Pharmacy School

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Pharmacy School
2012-06-05 23:39:34
Flashcards final

Everything for final midterm
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  1. DEXA scans and interpretation
    • Osteoporosis - bone mass measurement data
    • Absolute value (gm/cm2) for patient
    • Comparison to sex- and age-matched mean peak reference values (Z Scores)
    • Comparison to premenopausal mean peak reference values (T Scores)
    • Interpretation refers to T scores:
    • Normal: better than (-)1 SD
    • Osteopenia: (-)1 SD to (-)2.5 SD
    • Osteoporosis: More than (-)2.5 SD
  2. nTx
    • Urinary N-telopeptide collagen
    • Biochemical Bone Turnover Markers
    • Assess rate of bon turnover (bond remodeling)
    • Monitor effects of treatment
    • Help evaluate patient compliance
  3. Calcium in Osteoporosis
    • Increases BMD 1-2%
    • Decreases fractures 30%
    • Calcium carbonate contains 40% elemental calcium (should be takent with meals, requires stomach acid, constipating)
    • Calcium citrate contains 21% elemental calcium (can be taken on an empty stomach, does not constipate)
    • Calcium lactate contains 13% elemental calcium
    • Calcium gluconate contains 9% elemental calcium
  4. Vitamin D in Osteoporosis
    • Level required?
    • Amount required
  5. Indications for treatment of Osteoporosis
    • Consider Rx in postmenopausal women who have:
    • Osteoporotic hip or vertebral fracture
    • T-score -2.5 or below at femoral neck, total hip or spine
    • T-score from -1.0 to -2.5 AND …
    • 1. 10 year probability of hip fracture >3% (FRAX)
    • 2. 10 year probability of major osteoporosis—related fracture >20% (FRAX)
    • Presence of fragility fracture after age 50 should be treated
    • Women older than 68 with T-score worse than -2.5 should be treated
    • Women older than 70 with fracture risk better than 3% don't need treatment
  6. Hormone Replacement Therapy in Osteoporosis
    • Benefits: vasomotor symptoms, osteoporosis, colorectal cancer, cognition and dementia?, urogenital atrophy
    • Harms: CV disease, stroke venous thromboembolism, breast cancer, cholecystitis
    • Bone mineral density increases by 5%
    • Fracture rates: RR -0.39 to 0.66 versus placebo (so decreased relative risk compared to placebo)
    • 2nd line, appropriate for younger women (surgical menopause) at high risk for fracture, especially with vasomotor symptoms
  7. Anabolic Hormones for Osteoporosis
    • Historical interest only
    • Alternative for men
    • Increases bone density 5%
  8. Bisphosphonates
    • Mechniams of action: potent inhibitors of osteoclastic bone resorption (encourage osteoclasts to undergo apoptosis)
    • Build bone mass
    • Reduce incidence of both vertebral and nonvertebral fractures, including hip fractures
    • Majority of patients respond to therapy
    • Prevents bone loss: increases bone mass 5-10%
    • Decreases fractures by 50%
    • Low oral bioavailability (0.78%)
    • Absorption: Adm. 30 min before meal, beverage (except
    • water) or medication
    • No Metabolism
    • Elimination exclusively renal
    • Incorporated into bone
    • T 1/2: forever
    • Risk of atypical femur fractures after 5 years
    • DC after 5 years, use nTx to guide therapy
    • Contrainidications: several + Extensive dental work—can cause Jaw necrosis (osteonecrosis of the jaw)
  9. Individual Bisphosphonate Drugs
    • Etidronate 400 mg qd x 2 weeks, quarterly (Didronel)
    • Alendronate 5-10 mg qday (Fosamax)
    • Alendronate 70mg qweek (Fosamax)
    • Risedronate 5 mg qday (Actonel)
    • Risedronate 35 mg qweek (Actonel)
    • Ibandronate 150 mg qmonth (Boniva)
    • Ibandronate 2.5 mg qday (Boniva
    • Zoledronic acid 5 mg IV qyear (Zometa)
  10. Calcitonin
    • For osteoporosis
    • Protein hormone - prevents bone resorption
    • Efficacy: Minimal prevention of bone loss, fracture reduction
    • Alternative therapy
    • Analgesic effect
    • SAFE!
  11. Raloxifene
    • Selective estrogen-receptor modulator (SERMs)
    • Adverse Effects: Leg cramps, Hot flashes, Venous thromboembolism (3 fold risk), Protects against breast cancer
    • Notes: 2nd line for younger women with vertebral fractures (no evidence for decreased fracture at other sites)
  12. Teriparatide
    • Business end of parathyroid hormone
    • Forteo
    • Stimulates bone formation (the only anabolic)
    • Efficacy: Builds bone mass: increases BMD 5-10%
    • Reduces vertebral and non-vertebral fractures., not hip
    • 20 mcg QD; SQ pen administration, 18-24 mo
    • Doesn’t work with bisphosphonate
    • ADR: nausea, dizziness, leg cramps, HA, osteosarcoma, hypotension, hypercalcemia
    • Notes: $; unable to tolerate; unresponsive
  13. Denosumab
    • Prolia
    • Den: Density, OS: Bone, U: Human, MAB: Monoclonal antibody
    • Humanized IgG mnoclonal Ab
    • Antibody to RANK ligand (which is necessary for osteoclast formation, function and survival)
    • Antiresorptive:
    • Efficacy: Builds bone mass: increase BMD 5-10%, 20-40% reduction in vertebral and nonvertebral fractures
    • 60 mg SQ Q 6 mo
    • Contraindications: Serious infections, Pg, CLD and CKD, Kids
    • ADR: Hypocalcemia, Cellulitis, Eczema
  14. Cognitive Behavior Therapy for Insomnia
    • CBT involves the following components:
    • Cognitive therapy to alter faulty beliefs and attitudes that exacerbate insomnia (unrealistic expectations about sleep requirements, misattributions of consequences of insomnia, erroneous beliefs about strategies to promote sleep)
    • Stimulus control to regulate the sleep-wake schedules & associate bed & bedtime stimuli with sleep (go to bed only when sleepy, use bed and bedroom only for sleep and sex, leave the room when unable to fall asleep, no naps, arise at the same time every morning regardless of the amount of sleep the previous night)
    • Sleep restriction to increase sleep efficiency (curtail time in bed to actual sleep time)
    • Sleep hygiene because it makes sense (education, minimize random noise, optimally manage medical illnesses, control night-time pain, avoid caffeine, nicotine, and alcohol, avoid stimulating drugs in the vening, regular exercise before evening, evening fluid restriction, use regular times for sleeping, discourage daytime napping, save bedroom for sleeping
    • CBT therapy (all components) and sleep restriction (alone) are effective for improving insomnia; each of the other components are NOT effective alone (e.g cognitive therapy, stimulus control or sleep hygiene).
  15. Ramelteon
    • Rozerem
    • A melatonin receptor agonist with higher selective affinity for melatonin MT1 and MT2 receptors verses the MT3 receptor (reduces time to sleep onset but not maintenance). Not a controlled substance
  16. Pharmacotherapeutic Treatment Guidelines for Insomnia
    • If have difficulties with sleep onset (Note: these agents not likely to be effective if patient has problem with sleep maintenance): zaleplon, zolpiden, triazolam, ramelteon
    • If wake up in the middle of night (if have enough time for sleep ~4 hours) could use: zolpidem SL, zaleplon. This strategy might avoid nightly use of sleep agents and patient can use just if they have sporadic “middle of the night” awakenings.
    • Avoid BZD: patients with severe pulmonary disease, elderly (for the most part), hx substance abuse
    • Sedating antihistamines: Limited data but are used and helpful for some people. Caution with anticholinergic effects (especially older adults).
    • Trazodone (25-100 mg), mirtazapine: Limited data but may be helpful for some people. Lower doses used for insomnia than what is used for depression
  17. Non-benzodiazepine hypnotic agents
    • Zolpidem (Ambien®), Zaleplon (Sonata®), & Eszopiclone (Lunesta®)
    • Bind to benzodiazepine-1 receptor
    • Newer short-acting non-benzodiazepine hypnotics, produce less withdrawal andtolerance effects than benzodiazepines
    • Limited data indicate that development of tolerance does not occur with thenewer non-benzodiazepines when used nightly for six months or longer
    • Side effects minimal
    • Dizziness, headache, and somnolence
    • Little psychomotor
    • Little memory impairment at moderate doses—reports of more with zolpidem than others?
    • Somnambulism—more associated with zolpidem?
  18. Regulation of smooth muscle contractility
    • Sexual stimulation
    • Release of nitric oxide (NO)
    • NO activates guanylyl cyclase
    • Guanylyl cyclase increases cGMP
    • cGMP decreases cellular Ca++
    • Phosphodiesterase 5 (PDE5) degrades cGMP
  19. Phosphodiesterase Inhibitors
    • Viagra ® (sildenafil)
    • Levitra ®(vardenafil)
    • Cialis ®(tadalafil)
    • See notes for differences
    • Sexual stimulation necessary
    • Potential cardiac risk of sexual activity
    • Symptoms of cardiac ischemia
    • No nitrates
    • May take more than one attempt to work
    • No more than 1 dose per day
    • Immediate medical attention sought if:
    • painful or prolonged erection > 4 hrs duration
    • sudden loss of vision in one or both eyes
  20. Testosterone
    • Patients with primary or secondary hypogonadism
    • Never those with normal testosterone levels
    • MOA = hormone replacement
    • Available: orally, parenterally, topically
    • Adequate trial = 2-3 months
    • Screen for BPH & prostate CA prior to therapy
    • Adverse effects: sodium retention leading to weight gain, HTN, CHF & edema, hepatotoxicity, abnormal lipid profile, polycythemia
  21. Alprostadil
    • Stimulates adenylyl cyclase, increases production of cAMP which enhances blood flow to corpora
    • Injectable vasoactive agents
    • Alprostadil [synthetic prostaglandin E1 (Pg E1)]
    • Products approved by FDA for intracavernosal injection
    • Caverject®
    • Edex®
    • Dose = 5 - 40mcg
    • 5 -10 minutes before intercourse
    • Inject at right angle into lateral surface of penis
    • Massage 30 seconds
    • Maximum use q48hrs
    • Erection within 30 min
    • Lasts up to 3hrs
    • Adverse effects: cavernosal plaques or areas of fibrosis, penil pain, priapissm, injection site hematoma/bruising, rare systemic effects include dizziness and hypotension
    • Contraindications: sickle cell anemia, multiple myeloma, or leukemia, recent MI or CVA
    • Intraurethral therapy-medicated urethral system for erection (MUSE)
    • Pellet is inserted into urethra via applicator
    • Dose = 125 –1000mcg
    • 5 –10 min before intercourse
    • Massage 30 seconds
    • Maximum use q24hrs
    • Erection within 30 min
    • Lasts 30-60 minutes
    • Adverse effects: urethral injury, pain, vaginal burning, itch or pain in partner, priapism (rare), rare dizziness or hypotension
    • Contraindications: urethral structure, urethritis
  22. Injectable alprostadil combination
    • o
    • Bimix: alprostadil + papaverine
    • Trimix: alprostadil + papaverine + phentolamine
    • Papaverine inhibits phosphodiesterase
    • Phentolamine nonselective alpha-adrenergic antagonist
    • Not FDA approved
    • Not commercially available; compounded
  23. Alpha Adrenergic Antagonists for BPH
    • Selective alpha-1-antagonist
    • Alfuzosin—UroXatral
    • Doxazosin—Cardura
    • Terazosin—Hytrin
    • Selective alpha-1A-antagonist (third generation uroselective)
    • Tamsulosin—Flomax
    • Silodosin—Rapaflo
    • For alpha 1 antagonists
    • Advantages:
    • Can increase PUFR by 2-3mls in 60-70% of patients (Peak urinary flow rate)
    • Can decrease PVRV in 60-70% of patients (post void residual volume)
    • Can decrease symptoms within a few weeks
    • Efficacy may continue for many years
    • No effect on PSA
    • Most can be taken once daily
    • No dosage adjustment for renal dysfunction
    • Disadvantages:
    • Terazosin & doxazosin require dose titration
    • Cardiovascular side effects
    • Caution in patients with concomitant cardio-vascular iseases or volume depletion:
    • Poorly controlled angina
    • Serious cardiac arrhythmias
    • CHF
    • Hypertension requiring multiple medications
    • Dosage adjustment in hepatic disease
    • Common adverse effects
    • Syncope, hypotension, reflex tachycardia, dizziness, decrease ejaculate, nasal congestion, tiredness, asthenia
  24. Tamsulosin
    • Flomax
    • Alpha 1a antagonist
    • Selective for alpha-1A-receptors
    • Minimal dose titration
    • Once daily on empty stomach
    • Minimal effect on blood pressure
    • Good for patients with other comorbidities
    • Similar efficacy to nonselective antagonists
    • Most common side effect = nasal congestion
    • Slightly > abnormal ejaculation rates than nonselective agents
    • Available as a generic
    • Floppy iris syndrome
  25. Silodosin
    • Rapaflo
    • Selective for alpha-1A-receptors
    • No dose titration
    • Once daily with a meal
    • Contraindicated in CrCl<30mL/min & severe hepatic impairment
    • Dosage decrease in CrCl 50-30mL/min
    • Retrograde ejaculation >22%
    • Similar efficacy to nonselective antagonists
    • Avoid administration with strong CYP3A4 inhibitors
    • Long-term efficacy & tolerability unknown
  26. 5 alpha reductase inhibitors
    • Finasteride (Proscar®, generic)
    • Dose: 5mg qday
    • Dutaseride (Avodart®)
    • Dose: 0.5mg qday
    • Advantages:
    • More effective than alpha adrenergic antagonists in decreasing prostate size
    • May decrease risk of acute urinary retention
    • Decreases DHT levels & increases testosterone levels
    • Decreases hormone related hair loss
    • No dose titration
    • No clinically relevant drug interactions
    • Disadvantages
    • Time to reach max effect 6-12 months
    • Decreases PSA which is a screening tool for CA
    • Pregnancy category X
    • Not effective without prostatic enlargement
    • Not as effective as alpha adrenergic antagonists in improving LUTS
    • High incidence of sexual side effects
    • Common adverse effects of 5 alpha-reductase inhibitors
    • Sexual dysfunction:
    • Ejaculation disorders (6-19%): Decrease in prostatic secretions?
    • Erectile dysfunction (3-5%): Drug-induced inhibition of nitric oxide
    • Decrease in libido
    • Other:
    • GI (abdominal pain, flatulence, nausea)
    • Breast tenderness
  27. Physiology of BPH Pharmacology Treatment
    • High density of Alpha-1-adrenergic receptors in prostate (stroma & capsule), bladder neck, & urethra
    • Norepinephrine causes constriction of smooth muscle, leads to extrinsic compression of urethra, decrease in lumen diameter, & decrease in bladder emptying
    • Alpha-1 antagonism at these sites decreases smooth muscle tone, & decreases resistance to urinary flow
    • In untreated BPH, pressure at the bladder neck and on the urethra as it passes through the prostrate causes urinary symptoms
    • With alpha 1-blockers, the pressure is reduced and urine can flow more easily
    • Two primary androgens in males are testosterone & androstenedione:
    • Both converted by 5-alpha-reductase to dihydrotestosterone
    • (DHT)
    • DHT binds to prostatic androgen receptors & stimulates cell hyperplasia
    • 5-alpha-reductase inhibitors inhibit conversion of testosterone to dihydrotestosterone (DHT)
    • Resulting in decreased growth of glandular epithelial tissue & decreased prostate size
  28. Lab values in BPH
    • PSA: Prostrate specific antigen
    • IPSS: International Prostate Symptoms Score
    • PUFR: Peak urinary flow rate
    • PVRV: post void residual volume
  29. Lower urinary tract symptoms LUTS
    • Obstructive: dynamic &/or static factors lead to decrease in bladder emptying
    • Decrease in urine stream leads to voiding that takes longer &/or is incomplete
    • Difficulty initiating urine flow (hesitancy)
    • Straining
    • Bladder feels full even after emptying
    • Irritative: (usually occurs later in disease)
    • Bladder muscle hypertrophies and becomes very sensitive (i.e. easily irritated by urine in bladder)
    • Results in increasing frequency, urgency & nocturia
  30. BPH drug-induced exacerbation
    • Alpha-adrenergic agonists: Stimulate alpha receptors in prostate which leads to contraction
    • Anticholinergics (drugs with anticholinergic side effects): decrease in detrusor muscle contractility in bladder
    • Diuretics: Produce polyuria leading to urinary frequency, Including foods/beverages w/diuretic potential
    • Testosterone: Provides additional substrate for metabolism to DHT
  31. Oxybutynin
  32. Tolterodine
  33. Trospium
    • sanctura
    • 1 hour prior to meals on an empty stomach
  34. Solifenacin
  35. Darifenacin
  36. Fesoterodine
  37. Management of Delirum
  38. Gilenya
    • Fingolimod
    • 10 mg every day
  39. Rebif
    • Interferon beta-1a
    • 22 or 44 mcg, SC, 3 times/week
  40. Avonex
    • Interferon beta-1a
    • 30 mcg, IM, once/week
  41. Betaseron
    • Interferon beta-1b
    • 250 mcg, SC, every other day
  42. Copaxone
    • Glatiramer Acetate
    • 20 mg, SC, every day
  43. Tysabri
    • Natalizumab
    • 300 mg, IV, once a month
    • PML
    • Touch program
  44. Novantrone
    • Mitoxantrone
    • 12 mg/m2, IV, every 3 months