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71 Cards in this Set
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Muscle relaxants used to treat -sprains, strains, and pulled muscles - pain, spasm, abnormal contraction, impaired mobility. |
Muscle relaxants are prescribed for patients to relieve muscle spasm, and stiffness associated with these injuries, muscle tetany (MS), cerebral palsy, stroke and spinal cord injury. |
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Acute, painful musculoskeletal conditions (backache or neck strain) are treated with = combination of muscle relaxants, rest, physical therapy (hot or cold packs) and mild analgesics (NSAIDS) |
Muscle relaxants are given - on short-term basis - after acute pain subsides - exercises usually prescribed by physician to strengthen weak muscles |
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Most Muscle relaxant drugs affect .. - The CNS (spinal cord and brain) with no direct effect on skeletal muscle = reduces muscle spasm, causes alterations in perception of pain, and produces a sedative effect, promoting rest and relaxation of affected part |
Benzodiazepines, diazepam (Valium) and methocarbamol (Robaxin) = centrally acting drugs used to treat acute, painful musculoskeletal conditions |
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dantrolene - causes direct effect on skeletal muscles - used in management of spasticity resulting from upper motor neuron disorders (such as multiple sclerosis and cerebral palsy) * ineffective for amyotrophic lateral sclerosis (ALS) *not indicated for treatment of muscle spasms resulting from rheumatic disorders or musculoskeletal trauma |
Side Effects of Skeletal muscle relaxants - drowsiness, dizziness or dry mouth - weakness, tremor, ataxia and seizures - headache - confusion and nervousness - slurred speech - blurred vision - hypotension - GI symptoms: nausea, vomiting, diarrhea or constipation - urinary problems" enuresis, frequency or retention - hypersensitivity reactions, (liver toxicity wit dantrolene and tizanidine - respiratory depression |
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Precautions or contraindications for skeletal muscle relaxants - hypersensitivity to muscle relaxant - pregnancy or lactation - history of drug abuse - impaired kidney function - liver disorders - blood dyscrasias - chronic obstructive pulmonary disease (COPD) - Cardiac Disorders - older adults - abrupt discontinuation - closed-angle glaucoma |
Interactions with potentiation of effect occur between skeletal muscle relaxants and - alcohol - analgesics - psychotropic medications - antihistamines *medline plus good resource for patient education and written materials on back pain |
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patient education on skeletal muscle relaxants - potential side effects; care with driving - avoidance of other CNS depressants at same time (tranquilizers, antihistamines, or alcohol) can cause serious CNS depression, and care with analgesics (only as prescribed by a physician) - RICE (rest, ice, compression [elastic bandage], elevation_ represents appropriate care initially for musculoskeletal injuries to extremities - additional on prevention of injury (PRICE) - take meds only as long as absolutely necessary and observing caution regarding prolonged use (could lead to physical or psychological dependence with withdrawal symptoms (e.g. seizures from abrupt baclofen or diazepam withdrawal after prolonged use. |
Neuromuscular Blocking Agents - another type of muscle relaxants cause a direct effect on muscles including the diaphragm = neuromuscular blocking agents (NMBAs) = succinylcholine and rocuronium (Zemuron) - used during surgical, endoscopic or orthopedic procedures *potentially dangerous and can result in respiratory arrest because of potential to paralyze the major muscle of ventilation, the diaphragm |
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NMBAs (neuromuscular blocking agents) - administered only by anesthesiologists or specially trained personnel skilled in intubation, medically induced paralysis and cardiopulmonary resuscitation = paralyze muscles: require mandatory concurrent meds with analgesics and sedatives because patient can still feel the pain but cannot react to it. |
Anti-inflammatory drugs - treat disorders in which musculoskeletal system is not functioning properly due to inflammation Treat Conditions: arthritis, bursitis, spondylitis, gout and muscle strains and sprains can cause swelling, redness, heat, pain and limited muscle and joint mobility. |
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Analgesics and corticosteroids are used at times for acute stages of arthritis, bursitis, spondylitis, gout and muscle strains and sprains - corticosteroids are not used for extended periods of time because of serious side effects - NSAIDs frequently given for lengthy time periods in maintenance doses as low as possible for effectiveness |
Anti-Inflammatory Drugs: NSAIDS - ibuprofen, inhibit synthesis of prostaglandins (responsible for producing much of inflammation and pain of rheumatic conditions: sprains, and menstrual cramps) = no cure yet but meds used to alleviate pain and crippling effects |
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Anti-Inflammatory Drugs: NSAIDS - salicylates (e.g. aspirin) oldest drug in NSAIDS on market - many nonsalicylates are tolerated better than aspirin by some, esp as short-term analgesics = with large doses or long term: all share same side effects and interactions to a greater or lesser degree |
Prolonged therapy using any NSAIDS should be monitored carefully - older adults or debilitated patients do not tolerate ulceration or bleeding (can be silent) most reports of fatal GI events in these populations - if chronic Anti-inflammatory therapy must be continued, (despite GI ulceration), several options available = after ulcer heals: patients could resume NSAID with either misoprostol (Cytotec) or a proteon pump inhibitor with close clinical monitoring for ulcer recurrence. |
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Combined (ex: Arthrotec combines diclofenac (Voltaren) with misoprostol to protect the gastric muscosa |
Diclofenac available topically as 1% gel and 1.3% patch - topical NSAIDs seem unlikely to be associated with increased risk of GI bleeding or renal failure - serum concentrations of topical NSAIDs are much lower than those of oral NSAIDS = drug concentrations in meniscus, cartilage and tendon sheath are much higher due to direct absorption of drug thru skin into tissues of joints = same ORAL NSAIDs warning and precautions apply to topical formulations also |
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FDA issued warning regarding OTC nonselective NSAIDs - should be used in strict accordance with label directions - self-treatment with an OTC NSAID should not exceed 10 days unless directed by a physician |
Anti-Inflammatory Drugs: NSAIDS NSAIDs are used to reduce the inflammation and pain associated with arthritis. Traditional NSAIDs include medications such as ibuprofen, naproxen, ketoprofen, and indomethacin. They are associated with many side effects, including GI upset and possible ulceration and worsening of impaired kidney function. |
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NSAIDs: COX-2 inhibitor Celecoxib (Celebrex) exhibits anti-inflammatory, analgesic, and antipyretic activities by selectively inhibiting cyclooxygenase-2 (COX-2) prostaglandin synthesis - does not inhibit COX-1 (does not inhibit platelet aggregation = clotting) or inhibit production of mucosal-protective prostaglandins - * does not pose bleeding risks of other nonselective NSAIDs described previously = due to specific action inhibiting COX-2 prostaglandin synthesis, Celebrex (other partially selective NSAIDs) has potential to cause fewer gastric problems and poses less risk of GI bleeding unless used concurrently with aspirin |
Suppressing both types (good and bad prostaglandin) in the way nonselective NSAIDs do would theoretically help the heart - if NSAIDs are prescribed, current evidence suggests that naproxen may have the best cardiovascular safety profile |
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Selective COX-2 inhibitors shut down only the "Good" prostaglandin - raising risk of high blood pressure, atherosclerosis, and clotting = both traditional NSAIDs and COX-2 inhibitors can increase risk of adverse events (recurrent MI or death) in patients who have a history of or who are at high risk for cardiovascular disease = benefits and risks (pain relief and cardiovascular and GI safety must be weighed carefully) |
Side Effects of NSAIDS frequently include - GI ulceration and bleeding (may not precede by warning signs or symptoms) - epigastric pain, nausea, heartburn and gastroesophageal reflux disease (GERD) - Myocardial Infarction (MI), thromboembolism, stroke, hypertension, and heart failure - Fluid retention and peripheral edema - constipation - Tinnitus and hearing loss - headache or dizziness - visual disturbances - hematuria and albuminuria (albumin in the urine) - rash, hypersensitivity reactions and bronchospasm (esp with aspirin) - blood dyscrasias, esp prolonged bleeding time, anemia - liver toxicity |
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Precautions or Contraindications for NSAIDS apply to - asthma (may manifest aspirin sensitivity as bronchospasm) - cardiovascular disorders (hypertension, heart failure; may cause fluid retention and edema) - kidney disease - liver dysfunction - history of GI ulcer or inflammatory bowel disease - blood dyscrasias, esp clotting disorders or anemia - children with viral infections (danger of Reye's syndrome with salicylates) - GERD - older adults pregnancy and lactation - those with aspirin and NSAID hypersensitivity - those with sulfonamide hypersensitivity (should not take Celebrex) ** should be given with meals or milk to reduce GI side effects - enteric-coated, timed-released capsules or buffered aspirin are sometimes also recommended to reduce gastric irritation |
Interactions of NSAIDS (esp salicylate ) are many but most important clinically occur with - alcohol (potentiates possibility of GI bleeding) - anticoagulants (potentiate possibility of bleeding; also true of vitamin E) - Corticosteroids (increase chance of GI effects with prolonged administration of NSAID) - Aspirin (increases adverse GI effects and diminishes the risk-reducing effects of COX-2 inhibitors in GI tract); nonselective NSAIDs may decrease antiplatelet effects of aspirin (give the NSAID 30 min after or 8h prior to aspirin ingestion) - antihypertensives (attenuated response) - Lithium (decreased clearance) - Methotrexate (potentiates and increases risk of methotrexate toxicity) - Uricosurics (probenecid or sulfinpyrazone) whose action is antagonized by salicylates |
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Patient Education - administer meds with food to reduce gastric irritation - caution with dosage (follow physician's directions carefully regarding amount of drug to reduce chance of overdose) - discontinuing drug and reporting to physician any sign of abnormal bleeding (gums, stool, urine, bruising) epigastric pain or nausea, ringing in ears or hearing loss, visual disturbances, weight gain or edema and skin rash - avoid taking any other drugs either prescribed or OTC without checking first with a physician or pharmacist regarding possible interactions and duplication of meds) - avoid taking large amounts of aspirin or other NSAIDs with kidney, liver, or heart disease or with a history of GI ulcer (with these conditions, take under medical supervision), Patients with asthma may manifest sensitivity to aspirin and other NSAIDs - danger that GI ulceration and bleeding can occur without previous warning signs or symptoms - Discontinuing NSAIDs before elective surgery or dental procedures to reduce risk of serious bleeding - not taking Celebrex if allergic to sulfa* |
Nonselective Traditional NSAIDs Ibuprofen - Flector (1 patch BID) - Motrin - Motrin IB, Advil (OTC) - Caldolor diclofenac - Voltaren DR - Voltaren XR - Voltaren indomethacin - Indocin ketorolac - Toradol naproxen - Naprozyn, Anaprox, - ALeve OTC oxaprozin - Daypro |
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Partially Selective NSAIDS etodolac - Lodine meloxicam - Mobic nabumetone - Relafen Selective COX-2 Inhibitor celecoxib - Celebrex Combinations diclofenac/misoprostol - arthrotec 50, 75 |
Osteoporosis - porous bone: systemic skeletal disease characterized by low bone mass and deterioration of bone tissue , leading to bone fragility and increased susceptibility to fractures, especially of hip, spine and wrist = commonly affect older populations, primarily postmenopausal women - Osteoporosis is a metabolic bone disease. It occurs when the rate of bone resorption (break down) is greater than the rate of bone formation. It especially affects women who are 50 years of age or older and postmenopausal. Bones become brittle, porous and vulnerable to fracture due to decreased calcium and phosphate in bones. |
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Risk factors for osteoporosis include prolonged inadequate dietary intake of calcium, a sedentary life style, poor or declining adrenal function, and faulty protein metabolism due to estrogen deficiency. Common treatment consists of estrogen replacement therapy, calcium supplementation, the use of biphosphonates and the SERMs. Diagnosis of Osteoporosis - measure one's bone mineral density (BMD) = predictor of future fracture risk |
Treatment: |
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Anti-Inflammatory Drugs Arthritis is also called inflammatory joint disease. It is characterized by inflammatory damage or destruction in the synovial membrane or articular cartilage and by systemic signs of inflammation |
Anti-Inflammatory Drugs Osteoarthritis (primary vs. secondary) equals degenerative joint disease. Primary disease is idiopathic disease, and is not associated with any known risk factors. Secondary disease has known risk factors e.g. joint stress, congenital abnormalities, joint instability caused by trauma. Treatment is directed conservatively toward resting of the joint until inflammation resolves, range of motion to prevent joint capsule contraction, decrease weight bearing on joint, and analgesic and anti-inflammatory drug therapy to reduce swelling and pain. |
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NSAIDs are used to reduce the inflammation and pain associated with arthritis. Traditional NSAIDs include medications such as ibuprofen, naproxen, ketoprofen, and indomethacin. They are associated with many side effects, including GI upset and possible ulceration and worsening of impaired kidney function. Newer anti-inflammatory agents are the COX-2 inhibitors and are thought to have less GI and kidney effects. These agents include Celebrex, Vioxx, and Bextra. However, Bextra and Vioxx were recently withdrawn from the market due to concerns over an increased incidence of cardiovascular complications. There is current investigation to see if the other COX-2 inhibitors and NSAIDs pose a risk as well. |
Hormones - Estrogens - Selective Estrogen Receptor Modifiers - Calcitonin-Salmon - Paraythyroid Hormone |
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Osteoporosis Therapy: Hormones - helps maintain normal bone reabsorption rate in women (before menopause) Hormone replacement therapy (HRT), estrogen with or without progestin, is recommended for postmenopausal osteoporosis prevention only when unable to take other agents, and when benefits outweigh risks FDA recommends prescribing lowest possible dose for shortest period of time - if HRT started sooner after menopause, estrogen prevents accelerated phase of bone loss that occurs in the first five years after onset of menopause |
Osteoporosis Therapy: Selective estrogen-receptor modifiers (SERMs) - Raloxifene (Evista) is a selective estrogen receptor modifier with estrogen agonist activity on bone and lipids and estrogen antagonist activity on breast and uterine tissue - Increase bone mineral density, decrease bone reabsorption, and reduce fracture risk without promoting breast or endometrial cancer - incidence of vaginal bleeding and breast tenderness is lower with raloxifene than with HRT - in contrast to HRT, raloxifene can cause hot flashes and muscle cramps in legs - Raloxifene is contraindicated in pregnancy and women with history of thromboembolic disorders |
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Osteoporosis Therapy: Calcitonin-salmon - Synthetic form of the hormone calcitonin is available as a nasal spray (Miacalcin) or as a subcutaneous injection (treat postmenopausal osteoporosis in women more than 5 years past menopause) -Calcitonin Involves with calcium regulation, increases spinal bone density, and provides an analgesic effect in acute vertebral fractures - Reserved for women who refuse or cannot tolerate HRT or in whom HRT is contraindicated - local nasal effects (irritation, redness, rhinitis and epistaxis = nosebleed) are most common adverse effects from nasal spray - store unopened bottle of calcitonin in refrigerator, once pump has been activated, store at room temp in upright position. Discard all unrefrigerated bottles after 30 days. |
Osteoporosis Therapy: Parathyroid Hormone - Teriparatide (Forteo) is an injectable form of parathyroid hormone approved for postmenopausal women and men with osteoporosis at a high risk for having a fracture - Increases GI calcium absorption and renal tubular reabsorption of calcium, increasing bone mineral density, bone mass, and strength - Common adverse effects: nausea, hypotension, dizziness, arthralgia (joint pain), and leg cramps - safety and efficacy beyond two years has not been established and is not recommended |
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Bisphosphonates: nonhormonal agent Osteoporosis Therapy: Bisphosphonates - Nonhormonal agents - Act directly to inhibit bone reabsorption, increasing bone mineral density at the spine and hip, and decreasing incidence of first and future fracture - Bind strongly to and accumulate in bone, creating a reservoir of drug that is released back into systemic circulation gradually over a period of months or years after treatment is stopped - Alendronate (Fosamax), ibandronate (Boniva), and risedronate (Actonel) have been approved for both prevention and treatment of osteoporosis and considered First Line Therapy - bisphosphonates are also indicated for management of Piaget's disease of bone (chronic disorder characterized by fractures, skeletal abnormalities and significant bone pain) - bisphosphonates bind strongly to and accumulate in bone = create reservoir of drug that is released back into systemic circulation gradually over a period of months or years after treatment is stopped - Beneficial Effects on BMD persist for some time, suggesting that a "drug holiday" could mitigate some of risks associated with bisphosphonate therapy. |
Side Effects of bisphosphonates can include - GI distress (nausea, dyspepsia, and esophagitis) - abdominal and chest pain; bone and musculoskeletal pain
Precautions or Contraindications for bisphosphonates apply to - hypocalcemia - renal failure - drugs associated with gastric irritation (ASA, NSAIDs) - inability to sit upright for 30-50 min after taking the drug |
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Patient Education with Bisphosphonates - taking meds with full glass or water (6-8oz) at least 30 min before first food and beverage or medication of the day - not lying down or eating or drinking anything else for at least 30-60 min to prevent reflux and avoid esophageal irritation - contacting health care provider if there is pain while swallowing, difficulty swallowing, worsening heartburn or thigh or groin pain - taking supplemental vitamin D and Calcium if dietary intake is inadequate - performing weight bearing exercises - modification of cigarette smoking and alcohol and caffeine consumption if these factors exist |
All Bisphosphonates : alendronate, ibandronate and risedronate are by mouth PO except ibandronate can be used by IV 3 mg bolus q3 Hormones: raloxifene: PO 60 mg (can be given without regard to meals) |
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Skeletal Muscle Relaxants - baclofen (Lioresal): PO, intrathecal (location of CSF) = for spasticity associated with spinal cord injury or spinal cord diseases - carisoprodol (Soma): PO = caution with asthma; watch for abuse potential (C-IV controlled substances) - cyclobenzaprine (Flexeril): PO = strongly anticholinergic side effects (structurally related to amitriptyline - dantrolene (Dantrium): PO (titrate to lowest effective dose) = for multiple sclerosis and cerebral palsy, not for trauma or rheumatic fever) - methocarbamol (Robaxin): PO (oral), also IM and IV=for acute painful musculoskeletal conditions - tizanidine (Zanaflex): PO, for increased muscle tone associated with spasticity for ex multiple sclerosis or spinal cord trauma |
Dantrolene: muscle relaxant for multiple sclerosis Arthrotec: partially selective NSAID Mobic: trade name for melcoxicam (partially selective NSAIDs) Actonel: trade name for risedronate (Bisphosphonates) = osteoporosis therapy Voltaren: tradename for diclofenac (Nonselective traditional NSAIDs) Flexeril: tradename for cyclobenzaprine = skeletal muscle relaxant Nabumetone: (Relafen): partially selective NSAIDs Evista: trade name for raloxifene = hormones (Osteoporosis Therapy) Celebrex: (tradename for celecoxib): selective COX-2 inhibitor |
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patients with which respiratory condition may manifest a sensitivity to aspirin and other NSAIDs? = Asthma |
A patient taking an NSAID who develops ringing in the ears should be instructed to take which action? = Discontinue the drug |
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The mechanism of action of bisphosphonates is to: = Inhibit bone resorption (reabsorption) |
Which of the following is a selective estrogen receptor modifier? = Raloxifene |
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What is a key point to review with a patient taking a bisphosphonate? = Sit upright for 30-60 min after taking the drug. |
Combining salicylates and alcohol increases the risk for: = The possibility of GI bleed. |
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Unless otherwise directed by a physician, what is the maximum number of days that an OTC NSAID should be taken? = 10 Days |
The muscle relaxant dantrolene is used to treat: = Spasticity associated with cerebral palsy. |
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Suppose NSAIDs are suggested as a treatment for a lengthy time period. How will they most likely be prescribed? = A dose as low as possible for effectiveness. |
Which drug category may potentiate the possibility of bleeding when taking NSAIDs? = Anticoagulants |
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Chapter 22 |
Seizure are brief, abnormal neuronal discharges in brain that occur repeatedly and without warning |
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Anticonvulsants Reduces the number and/or severity of seizures in patients with epilepsy = Epilepsy: recurrence of unprovoked seizures, characterized by sudden attacks of altered consciousness, motor activity, or sensory impairment Treatment is based on type, severity, and cause of seizures = Treatment failure can result from inappropriate anticonvulsant selection = less than half of epileptic seizures have identifiable cause, seizures may sometimes be associated with cerebrovascular disease, cerebral trauma, intracranial infection or fever, brain tumor, intoxication or chemical imbalance |
Epilepsy is the 4th most common neurological disorder in the US after migraine, stroke and Alzheimer's disease The International Classification of Epilepsies and Epileptic Syndromes currently classifies seizure disorders into 3 main categories 1. Generalized seizures - bilaterally symmetrical and without local onset; further classified as convulsive (tonic, clonic, and tonic-clonic) or nonconvulsive (absence, myoclonic and atonic) 2. Partial seizures - (aka temporal lobe or psychomotor seizures) - onset limited to one cerebral hemisphere and involve no loss of consciousness (simple) or loss of consciousness (complex symptomatology) 3. Atypical or unclassified - insufficient data to classify |
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Treatment failure can be result of inappropriate selection of an anticonvulsant for specific type of seizure Ex: carbamazepine used to treat many types of seizures; however, well known to aggravate myoclonic and absence seizures. - Drug therapy is individualized and selection of most appropriate drug based on seizure type and other patient factors - once treatment started, approx 50% of patients achieve adequate seizure control with monotherapy (one drug) |
Generalized Seizures (grand mal) and absence (petit mal) - Tonic-clonic (grand mal): abrupt loss of consciousness; falling, with tonic extension of trunk and extremities (tonic), followed by alternating contractions and relaxation of the muscles (clonic) lasts 2-5 min. Urinary and fecal incontinence may occur, During recovery: patient are confused and sleepy and may complain of headache - absence epilepsy (petit mal): absence of convulsions; sudden onset; brief loss (10-20 sec) of consciousness with no falling, usually occurs initially in children (not associated with postrecovery drowsiness). - Febrile seizures: most common childhood (3% of children ages 6 months to 6 years) seizure disorder; single, "simple" brief, and generalized, (less than 15 min in duration) |
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Generalized Seizures - initial treatment consists only of preventing injury by removing any objects that could cause trauma, cushioning head and turning it to side and loosening tight clothing, especially collars and bets. Do not try to open mouth or force anything between teeth. - if seizures prolonged or so frequent that patient does not regain consciousness between seizures = Status Epilepticus and considered to be a true neurologic emergency. = fatality 30-40% after diagnosis = treatment of choice is IV lorazepam (Ativan) administered slowly. = simultaneous loading with IV phenytoin or fosphenytoin is also recommended |
Partial seizures (psychomotor epilepsy or temporal lobe seizures) account for up to 60% of new cases of epilepsy - accounts for up to 60% of new cases of epilepsy - Caused by a lesion in the temporal lobe of the brain and limited to one cerebral hemisphere - Last from 10 seconds to five minutes Complex symptoms: confusion, impaired understanding and judgment, staggering, purposeless movements, bizarre behavior and unintelligible sounds, but no convulsions. - partial seizure may be preceded by a subjective but recognizable sensation (an aura) that a seizure is going to occur Unilateral seizures Affect only one side of the body - some may have mixed seizures patterns combining more than one type. Atypical or unclassified |
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Drug Therapy For Generalized And Partial Seizures First generation anticonvulsants - Prophylactic treatment of generalized and partial seizures should start with a single drug such as valproate, lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, or phenytoin - dosage should be titrated to achieve seizure control or until maximally tolerated dose reached = Aim of therapy is to prevent seizures without oversedation, dosage adjusted according to individual patient response and serum drug levels when available |
Side Effects of phenytoin - sedation, ataxia, dizziness and headache - blurred vision, nystagmus, and diplopia - gingivitis (inflamed gums) - GI distress (nausea, vomiting, anorexia, constipation, or diarrhea) - rash and dermatitis, stevens-johnson syndrome (severe inflammatory disease affecting children and young adults, and lupus-like symptoms - megaloblastic anemia (treated with folic acid) - Osteomalacia (bone softening, treated with Vitamin D) - Syncope, arrhythmias and hypotension with IV use |
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Precautions or Contraindications with phenytoin - kidney or liver disease - diabetes - heart failure, bradycardia, heart block and hypotension - pregnancy and lactation - hematological disease - abrupt discontinuation Drug interactions and food or nutrient interactions with phenytoin - Cimetidine, isoniazid, salicylates, SSRIs, sulfonamides, topiramate, and trimethoprim may increase the levels of phenytoin. - Phenytoin may decrease effectiveness of "azole" antifungals, carbamazepine, estrogens, oral contraceptives, protease inhibitors, certain antidepressants and antipsychotics, valproic acid and "satins" |
Carbamazepine (Tegretol) First generation anticonvulsants - sometimes used for partial, generalized or mixed seizures - has advantage of minimal sedation and cognitive adverse effects |
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Side Effects of cabamazepine First generation anticonvulsants - ataxia, syncope (fainting) and visual difficulties - risk for hyponatremia (decreased level of sodium in blood) - cardiac, hematological, kidney, liver, and pancreas complications - rash for ex: Stevens-Johnson syndrome - likely occur in Asian patients who test positive for inherited variant of an immune system gene; FDA recommends genetic testing of patients of Asian descent prior start therapy. |
Multiple interactions of carbamazepine - phenytoin, phenobarbital, and rifampin (decrease levels of carbamazepine) - calcium channel blockers, cimetidine, macrolides (erythromycin), azole antifungals, certain antipsychotics, protease inhibitors, valproic acid, and isoniazid (increase levels of carbamazepine) - Warfarin (increased metabolism, decreased effect |
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Grapefruit juice potentiates action and can increase risk of serious adverse effects (do not take grapefruit juice with carbamazepine) Oxcarbazepine (Trileptal) a second-generation oral anticonvulsant indicated for treatment of partial seizures is analogue of carbamazpime - as effective as first-generation agents and may be less lkely than carbamazepime to cause CNS side effects and hematological abnormalities - Oxcarbazepine does not generally require drug level monitoring and appears to have less significant drug interactions - Vaproic Acid (Depakene, Depakote) broad spectrum anticonvulsant, useful for management of many seizure types (generalized tonic-clonic, absence, and myoclonic seizures) Dosage adjustments may be needed in hepatic diseases |
Side Effects of Valproic acid - weight gain, and dyspepsia - alopecia, rash and tremor - hepatotoxicity, life-threatening pancreatitis (block box warning) and blood dyscrasias Multiple interactions of valproic acid occurs with - Carbamazepine, phenytoin, phenobarbital protease inhibitors, and rifampin (decrease valproic acid levels) - Chlorpromazine, felbamate, guanfacine, salicylates, and topiramate (increase valproic acid levels or effects) |
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Drug Therapy for Febrile Seizures Routine treatment of febrile seizures - Involves searching for the cause of the fever and taking measures to control it - Most children with febrile seizures do not require anticonvulsant drugs = Those that do may be treated with rectal diazepam gel if the seizure lasts longer than five minutes = American Academy of Pediatrics Subcommittee on Febrile Seizures does not recommend continuous or intermittent antiepileptic prophylactic drug (AED) therapy for children with one or more simple febrile seizure |
Drug Therapy For Absence Seizures Drug of choice for management of absence epilepsy is ethosuximide (Zarontin) - Effective only for this type of epilepsy - Lacks idiosyncratic hepatotoxicity of valproic acid Other drugs in use include clonazepam (Klonopin), valproic acid (Depakene), and lamotrigine (Lamictal) = sometimes used as treatment of absence seizures |
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Side Effects of drugs used for absence epilepsy can include - hepatic or renal disease - pregnancy - pancreatitis (with valproate) - abrupt discontinuation Interactions occur between ethosuximide and - carbamazepine, phenytoin, primidone, phenobarbital, valproic acid, rifampin, isoniazid, and antiretroviral protease inhibitors - alternative formulations of tradiational anticonvulsants Ex: carbazmazepine (Tegretol XR - extended release), diazepam (Diastat-rectal) fosphenytoin (Cerebyx- IM/IV), and valproate (Depacon-IV; Depakote ER - extended release = primary advantage of these formulations: improved adherence (fewer doses and or better tolerability) or availability of injectable formulation e.g. Depacon) |
Second Generation Anticonvulsants - Gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine, topiramate (Topamax), etc. = For adjuvant treatment of partial (psychomotor) and generalized seizures (not superior in efficacy to first-generation anticonvulsants with seizure control_ - however, these second gen do not require drug level monitoring, have fewer adverse effects (effects of cognition) have fewer interactions than first generation anticonvulsants and may improve adherence with once or twice daily dosing Compared to first-generation anticonvulsants - Not yet considered superior in efficacy for seizure control - Fewer adverse effects and drug interactions; does not require drug level monitoring; daily dosing *all agents require a slow titration period to avoid CNS adverse effects and minimize potential of a severe life-threatening rash with lamotrigine. - second gen should be used with caution in pregnant and lactating women and not be abruptly discontinued ** |
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Anticonvulsants table page 431 First and Second Gen First = carbamazepine, clonazepam, fosphenytoin, phenytoin, ethosuximide, valproic acid Second = gabapentin, lamotrigine, leveltiracetam, oxcarbazepine, topiramate |
Patient Education taking anticonvulsants - reading provided med guide before start taking anticonvulsant and each time they get refill - caution with driving or operating machinery until regulated with med because of drowsiness or dizziness - report any side effects (rash, or eye problems, staggering, slurred speech and any other) - careful oral hygiene until tenderness of gums subsides as treatment progresses - always taking meds on time and never omitting dosage (abrupt withdraw of med can lead to status epilepticus) - wearing Medic-Alert tag or bracelet all time in case of accident or injury - taking med with food or milk to lessen stomach upset - check with health care provider before initiating new treatments (OTC and herbs) - Anticonvulsants associated with numerous and potentially harmful drug -drug interactions - not significantly altering the ingestion of grapefruit juice while on carbamazepine (Tegretol) because of potentiation effect - parents and teachers should be cautioned to observe and report changes in cognitive function, mood and behavior in children receiving anticonvulsants - some anticonvulsants increased risk of birth defects if used during pregnancy = women of childbearing age taking anticonvulsants should be educated on using proper contraception |
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Antiparkinsonian Drugs - are usually given for Parkinson’s disease (PD) - Chronic neurological disorder characterized by fine, slowly spreading muscle tremors, rigidity, and generalized slowness of movement - most common neurodegenerative diseases in adults - as disease advances, patients develop a tendency to fall, dementia, confusion, psychosis, sleep disturbances, and declining cognitive function - most PD patients progress to severe disability over 10-20 years - Underlying pathology is not completely understood (no cure for PD and goal of treatment is relieve symptoms and maintain mobility) - Normal dopamine activity as it relates to acetylcholine is diminished, with resulting relative overactivity of cholinergic output (serve as foundation of treatments for PD) |
Before start treatment: rule out drug-induced parkinsonism (DIP) as a causative factor of PD - DIP is most common form of secondary parkinsonism and frequently unrecognized or misdiagnosed. - Causes: dopamine receptor antagonists and other drugs interefere with dopamine synthesis or release - switching from, reducing or discontinuing the offending agents (antipsychotics, calcium channel blockers, anticonvulsants, lithium, metoclopramide and antidepressants) may be the most effective treatment option available |
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Dopamine replacement - Carbidopa-Levodopa crosses the blood-brain barrier, where it is converted to dopamine = Enhances effects of levodopa, increasing therapeutic effect of dopamine in CNS and reducing adverse reactions (nausea, vomiting, and low blood pressure upon standing) - Sinemet (combo of levodopa and carbidopa) most often used for long-term treatment and recommended as initial drug treatment for patients with bradykinesia uncontrolled by other PD meds. - As PD progresses, most patients will eventually require treatment with Levodopa |
Side Effects of Sinemet (numerous and frequent) - Dyskinesias (involuntary movements of many parts of body) - nausea, vomiting, and anorexia (if given food to prevent nausea, protein load should be low to avoid competition for transport across GI Tract) - Behavioral changes, anxiety, agitation, confusion, sleep disturbances, depression, hallucinations and psychosis - hypotension, dizziness and syncope |
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Precautions or Contraindications for Sinemet - abrupt discontinuation (could lead to neuroleptic malignant syndrome) - characterized by delirium, rigid muscles, fever and autonomic nervous system instability - bronchial asthma or emphysema - cardiac disease or hypotension - active peptic ulcer - Diabetes and renal or hepatic disease - glaucoma - psychoses - pregnant, postpartum or nursing women |
Interactions of Sinemet may occur with - Antihypertensives (may potentiate hypotensive effect) - Antipsychotics (antagonistic by blocking dopaminne receptor) - phenytoin (antagonizes levodopa) - iron salts (reduced bioavailability) - non-specific (type A) MAOIs - may cause hypertensive crisis *patients receiving Sinemet for prolonged periods of time (2-5 years) may develop a tolerance = ineffectiveness of drug (wearing off) - sometimes changing timing of doses, add extra dose at end of day or add another agent from one of drug classes may bring symptoms back under control |
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Dopamine agonists pramipexole (Mirapex - non ergot derivatives), and ropinirole (Requip) are commonly used in conjunction with levodopa - to Delay onset of levodopa-caused motor complications or given alone in early PD or in younger patients as a "levodopa-sparing" strategy - dopamine agonist may reduce the required dose of levodopa for patients with advanced parkinson's - the older dopamine agonist (ergot derivatives such as bromocriptine (Parlodel) used much less frequently now in PD due to serious adverse effects - recommend dopamine agonists as initial monotherapy in less than 60 years old (have greater specificity for dopamine receptors and may have a neuroprotective effect which leads to less dyskinesia, may delay wearing off effect, can postpone the need for Sinemet by several years |
Side Effects of Dopamine Agonists similar to Sinemet - psychosis, hallucinations, obsessive behavior, impulsivity, confusion and somnambulism or sleepwalking (higher risk compared to Sinemet) - excessive sedation leading to "sleep attacks" during daily activities including driving - hypotension, syncope, and peripheral edema - nausea and vomiting - pulmonary, renal, and cardiac valve fibrosis with bromocriptine - neuroleptic malignant syndrome with abrupt discontinuation |
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Interactions of dopamine agonists - antidopamine agents (antipsychotics, pehnothiazines, metoclopramide) may decrease efficacy of each agent - CNS depressants (anxiolytics and hypnotic and sedative agents may increase risk of somnolence) |
Rotigotine (Neupro patch) is a dopamine agonist applied topically with once daily dosing - continuous transdermal delivery of drug may be advantageous for patients who have poor controlled PD symptoms in early morning., slowed GI motility (levodopa treatment), dysphagia or have difficulty swallowing - Side effects similar to other dopamine agonists, in addition to application site reactions (rotate patch location) |
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Antiparkinsonian Drugs
MAO-B inhibitors: Monoamine Oxidase-B is responsible for breaking down dopamine and tyramine in the brain - In PD, increase levels of dopamine (MAO-B inhibitors) = MAO-B Inhibitors Selegiline (Eldepryl) and rasagiline (Azilect) are selective MAO type-B inhibitors = Sometimes prescribed as adjunctive monotherapy for early PD or after levodopa has been used for several years and begins to "wear off" or become less effective - when Sinemet and selegiline or rasagiline are used concurrently, the Sinemet dosage is reduced by 10-30% to lessen chance of additive side effects |
Side Effects of MAO B Inhibitors - nausea, dizziness, confusion, abdominal pain, hallucinations, dry mouth, vivid dreams, dyskinesias and headache. - Selegiline is metabolized to amphetamine metabolites (contribute to its side effects: anxiety and sleeplessness)* therefore drug should be given no later than early afternoon |
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Contraindicated with following drugs can interact with selegiline result in rare but severe CNS toxicity, hyperpyrexia, hypertensive crisis and even death. DO NOT USE SELEGILINE WITH - Meperidine (Demerol) methadone and tramadol - Tricyclic antidepressants - SSRIs and SNRIs - Sympathomimetics (epinephrine ephedrine, pseudoephedrine) - Dextromethorphan and St. John's Wort - Abrupt discontinuation is contradindicated *when given at recommended dosesages, minimal danger of hypertensive crisis associated with interactions of other MAOs and certain food "cheese reactions" if exceeded dose - oral disintegrating tablet (ODT) formulation of selegilene (Zelapar) can be adjunct to levodopa - Selegilene ODT absorbed thru buccal membrane (avoid first pass hepatic metabolism) = results in a faster onset of action, use of a lower dose, and fewer amphetamine metabolites |
Rasagiline (Azilect) is currently the only MAO-B inhibitor approved as initial monotherapy for PD - Also approved as an addition to levodopa later in the disease - given once daily, no amphetamine metabolites and generally well tolerated - Side effects: headache, nausea, joint pain, hypotension, hallucinations, dyskinesias, depression, and dyspepsia (contraindications are similar to selegiline) |
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Drugs with anticholinergic and antihistaminic actions were first to be used for tremors associated with PD and still useful in early stages of disease in younger patients and for DIP
- these agents restore cholinergic-dopaminergic balance in PD |
Anticholinergics - restore the cholinergic-dopaminergic balance in PD - Include synthetic atropine-like drugs, such as benztropine (Cogentin) and trihexyphenidyl (Artane) = used to treat other forms of parkinsonian syndromes |
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Side Effects of Anticholinergic agents - dry mouth - dizziness and drowsiness - blurred vision - constipation or urinary retention - confusion - depression - nausea - tachycardia |
Precautions or Contraindications for anticholinergics - abrupt discontinuation (leads to rebound symptoms) - closed-angle glaucoma - use with caution in older patients because of the risk of cognitive impairment. Those with benign prostatic hypertrophy (BPH) are also at risk for urinary retention |
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Amantadine - unrelated to other antiparkinsonian agents - alters dopamine release and has anticholinergic properties - used to treat parkinsonism (extrapyramidal reactions) associated with the prolonged use of phenothiazines, carbon monoxide poisoning or cerebral anteriosclerosis in older adults - For PD, amantadine is generally used early in the disease as monotherapy, its efficacy may wane rather quickly, and of little benefit when added to levodopa |
Side Effects of Amantadine (usually dose related and reversible) - CNS disturbances, including depression, confusion, hallucinations, anxiety, depression, irritability, nervousness and dizziness - heart failure, edema and hypotension - GI distress, constipation and urinary retention |
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Precautions or Contraindications for amantadine - Abrupt discontinuation - liver and kidney diseases( requires renal close adjustment - cardiac disorders - psychosis, neurosis and mental depression - epilepsy - patients taking CNS drugs |
COMT inhibitors (Catechol-O-methyl-transferase) - block the enzyme responsible for metabolizing peripheral levodopa - COMT inhibitors increase concentration of levodopa and dopamine (allows patient's dose of levodopa to be lowered and results in a decrease in incidence or severity of dose-related side effects of levodopa (dyskinesias, nausea) - Increase concentration of levodopa and dopamine - drugs: entacapone (Comtan) and tolcapone (Tasmar) - Entacapone (available in combo with carbidopa/levodopa (Stalevo) provides convenience of fewer pills, but dosing is less flexible for patients who need varying amounts of levodopa throughout day. - Tolcapone - severe nature adverse effects and extensive monitoring = reserved for those who do not respond to other therapies |
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Side Effects of Entacapone and Tolcapone (Comt Inhibitor) - Orthostatis hypotension - hallucinations - Dyskinesia (levodopa dose may need to be decreased) - nausea and vomiting - diarrhea (can be severe) and abdominal pain - orange coloration of urine - hepatic injury with tolcapone (black box warning) treating physician is to obtain a parent-signed consent form acknowledging this risk; monitor hepatic enzymes throughout the treatment |
Drug Interactions with COMT inhibitor entacapone or tolcapone - should not receive nonselective MAOIs (phenelzine or tranylcypromine) - but can take a selective MAOI such as selegiline - concomitant use of CNS depressants should be avoided to prevent additive sedation |
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Patient Education for antiparkinsonian drugs - admin on regular schedule as prescribed with food to lessen GI distress; give cabidopa/levodopa with a low-protein meal if food is necessary to offset nausea - avoid abrupt withdrawal of med, which may greatly increase parkinsonian symptoms and risk of neuroleptic malignant syndrome - several weeks sometimes required before benefit is apparent - caution with CNS drugs, alcohol, or antihypertensives (not taking other medicines, including vitamins, without physician approval) - caution with driving or operation of machinery - drugs may cause drowsiness, dizziness or lightheadedness with pramipexole (may have no warning sign) - Reporting adverse side effects to physician - with dopamine agonists: may be intense urges to gamble or spend money, increased sexual urges, bouts of binge eating and other intense urges - report any signs that drug is no longer effective after prolonged use, avoid dosage change without medical supervision - maintaining physical activity, self care and social interaction, essential part of therapy for Parkinson's disease - rising slowly |
Page 438 Antiparkinsonian Drugs Dopamine Replacement - cabidopa and levodopa Dopamine Agonists - bromocriptine - pramipexole - ropinirole - rotigotine |
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Table 22-2 Antiparkinsonian Drugs page 439 Anticholinergics: benztropine, trihexyphenidyl COMT inhibitor : entacapone, with carbidopa/levodopa MAO B inhibitors: rasagiline, selegiline Other: amantadine (Symmetrel) |
Agents for Restless Legs Syndrome - Restless Legs Syndrome (RLS) is a sensorimotor neurologic disorder characterized by a distressing urge to move legs, often accompanied by a marked sense of discomfort in legs (aching, burning, pulling, itching or tingling) = Triggered by rest or inactivity and is temporarily relieved by movement = usually disruptive to sleep which is primary reason patients seek treatment = Follows a circadian pattern, with symptoms being most intense in the evening and nighttime = May be primary or secondary (etiology) |
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RLS Etiology: Primary RLS involves the CNS and the dopaminergic pathway - dopamine agonists pramipexole (Mirapex), ropinirole (Requip) and rotigotine (Neupro patch) used to treat PD even though RLS is not related to PD) are FDA approved for RLS treatment as well. - dosages of oral agents used to treat RLS typically only 10-20% of those used to treat PD (50% for transdermal patch) and are usually given 1-3 h before bedtime as a single daily dose - apply the rotigotine patch at approximately the same time every day. The most worrisome side effects with dopamine agonists in PD such as dyskinesias, have not been observed in patients treated for RLS |
Agents for RLS restless leg syndrome Gabapentin (Neurontin), benzodiazepines (clonazepam) and opiods (hydrocodone, oxycodone, tramadol) are second-line agents for RLS involving specific symptoms like continuous sleep disturbances or painful sensations in the extremities |
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RLS may be secondary to other causes: iron deficiency (with or without anemia) renal failure, diabetes, rheumatoid arthritis, fibromyalgia, vitamin deficiency (folate B12) hypothyroidism, and pregnancy - Treatment of secondary RLS: identify and treat underlying cause Medications: potential to aggravate RLS symptoms: metoclopramide, all neuroleptics, and many antidepressants, and antihistamines, (should be discontinued fi possible) |
Agents for Restless Legs Syndrome (cont’d.) - Primary RLS involves the CNS and dopaminergic pathway = Dopamine agonists pramipexole (Mirapex), and ropinirole (Requip), and rotigotine (Neupro patch) are FDA-approved treatments - Second-line agents = Gabapentin (Neurontin), benzodiazepines (such as clonazepam), and opioids (hydroco-done, oxycodone, tramadol) |
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Agents for Alzheimer's Disease What is dementia? = Variety of diseases and conditions that develop when nerve cells in the brain die or no longer function normally - Alzheimer's Disease or Dementia is Devastating, progressive decline in cognitive function, = most common type of dementia, having gradual onset, = begins between 60 and 90 years of age, followed by increasingly severe impairment in social and occupational functioning - AD is ultimately fatal |
Precise etiology of Alzheimer's disease is uncertain, cholinergic systems appear to be most clearly compromised and frequently the target of current drug treatment - As AD progresses, behavioral and psychiatric symptoms are common - nondrug interventions include trying to identify problematic behaviors, understanding triggers, and minimizing or eliminating those causes (maintain stable, low-stress environment; avoiding noise and glare; providing security objects; and daytime activity to improve nighttime sleep. |
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Cholinesterase Inhibitors Agents for Alzheimer's Disease - Prevent breakdown of acetylcholine in the synaptic cleft, thereby increasing acetycholine levels and improving cognitive function - Do not treat underlying pathology - May slow the progression, but do not cure the disease - Examples: donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon) |
Agents for Alzheimer’s Disease: Cholinesterase Inhibitors Tacrine (Cognex) was the first drug approved in this class but was associated with significant hepatotoxicity and frequent dosing schedule and is no longer available - Donepexil (Aricept), galantamine (Razadyne) and rivastigmine (Exelon) are not associated with hepatotoxicity but do exhibit cholinergic side effects and dizziness (all drugs in this class cause GI upset - nausea, vomiting, diarrhea, abdominal cramps, anorexia and weight loss, requiring slow dose titration to improve patient tolerance |
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Interactions of cholinesterase inhibitors (Agents for AD) - anticholinergics (may decrease effectiveness- avoid using together) - cholinergics (bethanechol) and succinylcholine (may have a synergistic effect - monitor patient closely) |
Precautions or Contraindications for Cholinesterase Inhibitors - GI bleeding, and peptic ulcer disease - Cardiac disease (potential for bradycardia or syncope) - COPD (exacerbates the underlying disease) - Jaundice and renal disease - Pregnancy and lactation |
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NMDA receptor antagonist - Memantine (Namenda) is thought to selectively block the excitotoxic effects with abnormal transmission of the neurotransmitter glutamate - Can be used as monotherapy or in combination therapy with cholinesterase inhibitors - may be efficacious in earlier stages of Alzheimer's disease, delaying progression of symptoms - allowing patients to maintain certain daily functions for a little longer than they would without the drug |
Side Effects of memantine involve CNS are dose-dependent - confusion, cerebrovascular disorders, falls and agitation - dizziness, headache, constipation and cough |
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Precautions or contraindications - pregnancy, lactation, use in children, and renal disease Drug Interactions occur with - NMDA antagonists (amantadine, ketamine, and dextromethorphan) and certain antiarrhythmics - decision to continue drug therapy in Alzheimer's patients is based on quality of life, treatment goals, potential benefits, adverse effects and costs. = If quality of life is poor, stabilizing or slowing further decline may not be an appropriate goal, and drug therapy should be discontinued |
Table 22-3 Agents for Alzheimer's Disease (AD) Cholinesterase Inhibitors - donepezil (Aricept) - rivastigmine (Exelon) patch or oral - galantamine (Razadyne, Razadyne ER) caution with hepatic or renal disease PO with food
- memantine (Namenda, Namenda XR) Namenda XR do not crush or chew, may open capsule sprinkle over food before swallowing |
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Aricept - Alzheimer's Depakote - Treatment of Parkinson's Keppra - Treatment of seizures Dilantin - Treatment of seizures Neurontin - Treatment of seizures Lyrica - pregabalin, Anticonvulsant for epilepsy and migraines Mirapex - Treatment for Parkinson's Trileptal - Treatment of seizures Neurontin - Treatment of absence seizures Sinemet - Treatment of Parkinson's Tegretol - Treatment for seizures Topamax - Treatment for seizures |
A common side effect of phenytoin is __ = sedation |
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Health care professionals should closely monitor patients receiving anticonvulsants for which condition? = suicidal ideation |
Which of the following can interact with carbamazepine (Tegretol), potentiating the risk of side effects? = grapefruit juice |
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Anticholinergics used to treat younger patients with Parkinsons may cause which side effect? - dry mouth |
Caution should be used when administering memantine to patients with Alzheimer's disease because there is an increased risk of __ - falls |
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Patients taking any anticonvulsant medication should be instructed to take the medication with = food |
Treatment for Parkinson's = Entacapone |
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Treatment for seizures = Lamictal |
Treatment for absence epilepsy - Zarontin |
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Marlee has heard that COX-2 inhibitors are less likely to cause GI bleeds than are NSAIDs. What property of COX-2 inhibitors makes them less likely to cause GI bleeds? = COX-2 inhibitors do not inhibit platelet aggregation. |
Cayden is using a diclofenac patch for pain from his recent knee injury. How does the patch compare to oral medications? = Concentrations in joint tissues are higher with the patch. |
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While helping her friend move into a third floor walk-up, Elisabeth experiences painful muscle spasms in her back. Her doctor prescribes a centrally acting muscle relaxant. This medication is most likely ____. = diazepam |
Caitlin strained her back and her doctor prescribes a centrally-acting muscle relaxant during the initial checkup. After the pain subsides, her doctor is likely to prescribe ____. = exercise |
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Rajesh, an active and fit young adult, injures his shoulder in a weekend baseball game. His doctor tells him to take an NSAID and reminds him of the acronym RICE. What does the R indicate? = rest |
Epilepsy is defined as the recurrence of ____. = unprovoked seizures |
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Alex, 34 years of age, was recently diagnosed with Parkinson's. What medication might he be prescribed as a "levodopa-sparing" strategy? = ropinirole |
Jim has been taking a carbidopa-levodopa agent for almost two years and is experiencing wearing off. What medication might be useful? = selegiline |
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Kerri is the primary caregiver for her mother, who has moderate Alzheimer's dementia and appears to be deteriorating. What medication has been approved for patients whose dementia has progressed to the moderate or severe stages? = memantine |
Kristian has generalized epilepsy that is not as well-controlled in his opinion. He wonders if he should be switched to a second-generation anticonvulsant. How are second-generation anticonvulsants typically used in the management of epilepsy? = as adjuvants |
