NAPLEX Analgesics PG 132.

NAPLEX Analgesics PG 132

Treatment Algorithm for Pain

Treating Specific Types of Cancer Pain
Bone pain NSAIDs, bisphosphonates, corticosteroids, opiates Visceral pain NSAIDs, opiates Neuropathic pain TCAs, gabapentin, carbamazepine, corticosteroids Muscle spasms Benzodiazepines, baclofen

Non Opioid Analgesics PG 134 Drug Dose Interval Renal Adjustment
Hepatic Adjustment Acetaminophen mg Max: 4 g 4-6 hours GFR: >50 ml/min q4h, 10-50 ml/min q6h, <10 ml/min q8h 1/2 life is increased, Can be given safely Aspirin mg Avoid Celecoxib mg Max: 800 mg 12 hours Decrease dose by 50 % Rofecoxib (off market) 12.5 mg-25 mg Max: 50 mg Daily Valdecoxib 10-20 mg Max: 40 mg PG 134

Non Opioid Analgesics con’t
Drug Dose Interval Renal Adjustment Hepatic Adjustment Ibuprofen mg Max: 3.2 g/day 4-6 hours Use with caution Contraindicated in renal failure No dose alterations, Kinetics minimally effected Naproxen 550 mg initial, 250 subsequent Max: 1.5g/day 6-8 hours Use with caution Reduce dose 50% Indomethacin 25 mg Max: 200mg/day 8-12 hours Avoid Ketoralac 30 mg or 60 mg IM Max: 5 days of combine treatment (IM & PO) 6 hours

NSAID's Propionic Acids Carboxylic Acids oxaprozin naproxen
ibuprofen ketoprofen fenoprofen flurbiprofen Nonacetylated Salicylates Salicylates ASA salsalate diflunisal choline Oxicams piroxicam meloxicam Acetic Acids Naphthylalkanone sulindac etodolac indomethacin tolmetin diclofenac ketorolac nabumetone Of these NSAID classes, drugs tend to be equal in efficacy and to some extent toxicity if used in equi-potent antiinflammatory doses. Probably the biggest difference between these agents can be seen in their dosing frequency and ultimate cost. NON-acetylated salixylates – Advantages – Effective for moderate to severe pain, less risk of GI toxicity compared to NSAIDs, does not affect platelet aggregation. Fenamates GI Sparing Agents meclofenamate mefenamic acid diclofenac/misoprostol

Weak Opioid Analgesics
Drug Dose Interval Renal Adjustment Hepatic Adjustment Codeine 15-60 mg Max: 120 mg 4-6 hours CrCl: 10-50 ml/min=75% of dose, <10 ml/min=50% of dose A dosage adjustment decrease Oxycodone w/ -acetaminophen -aspirin 5 mg Max: 4 g* Be conservative, drug levels increase by 50% 1/3 to 1/2 of usual dose, Elimination 1/2 life increase by 2.3 hours Hydrocodone w/ -ibuprofen (7.5/200) (5/500) 1-2 tabs Max: 5 tabs Use cautiously in mild to moderate renal failure, avoid in severe renal failure Avoid Tramadol (37.5/325) mg Max: 400mg 2 tabs Max: 8 tabs CrCl < 30 ml/min increase dosing interval to q12h with a max of 200 mg per day Cirrhosis 50 mg q12h

Weak Opioid Analgesics con’t
Drug Dose Interval Renal Adjustment Hepatic Adjustment Propoxyphene -acetaminophen -aspirin 1-2 tabs Max: 4 g* 4 hours Don’t give in severe renal failure, use cautiously in mild and moderate renal failure Avoid

Strong Opioid Analgesics
Drug Dose Interval Renal Adjustment Hepatic Adjustment Meperidine - Binds opiate receptors mg Metabolite accumulation (normeperidine) Anxiety, agitation, tremor &/or seizures 3-4 hours GFR >50 ml/min No adjustment 10-50 ml/min 75% of dose <10 ml/min 50% of dose Decrease dose, 1/2 life is increased Morphine (gold standard) -immediate release -IV, IM, SQ, continuous infusion -epidural -intrathecal -rectal 10-30 mg mg 0.8 to 10 mg/hr Max: 80 mg/hr 5mg bolus, redose 1 hr 1 to 2 mg Max: 10 mg/24 hr 0.2 to 1 mg 10-20 mg Titrate to response 2-6 hours No repeat dose 4 hours 10-50 ml/min 75% of dose <10 ml/min % of dose (morphine-6-glucuronide) accumulates in renal failure 1/2 life prolonged increase interval by 1.5 to 2 times

Strong Opioid Analgesics con’t
Drug Dose Interval Renal Adjustment Hepatic Adjustment Hydromorphone -PO, IM, IV, SQ -rectal 1-4 mg 3 mg 4-6 hours 6-8 hours Decrease dose Oxycodone - percocet (APAP) - percodan (ASA) 5 mg May titrate to response – no maximum dose 6 hours – Be conservative, drug levels increase by 50% 1/3 to 1/2 of usual dose, Elimination 1/2 life increase by 2.3 hours Methadone -PO, IM, SQ -IV mg Max:1000 mg 0.1mg/kg 3-8 hours 4 hrs x 3 doses then 6-12 hours GFR >50ml/min q6h 10-50 ml/min q8h <10 ml/min q12h CrCl <10 ml/min 50-75% dose No Change in dose mild to moderate disease, Avoid in severe liver disease

Strong Opioid Analgesics con’t
Drug Dose Interval Renal Adjustment Hepatic Adjustment Fentanyl -transdermal -transmucosal Parenteral Initial 25 mcg/hr Initial 200 mcg 72 hours 30 min CrCl 10-50 ml/min 75% of dose <10 ml/min 50% of dose Unaffected by cirrhosis, effected by hepatic blood flow Remind patients that heat can increase fentanyl absorption. Warn against extended exposure of the patch to heating pads, hot tubs, sunbathing, high fever, etc.

Opioid Equianalgesic Dosing
Drug Oral (mg) Parenteral (mg) Morphine 30 10 Hydromorphone 7.5 1.5 Oxycodone 20-30 10-15 Methadone 10-20 acute? 2-4 chronic 10 acute? Levorphanol 4 acute 1 chronic 2 acute Fentanyl x Oxymorphone 1 Meperidine 300 75

Morphine Analogs---table 2-28, pg.132 General properties
CNS depression Respiratory depression Reduce propulsive activity of the gut Urinary retention Toxicity causes pinpoint pupils No maximum dose

Meperidine Analogs---See Table 2-28, pg.132
General properties Good analgesic (parenteral) Less CNS depression or constipation than opiates Spasmolytic action - may be useful for pain related to uterus, GI, bronchi, etc. Combination with hydroxyzine or promethazine permits 25–50% dosage reduction Principal drugs Meperidine (Demerol)---accumulates in renal disease, metabolite can cause siezures Diphenoxylate + atropine (Lomotil) – C-V - antidiarrhea - subtherapeutic dose of atropine to prevent abuse

For neuropathic pain-----See other sections
Central Analgesics Tramadol (Ultram) – oral - binds to u-opiate receptors in the CNS - inhibits reuptake of NE & 5HT in ascending pain pathway - CYP 450 2D6 - renal adjusted Clonidine (Duraclon) - epidural, PO or patch for HTN For neuropathic pain-----See other sections PG 133

Drugs for Migraine Headache Types - Tension, Cluster, Migraine
- Migraine is unilateral, pulsating, throbbing, with or w/o aura, nausea, photophobia, sonophobia Treatments – Prophylactic and Abortive Abortive Aspirin - analgesic, antipyretic, anti-inflammatory, anti-platelet Acetaminophen—analgesic, antipyretic NSAIDs - analgesic, antipyretic, anti-inflammatory (See Table pg. 133) • Mechanism of action • Common adverse effects: GI toxicity, hypersensitivity, renal effects PG 133

Contraindications to the use of Imitrex include
which of the following: I. uncontrolled HTN II. use of and MAOI within the past 2 weeks III. ischemic heart disease a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Drugs for Migraine Abortive - (cont.) PG 132
Dihydroergotamine (Migranal) - nasal spray; dose may be repeated after 15 min – MOA – blocks alpha adrenergic causing vasoconstrition 5-HT1D Receptor Agonists - avoid in patients with cardiovascular disease • Almotriptan (Axert) • Eletriptan (Relpax) – tablets; newest agent on the market – another “me-too” • Frovatriptan (Frova) – tablets; longest half life among agents • Naratriptan (Amerge) - tablets • Rizatriptan (Maxalt) - tablets; also Maxalt MLT (oral disintegrating tab) • Sumatriptan (Imitrex) - injection, tablet, nasal spray • Zolmitriptan (Zomig) - tablets; also Zomig ZMT (oral disintegrating tab) PG 132

Drugs for Migraine Prophylactic Therapy treatment Drugs of Choice:
- Given to patients with >2-3 HA/month, severe HA, ineffective treatment Drugs of Choice: - propranolol (Inderal) – use if patient also has HTN - amitriptyline (Elavil) – concomitant depression - valproate (Depakote) - concomitant seizures Other agents: - verapamil, topiramate PG 133

Pathophysiology Pathogenesis of the inflammatory response. PHASE l: Antigen-presenting cells phagocytic antigen. PHASE 2: Antigen is presented to T lymphocyte. T lymphocyte attaches to antigen at MHC {major histocompatibility complex) portion of the cell wall causing activation. PHASE 3: Activated T -cell stimulates T and B lymphocytes production, promoting inflammation. PHASE 4: Activated T -cells and macrophages-release factors (e.g., Cytotoxins, cytokines, prostaglandins that promote tissue destruction, increase blood flow, and result in cellular invasion of Synovial tissue and joint fluid, thus amplifying and sustaining the intraarticular inflammatory response. Results – synovium develops numerous folds which cover the articular cartilage (referred to as pannus); pannus destroys articular cartilage and subchondral bone, leading to bony erosions (seen on x-Ray) and narrowed joint space.

Complications Source:

Rheumatoid Arthritis Corticosteroids – early, acute, not long-term
- also NSAIDs / COX-2 Inhibitors Disease Modifying Antirheumatic Drugs (DMARDs) – liver, heme Auranofin (Ridaura) Aurothioglucose (Solganol) Azathioprine (Imuran) Cyclophosphamide (Cytoxan) Cyclosporine (Neoral, Sandimmune) Gold sodium thiomalate (Myochrysine) Hydroxychloroquine (Plaquenil) – retinal toxicity – Q 6 months Methotrexate (Rheumatrex) Leflunomide (Arava)---Preg Cat X, long half-life, hepatotoxic Penicillamine (Cuprimine, Depen) Sulfasalazine (Azulfindine) – orange-yellow urine Gold PG 134

PG 134 Biologic Response Modifiers
Etanercept (Enbrel) – avoid with live vaccine (soluble receptor TNF inhibitor) Anakinra (Kineret) – monitor for pulmonary problems (IL-1 receptor antagonist) Infliximab (Remicade) – monitor for infection (monoclonal antibody for TNF) Adalimumab (Humira) – monitor for infection (monoclonal antibody for TNF receptor) Abatacept (Orencia®) – monitor for infection (Inhibits T-Cell (T-lymphocytes activation by binding to CD80 and CD86 on antigen presenting cells) Osteoarthritis (OA) - acetaminophen & NSAIDs - surgery – knee/hip replacement - glucosamine/chondrotin – NIH study (GAIT) PG 134

Joint Distribution: RA Compared to OA
Rheumatoid Arthritis Osteoarthritis

SLE (systemic lupus erythematosus) occurs more frequently in:
a. male African Americans b. Asians c. post-menopausal women d. people of Mediterranean origin e. young women

Patients who are life time smokers have the greatest risk of leg pain associated with?
a. hypokalemia b. rhabdomylosis c. intermittent claudication d. dopamine deficiency e. myocardial infarction

a. hypokalemia (cramps)
Patients who are life time smokers have the greatest risk of leg pain associated with? a. hypokalemia (cramps) b. rhabdomylosis (statins) c. intermittent claudication (PVD) d. dopamine deficiency (RLS) e. myocardial infarction

Trigeminal neuralgia is treated by the use of: a. aspirin
b. carbamazepine c. dipyridamole d. methylprednisolone e. thiamine

a. I only b. III only c. I and II only d. II and III only
When dispensing a prescription for Robitussin AC, the pharmacist should attach label(s) indicating: I. May cause drowsiness II. Shake well before using III. Finish all of this medication a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Which of the following is/are appropriate warning(s) for the use of Duragesic transdermal system patches? I. Do not cut patches before applying II. Not intended for use in children under the age of 12 III. Replace patch every day unless pain is under control a. I only b. III only c. I and II only d. II and III only e. I, II, and III

The upper daily dosing regimen for naproxen is NOT more than: a. 0.5 g
b. 1 g c. 1.5 g d. 2.5 g e. 4 g

The upper daily dosing regimen for naproxen is NOT more than: a. 0.5 g
b. 1 g (mefenamic) c. 1.5 g (naproxen) d. 2.5 g e. 4 g (acetaminophen) Ibuprofen (3.2g) Indomethacin (200mg)

Which of the following ingredients is are present in Percodan but not in Percocet: I. Aspirin II. Acetaminophen III. Oxycodone a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Drugs for the Treatment of Asthma
NAPLEX Drugs for the Treatment of Asthma PG 142

Classification Symptoms Nighttime Symptoms Lung Function
Symptoms Nighttime Symptoms Lung Function Step 1 Mild Intermittent ¨ Symptoms ≤ 2 times a week ¨ Asymptomatic and normal PEF between exacerbations ¨ Exacerbations brief (from a few hours to a few days); intensity may vary ≤ 2 times a month ¨ FEV1/PEF ≥ 80% predicated ¨ PEF variability < 20% Step 2 Persistent ¨ Symptoms > 2 times a week but < 1 time a day ¨ Exacerbations may affect activity > 2 times a month ¨ FEV1/PEF ≥ 80% predicated ¨ PEF variability < 20-30% Step 3 Moderate ¨ Daily symptoms ¨ Daily use of inhaled short-acting beta-2 agonist ¨ Exacerbations affect activity ¨ Exacerbations ≥ 2 times a week; may last day > 1 time a week ¨ FEV1/PEF > 60 - < 80% predicated ¨ PEF variability > 30% Step 4 Severe ¨ Continual Symptoms ¨ Limited Physical Activity ¨ Frequent Exacerbations Frequent ¨ FEV1/PEF ≤ 60% predicated ¨ PEF variability > 30%

phosphodiesterase Adenyl cyclase cyclic AMP (bronchodilation) elimination Sympathomimetics Increase formation of cyclic AMP Nonselective • Ephedrine • Epinephrine (Adrenalin, Medihaler-Epi, Bronkaid, Primatene, etc.) • Ethylnorepinephrine (Bronkephrine) PG 142

Selective Short-Acting Beta-2 Agonists. Provide quick relief; may cause tachycardia, tremor, etc. • Albuterol (Proventil, Ventolin, Airet, Volmax) 0.5hr peak, hours duration • Albuterol - oral sustained-release product • Pirbuterol (Maxair) – Autoinhaler – longer duration 6 hrs (tertiary butyl group) • Levalbuterol (Xopenex) – active isomer of albuterol, neb., less cardiac side effects • Metaproterenol (Alupent, Metaprel) – delayed onset (1 hour) & prolonged effect (4 hour) • Terbutaline (Brethine, Bricanyl) – delayed onset 1 hour & prolonged duration (6hr) – no-inhalation in U.S. & (management of pretermed labor) • isoproterenol (Isuprel, Medihaler-Iso) – beta-1 & beta-2 activity PG 143

Drugs for the Treatment of Asthma (cont.)
Long-Acting Beta-2 Agonists. For long-term symptom control; frequently used with inhalational corticosteroids; may cause tachycardia, tremor, etc.; for prophylaxis only. • Formoterol (Foradil) – DPI - capsule • Salmeterol (Serevent) – DPI – Diskus NOT SUITABLE AS A RESCUE INHALER!!!!!!!!!!!!!! PG 142

Drugs for the Treatment of Asthma Xanthines
Phosphodiesterase inhibitors; generally for prophylaxis; adverse effects similar to caffeine • Theophylline (Slo-Phyllin, Theolair, Theo-Dur)----Think drug interactions, serum levels 10-20, arryhthimogenic at high levels • Dyphylline (Lufyllin).theophylline derivative • Aminophylline (Somophyllin-CRT).anhydrous contains 86% - 300mg theo (PO) = 380mg Amino (IV) theophylline, dihydrate 79% • Oxtriphylline (Choledyl).contains 64% theophylline Leukotriene receptor drugs For prophylaxis; may reduce need for beta-2 agonist • Zafirlukast (Accolate).leukotriene receptor antagonist • Montelukast Sodium (Singulair).leukotriene receptor antagonist • Zileuton (Zyflo).inhibits leukotriene formation (5-lipoxygenase inhibitor); monitor hepatic function, think DIs---potent inhibitor PG 142

Zyflo CR will be given BID instead of QID
Zyflo CR will be given BID instead of QID. But patients will still need liver function tests every month for the first 3 months...then every 2 to 3 months for the rest of the first year. – 2007 Omalizumab. Save the monoclonal antibody, Xolair, for patients with severe asthma and allergies...who are not responding adequately to high-dose inhaled steroids and long-acting beta-agonists. New NIH guidelines will improve asthma treatment. You'll see renewed emphasis on controlling symptoms...patient education...and avoiding allergens.

Corticosteroids Inhalational; reduce inflammation and bronchial reactivity; may cause oral candidiasis, cough, and other steroid effects (with prolonged use). Prophylaxis only. • Beclomethasone dipropionate (Beclovent, Vanceril) • Triamcinolone acetonide (Azmacort) • Flunisolide (Aerobid) • Fluticasone propionate (Flovent) • Mometasone (Asmanex Twisthaler) • Budesonide (Pulmicort) (Pulmicort Respules – only neb ICS) Anticholinergics Ipratropium bromide (Atrovent); bronchodilator. Reduces secretions; alternative to beta-2 agonists; anticholinergic adverse effects - combivent – albuterol and ipratropium Tiotropium (Spiriva)----long acting, dry powder capsule for inhalation PG 142

Mast cell stabilizers Anti-inflammatory; very safe; for prophylaxis only • Cromolyn sodium (Intal, Nasalcrom) • Nedocromil sodium (Tilade) Combination products Ipratropium bromide/albuterol sulfate (Combivent) Salmeterol xinafoate/fluticasone propionate (Advair Diskus) Symbicort contains the corticosteroid budesonide (Pulmicort)...plus the long-acting beta-agonist formoterol (Foradil) puffs BID PG 143

Side effects of oral corticosteroids include all of the following except:
a. hyperglycemia b. nervousness c. fluid retention d. HPA axis suppression e. thrombocytopenia

Patients exhibiting Cushing syndrome should avoid products containing:
a. corticosteriods b. iodine c. sulfas d. penicillins e. salicylates

Which of the following drugs is/are administered by dry powder inhalation?
I. Ipratropium (atrovent of combivent) II. Pirbuterol (MaxAir Turboinhaler) III. Salmeterol (Diskus) a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Which of the following drug(s) is/are administered by dry powder inhalation?
I. Ipratropium (atrovent of combivent) II. Pirbuterol (MaxAir Turboinhaler) III. Salmeterol (Diskus) a. I only b. III only c. I and II only d. II and III only e. I, II, and III

All of the following drugs are available as aerosol units EXCEPT:
a. Spiriva b. Azmacort c. Rhinocort d. Beconase e. Combivent

Drugs Used to Treat Glaucoma
NAPLEX Drugs Used to Treat Glaucoma

Causes of Glaucoma • Wide or open angle – most common, malfunction of trabecular meshwork • Narrow angle or closed angle – obstruction of the outflow of aqueous humor through the trabecular meshwork. PG 136

An instrument used to measure intraocular pressure is a(n):
a. gonioscope b. otoscope c. ophthalmoscope d. tonometer e. barometer

An instrument used to measure intraocular pressure is a(n):
a. gonioscope (lens to study angle of eye) b. otoscope (instrument to examine the drum membrane of the ear) c. ophthalmoscope (device to study interior of eye) d. tonometer (device to measure intraocular pressure) e. barometer (device to measure the atmospheric pressure)

Drugs for Glaucoma Treatment
Goal of Therapy – reduced intraocular pressure (IOP) - measured by a tonometer (10-20mmhg) - decrease rate of aqueous humor production - increase rate of outflow (drainage) of aqueous humor Sympathomimetics— increase outflow and decrease production of aqueous humor - epinephrine (Epifrin, Glaucon) – discard if color change occurs - dipiverfrin (Propine) – epinephrine prodrug – less side effects - apraclonidine (Iopidine) – alpha-2 agonist; watch for ocular allergy - brimonidine (Alphagan) - alpha-2 agonist, more selective PG 136

Miotics (direct acting)—have direct cholinergic action causing miosis; increases outflow, may cause eye pain, burning, blurred vision; less with gel and Ocusert formulations - acetylcholine (Miochol) - carbachol (Isoptocarbachol) - Pilocarpine (Isoptocarpine, Pilocar, Pilostat, Pilopine HS, Ocusert Pilo) Miotics (cholinesterase inhibitors)—increase cholinergic action by inhibiting cholinesterase; similar adverse effects as direct-acting miotics - physostigmine (Eserine) – may cause cataracts - Demecarium (Humersol) - Echothiophate (phospholine iodide) mydriasis PG 136

Beta-adrenergic blocking agents — reduce production of aqueous humor; watch for possible breathing difficulty, bradycardia, hypotension, and CNS depression - betaxolol (Betopic, Betoptic S) – beta 1 selective - levobetaxolol (Betaxon) – beta 1 selective - carteolol (Ocupress), levobunolol (Betagan, AKBeta) - metipranolol (Optipranolol), - timolol (Timoptic, Timoptic XE) B1 & B2 Prostaglandin analogs — increase outflow of aqueous humor; may darken iris color and cause thickened lashes - latanoprost (Xalatan) - bimatoprost (Lumigan) - travoprost (Travatan) - Unoprostone (Rescula) Not available in U.S. PG 136

Carbonic anhydrase inhibitors — suppress production of aqueous humor; watch for urinary frequency and nephrolithiasis - dichlorphenarnide (Daranide) - acetazolamide (Diamox)----oral capsules, IV – Also used for mountain sickness - methazolamide (Neptazane) - dorzolamide (Trusopt) - brinzolamide (Azopt) Osmotic diuretics----given orally or IV - glycerin (Osmoglyn) , mannitol (Osmitrol) - urea (Ureaphil), isosorbide (Isomotic) PG 136

Timoptic dosage forms include:
I. capsule II. tablet III. ophthlamic solution a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Dosage forms for timolol maleate include:
I. gel II. tablet III. ophthlamic solution a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Glaucoma Case Study Page 138

Pilocarpine can be classified as a(n):
a. anticholinergic agent b. carbonic anhydrase inhibitor c. beta-adrenergic blocking agent d. cholinergic agent e. sympathomimetic agent

An Ocusert Pilo-20 system:
a. is administered orally once daily b. releases 20 mg of pilocarpine each day c. must be replaced each month d. releases 20 µg of pilocarpine each hour e. must be soaked in normal saline just prior to use

A normal intraocular pressure reading would be:
a mm Hg b mm Hg c mm Hg d mm Hg e mm Hg

Special caution must be used when timolol is used in patients with:
a. sulfonamide allergy b. asthma c. cancer d. hypertension e. NSAID hypersensitivity

NAPLEX Analgesics PG 132.

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