For the following medications know what category of medication it is, mechanism of action, adverse effects, interactions and nursing considerations. • Gentamicin – interferes with protein synthesis Antibiotics (Aminoglycosides); treat primarily gram-negative infections; gram-positive; usually given with penicillin; never used alone to treat gram positive infections; also used for prophylaxis in procedures involving GI or GU tract bec such procedures carry high risk for enterococcal bacteremia; also given in combination with ampicillin or vancomycin to surgical patients with a history of valvular heart disease; caution in premature and full-term neonates bec of renal immaturity; can be used in pediatrics with pneumonia, meningitis, and UTI; nephrotoxic and ototoxic; ADE greater in PT with renal impairment; INTERACTS with vancomycin, cyclosporine, amphotericin B, loop diuretics, reduces amt of Vit K, can potentiate warfarin toxicity, prolongs duration of action of NMBD Perform baseline hearing tests and assessment of vestibular function. Monitor renal function studies. Complete neuromuscular assessment bec of potential neurotoxicity. BUN and GFR needs monitoring as well. Consume probiotics to help prevent abx-induced superinfections. Nausea, vomiting with motion, ataxia, nystagmus, and dizziness should also be reported immediately. For IV, only admin clear solutions. NOTE: with any ABX, note for any superinfection (diarrhea, vaginal discharge, stomatitis, loose and foul-smelling stools, cough) • Amphotericin B – Antifungal; acts by binding to sterols in the cell membranes of fungi. K and Mg ions leaks out of the cell which cause fungal cellular metabolism to be altered; leading to cell death. Active for a wide range of fungi; sometimes given with flucytosine in the treatment of Candida and cryptococcal infections bec of the synergy of 2 drugs; Mostly systemic infections ADE include fever, chills, hypotension, tachycardia, malaise, muscle and joint pain, hypokalemia, anorexia, N/V and headache Lipid formulations has fewer adverse effects but more expensive Also used as local irrigant for treatment of candidal cystitis NOTE: Drug interactions and hepatoxicity are the primary concerns in pts receiving antifungal drugs; Assess and document VS, weight, Hgb level, Hct, RBC counts, CBCs, liver and renal test results and culture and sensitivity test results Admin aspirin/acetaminophen, antispasmodics, antiemetics, antihistamines, antipyretics, and corticosteroids to prevent or minimize infusion-related reactions; also admin between 2-6 hours for IV; caution in severe bone marrow suppression and renal impairment; often a 1 mg dose over 20-30 mins is given to see if pt will tolerate drug; use IV pump; monitor VS every 15 mins Interactions for all antifungals is that they are metabolized by the cytochrome P-450 enzyme system. Result is the coadmin of 2 drugs that are both broken down by this system is they compete for limited amount of enzymes, and 1 drug ends up accumulating Ampho-B interacts with digitalis glycosides, nephrotoxic drugs and thiazide diuretics • Linezolid (Zyvox) – ABX known as oxazolidinones; inhibits bacterial protein synthesis Treats VRE; used to treat health-care associated pneumonia, complicated skin and skin structure infections, including those caused by MRSA and gram-positive infections in infants and children; most common ADE are headache, nausea, diarrhea, and vomiting, also shown to decrease platelet count; Interacts and strengthen the vasopressor effects of vasopressive drugs such as dopamine. Also cause serotonin syndrome when used with SSRI. Tyramine such as aged cheese or wine, soy sauce, smoked meats or fish, and sauerkraut raises BP Protect IV doses from light and infuse over 30-120 minutes; do not mix with any other medication • Levetiracetam (Keppra) – Anticonvulsant (decreases abnormal excitement in brain; control seizure activity) MOA for this drug is unknown (only PO) Used to prevent convulsive seizures typically associated with epilepsy; for partial seizures; may increase GABA Levels NO INTERACTING DRUG!!! Has a therapeutic plasma level of 12-46 ADE: Dizziness, drowsiness, hyperactivity, behavior changes such as anxiety, hostility, agitation, or suicidal ideation; CNS depression may occur when used in combination with other sedating drugs; sleepiness is common Before giving med, review RBC and WBC count, clotting studies, renal and/or liver function studies. • Azithromycin (Zithromax) – Antibiotic (Macrolide) – bacteriostatic that inhibit protein synthesis by binding reversibly to the 50S ribosomal subunits of susceptible microorganisms. Semisynthetic macrolide ABX that differ structurally from erythromycin and as a result have advantages over it. Fewer adverse effects; for GU and upper and lower respiratory tract infections; usually combined with cephalosporins; for MAC infections also, a common opportunistic infection associated with HIV/AIDS; long duration of action that allows once daily dosing; taking drug with food decreases both rate and extent of GI absorption Lots of interactions bec highly protein-bound and are metabolized In the liver. These drugs include carbamezipine, cyclosporine, theophylline, digoxin and warfarin. Also oral contraceptives HOWEVER side effects are minimal with AZITHROMYCIN…. ADE include GI effects such as N/V, QT prolongation, headache, dizziness, vertigo, hepatotoxicity, vomiting, diarrhea, heartburn, jaundice, anorexia, rash, urticaria, hearing loss Assess baseline cardiac function and VS bec of potential adverse effects of palpitations, chest pain, and ECG changes. Note hearing status. Assess liver function and hx of liver dx. • Metoclopramide (Reglan) – Prokinetic drug Promotes movement of substances through GI tract and increase GI motility; The only drug that is also used to prevent N/V Best taken 30 mins before meals at bedtime. Keep solutions for parenteral dosing for only 48 hrs and protect from light This drug is often reserved for TX of N/V associated with antineoplastic drug therapy or radiation therapy and for the treatment of GI motility disturbances; action of this drug is decreased with anticholinergics or opiates. Assess also for interaction with alcohol Available only by prescription bc it can cause severe ADE if not used correctly; for the treatment of delayed gastric emptying and GERD and as an antiemetic; do not use in pt with seizure disorder, pheochromocytoma, breast cancer or GI obstruction EPS effects can occur esp in young adults… tardive dyskinesia may occur with long-term use of metoclopramide • Doxorubicin (Adriamycin) – Cytotoxic Antibiotic Antineoplastic drug (SUBCLASS anthracyclines) Bone marrow suppression as common toxicity. OTHERS include acute left ventricular failure for this specific drug MOA- interact with DNA through a process called intercalation, in which the drug molecule is inserted between the 2 strands of a DNA molecule, ultimately blocking DNA synthesis. Also inhibits the enzyme topoisomerase II, which leads to DNA strand breaks; monitor for left ventricular failure with toxicity Use to treat solid tumors such as breast, bone and ovarian cancer and also some hematologic malignancies such as leukemia, neuroblastoma, HL, and NHL ALSO available as liposomal drug delivery system (Doxil)-in this formulation, drug is encapsulated in a lipid molecule bilayer called liposome = Reduced systemic toxicity and increased duration of action. Liposomal encapsulation extends the biologic half-life of doxorubicin to 50 to 60 hrs and increases its affinity for cancer cells; For AIDS-related kaposi sarcoma and ovarian cancer Extravasation may lead to severe tissue injury with complications such as permanent damage to muscles, tendons, and ligaments, and possible loss of limb. ADE: hair loss, N/V and myelosuppression; liver failure and CV toxicities esp cardiomyopathy with large doses IMPORTANT! Severe cases of cardiomyopathy are associated with large cumulative doses of doxorubin. Routine monitoring of cardiac function, cumulative dose limitations, and the use of cytoprotective drugs such as dexrazoxane can decrease the incidence of this devastating toxicity. 1) Once detected, contact prescriber, assess and document. Emergency mgmt is to be started immediately 2) Stop IV infusion promptly. 3) If peripheral infiltration occurs, stop infusion, discontinue drip, leave cannula in place, mark extravasated area and contact prescriber. Aspirate extravasated drug and attempt to draw blood back from the cannula; if protocol allows, injection of NS may aid in this. Follow mgmt protocols regarding heat and cold application. Rest the extremity and elevate as instructed 4) If central line, stop infusion, aspirate drug from line, leave line in place and inform prescriber. 5) Referral to plastic surgery may be indicated Interactions: Causes digoxin levels to increase, other chemotherapeutic drugs CT scans and ultrasound studies may be needed before and during treatment to assess cardiac ejection fraction bec of risk for cardiotoxicity; Monitor results of liver and renal function tests throughout therapy. Also heart sounds, daily weights, BP, PR, and monitoring for S/S of cardiovascular toxicities • Nystatin (Mycostatin) – same MOA as Ampho-B. Its usefulness is limited bec of its toxic effects when given in the dosages required to accomplish the same antifungal actions as Ampho-B; Most commonly used to treat oropharyngeal candidiasis or thrush and as a topical powder; lozenges not used in children younger than 5 years a polyene antifungal drug that is often applied topically for the treatment of candidal diaper rash, taken orally as prophylaxis against candidal infections during periods of neutropenia in patients receiving immunosuppressive therapy ADE include N/V, diarrhea, cramps, rash, urticaria • Hydroxychloroquine (Plaquenil) – Nonbiologic DMARD (1st line for RA) - drugs that modify the disease of RA. They exhibit anti-inflammatory, antiarthritic, and immunomodulating effects and work by inhibiting the movement of various cells into an inflamed, damaged area, such as a joint. Slow onset of action of several weeks, versus minutes to hours for NSAIDs. For this reason, DMARDs are sometimes also referred to as slow-acting antirheumatic drugs (SAARDs). NOTE TO ALL DMARD: The most common side effects include diarrhea, upper respiratory tract infection, headache, hypertension, lipid abnormalities, anemia, and insomnia. It should not be used in combination with other DMARDS or immunosuppressants. Contraindicated in eye problems; works in the erythrocytic or blood phase; Use for SLE and RA. It is an antimalarial and has also antiflammatory effects. Also for protozoal infections. In addition to malaria, it is also indicated for treatment of other parasitic infections, such as amebiasis. ADE: Diarrhea, anorexia, nausea, vomiting, Dizziness, headache, seizures, personality changes, Alopecia, rash, pruritus • Simethicone (Mylicon) - used to reduce the discomforts of gastric or intestinal gas (flatulence) and aid in its release via the mouth or rectum. It is therefore classified as an antiflatulent drug. Simethicone works by altering the elasticity of mucus-coated gas bubbles, which causes them to break into smaller ones. This reduces gas pain and facilitates the expulsion of gas via the mouth or rectum. Simethicone has no listed adverse effects, drug interactions, or pharmacokinetic parameters. Assess for abdominal distention and rigidity, which may indicate a medical emergency. • Pyridostigmine (Mestinon) - indirect-acting cholinergic drug Work to increase acetylcholine by inhibiting acetylcholinesterase. Pyridostigmine has been shown to improve muscle strength and is used to relieve the symptoms of myasthenia gravis; it is the most commonly used drug for symptomatic treatment of this disease. also useful for reversing the effects of nondepolarizing neuromuscular blocking drugs after surgery. They are also used in the treatment of severe overdoses of tricyclic antidepressants because of the significant anticholinergic effects associated with the tricyclic antidepressants and as antidotes after toxic exposure to nondrug anticholinergic agents, including those used in chemical warfare. Adverse effects include GI upset and excessive salivation. Others include hypotension or hypertension, syncope, convulsions, ataxia, N/V, diarrhea Interacting drugs include the anticholinergic drugs, antihistamines, sympathomimetics Cholinergic reduces HR Anticholinergics increases HR The desired effects come from muscarinic receptor stimulation; many of the undesirable adverse effects are due to nicotinic receptor stimulation. • Interleukins – lymphokines; antitumor action; It was formerly called T-cell growth factor because, among other actions, it aids in the growth and differentiation of T lymphocytes Agonist aldesleukin (IL-2) Antagonists – all 3 with parenthesis are for RA anakinra (IL-1) ixekizumab (ADE: neutropenia, immunogenicity, infection, injection site reactions) secukinumab (IL-17A) - ankylosing spondylitis, plaque psoriasis, and psoriatic arthritis tocilizumab and sarilumab (IL-6) Aldesleukin was previously indicated only for the treatment of metastatic renal cell carcinoma, a malignancy that originates in the kidney tissues. It is now also approved for the treatment of metastatic melanoma. Off-label uses include HIV infection and AIDS as well as and non-Hodgkin lymphoma. Oprelvekin is used to help patients produce platelets. The antagonists is approved for the treatment of moderate to severe plaque psoriasis IL-2 drug effects: Modulating Effects Proliferation of T cells Synthesis and secretion of cytokines Increased production of B cells (antibodies) Proliferation and activation of NK cells Proliferation and activation of LAK cells Enhancing Effects Enhancement of killer T-cell activity Amplification of the effects of cytokines Enhancement of the cytotoxic actions of NK cells and LAK cells Intervention: Assess for drug allergy as well as the contraindications of organ transplantation, abnormal thallium cardiac stress test, or abnormal pulmonary function tests. Assess vital signs and breath and heart sounds. Document any history of respiratory and/or cardiac disorders due to the severe toxicities of CLS (with aldesleukin). Interactions: Drug interactions of significance include antihypertensives, which produce additive hypotensive effects. Corticosteroid use is contraindicated because of a reduction in antitumor effectiveness. Tocilizumab is one interleukin drug that is indicated for severe RA and is not to be given with other BRMs. ADE: Capillary leak syndrome with aldesleukin can result in massive fluid retention (respiratory distress, HF, MI, Dysrhytmias) As mentioned earlier in the chapter, CLS results in massive fluid retention of 20 to 30 lb, leading to potentially life-threatening problems of respiratory distress and heart failure. These are reversible after discontinuation of the interleukin therapy. Assess liver function studies prior to therapy. Other adverse effects that may be associated with aldesleukin therapy are fever, chills, rash, fatigue, hepatotoxicity, myalgias, headaches, and eosinophilia. Tocilizumab has a high risk for causing anaphylaxis. • Abatacept (Orencia) – Biologic DMARD - drugs that modify the disease of RA. They exhibit antiinflammatory, antiarthritic, and immunomodulating effects and work by inhibiting the movement of various cells into an inflamed, damaged area, such as a joint. Selective costimulation modulator; it inhibits T-cell activation; For treatment of RA; Use with caution in patients with a history of recurrent infections or chronic obstructive pulmonary disease; May increase the risk for infections associated with live vaccines and may decrease the response to dead and/ or live vaccines Dosed according to body weight and at 4-week intervals; Filter to be used with IV administration; Half-life of 8-25 days INTERACTION: Abatacept is not to be given with anakinra or TNF-blocking drugs because of the risk for serious infections, or with the herb echinacea, which has immunostimulant properties. ALL DMARDS: Slow onset of action of several weeks, versus minutes to hours for NSAIDs. For this reason, DMARDs are sometimes also referred to as slow-acting antirheumatic drugs (SAARDs); • Zidovudine (Retrovir) – Antiviral the first NRTI that has had an enormous impact on the treatment and quality of life of patients who have AIDS. It was the very first and, for a long time, the only anti-HIV medication. Zidovudine, along with various other antiretroviral drugs, is given to HIV-infected pregnant women and even to newborn babies to prevent maternal transmission of the virus to the infant. ADE: The major dose-limiting adverse effect of zidovudine is bone marrow suppression Patient may experience headaches; therefore provide the appropriate form of analgesia Intervention: Before and during zidovudine therapy, the patient’s blood cell counts and clotting studies need to be reviewed • Rifapentine (Priftin) – Antitubercular drug Causes bodily fluids, waste and contact lenses to turn red-orange-brown in color Rifapentine (Priftin) is a derivative of rifampin. It offers advan-tages over rifampin in that it has a much longer duration of action and possibly better efficacy. It has been shown to have greater antimycobacterial efficacy and macrophage penetration. Its accumulation into tissue macrophages allows it to work synergistically against bacterial cells that are ingested by the macrophage during phagocytosis (“cell eating”). • Lithium – Mood stabilizer; For Bipolar treatment and maintenance (cycles of mania, hypomania, and depression) narrow therapeutic range (0.6 to 1.2 mEq/L) and requires blood level monitoring. serum lithium levels must be assessed every 3 to 4 days lithium ions alter sodium ion transport in nerve cells, which results in a shift in catecholamine metabolism. Keep sodium in normal range. Adverse effects tend to correlate with serum levels and include gastro-intestinal (GI) discomfort, tremor, confusion, somnolence, seizures, and possibly death. The most serious adverse effect is cardiac dysrhythmia. Other adverse effects include drowsiness, slurred speech, epilepsy-type seizures, choreoathetotic movements (involuntary wavelike movements of the extremities), ataxia (generalized disturbance of muscular coordination), and hypotension. Potentially interacting drugs include the thiazide diuretics, angiotensin-converting enzyme inhibitors and nonsteroidal antiinflammatory drugs, all of which can increase lithium toxicity. • Dantrolene (Dantrium) – Muscle relaxant Treats malignant hyperthermia; acts directly on skeletal muscle; exert its action by decreasing the amount of calcium released from storage sites in the sarcoplasmic reticula of muscle fibers ADE: Euphoria, lightheadedness, dizziness, drowsiness, fatigue, confusion, and muscle weakness are often experienced early in treatment. These adverse effects are generally short lived because patients grow tolerant to them over time. Less common adverse effects seen with muscle relaxants include diarrhea, GI upset, headache, slurred speech, muscle stiffness, constipation, sexual difficulties in males, hypotension, tachycardia, and weight gain. Interactions: When muscle relaxants are administered along with other depressant drugs such as alcohol and benzodiazepines, caution needs to be used to avoid overdosage. Mental confusion, anxiety, tremors, and additive hypoglycemic activity have also been reported with this combination. The greatest risk for hypotension associated with these drugs is usually within 1 hour of dosing, so the patient must be more cautious about activity during this time. • Alteplase (Activase, tPA) – Thrombolytic drug; activating plasmino-gen and converting it to plasmin, which is capable of digesting fibrin, a major component of clots. A pharmaceutically available t-Pa made through recombinant DNA techniques. It is fibrin specific and therefore does not produce a systemic lytic state. In addition, because it is present in the human body in a natural state, its administration for therapeutic use does not induce an antigen-antibody reaction. Therefore it can be readministered immediately in the event of reinfarction. t-Pa has a very short halflife of 5 minutes. It is believed to open the clogged artery rapidly, but its action is short-lived. Therefore, it is given with heparin to prevent reocclusion of the affected blood vessel. Alteplase is available only in parenteral form. There is also a smaller dosage form known as Cathflo Activase that is used to flush clogged IV or arterial lines. Tenecteplase (TNKase) is a form of alteplase that is given by IV push after MI. Alteplase is also used to treat ischemic stroke. concerns include a history of hypotension and cardiac dysrhythmias. Measure the patient’s fibrinogen level to check for the occurrence of fibrinolysis. With the break-down of fibrin (or fibrinolysis), INR will increase and aPTT will be prolonged. • Cholestyramine (Questran) – Bile acid sequestrant; bind bile and prevent resorption of the bile acids from the small intestine for the treatment of types IIa and IIb hyperlipidemia; also used to relieve pruritus; They lower the cholesterol level, in particular the LDL; a prescription-only drug that is contraindicated in patients with a known hypersensitivity to it and in those who have complete biliary obstruction or PKU. Other drugs must be taken at least 1 hour before or 4 to 6 hours after the bile sequestrant. ADE: Constipation, nausea, belching, bloating, Headache, tinnitus, burnt odor of urine • Prednisone (Deltasone) – Corticosteroid (Adrenal drug) specifically a glucocorticoid These drugs have half-lives that are more than double those of the short-acting corticosteroids (2 to 5 hours), and therefore they have longer durations of action. Prednisone is the most commonly used oral glucocorticoid for antiinflammatory or immunosuppressant purposes. Along with methylprednisolone and prednisolone, it is also used to treat exacerbations of chronic respiratory illnesses. Prednisone has only minimal mineralocorticoid properties and therefore alone is inadequate for the management of adrenocortical insufficiency (Addison’s disease). Prednisolone, a prednisone metabolite, is also the liquid drug form of prednisone. Prednisone itself comes in solid form. It is classified as a pregnancy category C drug. ADE include HF, edema, hypertension, hypokalemia, hypernatremia, cushings, convulsions, vertigo, hirsutism, urticaria and more Interacts with non-potassium sparing diuretics, aspirin, anticholinesterase drugs, hypoglycemic drugs, immunizing biologics, thyroid hormones, antifungal drugs. Barbiturates, hydantoins, warfarin, oral contraceptives Is given orally and with a snack and/ or a meal to help minimize GI upset. An order for an H2 receptor antagonist or a proton pump inhibitor may be prescribed to minimize GI upset and to minimize ulcer formation because these drugs are also ulcerogenic. Emphasize to patients the importance of avoiding alcohol, caffeine, and aspirin and other nonsteroidal antiinflammatory drugs to minimize gastric irritation and possible compounding of ulcerogenic effects. In long-term therapy, alternate-day dosing of glucocorticoids, if possible, may help to minimize the adrenal suppression. Because of the immunosuppression with these drugs, monitor patients for flulike symptoms, sore throat, and fever. If an incision or wound is present, assess the affected area for redness, edema, drainage, and approximation. • Nitroglycerin (Nitrobid) – Nitrate; prophylaxis and treatment for angina and other cardiac problems; It has traditionally been the most important drug used in the symptomatic treatment of ischemic heart conditions such as angina. When given orally, nitroglycerin goes to the liver to be metabolized before it can become active in the body. During this process, a very large amount of the nitroglycerin is removed from the circulation. This is called a large first-pass effect. For this reason, nitroglycerin is administered by other routes to avoid the first-pass effect. The nitrates have a potent dilating effect on the large and small coronary arteries; The nitrates are used to treat stable, unstable, and vasospastic (Prinzmetal) angina. Long-acting dosage forms are used more for prevention of anginal episodes. Rapid-acting dosage forms, most often sublingual nitroglycerin tablets, or an intravenous drip in the hospital setting, are used to treat acute anginal attacks. A common regimen with transdermal patches is to remove them at night for 8 hours and apply a new patch in the morning. This has been shown to prevent tolerance to the beneficial effects of nitrates. Patches are worn for 12–14 hours per day to decrease tolerance to its effect. Intravenous dosage forms are available as ready-to-use injectable doses and are administered using specific non–polyvinyl-chloride (PVC) plastic intravenous bags and tubing. The non-PVC infusion kits are used to avoid absorption or uptake of the nitrate by the intravenous tubing and bag. This prevents decomposition of the nitrate with breakdown into cyanide when the drug is exposed to light. Intravenous forms of nitroglycerin are stable for about 96 hours after preparation. If parenteral solutions are not clear and are discolored, discard the solution. ADE: The most common undesirable effect is headache, which generally diminishes soon after the start of therapy. Other cardiovascular effects include tachycardia and postural hypotension. If nitrate-induced vasodilation occurs too rapidly, the cardiovascular system over-compensates and increases the heart rate, a condition referred to as reflex tachycardia. Interactions: Nitrate antianginal drugs can produce additive hypotensive effects when taken in combination with alcohol, beta blockers, CCBs, phenothiazines, and erectile-dysfunction drugs such as sildenafil, tadalafil, and vardenafil. • Phenytoin (Dilantin) – Antiepileptic/Anticonvulsant (PO and IV) 1st line drug for epilepsy; for mgmt of tonic-clonic and partial seizures As point of reference, 150 mg of fosphenytoin (prodrug of phenytoin-to overcome some of the chemical disadvantages of phenytoin injection) is the equivalent of 100 mg of phenytoin, and the dose, concentration solution, and infusion rate of fosphenytoin is expressed as a phenytoin equivalent (PE); only use NS as dilutional drug; filter must be used; usually 150 mg PE/min or less to avoid hypotension and cardiorespiratory depression; IV dose has rapid onset of action; CNS depression always a concern; if infiltration occurs, D/C infusion but leave IV catheter in place until all orders from the prescriber has been received; ADE: Gingival hyperplasia, measles-like rash, focus on vision esp those related to eye mvmt, lethargy, abnormal mvmts, mental confusion, cognitive changes, acne, hirsutism, osteoporosis, dilantin facies, thrombocytopenia, agranulocytosis, hepatitis, GI upset INTERACTIONS: amiodarone, benzos, azole antifungals, INH, PPIs, sulfas, carbamezipine, cyclosporine, meperidine, rifampin, quetiapine, theophylline, warfarin (increased warfarin levels) Parenteral phenytoin is adjusted chemically to a PH of 12 with propylene glycol (antifreeze) for drug stability.. give by slow IV push (not exceeding 50 mg/min) directly into a large vein through a large-gauge catheter (20 gauge or larger)… follow each dose by an injection of saline flush to avoid local venous irritation. 10-20 mcg Therapeutic drug levels… at toxic levels, nystagmus, ataxia, dysarthria, and encephalopathy occurs. Drug has long half-life that allows for twice or once-daily dosing Phenytoin highly bounds to plasma proteins and competes with other highly-protein bound meds. It also induces hepatic microsomal enzymes, mainly cytochrome P-450 enzymes. This increases metabolism of other drugs and reduces blood levels… exaggerated phenytoin can be seen in PT with low serum albumin concentrations CBCs monitored w/n 1st yr of therapy, baseline neuromuscular stability w/ attention to coordinated movements, gait, and reflexes, assessment of speech for clarity and ability to form and express words appropriately; baseline liver function • Digoxin (Lanoxin) – Cardiac glycoside; The beneficial effect of digoxin is thought to be an increase in myocardial contractility—known as a positive inotropic effect. Digoxin decreases the velocity (rate) of electrical conduction and prolongs the refractory period in the conduction system. The particular site in the conduction system where this occurs is the area between the atria and the ventricles (SA node to AV node). Normal therapeutic levels for digoxin are 0.5 to 2 ng/mL. However, levels higher than 2 ng/mL are used for the treatment of atrial fibrillation. Low potassium or magnesium levels may increase the potential for digoxin toxicity. A decrease in renal function is a common cause of digoxin toxicity; symptoms of digoxin toxicity include bradycardia, headache, dizziness, confusion, nausea, and visual disturbances (blurred vision or yellow vision). With toxicity, ECG findings may include heart block, atrial tachycardia with block, or ventricular dysrhythmias; digoxin immune Fab may be indicated as antidote Digoxin is primarily used in the treatment of systolic heart failure and atrial fibrillation. The latest heart failure treatment guidelines recommend that it be used as an adjunct to drugs of other classes, including beta blockers, diuretics, ACE inhibitors, and ARBs in selected patients. Adverse Effects Bradycardia or tachycardia; hypotension, Headache, fatigue, confusion, convulsions Unusual colored vision (i.e., green, yellow), halo vision Anorexia, nausea, vomiting, diarrhea Interactions: The most important drug-drug interactions occurring with digoxin are interactions with amiodarone, quinidine, and verapamil; ginseng may increase digoxin levels, hawthorn may potentiate the effects of digoxin, licorice may increase the risk for cardiac toxicity due to potassium loss, and St. John’s wort may reduce digoxin levels. Drugs that lower serum potassium or magnesium levels can predispose patients to digoxin toxicity. • Selegiline (Eldepryl) – MAOI (Antiparkinson drugs); selegiline (Eldepryl) is selective MAO-B inhibitors indicated for Parkinson’s disease; Used alone or in conjunction with carbidopa-levodopa in early stages of disease; helpful with symptom fluctuations The primary role of MAO enzymes is the breakdown of catecholamines—such as dopamine, norepinephrine, and epinephrine—as well as serotonin. When an MAO-B inhibitor such as rasagiline or selegiline is given, it causes an increase in the levels of dopaminergic stimulation in the CNS. Selegiline is available as an oral tablet and an orally disintegrating tablet for buccal use known as Zelapar, which can provide improved drug absorption. In addition, a transdermal form of the drug, known as Emsam, is available; it is indicated only for major depressive disorder This dosage form is to be taken without liquids and given in the morning before breakfast. Foods and fluids are not to be consumed for 5 minutes before or after the drug is taken. Postural hypotension may be a transient problem; therefore the patient must move and change positions slowly and purposively. If dizziness is severe or if the patient experiences hallucinations, the prescriber must be contacted for further instructions. Interactions: meperidine and other opioids, tramadol, cyclobenzaprine, dextromethorphan, other MAOIs, serotonergic antidepressants, oxcarbazepine, carbamazepine, oral contraceptives buspirone ADE: Headache, insomnia, dizziness, nausea, hypotension, confusion, rash, weight loss, diarrhea, stomatitis, dyskinesia, back pain, somnolence, impulse control disorders • Hydromorphone (Dilaudid) – Opioid Analgesic; An agonist binds to an opioid pain receptor in the brain and causes an analgesic response—the reduction of pain sensation; The main use of opioids is to alleviate moderate to severe pain. a very potent opioid analgesic and is a Schedule II drug Strong opioids such as morphine, hydromorphone, and oxycodone are often used to control postoperative and other types of pain. Because morphine and hydromorphone are available in injectable forms, they are often first-line analgesics in the immediate postoperative setting. Seven times more potent than morphine. 1 mg hydromorphone = 7 mg morphine; Naloxone and naltrexone are opioid antagonists ADE: Hypotension, flushing, bradycardia, Sedation, disorientation, euphoria, lightheadedness, dysphoria Nausea, vomiting, constipation, biliary tract spasm, Urinary retention, Itching, rash, wheal formation, Respiratory depression and possible aggravation of asthma Interactions: Co-administration of opioids with alcohol, antihistamines, barbiturates, benzodiazepines, phenothiazine, and other CNS depressants can result in additive respiratory depressant effects. • Allopurinol (Zyloprim) – Antigout; inhibits the enzyme xanthine oxidase, which thereby prevents uric acid production For prevention of gout; indicated for patients whose gout is caused by the excess production of uric acid (hyperuricemia); also used to prevent acute tumor lysis syndrome Significant adverse effects of the drug include agranulocytosis, aplastic anemia, and serious and potentially fatal skin conditions such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Azathioprine and mercaptopurine both significantly interact with allopurinol Considerations: To be given with meals to minimize the occurrence of gastrointestinal symptoms such as nausea, vomiting, and anorexia. If allopurinol is to be administered in conjunction with chemotherapy (in an attempt to decrease hyperuricemia associated with malignancy and cell death from successful treatment), it is recommended that it be given a few days before the antineoplastic therapy • Enalapril (Vasotec) – ACE inhibitor; All ACE inhibitors have detrimental effects on the unborn fetus and neonate; reacts with NSAIDs Drug of choice for hypertensive patients with HF; “cardioprotective effect”; The parenteral formulation (enalaprilat) is an active drug. It offers the hemodynamic benefit of inhibiting ACE activity in an acutely ill patient who cannot tolerate oral medications. The other benefit to intravenous enalapril is that it does not require cardiac monitoring as do the intravenous beta blockers and CCBs. The oral form of enalapril differs from captopril in that it is a prodrug, and the patient must have a functioning liver for the drug to be converted into its active form. As with captopril, it has been shown in many large studies to improve a patient’s chances of survival after an MI and to reduce the incidence of heart failure. ADE: hyperkalemia, dry cough, angioedema, headache • Lisinopril (Prinivil) – ACE inhibitor (same ADE and action with enalapril); NOT PRODRUG is a commonly used ACE inhibitor and is available in a generic form. It is used for hypertension, heart failure, and acute myocardial infarction. Like all ACE inhibitors, it is classified as a category C drug for women in the first trimester of pregnancy and a category D drug for women in the second and third trimesters; it can cause fetal death when used in the last two trimesters. A dry cough is common with ACE inhibitors. Hyperkalemia may occur with any ACE inhibitor, and potassium supplementation or potassium-sparing diuretics need to be used with caution. Like all ACE inhibitors, lisinopril can cause a dry cough, which will not harm the patient but is annoying. Lisinopril (and all ACE inhibitors) may be associated with a decrease in renal function • Simvastatin (Zocor) – Statin The statins are often combined with niacin or fibrates; contraindications may include liver disease or elevation of liver enzyme levels; pregnancy category X; In patients taking amiodarone, amlodipine, and ranolazine, the dose is not to exceed 20 mg. In patients taking verapamil and diltiazem, the dose of simvastatin is not to exceed 10 mg. ADE: Abdominal pain, rash, and headache are most common; A clinically important adverse effect is myopathy (muscle pain), which may progress to a serious condition known as rhabdomyolysis. Interactions: These statins are to be used cautiously in patients taking oral anticoagulants. In addition, the co-administration of a statin with a drug metabolized by the cytochrome P-450 enzyme 3A4 (CYP3A4) (such as erythromycin, azole antifungals, verapamil, diltiazem, HIV and hepatitis C protease inhibitors, amiodarone, and grapefruit juice—may lead to the development of rhabdomyolysis.) First-line drug therapy for hypercholesterolemia (especially elevated levels of LDL cholesterol), the most common and dangerous form of dyslipidemia. More specifically, they are indicated for the treatment of types IIa and IIb hyperlipidemia and have been shown to reduce the plasma concentrations of LDL cholesterol by up to 50%. Their cholesterol-lowering properties are dose-dependent; that is, the larger the dose, the greater the cholesterol-lowering effects. • Filgrastim (Neupogen) – Colony-stimulating factors (CSFs) under the drug class Hematopoietic drugs; stimulates progenitor cells for the subset of WBC synthetic analogue of human granulocyte colony-stimulating factor that is commonly referred to as GCSF. Filgrastim promotes the proliferation, differentiation, and activation of the cells that make granulocytes. Granulocytes are the body’s primary defense against bacterial and fungal infections. Filgrastim has the same pharmacologic effects as endogenous human G-CSF, which is normally secreted by specialized leukocytes known as monocytes, macrophages, and mature neutrophils. Filgrastim is indicated to prevent or treat febrile neutropenia in patients receiving myelosuppressive antineoplastics for nonmyeloid (non–bone marrow) malignancies. Decrease the duration of chemotherapy-induced anemia, neutropenia, and thrombocytopenia and enable higher dosages of chemotherapy to be given; decrease bone marrow recovery time after bone marrow transplantation or irradiation; and stimulate other cells in the immune system to destroy or inhibit the growth of cancer cells as well as virus-or fungus-infected cells; produced by recombinant DNA technology; administer before patient develops infection Colony-stimulating factors stimulate neutrophils to grow and mature and thus directly oppose the detrimental bone marrow actions of chemotherapy. Because these drugs reduce the duration of low neutrophil counts, they reduce the incidence and duration of infections. Colony-stimulating factors also enhance the functioning of mature cells of the immune system, such as macrophages and granulocytes. This increases the ability of the body’s immune system to kill cancer cells as well as virus-and fungusinfected cells. Ultimately these properties allow patients to receive higher dosages of chemotherapy. When one or more colony-stimulating factors are administered as part of the drug therapy for bone marrow transplantation, bone marrow cell counts return to normal in a drastically shortened time. Interactions: Myelosuppressive antineoplastic drugs, lithium and corticosteroids Adverse effects of edema, nausea, vomiting, diarrhea, rash, flushing, cough, dyspnea, sore throat, fever, muscle ache, blood dyscrasias, headache, and bone pain. Intervention: Monitor WBC when taking this drug; From laboratory values, assess the chemotherapyinduced absolute neutrophil nadir (low point); this drug is not given within 24 hrs before or after a chemo drug; Assess for any existing bone or joint pain because of the ADE of mild to severe bone pain Once a patient’s absolute neutrophil count (ANC) reaches 10,000/mm3, discontinue the drug as recommended by the prescriber. Give filgrastim and use D5W to dilute the product. • Sirolimus (Rapamune) – Immunosuppressant drug; Sirolimus is a mTOR inhibitor that inhibits T lymphocyte activation and proliferation; primarily indicated for the prevention of organ rejection; Have long half-life; inhihits the phosphate required for IL-2 production. Sirolimus levels are increased when taken with high-fat meals. Black box warnings regarding the potential for developing lymphoma and serious infections, as well as lung dehiscence, hepatic artery thrombosis, and hypersensitivity reactions, including angioedema. Contraindicated in renal/hepatic failure, HTN and concurrent radiation therapy. ADE: Peripheral edema, HTN, Afib, palpitations, hypotension, tachycardia, thrombosis, headache, insomnia, dysuria, acne, rash, ARF, DM, hepatotoxic, neutropenia, seizures, necrosis All immunosuppressants have similar mechanisms of action in that they selectively suppress certain Tlymphocyte cell lines. By suppressing the T-lymphocyte cell lines, they prevent their involvement in the immune response. This results in a pharmacologically immunocompromised state Sirolimus is a macrocyclic immunosuppressive, antifungal, and antitumor drug, and tacrolimus is used to prevent rejection and to treat rejection once it occurs Interacts with cyclosporine, fluconazole, clarithromycin, verapamil, grapefruit juice, rifampin, phenytoin, phenobarbital, carbamezipine, St. John’s Wort; Avoid foods high in fat content Bc it increases sirolimus level Assess baseline renal and hepatic labs as well as neurologic and respiratory functioning; do not store IV solutions in polyvinyl chloride containers. • Heparin – Anticoagulant; for MI, unstable angina, Afib, given subcut; Heparin is commonly used for DVT prophylaxis in a dose of 5000 units two or three times a day given subcutaneously; it does not need to be monitored when used for prophylaxis Admin Protamine Sulfate as antidote; Monitor aPTT 45-70 secs Interacts with NSAID, other anticoagulants • Methylphenidate (Ritalin) – first line ADHD drug; Amphetamine; also for narcolepsy Contraindications to the use of amphetamine and nonamphetamine stimulants include known drug allergy or cardiac structural abnormalities. These drugs can also exacerbate the following conditions: marked anxiety or agitation, Tourette syndrome, hypertension, and glaucoma. The drugs must not be used in patients who have received therapy with any monoamine oxidase inhibitor (MAOI) in the preceding 14 days ADE: Both amphetamine and nonamphetamine stimulants have a wide range of adverse effects. These drugs tend to “speed up” body systems. For example, effects on the cardiovascular system include increased heart rate and blood pressure. Other adverse effects include angina, anxiety, insomnia, headache, tremor, blurred vision, increased metabolic rate (beneficial in treatment of obesity), gastrointestinal (GI) distress, dry mouth, and worsening of or new onset of psychiatric disorders, including mania, psychoses, or aggression. Interacts WITH CNS stimulants and MAOIs Amphetamines stimulate areas of the brain associated with mental alertness, specifically the cerebral cortex and the thalamus; The amphetamines and phenidates increase the effects of norepinephrine and dopamine in CNS synapses by increasing their release and blocking their reuptake The adverse effects of methylphenidate on the cardiovascular system include increased heart rate and blood pressure. Other adverse effects include angina, anxiety, insomnia, headache, tremor, blurred vision, increased metabolic rate, GI distress, dry mouth, and worsening of or new onset of psychiatric disorders (including mania, psychoses, or aggression). • Theophylline (Theo-24) - the most commonly used xanthine derivative, albeit not often used Xanthines are used to dilate the airways in patients with asthma or COPD. They may be used in mild to moderate cases of acute asthma and as an adjunct drug in the management of COPD. The beneficial effects of theophylline can be maximized by maintaining blood levels within a certain target range. If these levels become too high, unwanted adverse effects can occur. If the levels become too low, the patient receives little therapeutic benefit. Although the optimal level may vary from patient to patient, most standard references have suggested that the therapeutic range for theophylline blood level is 10 to 20 mcg/ mL. However, most prescribers now advise levels between 5 and 15 mcg/mL. Laboratory monitoring of drug blood levels is common to ensure adequate dosage, especially in the hospital setting. Contraindications Contraindications to therapy with xanthine derivatives include known drug allergy, uncontrolled cardiac dysrhythmias, seizure disorders, hyperthyroidism, and peptic ulcers Adverse Effects The common adverse effects of the xanthine derivatives include nausea, vomiting, and anorexia. Cardiac adverse effects include sinus tachycardia, extrasystole, palpitations, and ventricular dysrhythmias. Transient increased urination and hyperglycemia are other possible adverse effects. Overdose and other toxicity of xanthine derivatives are usually treated by the repeated administration of doses of activated charcoal. Interactions The use of xanthine derivatives with any of the following drugs causes an increase in the serum level: allopurinol, cimetidine, macrolide antibiotics (e.g., erythromycin), quinolones (e.g., ciprofloxacin), influenza vaccine, and oral contraceptives. Their use with sympathomimetics, or even caffeine, can produce additive cardiac and CNS stimulation. Rifampin and St. John’s wart increase the metabolism of theophylline, which results in decreased theophylline levels. Cigarette smoking has a similar effect because of the enzyme-inducing effect of nicotine. Perform a careful cardiovascular assessment, noting heart rate, blood pressure, and history of cardiac disease. Reflux may also occur with these drugs. Assess bowel patterns and for preexisting disease, such as reflux and/or ulcers. Conduct a baseline assessment of urinary patterns. • Levothyroxine (Synthroid) – Thyroid drug Monitor TSH and T3/T4 to titrate therapy replacement; used for hormone replacement for low levels and also after thyroidectomy; diagnosis of suspected hyperthyroidism; prevention or tx of various types of goiters; replace hormones after radiation to thyroid or neck in cancer pt; Synthroid is the most common (best if taken on empty stomach, dosed in mcg, Doses higher than 200 mcg need to be questioned in case this error has occurred. 100% T4); IV levo must be diluted, only given in severe cases; Oral levothyroxine should be taken consistently every morning 30-60 min before food. Tube feedings can impair its absorption. Contraindicated in recent MI, adrenal insufficiency and hyperthyroidism Thyroid replacement drugs are to be avoided with over-the-counter preparations with iodine, antacids, vitamins, or supplements containing iron and/or calcium within a 4-hour time frame. Encourage reading of labels of all prescribed and OTC medications. Iodized salt and iodine-rich foods, such as soybeans, tofu, turnips, high-iodine seafood, and some breads must also be avoided. If the patient is scheduled to undergo radioactive iodine isotope studies (thyroid uptake and scan), the thyroid replacement drug is usually discontinued about 4 weeks before the test, but only as prescribed. Older adult patients may require alteration of the dosage amount, with a decrease of up to 25% for patients 60 years of age and older. ADE: Tachycardia, palpitations, angina, dysrhythmias, hypertension Insomnia, tremors, headache, anxiety Nausea, diarrhea, cramps Menstrual irregularities, weight loss, sweating, heat intolerance, fever Interacts with phenytoin and fosphenytoin, cholestyramine, antacids, calcium salts, iron, estrogen, warfarin • Glipizide (Glucotrol) – Hyperglycemic drug; For this class of drugs to be effective, the patient must still have functioning beta cells in the pancreas. Thus these drugs work best during the early stages of type 2 diabetes and are not used in type 1 diabetes. Because they have different mechanisms of action, sulfonylureas can be used in conjunction with metformin and thiazolidinediones. Sulfonylureas should not be used in patients with advanced diabetes dependent on insulin administration, because the beta cells in such patients are no longer able to produce insulin. Once insulin is started, it is recommended that the sulfonylurea medication be stopped. ADE: The most common adverse effect of the sulfonylureas is hypoglycemia, the degree to which depends on the dose, eating habits, and presence of hepatic or renal disease. Another predictable adverse effect is weight gain because of the stimulation of insulin secretion. Other adverse effects include skin rash, nausea, epigastric fullness, and heartburn. second-generation sulfonylurea drug. In contrast to another second-generation sulfonylurea, glimepiride, it has a very rapid onset and short duration of action, with no active metabolites. The rapid onset of action allows it to function much like the body normally does in response to meals when greater levels of insulin are required rapidly to deal with the increased glucose in the blood. When a patient with type 2 diabetes mellitus takes glipizide, it rapidly stimulates the pancreas to release insulin. This, in turn, facilitates the transport of excess glucose from the blood into the cells of the muscles, liver, and adipose tissues. Glipizide use is contraindicated in cases of known drug allergy as well as in type 1 or brittle type 2 diabetes. Unlike most other oral diabetes drugs, it is not contraindicated in patients with severe renal failure. It works best if given 30 minutes before meals, usually before breakfast. This allows the timing of the insulin secretion induced by the glipizide to correspond with the elevation in blood glucose level induced by the meal, in much the same way as endogenous insulin levels are raised in a person without diabetes. The extended-release dosage form of glipizide can be given once daily. • Carbidopa-levodopa – Dopamine Replacement Drug; Usually started as soon as patient becomes functionally impaired; drug of choice for most older adults Dopamine replacement drugs stimulate presynaptic dopamine receptors to increase brain levels of dopamine. Dopamine must be administered orally as levodopa, because exogenously administered dopamine cannot penetrate the blood-brain barrier. Carbidopa (Lodosyn) alone is not used as therapy but rather as an adjunct to treat nausea associated with Sinemet. A variety of studies have shown that the controlled-release product Sinemet CR (or generic) increases “on” time and decreases “off” time. As with all sustained-release products, Sinemet CR must not be crushed; however, it can be split one time, unlike most other CR or XR drugs on the market. Carbidopa-levodopa is best taken on an empty stomach; however, to minimize GI side effects, it can be taken with food; Doses are given several hours before bedtime to decrease the incidence of insomnia, ADE: Palpitations, hypotension, urinary retention, depression, dyskinesia, confusion, hypotension, chorea Interacting drug: Nonselective MAOIs Benzodiazepines, antipsychotics, pyridoxine, TCA Carbidopa-levodopa must be used cautiously and with close monitoring in older adult patients, especially those with a history of cardiac, renal, hepatic, endocrine, pulmonary, ulcer, or psychiatric disease. Older adult patients taking carbidopa-levodopa are at an increased risk for experiencing adverse effects, especially confusion, loss of appetite, and orthostatic hypotension. • Benztropine (Cogentin) – antiCholinergic drug Benztropine (Cogentin) is an anticholinergic drug used in the treatment of Parkinson’s disease and also of extrapyramidal symptoms from antipsychotic drugs (see Chapter 16). Benztropine is to be used with caution in hot weather or during exercise because it may cause hyperthermia. Other adverse effects include tachycardia, confusion, disorientation, toxic psychosis, urinary retention, dry mouth, constipation, nausea, and vomiting. Anticholinergic syndrome can occur when benztropine is given with other drugs associated with a high incidence of anticholinergic effects. Alcohol is to be avoided. Benztropine is available as tablets and in injectable form. patients need to take the medication as prescribed, after meals or at bedtime and not at the same time as other medications. Patients also need to know that it may take a few days to several weeks for the drugs to show their therapeutic effects (e.g., improvement in tremors). Because of the risk for stomach upset (i.e., nausea, vomiting), it is recommended that these drugs be taken with a snack, such as ginger ale, graham crackers, or soda crackers. Ginger tea is sometimes a good choice to help with the GI upset. These medications are generally taken at night because of their sedating properties. • Furosemide (Lasix) – Loop diuretics It is used in the management of pulmonary edema and the edema associated with heart failure, liver disease, nephrotic syndrome, and ascites. It has also been used in the treatment of hypertension, usually that caused by heart failure. Furosemide use is contraindicated in patients who have shown hypersensitivity to it or to the sulfonamides (see previ-ous discussion regarding sulfonamide allergy) and in patients with anuria, hypovolemia, or electrolyte depletion. Furosemide has a black box warning regarding fluid and electrolyte loss. It is available in oral form as a solution and in tablets and also in an injectable form. It is classified as a pregnancy category C drug. Interactions: Aminoglycosides, vancomycin, Corticosteroids, digoxin, lithium, NSAIDs, Antidiabetic drugs ADE: Dizziness, headache, tinnitus, blurred vision, Nausea, vomiting, diarrhea, Agranulocytosis, thrombocytopenia, neutropenia Hypokalemia, hyperglycemia, hyperuricemia • Nitroglycerin • Fentanyl – for Cancer patients; for moderate to severe pain Indications: Procedural sedation or adjunct to general anesthesia Relief of moderate to severe acute pain Relief of chronic pain, including cancer pain Interactions and ADE same as Hydromorphone……. The injectable form is used most commonly in perioperative settings and in intensive care unit settings for sedation during mechanical ventilation. Fentanyl is a very potent analgesic. Fentanyl in a dose of 0.1 mg intravenously is roughly equivalent to 10 mg of morphine intravenously. The transdermal delivery system (patch) has been shown to be highly effective in the treatment of various chronic pain syndromes such as cancer-induced pain, especially in patients who cannot take oral medications. This route is not to be used in opioid-naïve patients or for acute pain relief. Fentanyl patches are difficult to titrate and are best used for nonescalating pain. Fentanyl patches take 6 to 12 hours to reach steady-state pain control after the first patch is applied, and supplemental short-acting therapy may be required. Most patients will experience adequate pain control for 72 hours with this method of fentanyl delivery. A new patch is to be applied every 72 hours. It is important to remove the old patch when applying a new one. It takes about 17 hours for the amount of fentanyl to reduce by 50% once the patch is removed. • Fluconazole (Diflucan) - imidazoles and triazoles; act as either fungistatic or fungicidal drugs, depending on their concentration in the fungus; they work by inhibiting fungal cell cytochrome P-450 enzymes that are needed to produce ergosterol also systemic; fungistatic or fungicidal; combats P-450 enzymes; can pass into CSF treating cryptococcal meningitis; effective against vaginal candidiasis; check IV site hourly for signs of tissue necrosis; requires close assessment on GI and renal/hepatic functioning Azole never given with cyclosporine, CCB, benzos, anticoagulants, hypoglycemics, statins, quinidine, phenytoin, rifampin, phenobarbital, carbamezipine Fluconazole (Diflucan) has proved to be a significant improvement in the area of antifungal treatment. It has a much better adverse effect profile than that of amphotericin B, and it also has excellent coverage against many fungi. In fact, it is often preferred to amphotericin B because of these qualities. Oral fluconazole has excellent bioavailability, which means that almost the entire dose administered is absorbed into the circulation. Fluconazole is available in both oral and injectable forms. A single oral dose of fluconazole is usually effective for the treatment of vaginal candidiasis infections. ADE include N/V, diarrhea, stomach pain, increased liver enzyme levels, dizziness Use in caution in PT with renal or hepatic dysfunction; protect IV dosage from moisture and light; diluted solutions only stable for 24 hours; need alternative contraception; report dark urine and claycolored stools; tissue extravasation at the IV infusion site leads to tissue necrosis so check site hourly Interactions include Cyclosporine, sirolimus, tacrolimus, CCB, Benzos, anticoagulants (increased effects), hypoglycemics and statins (reduced metabolism), quinidine (prolongs QT interval), phenytoin, rifampin, phenobarbital, carbamezipine Synthetic azole antifungal; treatment of esophageal, oropharyngeal, peritoneal, urinary tract, vaginal and systemic candida infections and cryptococcal meningitis; single oral dose is effective for TX of vaginal candidiasis infections • Misoprostol (Cytotec) – GI protectant Misoprostol (Cytotec), a prostaglandin E analogue, has been shown to effectively reduce the incidence of gastric ulcers in patients taking NSAIDs (see Chapter 44). Prostaglandins are thought to inhibit gastric acid secretion. They are also believed to protect the gastric mucosa from injury (cytoprotective function), possibly by enhancing the local production of mucus or bicarbonate, by promoting local cell regeneration, and by helping to maintain mucosal blood flow. Misoprostol is to be given with food and is usually ordered to be taken with meals and at bedtime. Use of misoprostol is contraindicated in patients with known drug allergy and in pregnant women (see later in the chapter). Adverse effects include headache, GI distress, and vaginal bleeding. There are no major drug interactions, although antacids may reduce drug absorption. Although some studies show that synthetic analogues of prostaglandins promote the healing of duodenal ulcers, the drugs must be used in dosages that usually produce disturbing adverse effects, such as abdominal cramps and diarrhea. Thus they are not believed to be as effective as H2 receptor antagonists and PPIs for this indication. Misoprostol is also used for its abortifacient properties, as discussed in Chapter 34. For this reason, it is classified a pregnancy category X drug. The usual dosage is 200 mcg four times daily with meals for the duration of NSAID therapy in patients at high risk for ulceration. • St. John's Wort – Herbal supplement Overview St. John’s wort herbal preparations consist of the dried above-ground parts of the plant species Hypericum perforatum. The herb is available over the counter in numerous oral dosage forms. St. John’s wort is sometimes referred to as the herbal Prozac. Common Uses Depression, anxiety, sleep disorders, nervousness Adverse Effects Gastrointestinal upset, allergic reactions, fatigue, dizziness, confusion, dry mouth, possible photosensitivity (especially in fair-skinned individuals) Potential Drug Interactions Monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, tricyclic antidepressants, benzodiazepines, phenytoin, valproic acid, phenobarbital, zolpidem and other hypnotic drugs, cyclosporine and other immunosuppressants, sympathomimetic amines, tyramine-containing foods, opioids, digoxin, estrogens, theophylline, warfarin, triptans, dextromethorphan, loratadine, cetirizine, fexofenadine, HIV drugs, and oral contraceptives Contraindications Contraindicated in patients with bipolar depression, schizophrenia, Alzheimer’s disease, and dementia • Duloxetine (Cymbalta) -SSRI (Antidepressant) - The inhibition of serotonin reuptake is the primary mechanism of action of the SSRIs 2nd generation antidepressant; inhibits serotonin reuptake; also used for relieving IBS symptoms and appear to reduce abdominal pain; also as anxiolytics; high suicide risk for PT taking these medications; 4-6 weeks to take effect ADE: Insomnia, weight gain, sexual dysfunction Although depression is their primary indication, they have shown benefit in treating a variety of other mental and physical disorders. Examples include bipolar disorder, obesity, eating disorders, obsessivecompulsive disorder, panic attacks or disorders, social anxiety disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, the neurologic disorder myoclonus, and various substance abuse problems such as alcoholism. Duloxetine (Cymbalta), like venlafaxine, is a selective serotonin-norepinephrine reuptake inhibitor (SSNRI). It is indicated for depression and GAD. It is also indicated for pain resulting from diabetic peripheral neuropathy or fibromyalgia. It is contraindicated in cases of known drug allergy and concurrent MAOI use, and it can worsen uncontrolled angle-closure glaucoma. Adverse effects include dizziness, drowsiness, headache, GI upset, anorexia, and hepatotoxicity. Drug interactions include SSRIs and triptans (increased risk for serotonin syndrome) and alcohol (increased risk for liver injury). The second-generation antidepressants are highly bound to albumin. When given with other drugs that are also highly protein bound (e.g., warfarin and phenytoin), they compete for binding sites on the surface of albumin. Duloxetine is available only for oral use. Levomilnacipran (Fetzima) is the newest SSNRI approved. Notable side effects include hyperhidrosis, tachycardia and urinary retention. SEROTONIN SYNDROME: • Delirium • Agitation • Tachycardia • Sweating • Myoclonus (muscle spasms) • Hyperreflexia • Shivering • Coarse tremors • Extensor plantar muscle (sole of foot) responses In more severe cases, the following may occur: • Hyperthermia • Seizures • Rhabdomyolysis • Renal failure • Cardiac dysrhythmias • Disseminated intravascular coagulation • Oxybutynin (Ditropan) – Anticholinergic to treat overactive bladder; decreases urinary frequency, urgency, and night time nocturia; dries up the body; this is an anticholinergic; Oxybutynin needs to be taken as directed either 1 hour before or 2 hours after meals, if tolerated. ADE for ALL ANTICHOLINERGICS: Can’t see “blurred vision, dry eyes”, can’t pee, can’t spit, can’t poop “increase fluid and fiber”, Avoid glaucoma PT, and BPH PT, and bowel obstruction; Teach slow position changes and avoid hyperthermia “too much sun exposure” Oxybutynin (Ditropan) is a synthetic antimuscarinic drug used for the treatment of overactive bladder (OAB). It is also used as an antispasmodic for neurogenic bladder associated with spinal cord injuries and congenital conditions such as spina bifida. Contraindications include drug allergy, urinary or gastric retention, and uncontrolled angle-closure glaucoma. Oxybutynin is available for oral use. A transdermal patch (Oxytrol) is available over-the-counter and is approved for treatment of OAB • Epinephrine – Vasopressor (Alpha and Beta); direct acting sympathomimetic; increases B/P; cardiac arrest; shock -works inside the heart (beta1-faster HR; stronger HR; more force and beats; increased CO;) antagonists on the other hand everything is lower, and lining of blood vessels (alpha1 constricts blood vessels). Antagonist on the other hand blocks constriction, less pressure and BP goes down (clonidine); temporary relief of conjunctival congestion and reduction of ocular pressure and dilation of pupils: treatment of open-angle glaucoma Beta2=dilates bronchi; albuterol; for lungs; BP can drop in high doses EP= elevates B/P; constricts the blood vessels; given for severely low BP such as septic shock; 1st primary drug in cardiac arrest such as asystole and pulseless electrical activity; EX Question (EPI is effective when vital signs go up); also used for anaphylaxis “epi pen” Vasopressin is a synthetic ADH; Adds Da H20; higher B/P; Given for DI; does not affect alpha and beta, only fluid volume Epinephrine is an endogenous vasoactive catecholamine. It acts directly on both the alpha-and betaadrenergic receptors of tissues innervated by the SNS. It is considered the prototypical nonselective adrenergic agonist. Epinephrine is administered in emergency situations and is one of the primary vasoactive drugs used in many advanced cardiac life support protocols. The physiologic response is dose related. At low dosages, it stimulates mostly beta1-adrenergic receptors, increasing the force of contraction and heart rate. It is also used to treat acute asthma (see Chapter 37) and anaphylactic shock at these dosages, because it has significant bronchodilatory effects via the beta2-adrenergic receptors in the lungs. At high dosages (e.g., IV drip), it stimulates mostly alpha-adrenergic receptors, causing vasoconstriction, which elevates the blood pressure. (See the dosages table on the previous page.) Epinephrine is available in two strengths for IV use, and it was historically labeled with a ratio, which led to many medication errors. It is available as 1 : 1000 (1 mg/mL) and also as 1 : 10,000 (0.1 mg/mL). As of May 2016, epinephrine injections are no longer labeled with ratios; instead these are labeled like all other injectable drugs in a mg/mL concentration, as 1 mg/mL or 0.1 mg/mL. • Donepezil (Aricept) -Alzheimer’s drug; cholinesterase inhibitor works centrally in the brain to increase levels of acetylcholine by inhibiting acetylcholinesterase. It is used in the treatment of mild to moderate Alzheimer’s disease. Similar cholinesterase inhibitors include galantamine and rivastigmine. Rivastigmine is also approved for treating dementia associated with Parkinson’s disease. Ginkgo may be used by some health care providers for organic brain syndrome Contraindications for donepezil include known drug allergy. Adverse effects are normally mild and resolve on their own; they can often be avoided with careful dose titration. Adverse effects include GI upset (including ulcer risk and GI bleed due to increased gastric secretions), drowsiness, dizziness, insomnia, and muscle cramps. The effects on the cardiovascular system are complex and may include bradycardia, syncope, hypotension with reflex tachycardia, or hypertension. Interacting drugs include anticholinergics (which counteract donepezil’s effects) and nonsteroidal antiinflammatory drugs (see Chapter 44). Donepezil is available for oral use only as both a tablet and a rapid-acting, orally disintegrating tablet. An overdose of cholinergic drugs may result in a cholinergic crisis, with early manifestations of abdominal cramp-ing, flushing of the skin, nausea, vomiting, and salivation. If left untreated, symptoms may progress to circulatory collapse, hypotension, and cardiac arrest. Transient syncope, orthostatic hypotension, and dyspnea may also occur. SLUDGE is an acronym used to remember the effects of cholinergic crisis (see pharmacology discussion). • Albuterol rescue inhaler – Beta agonist (Sympathomimetic); The beta agonists relax and dilate airways by stimulating the beta2-adrenergic receptors located throughout the lungs. Albuterol (Proventil HFA, Ventolin HFA, ProAir HFA) is a short-acting beta2-specific bronchodilating beta agonist. Other similar drugs include levalbuterol (Xopenex), pirbuterol (Maxair), and terbutaline (Brethine). Albuterol is the most commonly used drug in this class. If albuterol is used too frequently, dose-related adverse effects may be seen, because albuterol loses its beta2 specific actions, especially at larger dosages. As a consequence, the beta1 receptors are stimulated, which causes nausea, increased anxiety, palpitations, tremors, and an increased heart rate. Albuterol is available for both oral and inhalational use. Inhalational dosage forms include metered-dose inhalers (MDIs) as well as solutions for inhalation. The levorotatory isomeric form of albuterol, levalbuterol, is sometimes prescribed as an albuterol alternative for patients with certain risk factors (e.g., tachycardia, including tachycardia associated with albuterol treatment). Contraindications include known drug allergy, uncontrolled hypertension or cardiac dysrhythmias, and high risk for stroke ADE: The beta2 drugs can cause both hypertension and hypotension, vascular headaches, and tremor. Overdose management may include careful administration of a beta blocker while the patient is under close observation due to the risk for bronchospasm. Interactions: The use of beta agonists with monoamine oxidase inhibitors and other sympathomimetics is best avoided because of the enhanced risk for hypertension. Patients with diabetes may require an adjustment in the dosage of their hypoglycemic drugs, especially patients receiving epinephrine, because of the increase in blood glucose levels that can occur. • Hydromorphone (Dilaudid) - Opioid • Vitamin C - (ascorbic acid) can be used in many therapeutic situations. Prolonged ascorbic acid deficiency results in the nutritional disease scurvy, which is characterized by weakness, edema, gingivitis and bleeding gums, loss of teeth, anemia, subcutaneous hemorrhage, bone lesions, delayed healing of soft tissues and bones, and hardening of leg muscles. Scurvy has been recognized for several centuries, especially among sailors. In 1795, the British Navy ordered the consumption of limes to prevent the disease. It is required for several important metabolic activities, including collagen synthesis and the maintenance of connective tissue; tissue repair; maintenance of bone, teeth, and capillaries; and folic acid metabolism (specifically, the conversion of folic acid into its active metabolite). It is also essential for erythropoiesis. Vitamin C enhances the absorption of iron and is required for the synthesis of lipids, proteins, and steroids. It has also been shown to aid in cellular respiration and resistance to infections. Vitamin C is used to treat diseases associated with vitamin C deficiency and as a dietary supplement. It is most beneficial in patients who have larger daily requirements because of pregnancy, lactation, hyperthyroidism, fever, stress, infection, trauma, burns, smoking, and the use of certain drugs (e.g., estrogens, oral contraceptives, barbiturates, tetracyclines, and salicylates). Adverse effects: Vitamin C is usually nontoxic unless excessive dosages are consumed. Megadoses can produce nausea, vomiting, headache, and abdominal cramps, and will acidify the urine, which can result in the formation of cystine, oxalate, and urate renal stones. Furthermore, individuals who discontinue taking excessive daily doses of ascorbic acid can experience scurvy-like symptoms • Diazepam (Valium) – Benzodiazepine Diazepam (Valium) was the first clinically available benzodiazepine drug; as such, it is the prototypical benzodiazepine. It has varied uses, including treatment of anxiety, procedural sedation and anesthesia adjunct, anticonvulsant therapy, and skeletal muscle relaxation following orthopedic injury or surgery; must be used short-term when treating insomnia benzodiazepine receptors in the CNS are in the same area as those that play a role in alcohol addiction. Therefore some benzodiazepines (e.g., diazepam, chlordiazepoxide) are used in the treatment and prevention of the symptoms of alcohol withdrawal Contraindications Contraindications to the use of benzodiazepines include known drug allergy, narrow-angle glaucoma, and pregnancy. Adverse effects Commonly reported undesirable effects are headache, drowsiness, paradoxical excitement or nervousness, dizziness or vertigo, cognitive impairment, and lethargy. Benzodiazepines can create a significant fall hazard in older adults, and the lowest effective dose must be used in this patient population. Although these drugs have comparatively less intense effects on the normal sleep cycle, a “hangover” effect is sometimes reported (e.g., daytime sleepiness). Interactions: Azole antifungals, verapamil, diltiazem, protease inhibitors, macrolide antibiotics, grapefruit juice CNS depressants Olanzapine, kava and valerian rifampin • Insulins (short, intermediate, long acting) – Hyperglycemic drug Rapid=15 mins, 1-2 hr, 3-5 hr; Lispro, aspart, glulisine Short=30-60 mins, 2.5 hr, 6-10 hr; Only regular insulin Intermediate=1-2 hr, 4-8 hr, 10-18 hr; Only NPH Long=1-2 hr, no peak, 24 hr; Toujeo, Lantus, detemir, Basaglar(glargine) and degludec(Tresiba) Terms and Illnesses Korsakoff’s psychosis- a syndrome of amnesia with confabulation associated with chronic alcohol abuse; it often occurs together with Wernicke’s encephalopathy Parkinson’s Disease- a chronic, progressive, neurodegenerative disorder affecting the dopamineproducing neurons in the brain. “dopamine deficit” Tuberculosis (TB) – any infectious disease cause by species of Mycobacterium, usually Mycobacterium tuberculosis Miosis – pupillary constriction Mydriasis- Pupillary dilation Sacroma – tumor in the connective tissue Leukemia – malignant neoplasms of blood-forming tissues characterized by the replacement of normal bone marrow cells with leukemic blasts resulting in abnormal numbers and forms of immature white blood cells in the circulation; cancers of blood and bone marrow Lymphoma- tumor/cancer in the lymphatic tissue Monoclonal antibodies- quickly becoming standards of therapy in many areas of medicine, including the treatment of cancer, rheumatoid arthritis and other inflammatory diseases, multiple sclerosis, and organ transplantation; targeted drug therapy In cancer treatment, they have advantages over traditional antineoplastics in that they can specifically target cancer cells and have minimal effect on healthy cells. “mab” suffix is a common abbreviation; assess for cardiovascular disorders and history of GI and respiratory disorders; assess baseline temp as well as breath sounds and respiratory rate; cytokine release syndrome such as fever, dyspnea, tachycardia, sweating, chills, vomiting, diarrhea, muscle/joint pain, general malaise Inhibits cytotoxic T killer cell function Common side effects include nausea, nasopharyngitis, upper RTI, arthralgia, pyrexia, fatigue, headache, cough, and infusion-related reactions or flu-like symptoms Corticosteroid therapy- Glucocorticoids has inflammatory actions, carbohydrate and protein metabolism, fat metabolism, maintenance of normal BP, stress effects; Mineralicorticoids also has BP control, maintenance of serum potassium levels, maintenance of pH levels in the blood, and sodium and water resorption. Inhibits all stages of T-cell activation and used for induction, maintenance immunosuppression, and acute rejection. Used to treat rheumatologic diseases like RA, lupus or vasculitis (inflammation of the blood vessels); also used to prevent organ rejection NSAIDs- nonopioid analgesic; for mgmt of pain esp pain associated with inflammatory conditions such as arthritis bc they have significant anti-inflammatory effects in addition to their analgesic effects Possesses analgesic, anti-inflammatory, and antipyretic activity Antineoplastic therapy- Drugs used to treat cancer; effective on rapidly growing tumors; effects on the GI tract and bone marrow; therapy is held when neutrophil count is less than 500 cells/mm3 General anesthesia- a drug-induced state in which the CNS nerve impulses are altered to reduce pain and other sensations throughout the entire body. It involves complete loss of consciousness and depression of respiratory drive Influenza – characterized by abrupt onset of fever, myalgia, sore throat, and nonproductive cough. Severe malaise may last several days. HIV/AIDS- a common and devastating viral infection. 35.3 M people worldwide infected and over 1.2 M in the US. Most common routes are sexual contact, IV drug use, and perinatal transfer from mother to child. African-American males and females have a rate of HIV infection seven times higher than that seen in white Americans. A member of the retrovirus family and was so named upon discovery of a unique feature of its replication process. Retroviruses are all RNA viruses and are unique in their use of the enzyme reverse transcriptase during their replication process. Gout- hyperuricemia (elevated blood uric acid level); the arthritis caused by tissue buildup of uric acid crystals Arthritis – inflammation of one or more joints Fibromyalgia- also called fibrositis; this is a widespread muscle pain and tenderness often accompanied by fatigue and altered sleep, memory and mood Attention deficit hyperactivity disorder (ADHD)- formerly known as ADD, is the most common psychiatric disorder in children, affecting 4-10% of school-age children with 6.1% of children being treated with medication. Boys are affected 3 times more often than girls, although the disorder may be underdiagnosed in girls. Primary symptoms are inappropriate ability to maintain attention span and/or the presence of hyperactivity and impulsivity; May involve predominantly attention deficit, predominantly hyperactivity or impulsivity, or a combination of both. Usually diagnosed around 7 years of age, with symptoms typically appearing between 3 and 6 years.
