstrual irregularities, impotence, and deepening of the voice). Beta-blockers- first generation nonselective (propranolol), second generation cardioselective (metoprolol), and third generation vasodilating (carvedilol) MECHANISM: blocks beta-adrenergic receptors in the heart resulting in reduced heart rate, reduced force of contraction, and reduced velocity of impulse conduction through the atrioventricular node. USES: angina pectoris, hypertension, cardiac dysrhythmias, MI, reduction of perioperative mortality, heart failure, hyperthyroidism, migraines, performance anxiety, pheochromocytoma, and glaucoma. SIDE EFFECTS/CONTRAINDICATIONS: bradycardia, reduced cardiac output, cause heart failure, cause AV heart block, and rebound cardiac excitation. Can mask the symptoms of hypoglycemia and insulin-induced hypoglycemia. Abrupt discontinuation can make angina worse and increase the risk for an MI. Nitroprusside (nitropress)- MECHANISM: breaks down nitric oxide and activating guanylate cyclase (enzyme in vascular smooth muscle) causing vasodilation. USES: Severe hypertension or hypertensive emergencies. SIDE EFFECTS/CONTRAINDICATIONS: excessive hypotension, cyanide poisoning, and thiocyanate toxicity. o Diuretics: SpironolactoneFurosemideHydrochlorothiazideo Inhalers: Albuterol (Proventil or ventolin) MECHANISIM: causes beta-2 mediated bronchodilation USES: asthma SIDE EFFECTS/CONTRAINDICATIONS: administering large doses can cause cardiac stimulation such as tachycardia and tremors. ICS-inhaled corticosteroid/glucocorticoids- Fluticasone (Flovent), budesonide (Pulmicort), beclomethasone dipropionate (QVAR) and mometasone (asmanex) MECHANISM: reduce respiratory symptoms by suppressing inflammation through decreasing synthesis of and release of inflammatory mediators (leukotrienes, histamines, and prostaglandins), decrease infiltration and activity of inflammatory cells (eosinophilsand leukocytes), and decrease edema of the mucosal airway. By suppressing inflammation, there is a reduction in bronchial activity and decreased mucus production. USES: long term control of asthma and COPD. Should NOT be used to abort an attack. SIDE EFFECTS/CONTRAINDICATIONS: toxicity, oropharyngeal candidiasis and dysphonia. Long-term use especially in children can cause adrenal suppression (hypoglycemia, hypotension, and AMS), slowed growth, bone loss, cataracts and glaucoma. LABA (long-acting beta-2 agonist) MECHANISIM: are sympathomimetic drugs that activate beta-2 adrenergic receptors in the smooth muscle in the lungs to promote bronchodilation and relieve a bronchospasm. USES: inhaled once a day for individuals with frequent asthma attacks. Not the first line of therapy for asthma, but if given for asthma should be combined with a glucocorticoid. SIDE EFFECTS/CONTRAINDICATIONS: increased risk for asthma associated deaths if given alone so it is contraindicated. Anticholinergics (ipratropium, tiotropium, aclidinium, and umeclidinium) MECHANISIM: is a muscarinic antagonist so it works by blocking muscarinic cholinergic receptors in the bronchi preventing bronchoconstriction. USES: FDA approval for COPD treatment, off label use for asthma SIDE EFFECTS/CONTRAINDICATIONS: dry mouth and pharynx irritation. Can raise intraocular pressure in patients with glaucoma o Asthma: Theophylline- principle methylxanthine in asthma. Methylxanthines are derivatives of xanthine (a chemical stimulant compound naturally found in the body; artificially replicated in caffeine, tea, and colas). MECHANISIM: blocks adenosine receptors, which causes bronchodilation by relaxing smooth muscle. USES: maintenance therapy in asthma. Can decrease the frequency and severity of asthma attacks. SIDE EFFECTS/CONTRAINDICATIONS: should NEVER be crushed, or chewed the tablets or capsules because it will alter the sustained release action. Smokers require a higher dose than average. If you miss a dose, do NOT double the next dose. Limit the amount of caffeine consumed as it can intensify adverse effects of theophylline. Nausea, vomiting, diarrhea, abdominal discomfort, insomnia, restlessness, and palpitations are all signs of theophylline toxicity and if medical attention is not sought, severe dysrhythmias can occur followed by cardiorespiratory collapse and death. Theophylline levels should be between 10 and 20 units/mL. Greater than 15 units/mL shows little benefit. Zafikurlast (accolate) is a leukotriene receptor MECHANISIM: reduced infiltration of inflammatory cells resulting in reduced bronchoconstriction. USES: reduces bronchoconstriction and inflammatory response such as edema and mucous secretion.SIDE EFFECTS/CONTRAINDICATIONS: headache, GI disturbances, arthralgia, myalgia, depression, suicidal thinking, hallucinations, Churgstrauss syndrome, and liver injury. Zafikurlast can also raise levels of warfarin and thus increase the risk for bleeding. Steroidso Gout and arthritis therapies: Allopurinol (zyloprim) MECHANISIM: inhibit xanthine oxidase (enzyme needed for uric acid formation) and in doing so reduces blood uric acid levels preventing the development of new tophi and causes regression of present tophi improving joint function. USES: treats chronic tophaceous gout by reducing uric acid levels. SIDE EFFECTS/CONTRAINDICATIONS: nausea, vomiting, diarrhea, abdominal discomfort, drowsiness, headache, metallic taste, cataracts (after prolong use), bone marrow suppression, hepatotoxicity, and hypersensitivity. Severe cutaneous adverse reaction (SCAR) syndrome is more likely to occur in Korean, Chinese, and Thai ancestry. Etanercept (Enbrel)- the first tumor necrosis factor inhibitor available MECHANISIM: suppresses inflammation by binding tightly with TNF, and thereby inhibiting TNF from binding to TNF receptors and interacting with its natural reactor cells. USES: moderate to severe rheumatoid arthritis. SIDE EFFECTS/CONTRAINDICATIONS: increased risk for developing lymphoma and other malignancies, injection site reaction (itching, swelling, erythema, and pain), headache, rhinitis, dizziness, cough, abdominal pain severe allergic reaction heart failure, cancer, hematologic disorders, liver injury, and CNS disorders. Sulfinpyraxone- uricosuric MECHANISIM: USES: SIDE EFFECTS/CONTRAINDICATIONS: Methotrexate (trexall, otrexup, rasuvo) - first choice of DMARD in treating RA MECHANISIM: inhibits folate production, which is needed for DNA synthesis and cellular replication resulting in immunosuppression (and associated inflammation) secondary to reduced activity of B and T lymphocytes. USES: rheumatoid arthritis, severe psoriasis, acute lymphoblastic leukemia, polyarticular juvenile idiopathic arthritis. SIDE EFFECTS/CONTRAINDICATIONS: hepatic fibrosis, bone marrow suppression, GI ulceration, pneumonitis, fetal death, congential abnormalities (contraindicated in pregnancy), decreased life expectancy with use. Contraindicated in pregnant women, nursing mothers, patients with blood dyscrasias, immunodeficiency, and liver disease. o Hyperlipidemia: Statins (HMG-CoA reductase inhibitors)- lovastatin, rosuvastatin (crestor)MECHANISIM: increase the number of LDL receptors on hepatocytes. Cholesterol synthesis is inhibited which causes hepatocytes to increase LDL receptors and are better able to remove LDL from the blood. USES: hypercholesterolemia, primary and secondary prevention of an MI, angina, and, stroke, primary prevention, post MI therapy, and diabetes. Reduces LDL cholesterol, elevates HDL cholesterol, redues triglyceride levels, and stabilize atherosclerotic plaque build up. SIDE EFFECTS/CONTRAINDICATIONS: Myopathy (muscle aches, tenderness, and weakness), myositis (muscle inflammation) that can lead to rhabdomylosis (the breakdown of muscle) which causes an elevation in creatine kinase (CK) which can cause renal impairment; hepatotoxicity, and new-onset diabetes. Bile-acid-binding resins (colesevelam, cholestyramine, and colestipol) MECHANISIM: MECHANISM: reduces low-density lipoprotein by binding to bile acids in the GI tract and increasing LDL receptors on hepatocytes which increases the absorption and excretion of LDL in the blood stream. USES: reduce elevated LDL cholesterol. SIDE EFFECTS/CONTRAINDICATIONS: constipation, bloating, indigestion, and nausea. Older meds like colestipol decreased fat absorption and thus decreased lipid soluble vitamin absorption. Thiazide diuretics, digoxin, warfarin, and some abx may be insoluble if taken with bile sequesterants and should be taken an hour before a sequesterant or four hours after. Cholesterol absorption inhibitorsFibratesNiacin (nicotinic acid)- Removed from the hypertriglyceridemia and LDL lowering treatment guidelines MECHANISIM: inhibits a hormone-sensitive lipase in adipose tissue, which reduces the breakdown of triglycerides to free fatty acids, and the transport of free fatty acids to the liver USES: was once used to reduce LDL and TG levels. SIDE EFFECTS/CONTRAINDICATIONS: nausea, vomting, abdominal cramping, liver toxicity. Contraindicated in patients with patients with acanthosis nigricans because of an association with insulin resistance, patients with severe peptic disease, liver Disease, gout, and cardiac Arrhythmias. Omega-3 fatty acid supplementso Anticholinergics/cholinergics agents: o Agents for thyroid disease: LevothyroxineMethimazole-o Multiple sclerosis therapies: DantriumGlatirimerBaclofenTizanidineo Antiepileptics: PhenytoinEthosuximideDiazepamo Osteoporosis: Calcitonino Hypoglycemics: GlyburideGlipizideMetforminInsulino Pain: OpioidsMuscle relaxantsNSAIDSAcetaminophenTopical lidocaineo Orlistat: o Adrenergic Agonists: