Pharmacologic Analgesic Drugs PDF

WEEK 13 ANALGESIC DRUGS Pain Opioid Receptors (narcotic agonists), opium is a Greek word Pain receptors (nociceptors specialized nerve endings, that means “juice”...

WEEK 13 ANALGESIC DRUGS Pain Opioid Receptors (narcotic agonists), opium is a Greek word Pain receptors (nociceptors specialized nerve endings, that means “juice”. are crucial in detecting harmful stimuli.) Three main receptor families: The nerve endings of nociceptors are crucial in this μ (mu, MOR), process. They detect the initial stimulus and ensure the κ (kappa, KOR) pain signals are accurately transmitted to the central δ (delta, DOR). nervous system (CNS). Opioid agonist several types based on their responses: Thermal: These nociceptors respond to extreme MORPHINE temperatures. They detect heat and cold that can A prototype opioid obtained from the sap of seed pods of the cause damage. opium poppy plant. Mechanical: These receptors are activated by intense pressure or mechanical injury. It may be cuts Mechanism of Analgesic Action or bruises. mimicking the actions of endogenous opioid peptides, Chemical: These respond to chemical changes in primarily at mu receptors. tissues. They are caused by inflammation or tissue Parenterally, the onset of action is rapid, especially damage. when administered intravenously. The onset of action is slower for subcutaneous and intramuscular (IM) ❖ Acute pain- typically occurs over less than 6 weeks. injections. ❖ Chronic pain - Persistent or recurring pain that is often Therapeutic Uses difficult to treat acute pain resulting from acute myocardial infarction ❖ Deep pain -Pain that occurs in tissues below skin level (AMI) and cancer ❖ Breakthrough pain- Pain that occurs between doses of antitussive (cough suppression) effect. pain medication. relieves dyspnea resulting from pulmonary edema ❖ Cancer pain -Pain resulting from any of a variety of used as a preoperative medication to relieve anxiety causes related to cancer and/or the metastasis of cancer. Adverse effects ❖ Central pain- Pain resulting from any disorder that orthostatic hypotension causes central nervous system damage. Miosis ❖ Neuropathic pain - Pain resulting from a nerve's urinary retention function disturbance Constipation ❖ Phantom pain - Pain experienced in the area of a body Emesis part that has been surgically or traumatically removed. biliary colic ❖ Referred pain- Pain occurring in an area away from the respiratory depression organ of origin. Elevation of Intracranial Pressure causes drowsiness and mental clouding, reduces The Journey of Pain Signals Through the Body anxiety, and creates a sense of well-being (euphoria). Dysphoria Pain signals travel through a well-defined process. This is from Neurotoxicity their origin at the nerve endings to the spinal cord. Here’s a Tolerance and physical dependence simplified overview: Withdrawal syndrome Nerve Endings: Nociceptors detect harmful stimuli and convert them into electrical signals. Contraindications and cautions Peripheral Nerves: These electrical signals travel presence of any known allergy to any narcotic agonist along the sensory neurons. They belong to the diarrhea caused by toxic poisons peripheral nervous system and the spinal cord. Caution should be used in patients with respiratory Dorsal Horn of the Spinal Cord: Upon reaching the dysfunction spinal cord, the signals are relayed to the dorsal horn. This is typically processed and transmitted to higher Drug Interactions brain centers. CNS Depressants Ascending Tracts: Pain signals ascend through Anticholinergic Drugs specific tracts in the spinal cord. They are the Hypotensive Drugs spinothalamic tract, which carries the signals to the Monoamine Oxidase Inhibitors brain. Agonist-Antagonist Opioids Brain Processing: The signals are processed in the Opioid Antagonists thalamus. They are then sent to the somatosensory cortex. There, they are perceived as pain. Nursing process: Assessment Central Nervous System (CNS) medical history Brain and spinal cord drug history Two parts of the body that contain most nerves assess vital signs Neurotransmitter monitor urine output Function of the CNS assess pain (type, location, and duration) Sensory Functions Implementation Motor Functions Perform baseline and periodic pain assessments with Intellectual and Emotional Functions the patient Record the patient’s urine output Check bowel sounds Have naloxone available as an antidote Validate the dose of morphine before administration  Monitor the timing of analgesic doses control is equivalent to that achieved with an IV Use additional measures to relieve pain (e.g., back patient-controlled analgesia pump. rubs, stress reduction, hot packs, ice packs) Ionsys consists of a plastic case that houses a 3-volt battery, electronic control, and a reservoir FENTANYL [Duragesic, Abstral, Actiq, containing 10.8 mg of fentanyl hydrochloride. Fentora, Ionsys, Lazanda, Subsys] The upper surface of the device has a recessed dosing button and a light; the lower surface has A strong opioid analgesic with a high milligram potency (about adhesive to hold the device to the skin. 100 times that of morphine). When pain relief is needed, the patient presses Seven formulations are available for administration by four the dosing button twice within 3 seconds, causing different routes: delivery of a 40-mcg dose over a 10-minute interval. Parenteral One Ionsys device can be used for 24 hours or Transdermal delivery of 80 doses, whichever comes first. Ionsys Transmucosal should be applied to intact nonirritated, Intranasal nonirradiated skin of the chest or outer upper The drug is highly lipophilic and has a rapid onset arm. and short duration of action (15 to 30 minutes) Excessive hair should be removed by clipping, not It is used for surgical analgesia, chronic pain control, shaving. All patients should be titrated to comfort and control of breakthrough pain with an appropriate analgesic before Ionsys is employed. Transdermal Fentanyl Patches opioid-tolerant patients. (those in severe pain Transmucosal requiring daily, round-the-clock opioid treatment with Fentanyl for transmucosal administration is available alternative treatments being inadequate in pain in four formulations: control.) lozenges on a stick [Actiq] The transdermal patch creates a reservoir of the drug buccal tablets [Fentora] in the skin and has a delayed onset of at least 12 sublingual spray [Subsys] hours and a prolonged offset. The patch is used for sublingual tablets [Abstral] the management of chronic severe pain. approved only for breakthrough cancer pain in The patient needs to have been taking, for a week patients at least 18 years old who are already or longer, morphine 60 mg daily, oral oxycodone 30 taking opioids around the clock and have mg daily, or a minimum of 8 mg of oral developed some degree of tolerance hydromorphone daily or an equianalgesic dose of defined as needing, for 1 week or longer, at least: another opioid. 60 mg of oral morphine a day, or 30 mg of oral All other extended-released opioids must be oxycodone a day, or 25 mg of oral oxymorphone a discontinued or tapered before the initiation of day, or 8 mg of oral hydromorphone a day, or 25 mcg transdermal fentanyl therapy. of fentanyl per hour, or an equianalgesic dose of The dosing regimen is to be initiated for each patient another opioid. individually with the consideration of their prior Transmucosal fentanyl must not be used for acute analgesic treatment regimen(s) pain, postoperative pain, headache, or athletic monitor patients closely for respiratory injuries. depression, especially within the initial 24 to 72 Adverse effects hours which is the timeframe for peak effects of The most common are dizziness, anxiety, confusion, serum concentrations of the transdermal fentanyl. nausea, vomiting, constipation, dyspnea, weakness, highly effective in the treatment of various chronic and headache. pain syndromes such as cancer-induced pain, The biggest concerns are respiratory depression and especially in patients who cannot take oral shock. medications. HEAT- must never be applied over a transdermal fentanyl patch. The increased circulation that results from the Agonist-Antagonist Opioids application of heat may result in increased absorption of Low potential for abuse, produce less respiratory medication, causing an overdose. depression, and generally have less powerful The patch is customarily applied externally for 72 analgesic effects. Opioid agonist-antagonist drugs hours and then replaced with a new patch. are not given for cancer pain because of the risk Storage: of potential CNS toxicity from the high doses Do not store medications in warm, moist places such required. as medicine cabinets in the bathroom as this may They are used in situations requiring short-term result in the degradation of the drug. pain control, such as after obstetric procedures. not strong enough for management of longer-term chronic pain (e.g., cancer pain, chronic lower back Transdermal Iontophoretic System (Ionsys) pain). a self-contained credit card-sized device—is the They are not to be given concurrently with full opioid first needle-free patient-activated system for agonists. on-demand delivery of analgesia. These mixed opioid agonist-antagonists reduce the The device, which is applied to the skin, delivers risk of respiratory depression and drug abuse. fentanyl by iontophoresis, a process in which a low-intensity electrical field (generally imperceptible to the patient) drives the drug NALBUPHINE across the skin and into the systemic circulation. agonist at kappa receptors and an antagonist at mu Ionsys is approved only for acute management of receptors. low doses, nalbuphine has analgesic postoperative pain in hospitalized adult patients actions equal to those of morphine. However, as and should be removed before discharge. Pain dosage increases, a ceiling to analgesia is  reached. As a result, the maximal pain relief that NALOXONE can be produced with nalbuphine is much lower antidotes for drug toxicity of natural and synthetic than with morphine. opioid analgesics. nalbuphine does not affect the heart or increase blocks the receptor and displaces any opioid that blood pressure. would normally be at the receptor, which inhibits When used during labor and delivery, nalbuphine the opioid action. has caused serious adverse effects, including Reverse the effects of opioids, including respiratory bradycardia in the fetus and apnea, cyanosis, and depression, sedation, psychotomimetic effects and hypotonia (decreased muscle tone) in the neonate. hypotension. Dosage and Frequency Reversal of Neonatal Respiratory Depression - 10 and 20 mg/ mL for IV, IM, and sub Q injection. The The initial dose is 10 mcg/kg (IV, IM, or subQ). This usual adult dosage is 10 mg repeated every 3 to 6 dose is repeated every 2 to 3 minutes until respiration hours as needed. is satisfactory. Indications for opioid antagonists include reversal of Pharmacokinetics postoperative opioid depression and opioid overdose. Nalbuphine can be administered orally or via IM, sub-Q, or IV administered via an IM or IV route routes. It is rapidly absorbed parenterally. Has a short half-life. It is metabolized in the liver and excreted in the urine. Pharmacokinetics Narcotic antagonists may be administered Pharmacodynamics parenterally or orally. These drugs are well effective in alleviating moderate to severe pain. The onset of absorbed after injection and are widely distributed action is rapid, and peak time occurs within 30 minutes with IV in the body. They undergo hepatic metabolism and administration. The duration of action is the same for all are excreted primarily in the urine routes of administration: approximately 5 hours. Naloxone [Narcan, Evzio] is available in solution (0.4 Contraindications and Cautions and 1 mg/mL) for IV, IM, and sub Q injection, an should not be given to patients who are allergic to auto-injector (2 mg/0.4 mL) sulfites to avoid a cross-hypersensitivity reaction. Pharmacodynamics Caution should also be exercised in the following conditions: Naloxone has a shorter duration of action than opioids, and chronic obstructive pulmonary disease or other repeated doses are usually necessary respiratory dysfunction acute myocardial infarction (MI) Adverse Effects documented coronary artery disease (CAD), or acute narcotic abstinence syndrome hypertension nausea, vomiting, and, occasionally, hypertension and renal or hepatic dysfunction tachycardia. An unconscious patient who returns to consciousness Adverse Effects abruptly after naloxone administration may Respiratory depression with apnea and suppression hyperventilate and experience tremors. of the cough reflex is associated with respiratory center depression. Other analgesics Nausea, vomiting, constipation, and biliary spasms Light-headedness, dizziness, psychoses, anxiety, Tramadol hydrochloride fear, hallucinations, and impaired mental processes centrally acting analgesic that binds to the μ opioid GU effects, including ureteral spasm, urinary receptor. It creates a weak bond to the mu opioid retention, hesitancy, and loss of libido receptors and inhibits the reuptake of both norepinephrine and serotonin. Tramadol is indicated for the treatment of moderate BUTORPHANOL to moderately severe pain. The drug is an agonist at kappa receptors and an tramadol has less respiratory-depressant activity antagonist at mu receptors. Analgesic effects are compared to morphine. less than those of morphine. Analgesia begins 1 hour after oral dosing, is maximal administered parenterally (IM and IV) and by nasal at 2 hours, and continues for 6 hours. spray (primarily to treat migraine). The usual adult IV dosage is 1 mg every 3 to 4 hours Adverse Effects as needed. The usual IM dosage is 2 mg every 3 to 4 Respiratory depression is minimal at recommended hours as needed. doses. The usual intranasal dosage is 1 mg (1 spray from the The most common side effects are sedation, metered-dose spray device) repeated in 60 to 90 dizziness, headache, dry mouth, and constipation. minutes if needed. The two-dose sequence may then Seizures have been reported in over 280 patients, be repeated every 3 to 4 hours as needed. and hence the drug should be avoided in patients with Butorphanol is available in a nasal spray that has epilepsy and other neurologic disorders. been used for severe headaches, but it has been associated with abuse. Non-steroidal anti-inflammatory drugs (NSAIDs) Intervention Ketorolac (phenylacetic acid derivative) Give the IV form of the drug by slow injection, group of NSAIDs (1st generation) preferably in a diluted solution. Rapid IV injection increases the risk of adverse effects. Indication: Encourage a postoperative patient to turn, cough, Short–term management of pain and breathe deeply every 2 hours to avoid shown analgesic efficacy equal or superior to that of atelectasis. opioid analgesics administered intramuscularly in doses of 30 to 60 mg every 6 hours for adults.  Ketorolac is also available in oral, intravenous (IV), These receptors are thought to be either and intranasal preparations. gamma-aminobutyric acid (GABA) receptors or other adjacent receptors. GABA is the primary inhibitory Mechanism of action: neurotransmitter of the brain, and it serves to inhibits prostaglandin synthesis, but it has greater analgesic modulate CNS activity by inhibiting overstimulation. properties than other anti-inflammatory agents Pharmacokinetics Pharmacokinetics: The patient can receive benzodiazepines orally, Ketorolac is administered orally and parenterally (IM parenterally, or, in special situations, rectally. These or IV). drugs are absorbed rapidly and almost completely With parenteral administration, analgesia begins from the GI tract but are distributed at different rates. within 30 minutes, peaks in 1 to 2 hours, and persists Protein binding of benzodiazepines ranges from 85% for 4 to 6 hours. half-life of 4 to 6 hours. The half-life to 90%. may be prolonged in older adults and in those Benzodiazepines are metabolized in the liver to with renal impairment. multiple metabolites and are then excreted in urine. The benzodiazepines readily cross the placenta and Adverse effects: are excreted in breast milk. gastric irritation is still a common problem when NSAIDs are taken without food Pharmacotherapeutics sodium and water retention may occur. The benzodiazepines have three principal Alcoholic beverages consumed with NSAIDs may indications: increase gastric irritation and should be avoided. Anxiety Insomnia Assessment seizure disorders Check the patient’s history for allergy to NSAIDs such used as preoperative medications and to treat muscle as ibuprofen. spasms and withdrawal from alcohol. Obtain a drug and herbal history, and report any muscle relaxants. (They induce muscle relaxation possible drug-drug or herb-drug interactions. through effects on supraspinal motor areas, including NSAIDs can increase the effects of phenytoin, the cerebellum) sulfonamides, and warfarin. Most NSAIDs are highly Benzodiazepines are classified under Schedule IV of the protein-bound and can displace other highly Controlled Substances Act - because they have a potential protein-bound drugs like warfarin. for abuse and may lead to dependence. NSAIDs are contraindicated if a patient has severe renal or liver disease, peptic ulcer, or bleeding Adverse Effects disorder. CNS Depression Assess for GI distress and peripheral edema. Anterograde Amnesia Sleep Driving and Other Complex Sleep-Related Intervention: Behaviors Observe the patient for bleeding gums, petechiae, Paradoxical Effects ecchymoses, or black tarry stools. Respiratory Depression. Monitor vital signs and check for peripheral edema, Abuse. especially in the morning. Use in Pregnancy and Lactation. Benzodiazepines Advise pregnant patients to avoid NSAIDs. Congenital are highly lipid soluble and can readily cross the abnormalities may occur when NSAIDs are taken placental barrier. during early pregnancy, and excess bleeding might occur during delivery. Drug Interactions Inform patients that it may take several weeks to CNS Depressants. experience the desired drug effect of some NSAIDs flumazenil [Romazicon, Anexate ], a benzodiazepine and disease-modifying antirheumatic drugs antagonist. (antidote) (DMARDs). Assessment BENZODIAZEPINES Determine the nature of the sleep disturbance the most commonly prescribed sedative-hypnotic Identifying High-Risk Patients drugs Assess baseline vital signs for future comparisons. Benzodiazepines are classified as either Assess renal function sedative-hypnotics or anxiolytics, depending on Drug Administration their primary use. Oral. Advise patients to administer benzodiazepines with food The four benzodiazepine drugs that provide if gastric upset occurs. Instruct patients to swallow anticonvulsant effects are: sustained-release formulations intact, without crushing or diazepam (in the parenteral form) chewing. clonazepam Intravenous. Perform IV injections with care clorazepate To reduce complications, follow these guidelines: Lorazepam make injections slowly; Mechanism of Action and Drug Effects take care to avoid intra-arterial injection and The sedative and hypnotic action of extravasation benzodiazepines is related to their ability to if direct venous injection is impossible, inject into depress activity in the CNS. The specific areas that infusion tubing as close to the vein as possible are affected include the hypothalamic, thalamic, and follow the manufacturer’s instructions regarding limbic systems of the brain. suitable diluents for preparing solutions research suggests that there are specific receptors in have facilities for resuscitation available. the brain for benzodiazepines.  it may be injected slowly, at least 1 minute for each The therapeutic serum levels peak about 10 to 20 5 mg given, through the infusion tubing as close as minutes after the infusion. Phenytoin is available in possible to the vein insertion site. oral and parenteral forms. Do not use small veins, and be very cautious to avoid intraarterial administration or extravasation. Pharmacodynamics Do not administer intra-arterially because serious The pharmacodynamics of orally administered arteriospasm and gangrene could occur. Monitor phenytoin include the onset of action within 30 injection sites carefully for local reactions to institute minutes to 2 hours, peak serum concentration in 1.5 treatment as soon as possible. to 6 hours, steady state of serum concentration in 7 to Do not mix IV drugs in solution with any other 10 days, and a duration of action dependent on the drugs to avoid potential drug-drug interactions. half-life of up to 45 hours. Give IV drugs slowly because these agents have Oral phenytoin is most commonly ordered as a been associated with hypotension, bradycardia, and sustained-release (SR) capsule. The peak SR cardiac arrest. concentration time is 4 to 12 hours. Intravenous (IV) infusion of phenytoin should be Implementation administered by direct injection into a large vein via a Arrange to reduce the dose of narcotic analgesics and central line or peripherally inserted central catheter monitor closely in patients receiving a benzodiazepine (PICC). The drug may be diluted in saline solution; to decrease potentiated effects and sedation. however, dextrose solution should be avoided Monitor hepatic and renal function, as well as CBC, because of drug precipitation. during long-term therapy The IV line should always be flushed with saline Examine the patient’s skin for rashes before and after each dose to reduce venous Encourage patients to avoid alcohol and irritation. Intramuscular (IM) injection of phenytoin antidepressant, antipsychotic, and opioid drugs while irritates tissues and may cause damage. For this taking benzodiazepines. reason, and because of its erratic absorption rate, Taper dose gradually after long-term therapy, phenytoin is not given by the IM route. especially in epileptic patients. Adverse Effects Effects on the CNS HYDANTOINS (phenytoin-Dilantin) Gingival Hyperplasia generally less sedating than many other Dermatologic Effects- Stevens-Johnson syndrome antiepileptics, they may be the drugs of choice for (SJS) or toxic epidermal necrolysis (TEN) patients who are not willing to tolerate sedation Effects on Pregnancy. Phenytoin is a teratogen. and drowsiness. Phenytoin can decrease the synthesis of vitamin phenytoin is effective in treating tonic-clonic and K–dependent clotting factors and can thereby cause partial seizures but is not effective in treating bleeding tendencies in newborns. absence seizures. Cardiovascular Effects. When phenytoin is Hydantoins inhibit sodium influx, stabilize cell administered by IV injection (to treat SE), cardiac membranes, reduce repetitive neuronal firing, and dysrhythmias and hypotension may result. limit seizures. Hirsutism Increasing the electrical stimulation threshold in rickets and osteomalacia (softening of the bones). cardiac tissue also acts as an antidysrhythmic. It has a slight effect on general sedation, and it is Drug Interactions non-addicting. Interactions Resulting from the Induction of the first drug to suppress seizures without Hepatic Drug- Metabolizing Enzymes- oral depressing the entire CNS. contraceptives, warfarin, and glucocorticoids Drugs That Increase Plasma Levels of Phenytoin- Therapeutic Actions and Indications diazepam, isoniazid, cimetidine and alcohol stabilize nerve membranes throughout the CNS Drugs That Decrease Plasma Levels of Phenytoin- directly by influencing ionic channels in the cell Carbamazepine, phenobarbital, and alcohol membrane, thereby decreasing excitability and CNS Depressants- The depressant effects of alcohol, hyperexcitability to stimulation. barbiturates, and other CNS depressants will add to Decreasing conduction through nerve pathways those of phenytoin. reduces the tonic-clonic, muscular, and emotional responses to stimulation. Assessment antiseizure drug that is also used to treat Monitor the patient’s response to the prescribed drug digoxin-induced dysrhythmias. and serum levels as indicated. Epilepsy Monitor drug levels as ordered; therapeutic levels treatment of tonic-clonic (grand mal) and psychomotor range from 10 to 20 mcg/mL. (temporal lobe) seizures and for the prevention and CBC and calcium level every 6 months. treatment of seizures occurring during or following Periodically monitor hepatic function. neurosurgery. Implementation Pharmacokinetics Careful cardiac monitoring is needed during and after Phenytoin is slowly absorbed from the small intestine. administering intravenous phenytoin It is a highly protein-bound (90% to 95%) drug, Check the patient’s vital signs, blood pressure, and therefore a decrease in serum protein or albumin can electrocardiography (ECG) during IV administration. increase the free phenytoin serum level. With a small Phenytoin binds with tube feedings, thus decreasing to average drug dose, the half-life of phenytoin is the absorption of the drug. Turn off tube feedings for 2 approximately 24 hours, but the range can be from 7 hours before and after giving phenytoin, according to to 42 hours. your facility’s policy. Phenytoin has a narrow therapeutic range of 10 to 20 If used as an infusion, don’t mix the drug with mcg/mL dextrose 5% in water (D5W) because phenytoin will  precipitate. Clear IV tubing first with normal saline 3. Tumor susceptibility and the growth cycle solution. Mix with normal saline solution if necessary The fraction of tumor cells that are in the replicative and infuse over 30 to 60 minutes with an in-line filter. cycle (“growth fraction”) influences susceptibility to Avoid giving phenytoin by IV push into veins on the most cancer chemotherapeutic agents. Rapidly back of the hand to avoid discoloration known as dividing cells are generally more sensitive to purple glove syndrome. Inject into larger veins or a chemotherapy, whereas slowly proliferating cells central venous catheter, if available. are less sensitive to chemotherapy. Discard any unused drug 4 hours after preparation for In general, nondividing cells usually survive the IV administration. toxic effects of many chemotherapeutic agents. Patient Teaching & Education B. Treatment regimens and scheduling Patients should be advised to take medications as Drug dosages are usually calculated on the basis of body directed and that doses should be evenly spaced surface area, in an effort to tailor the dosage to each patient. throughout the day. It may take several weeks to 1. Log kill phenomenon obtain the desired medication effect. Destruction of cancer cells by chemotherapeutic Abrupt withdrawal of medication may cause status agents follows first-order kinetics (that is, a given epilepticus. dose of a drug destroys a constant fraction of Patients should avoid alcohol and other CNS cells). The term “log kill” is used to describe this depressants while taking anticonvulsant drug therapy. phenomenon. diabetic patients should monitor their blood glucose 2. Pharmacologic sanctuaries levels carefully. Leukemic or other tumor cells find sanctuary in Contraindicated with the patient with heart block tissues such as the central nervous system (CNS), Monitor the patient for increased seizure activity; where transport constraints prevent certain mononucleosis may decrease the phenytoin level. chemotherapeutic agents from entering. Administer oral forms with food to reduce GI irritation. Therefore, a patient may require irradiation of the craniospinal axis or intrathecal CHEMOTHERAPEUTIC AGENTS administration of drugs to eliminate leukemic Principles of Cancer Chemotherapy cells at that site. Similarly, drugs may be unable to cause a lethal cytotoxic event or apoptosis in the penetrate certain areas of solid tumors. cancer cells that can arrest the progression of tumor 3. Treatment protocols growth. The attack is generally directed toward DNA Combination chemotherapy is more successful or against metabolic sites essential to cell than single-drug treatment in most cancers for replication. which chemotherapy is effective. Unfortunately, most traditional anticancer drugs do not a. Combination chemotherapy. Cytotoxic agents specifically recognize neoplastic cells but, rather, with different toxicities, and with different affect all kinds of proliferating cells, both normal molecular sites and mechanisms of action, are and abnormal. Therefore, almost all antitumor agents usually combined at full doses. This results in have a steep dose-response curve for both higher response rates, due to additive and/or therapeutic and toxic effects. potentiated cytotoxic effects, and nonoverlapping host toxicities. A. Treatment strategies b. Advantages of combinations 1. Goals of treatment 1) provides maximal cell killing within the range The ultimate goal of chemotherapy is a cure (that of tolerated toxicity, is, long-term, disease-free survival). A true cure 2) is effective against a broader range of cell requires the eradication of every neoplastic lines in the heterogeneous tumor population, cell. If a cure is not attainable, then the goal and becomes control of the disease (prevent the cancer 3) may delay or prevent the development of from enlarging and spreading) to extend survival resistant cell lines. and maintain quality of life. c. Treatment protocols chemotherapeutic drugs may be used to relieve Many cancer treatment protocols have been symptoms caused by the cancer and improve developed, and each applies to a particular the quality of life, even though the drugs may not neoplastic state. They are usually identified by extend survival. an acronym. For example, a common regimen 2. Indications for treatment called R-CHOP, used for the treatment of Chemotherapy is sometimes used when non-Hodgkin lymphoma, consists of rituximab, neoplasms are disseminated and are not amenable cyclophosphamide, hydroxydaunorubicin to surgery. (doxorubicin), Oncovin (vincristine), and Chemotherapy may also be used as a prednisone. supplemental treatment to attack micrometastases following surgery and Therapy is scheduled intermittently to allow recovery or radiation treatment, in which case it is rescue of the immune system, which is also affected by the called adjuvant chemotherapy. (any type of chemotherapeutic agents, thus reducing the risk of serious therapy that follows the primary treatment). infection. Chemotherapy given before the surgical procedure in an attempt to shrink the C. Resistance and toxicity with chemotherapy cancer is referred to as neoadjuvant Cancer drugs are toxins that present a lethal threat to the chemotherapy cells. It is, therefore, not surprising that cells have evolved chemotherapy given in lower doses to elaborate defense mechanisms to protect themselves from assist in prolonging remission is known chemical toxins, including chemotherapeutic agents. as maintenance chemotherapy. 1. Resistance Some neoplastic cells (for example, melanoma) are inherently resistant to most anticancer drugs. Other tumor types may acquire  resistance to the cytotoxic effects of a drug by ANTIMETABOLITES mutating, particularly after prolonged structurally related to normal compounds that exist administration of suboptimal doses. within the cell. They generally interfere with the The development of drug resistance is availability of normal purine or pyrimidine nucleotide minimized by short-term, intensive, intermittent precursors, either by inhibiting their synthesis or by therapy with combinations of drugs. competing with them in DNA or RNA synthesis. 2. Multidrug resistance A. Methotrexate, pemetrexed, and pralatrexate Stepwise selection of an amplified gene that The vitamin folic acid plays a central role in a variety codes for a transmembrane protein of metabolic reactions involving the transfer of (P-glycoprotein for “permeability” one-carbon units and is essential for cell replication. glycoprotein) is responsible for multidrug Folic acid is obtained mainly from dietary sources and resistance. from that produced by intestinal flora. Methotrexate This resistance is due to adenosine [meth-oh-TREK-sate] (MTX), pemetrexed triphosphate–dependent pumping of drugs out of [pem-e-TREX-ed], and pralatrexate [pral-a-TREX-ate] the cell in the presence of P-glycoprotein. are antifolate agents. Cross-resistance following the use of structurally unrelated agents also occurs. Mechanism of action It has been suggested that the presence of MTX is structurally related to folic acid and acts as an P-glycoprotein may account for the intrinsic antagonist of the vitamin by inhibiting mammalian dihydrofolate resistance to chemotherapy observed with reductase (DHFR), the enzyme that converts folic acid to its adenocarcinomas. active, coenzyme form, tetrahydrofolic acid (FH4 ). 3. Toxicity Pemetrexed is an antimetabolite similar in mechanism to Therapy aimed at killing rapidly dividing cancer methotrexate. However, in addition to inhibiting DHFR, it also cells also affects normal cells undergoing inhibits thymidylate synthase and other enzymes involved in rapid proliferation (for example, cells of the folate metabolism and DNA synthesis. buccal mucosa, bone marrow, gastrointestinal Pralatrexate is an antimetabolite that also inhibits DHFR. [GI] mucosa, and hair follicles), contributing to the toxic manifestations of chemotherapy. Therapeutic uses MTX, usually in combination with other drugs, is effective A. Common adverse effects against acute lymphocytic leukemia, Burkitt lymphoma in Myelosuppression, also known as bone marrow children, breast cancer, bladder cancer, and head and neck suppression or bone marrow depression, is another carcinomas. In addition, low-dose MTX is effective as a single unwanted adverse effect of certain antineoplastics. It agent against certain inflammatory diseases, such as severe commonly results from drug- or radiation-induced psoriasis and rheumatoid arthritis, as well as Crohn's disease. destruction of rapidly dividing cells in the bone All patients receiving MTX require close monitoring for possible marrow, primarily the cellular precursors of WBCs, toxic effects. RBCs, and platelets. Pemetrexed is primarily used in non–small cell lung cancer. Extravasation is the unintended leakage of a Pralatrexate is used in relapsed or refractory T-cell lymphoma. chemotherapy drug (with vesicant potential) into the Adverse effects surrounding tissues outside of the IV line. Adverse effects of MTX N/V/D, Stomatitis, rash, alopecia, Reduction in fertility is a major concern in myelosuppression, high dose renal damage post-pubertal patients. Cancer also complicates 1 in IT: neurologic toxicities 1000 pregnancies. Pemetrexed and pralatrexate should be given with folic acid Chemotherapy drugs are classified as pregnancy and vitamin B12 supplements to reduce hematologic and GI Category D (studies, adequate well-controlled, or toxicities. Pretreatment with corticosteroids to prevent observational, in pregnant women have demonstrated cutaneous reactions is recommended with pemetrexed. a risk to the fetus. However, the benefits of the therapy outweigh the potential risk) or Category X (is the only rating that denotes a drug is contraindicated PURINE ANTAGONIST for use during pregnancy) - cladribine, fludarabine, mercaptopurine, pentostatin, and Vomiting is often controlled by the administration of thioguanine. antiemetic drugs. -Mercaptopurine and thioguanine are administered orally, myelosuppression that predisposes to infection, is whereas the other three are available only in injectable form. common in many chemotherapeutic agents These drugs are used largely in the treatment of leukemia and other adverse reactions are confined to specific lymphoma. agents, such as: bladder toxicity with cyclophosphamide CLADRIBINE cardiotoxicity with doxorubicin Cladribine (Leustatin) is indicated specifically for the treatment pulmonary fibrosis with bleomycin. of a certain type of leukemia known as hairy cell leukemia, so named because of the appearance of its cancerous cells under 4. Treatment-induced tumors the microscope. Because most antineoplastic agents are mutagens, neoplasms (for example, acute FLUDARABINE nonlymphocytic leukemia) may arise 10 or more Fludarabine (Fludara), like cladribine, also has a very specific years after the original cancer is cured. single indication—in this case, chronic lymphocytic leukemia. [Note: Treatment-induced neoplasms are especially a problem after therapy with alkylating agents.] Most tumors that develop from cancer chemotherapeutic agents respond well to PYRIMIDINE ANTAGONIST The currently available pyrimidine antagonists are treatment strategies. capecitabine, cytarabine, floxuridine, fluorouracil, and gemcitabine. These drugs are used more commonly than the purine antagonists. They are available only in parenteral formulations except for capecitabine, which is currently Indications available only in tablet form. Mitotic inhibitors are used to treat a variety of solid tumors and some hematologic malignancies. CAPECITABINE used in combination with chemotherapy regimens to Capecitabine (Xeloda) is a pyrimidine antagonist indicated enhance the overall cytotoxic effect. primarily for the treatment of metastatic breast cancer and colon cancer. Adverse Effects: contraindicated in patients with known hypersensitivity to it or hair loss fluorouracil and in patients with severe renal impairment. nausea and vomiting myelosuppression CYTARABINE Toxicity and management of extravasation Cytarabine (ara-C) (Cytosar) is used primarily for the treatment Mitotic Inhibitor and Etoposide Extravasation: Listed of leukemias (acute myelocytic and lymphocytic leukemia and Specific Antidote meningeal leukemia) and non-Hodgkin lymphomas. It is available only in injectable form and may be given IV, subcutaneously, or intrathecally. Cytarabine has a unique set of adverse reactions, called “cytarabine syndrome”. Cytarabine syndrome is characterized by : fever muscle and bone pain Interactions maculopapular rash A variety of drug interactions are possible with most conjunctivitis, and antineoplastic drugs, some more significant than malaise. others. It usually occurs 6 to 12 hours following cytarabine The use of multiple antineoplastic drugs can cause administration. The syndrome may be treated or prevented by severe neutropenia and infection, due to additive the use of corticosteroids. bone marrow suppression. Monitor and treat patients accordingly for FLUOROURACIL hematologic toxicity and infections Fluorouracil (5-FU) (Efudex, Adrucil) is used in a variety of treatment regimens, including the palliative treatment of Selected Mitotic Inhibitors and Etoposide: Common Drug cancers of the colon, rectum, stomach, breast, and pancreas. It Interactions also is used in the adjuvant setting in the treatment of breast and colorectal cancer. GEMCITABINE Gemcitabine (Gemzar) is an antineoplastic drug structurally related to cytarabine. Gemcitabine is believed to have antitumor activity superior to that of cytarabine. It is used as first-line therapy for locally advanced or metastatic cancer of the pancreas and for the treatment of non–small cell lung cancer. Gemcitabine is increasingly used to treat other solid tumors, including breast cancer. WEEK 14 CHEMOTHERAPEUTIC AGENTS Mitotic Inhibitors include natural products obtained from the periwinkle plant and semisynthetic drugs obtained from the mandrake plant (also known as the “may apple”). Alkaloid Topoisomerase II Inhibitors Periwinkle plant- antineoplastic alkaloids Etoposide and teniposide are derivatives of vinca alkaloids include : epipodophyllotoxin. They exert their cytotoxic effects by vinblastine inhibiting the enzyme topoisomerase II, which causes breaks in vincristine DNA strands. vinorelbine Etoposide - Etoposide (VP-16) (generic) is a topoisomerase Mechanism of Action and Drug Effects II inhibitor. Its structure, mechanism of action, and adverse The vinca alkaloids (vincristine, vinblastine, and effect profile are similar to those of teniposide. It is believed to vinorelbine) bind to the protein tubulin during the kill cancer cells in the late S phase and the G2 phase of metaphase of mitosis (M 2195 phase). the cell cycle. This prevents the assembly of key structures It is indicated for the treatment of small-cell lung called microtubules. This, in turn, results in the cancer and testicular cancer. dissolution of other important structures known available in both oral and injectable forms as mitotic spindles. Without these mitotic spindles, cells cannot reproduce G0: Resting phase properly. This results in inhibition of cell division and Most normal human cells exist predominantly in this phase. cell death. Cancer cells in this phase are not susceptible to the toxic effects of cell cycle-specific drugs. G1: First gap phase or postmitotic phase platinum-containing regimens (e.g., cisplatin, Enzymes necessary for DNA synthesis are produced. carboplatin) and paclitaxel. Topotecan is also used to treat small-cell lung cancer. S: DNA synthesis phase Irinotecan is currently approved for the treatment of DNA synthesis takes place, from DNA strand separation to metastatic colorectal cancer, small-cell lung cancer, replication of each strand to create duplicate DNA molecules and cervical cancer. G2: Second gap phase or premitotic phase Adverse Effects RNA and specialized proteins are made. The main adverse effect of topotecan is bone marrow suppression. M: Mitosis phase include mild to moderate nausea, vomiting, and Divided into four subphases: prophase, metaphase, anaphase, diarrhea; headache; rash; muscle weakness; and and telophase; the cell divides (reproduces) into two daughter cough. cells. Irinotecan causes more severe adverse effects than topotecan. In addition to producing similar Indications: Selected Mitotic Inhibitors and Etoposide hematologic adverse effects, it has been associated with severe diarrhea known as cholinergic diarrhea. There is a moderate risk for nausea and vomiting with irinotecan, which requires appropriate supportive care such as IV rehydration and antiemetic drug therapy. Interactions Topotecan has a unique drug interaction involving the granulocyte colony-stimulating factor filgrastim. Filgrastim is commonly used to enhance WBC recovery after chemotherapy. Topotecan is given along with filgrastim, myelosuppression has been shown to be worsened. Paclitaxel It is recommended that filgrastim be administered Paclitaxel (Taxol) is a natural mitotic inhibitor that was 24 hours after completion of the topotecan originally isolated from the bark of the Pacific yew infusion. tree. Water insoluble (hydrophobic), and for this Laxatives and diuretics are not given with reason it is put into a solution containing oil rather irinotecan because of the potential to worsen the than water. The particular oil used is a type of castor dehydration resulting from the severe diarrhea that oil called Cremophor EL, the same oil with which this drug can produce. cyclosporine is formulated. Irinotecan when given with fluorouracil and available only in injectable form. leucovorin- Severe cardiovascular toxicity, including thrombosis, pulmonary embolism, stroke, and acute fatal myocardial infarction. Vincristine Vincristine is an alkaloid isolated from the periwinkle Irinotecan: Common Drug Interaction plant that is indicated for the treatment of acute lymphocytic leukemia and other cancers. It is available only in injectable form. most significant neurotoxin of the cytotoxic drug class, but it continues to be used in part because of its relative lack of bone marrow suppression. The World Health Organization and the Institute for Safe Medication Practices suggest that vincristine be diluted in 25 to 50 mL of fluid and never dispensed via a syringe, to prevent this lethal error from occurring. Topoisomerase I Inhibitors Topoisomerase I inhibitors are a relatively new class Irinotecan of chemotherapy drugs. The two drugs currently Irinotecan (Camptosar) is often given with both available in this class are topotecan and irinotecan. fluorouracil and leucovorin. Both are semisynthetic analogs of the compound It is available only in injectable form. camptothecin. Mechanism of Action and Drug Effects Topotecan The camptothecins inhibit proper DNA function in the After initial therapy with other antineoplastics, cancer S phase by binding to the DNA–topoisomerase I cells commonly become resistant to their effects. The complex. This complex normally allows DNA strands use of topotecan (Hycamtin) to treat ovarian cancer to be temporarily cleaved and then reattached in a and small cell lung cancer. critical step known as relegation. The binding of the available only in injectable form. camptothecin drugs to this complex retards this religation process, which results in a DNA strand Antineoplastic Enzymes break. Two antineoplastic enzymes are commercially available: asparaginase and pegaspargase. Indications to treat ovarian and colorectal cancer Indications: Topotecan is effective even in cases of metastatic treatment of acute lymphocytic leukemia. ovarian cancer that have failed to respond to Selected Antineoplastic Enzymes: Common Drug administration of oral corticosteroids (e.g., Interactions dexamethasone) beginning several days before day 1 of therapy to help decrease the risk for hypersensitivity With the topoisomerase I inhibitors irinotecan and topotecan, monitor blood counts closely with every treatment. The patient may receive an intradermal test dose of asparaginase before therapy begins or if a week or longer has passed between doses. With asparaginase and pegaspargase, if the solution comes in contact with the skin, thoroughly wash or rinse the area with copious amounts of water for a minimum of 15 minutes. Adverse Effects: Impaired pancreatic function. This can lead to hyperglycemia WEEK 15-16 and severe or fatal pancreatitis. dermatologic, hepatic, HORMONAL AGENTS AND TARGETED DRUGS genitourinary, neurologic, musculoskeletal, GI, and Used for breast cancer and prostate cancer, mimic or cardiovascular effects. suppress the actions of endogenous hormones Principal treatment modalities are surgery, radiation, Asparaginase cytotoxic drugs (chemotherapy), and hormonal drugs Asparaginase (Elspar) is used for the treatment of acute lymphocytic leukemia. Treatment for a woman with early-stage breast cancer catalyzes the conversion of the amino acid often consists of the following steps: asparagine to aspartic acid and ammonia. Surgery: Either the entire breast (total mastectomy) or just the tumor-containing portion (lumpectomy) is Pegaspargase removed to remove the malignant tissue. Pegaspargase (Oncaspar) has a mechanism of Radiation therapy: To eradicate any cancer cells that action, indications, and contraindications similar to may still be present in the area following surgery, those of asparaginase. radiation is applied. same enzyme that has been formulated to reduce its Chemotherapy: Drugs are administered to eradicate allergenic potential. This process involves the any remaining cancer cells, including those that may chemical conjugation of the enzyme with units of a have spread to other areas of the body. relatively inert compound known as Hormonal therapy: To reduce the risk of recurrence, monomethoxypolyethylene glycol. drugs are taken for a few years if the cancer is hormone-sensitive. Nursing Process This methodical technique lowers the chance of Hair loss typically begins anywhere from 2 to 4 weeks recurrence and helps guarantee that the cancer is after treatment has started and may fall out quickly in treated efficiently. clumps or may occur slowly. chemotherapy is used before surgery—so-called neoadjuvant Hair loss generally continues throughout treatment therapy—to shrink large tumors and thereby permit and for up to weeks afterward, and it may vary from lumpectomy in women who would otherwise require thinning to complete balding depending on the mastectomy. specific treatment regimen. Antineoplastic-induced bone marrow suppression Hormonal agents for breast cancer fall into two major groups: leads to anemias, leukopenia, neutropenia, and antiestrogens (e.g., tamoxifen [Soltamox]) - block thrombocytopenia. receptors for estrogen, Anemias result in fatigue and loss of energy and are aromatase inhibitors (e.g., anastrozole [Arimidex])- common adverse effects of therapy and the malignant block estrogen biosynthesis disease process. Anemias may require blood transfusions, peripheral TAMOXIFEN: the gold standard for endocrine blood stem cell treatment, or treatment with treatment of breast cancer prescribed medications such as iron preparations, folic acid, or erythropoietic growth factors (e.g., Mechanism of Action in Breast Cancer epoetin, darbepoetin alfa). a drug that undergoes hepatic conversion to active Risk for infection from leukopenia or neutropenia metabolites. These metabolites then block ERs (estrogen and/or immunosuppression is one of the more receptors)on breast cancer cells and thereby prevent receptor significant adverse effects that require close attention. activation by estradiol, the principal endogenous estrogen Thrombocytopenia is another adverse effect of antineoplastic therapy and increases the patient's Pharmacokinetics risk for bleeding. Tamoxifen is readily absorbed following oral Do not add fluorouracil to any other IV infusions; administration. administer the drug by itself in the appropriate diluent. Because clearance is slow, once-daily dosing is Gemcitabine, another antimetabolite, is dosed based adequate. on absolute granulocyte counts and platelet nadirs. Keep IV solutions at room temperature to avoid Use for Treatment of Breast Cancer crystallization, and use within 24 hours. Give infusions Two treatment applications: as ordered. Antiemetics and antidiarrheals may be (1) As adjuvant therapy to suppress the growth of residual needed. cancer cells following surgery and For the mitotic inhibitors, specifically the taxane family (2) treatment of metastatic disease. of drugs and docetaxel in particular, premedication protocols are usually specified and include the Adverse Effects Mechanism of Action hot flashes, Prostate cells, both normal and neoplastic, are fluid retention androgen-dependent. Leuprolide provides palliation vaginal discharge by suppressing androgen production in the testes. nausea, vomiting, During the initial phase of treatment, leuprolide menstrual irregularities. mimics GnRH. The drug acts on the pituitary to In women with bone metastases, tamoxifen may stimulate the release of interstitial cell-stimulating cause transient hypercalcemia and a flare in bone hormone (ICSH), which acts on the testes to increase pain testosterone production. poses a small risk of thromboembolic events, As a result, there may be a transient “flare” in including deep vein thrombosis, pulmonary embolism, prostate cancer symptoms. and stroke. With continuous exposure to leuprolide, GnRH endometrial cancer receptors in the pituitary become desensitized. As a result, the release of ICSH declines, causing Dosage and Administration testosterone production to decline too. The usual dosage for adjuvant treatment of breast cancer is 20 After several weeks of treatment, testosterone levels mg PO once a day. Larger doses do not increase benefits. In are equivalent to those seen after surgical castration. most cases, treatment should continue for 5 years. The Because leuprolide therapy mimics the effects of dosage for prevention of breast cancer in high-risk women orchiectomy, treatment is often referred to as is 20 mg PO daily for 5 to 10 years chemical castration. TOREMIFENE Adverse Effects Toremifene [Fareston] is an antiestrogen indicated for Leuprolide is generally well tolerated. Hot flashes are metastatic breast cancer in postmenopausal women with the most common adverse effect, but these usually ER-positive tumors or tumors for which ER status is unknown decline as treatment continues. Reduced testosterone may also lead to erectile Pharmacokinetics dysfunction, loss of libido, gynecomastia, reduced Toremifene is well absorbed following oral administration. muscle mass, new-onset diabetes, myocardial Plasma levels peak in 3 hours infarction, and stroke. may increase the risk of osteoporosis and related fractures. Bone loss can be minimized by consuming FULVESTRANT adequate calcium and vitamin D and by performing Fulvestrant [Faslodex] is an antiestrogen indicated for regular weight-bearing exercise. metastatic ER-positive breast cancer in postmenopausal women. Preparations, Dosage, and Administration Pure estrogen receptor antagonist. As with other Leuprolide is supplied in two basic formulations for antiestrogens, benefits derive from depriving breast cancer parenteral dosing: cells of required hormonal stimulation Leuprolide short-acting injection [Lupron ] is supplied as a 5-mg/ mL solution for subQ Pharmacokinetics administration. The recommended dosage is 1 mg Plasma levels peak about 7 days after IM injection and remain once a day. therapeutic for at least 1 month. Leuprolide depot injection is available in single-dose kits under two brand names: Adverse Effects and Drug Interactions ❖ Lupron Depot (for IM injection) Fulvestrant is generally well tolerated. The most ❖ Eligard (for subQ injection). common adverse effects are GI disturbances, hot With either product, the dosage is 7.5 mg once a flashes, headache, pharyngitis, and bone and back month, 22.5 mg every 3 months, 30 mg every 4 pain. Thromboembolism can occur but is uncommon. months, or 45 mg every 6 months. In contrast to tamoxifen, fulvestrant poses no risk of endometrial cancer. Fulvestrant has no known drug interactions TRIPTORELIN, GOSERELIN, HISTRELIN are GnRH analogs indicated for the palliative treatment of Preparations, Dosage, and Administration advanced prostate cancer. All three have the same mechanism Fulvestrant is supplied in solution (50 mg/mL) for and adverse effects of leuprolide, our prototype GnRH agonist. administration by slow IM injection (1 to 2 minutes). The dosage is 500 mg on days 1, 15, and 29, followed by 500 mg Preparations, dosage, and administration are as follows: once a month thereafter. Each dose is administered as two Triptorelin [Trelstar] is administered by IM injection. 5-mL injections, one into each buttock. The recommended dosage is 3.75 mg once a month, 11.25 mg once every 3 months, or 22.5 mg once DRUGS FOR PROSTATE CANCER every 6 months. For men with localized prostate cancer, the preferred Goserelin [Zoladex] is formulated as pellets (3.6 mg treatments are surgery and radiation, with or without adjunctive and 10.8 mg) for subQ implantation in the upper use of drugs. For men with metastatic prostate cancer, drug abdominal wall. The 3.6-mg pellets are implanted therapy, and castration (surgical-bilateral orchiectomy and every 4 weeks, and the 10.8-mg pellets are implanted medical) are the only options. every 12 weeks. Histrelin [Vantas] is formulated as a 50-mg pellet for Agents for androgen deprivation therapy (ADT) subQ implantation in the inner aspect of the upper arm once every 12 months. LEUPROLIDE Leuprolide is indicated for advanced carcinoma of the prostate. TARGETED ANTI-CANCER DRUGS Palliation is the primary benefit. For patients with prostate Targeted anticancer drugs are designed to bind with cancer, leuprolide represents an alternative to orchiectomy specific molecules (targets) to suppress tumor growth. (surgical castration). Leuprolide may be administered daily The hope is that these drugs will be more selective (subQ); monthly (IM); or every 3, 4, or 6 months (IM)  than hormones and cytotoxic anticancer drugs, sepsis and abscesses that require incision and and hence will be able to destroy cancer cells while drainage. leaving normal cells untouched Sunlight can exacerbate dermatologic reactions; How do targeted drugs work? Many of these drugs hence, patients should limit sun exposure, use are antibodies that bind with specific antigens on sunblock, and wear protective clothing. Very rarely, tumor cells; others are small molecules that inhibit cetuximab has been associated with interstitial lung intracellular enzymes. disease, characterized by inflammation, scarring, and Some antibodies mark cancer cells for immune hardening of the lungs. attack, some block cell-surface receptors, some One case of fatal interstitial pneumonitis with deliver toxic drugs or radioactivity, and some inhibit pulmonary edema has been reported. Whether angiogenesis(formation of new blood vessels) and cetuximab is truly the cause of these lung disorders thereby deprive tumor cells of their blood supply has not been established. The combination of cetuximab and irinotecan often EGFR (epidermal growth factor receptor) causes GI toxicity, manifesting as diarrhea, nausea, abdominal pain, vomiting, anorexia, and constipation. Tyrosine Kinase Inhibitors In clinical trials, hypomagnesemia developed in 55% Cetuximab [Erbitux] is a monoclonal antibody that of patients and was severe in 6% to 17%. Magnesium blocks EGFRs. The drug is approved for refractory supplements are often required. colorectal cancer and for carcinoma of the head and neck. Infusion reactions, acneiform rash, low Dosage and Administration. magnesium, and GI symptoms are common. Cetuximab [Erbitux] is given by slow IV infusion. Treatment consists of a loading dose (400 mg/m2 infused over Mechanism of Action 2 hours) followed by maintenance doses (250 mg/m2 infused Cetuximab acts as a competitive antagonist at over 1 hour), given either weekly (for head and neck cancer) or EGFRs. These receptors, which help regulate cell every other week (for colorectal cancer). growth, are overexpressed in certain cancers, including those of the colon and rectum. EGFR DRUGS FOR ADJUVANT THERAPY OF BREAST CANCER blockade inhibits cell growth and promotes apoptosis (cell death). Therapeutic Uses Colorectal Cancer. Cetuximab is approved for metastatic, EGFR-positive colorectal cancer. The drug may be added to an irinotecan-based regimen (if the cancer has progressed despite irinotecan treatment), or it may be used alone (in patients who cannot tolerate irinotecan). In clinical trials, cetuximab delayed tumor growth and promoted tumor regression. Treatment improves quality of life and can improve survival rate at 3 years. Head and Neck Cancer. Cetuximab, in combination with radiation, is approved for initial treatment of locally or regionally advanced squamous cell DRUGS FOR PROSTATE CANCER carcinoma of the head and neck. The drug can be used for recurrent or metastatic cancers that have progressed despite treatment with a platinum-based regimen. Adverse Effects The effects of greatest concern are severe infusion reactions, severe rash, and interstitial lung disease (ILD). Cetuximab causes severe infusion reactions in 2% to 5% of patients. Manifestations include rapid-onset airway obstruction, hypotension, shock, loss of consciousness, myocardial infarction, and DRUGS FOR EYE AND EARS DISORDER cardiopulmonary arrest. Severe reactions can happen with any infusion, but OPHTHALMIC most (90%) occur with the first infusion. If a severe EYE DISORDERS: reaction develops, cetuximab should be discontinued Glaucoma – under constant IOP (increased) –> increased immediately and never used again. pressure –> ocular damage (optic nerve damage) –> Agents for medical management—epinephrine, decreased peripheral vision –> blindness glucocorticoids, IV antihistamines, Types: bronchodilators, and oxygen—should always be on Chronic open-angle – most common; open drainage hand. blockage in the angle of the eye –> nerve damage –> gradual To reduce the risk of a severe reaction, IOP and painless vision loss premedication with an IV antihistamine (e.g., 50 Angle-closure – complete blockage on the drainage angle of mg diphenhydramine) is recommended. the eye –> pressure builds up rapidly –> severe eye pain, Acne-like rash, mainly on the face and upper torso, blurred vision, headache, rainbow haloes around lights, develops in 88% of patients and is severe in 12%. nausea, and vomiting –> blindness Severe rash has led to Staphylococcus aureus  Contraindications / Drug to Drug interactions / Food Interactions: These effects are dose-dependent and have been demonstrated with the laser flare cell meter and fluorophotometry. For this reason, miotics should be avoided in uveitic glaucoma, neovascular glaucoma, or any other condition where the blood-aqueous barrier is already compromised MYDRIATICS: Drug Name: epinephrine, phenylephrine (Altafrin), atropine (Isopto Atropine), cyclopentolate (Cyclogyl), homatropine (Homatropaire), scopolamine, tropicamide (Mydriacyl) Class: Adrenergic agonists, Antimuscarinics Action: Mydriatic effects: stimulation of the iris dilator muscle → pupillary dilation; stimulation of the iris dilator muscle → pupillary dilation Cycloplegic effects: paralysis of the ciliary muscle of the eye → loss of lens accommodation Indications for use: Eye exams; Ophthalmic procedures Routes of Administration: Topical: eye drops and ointment Side Effects: Photophobia Blurred vision Systemic absorption: confusion, drowsiness, dry mouth, flushing, tachycardia, hypertension, constipation Contraindications: Narrow-angle glaucoma Nursing Consideration: Ensure medications are labeled with name, strength, amount, and expiration date. Client education: Purpose of medication: provide comfort during the procedure; facilitate ophthalmologist examination of the eye MIOTICS: Drops may sting with application Drug Name: Carbachol, Pilocarpine Side effects: blurry vision; increased sensitivity to Action: Miotics (drugs that cause the pupil to contract) light improve the aqueous outflow as part of the treatment of Avoid light glaucoma and reduce the risk of a posteriorly luxated lens Wear sunglasses entering the anterior chamber. Avoiding scratching or rubbing the eye Indications for use: Antiglaucoma miotics are used to reduce Administration: intraocular pressure in the following conditions: To treat Verify the correct eye needs medication glaucoma, a progressive disease that damages the optic Position client: leaning back and looking at the ceiling nerve. Glaucoma is most often characterized by elevated Gently pull down on the skin below the eye intraocular pressure which can further damage the nerve. Administer the prescribed number of drops into the Pre -Assessment/Nursing interventions: center of the conjunctival sac Assess patients for cardiac problems (e.g. heart Avoid getting drops directly on the cornea or touching conduction system problems, heart blocks). the tip of the dropper to the eye Check the patient’s eye pressure before miotics Ask the client to close their eyes and gently apply administration. pressure over the eyelid above the lacrimal duct Post Administration /Nursing intervention: Monitoring: Because miotic agents can produce paradoxical Monitor for side