Drugs Fall 2021/2022

What are the 4 categories of blood pressure and their readings according to 2017 ACC/AHA guidelines?

(see image)

Calcium Channel Blockers (CCBs): 2 subclasses

*Normally, Ca2+ influx causes vasoconstriction and contraction of heart and vascular smooth muscles* **Think: More Calcium = Constriction and Contraction** ∙MOA: CCBs inhibit L-type Ca2+ channels causing a ↓ of Ca2+ entry into cells and resulting in vasodilation, decreased contractility and reduction in HR. two subclasses: Dihydropyridines (DHP) and Non-dihydropyridines (Non-DHP)

What are the 5 A's of smoking cessation?

1. Ask about tobacco use 2. Advise to quit 3. Assess readiness/willingness to make an attempt to quit 4. Assist with quitting 5. Arrange follow-up

How frequent does a patient have to check their BP if the reading is 120 - 129/<80 mmHg?

3 to 6 months

How frequent does a patient have to check their BP if the reading is 130 - 139/80 - 89 mmHg and pharmacotherapy is not yet indicated?

3 to 6 months

What is BP treatment goal in adults with chronic HTN <65 years of age, which is significant for those with a confirmed HTN dx and either known CVD or a 10-year ASCVD risk score of ≥ 10%?

<130/80 mmHg

What are the first line of therapy for HTN?

ACEIs ARBs CCBs (DHPs and Non-DHPs) Diuretics

How frequent does a patient have to check their BP if the reading is <120/80 mmHg?

Annually

Medications for T2DM

Biguanides Thiazolidinediones (TZDs) Sulfonylureas (SFUs) DPP-4 Inhibitor GLP-1 Receptor Agonist SGLT2-Inhibitor

How frequent does a patient have to check their BP if the reading is ≥140/≥90 mmHg, and receiving pharmacotherapy?

Monthly until at goal 3 to 6 months if at goal

What are the pharmacotherapy options for smoking cessation?

Non-nicotine therapies: buproprion (Zyban) and varenicline (Chantix); Nicotine Replacement Therapy (NRT)

MDI counseling points

Remember SPORTT S - SHAKE well before each use P - PRIME before first use by shaking well for 5 seconds and then spraying into the air 3 times away from the face. This should be repeated if the inhaler has not been use for more than 7 days. O - Take a deep breath and breath OUT all the way R - REST the mouth piece inside the mouth and seal tightly with your lips around it. T - TAKE a deep breath in as you press all the way down on the inhaler to release the medication T - Hold your breath for about TEN seconds or for as long as you can and then exhale.

Difference between T1DM and T2DM

T1DM: cannot produce any insulin naturally as the β-cells (insulin-producing cells) in their pancreas are destroyed T2DM: can produce some insulin but overtime, the amount of insulin produced decreases as more of β-cells become damaged.

True or False: When evaluating a patient, it is important to consider the cause of HTN to assist in the development of a treatment strategy?

True

True or False: Adults ≥65 years of age living in the community should aim for an SBP of <130 mmHg.

True, however, different goals may be considered for older patients who have a high comorbidity burden and limited life expectancy (clinical judgement should be used to adjust goals based on risk vs benefit considerations and patient preference).

Deep Vein Thrombosis (DVT)

a condition where a blood clot forms in a deep vein (usually the legs) and can break off, travel to the lungs, leading to a pulmonary embolism (blood clot in the lungs)

Anemia

a condition where you lack enough health RBCs to carry adequate O₂ to your body's tissues leading to symptoms such as fatigue, SOB, lightheadedness or dizziness

Hematinics

important nutrients (e.g. Fe³⁺, folic acid, vit B12) required for the proper formation of blood cells

DOAC dosing for renal impairment

in severe or ESRD, warfarin remains the anticoagulant of choice ∙Pradaxa: No recommendations for CrCl < 30 or on HD; Avoid P-gp inhibitor if CrCl < 50 ∙Xarelto: Avoid if CrCl < 30 ∙Eliquis: No dose change (Not studied in CrCl ≤ 25 or SCr > 2.5)

Smoking cessation

is by far the most effective preventive intervention in almost all patients regardless of disease status.

Diuretics: Loop

most potent diuretics ∙HTN, edma, preferred in HFrEF ∙MOA: block Na+/K+/2Cl- symporter in the ascending loop of Henle (thus they are called Loop Diuretics), producing a potent diuretic effect that causes an increased excretion of Na, Cl, K, Mg, Ca, and H2O. They cause retention of bicarbonate and uric acid. ∙bumetanide (Bumex), furosemide (Lasix), torsemide (Demadex) ∙SIG: (see image); Take early in the day to avoid nocturia ∙SE: orthostatic hypotension, dehydration, electrolyte imbalances (↓K+/Mg2+/Ca2+), thirst, fatigue, rash, photosensitivity, ototoxicity (rare) ∙Key Points: ・Always take early in the day to avoid nocturia ・Rare risk of hearing loss/damage--report any unusual ringing in ears (Tinnitus) to provider ・Monitor patients with diabetes ・Avoid NSAIDs → lower efficacy of loop diuretics ・May increase risk of a gout flare ・Avoid lithium and sulfonamide-derived drugs ・C/I in patients with anuria

What are the risk factors of HTN that are NON-modifiable?

psych stress, premature birth, CKD, family hx, age, male, low economic stats

Which of the statins are bedtime dosing?

simvastatin (Zocor), lovastatin (Mevacor), fluvastatin (Lescol)

What are the secondary antihypertensive drugs?

β-blockers Loop diuretics K+ sparring Diuretics Aldosterone Antagonists ⍺1-blockers Central ⍺2-agonists Direct Vasodilators Direct Renin Inhibitors

What are the risk factors of HTN that are modifiable?

↑Na+, ↓K+, alcohol, smoking, T2DM, high cholesterol, obesity, diet, inactivity

GLP-1 Analogs: liraglutide (Victoza)

∙Adult Dosing: ・Initial Dosing: 0.6 mg subcutaneously once daily for 1 week ・After 1 week, increase to 1.2 mg daily ・If additional glycemic control is required, increase to 1.8 mg daily after at least one week of treatment with 1.2 mg daily ・Max Dosing: 1.8 mg daily ・The dose of 0.6 mg daily is not effective for glycemic control in adults and is being used to limit gastrointestinal symptoms during initial titration. ∙Pediatric Dosing: ・Initial Dosing: 0.6 mg subcutaneously once daily for 1 week ・After 1 week, increase to 1.2 mg daily ・After 1 week, increase to 1.8 mg daily for added glycemic control ・Max Dosing: 1.8 mg daily

GLP-1 Analogs: exenatide (Byetta IR; Bydureon ER)

∙Adult Dosing: Byetta (exenatide immediate-release) ・Initial Dosing: 5 mcg subcutaneously twice daily (within 60 minutes of meals) ・Dosage should be adjusted according to clinical response ・After 1 month of therapy, the dose may be increased to 10 mcg twice daily for added glycemic control ・Max Dosing: 10 mcg twice daily Bydureon & Bydureon BCise (exenatide extended-release) ・Recommended Dosing: 2 mg subcutaneously once weekly ・Max Dosing: 2 mg weekly ∙Pediatric Dosing: Bydureon & Bydureon BCise (exenatide extended-release) ・Recommended Dosing: 2 mg subcutaneously once weekly ・Max Dosing: 2 mg weekly

Leukotriene Receptor Antagonist (LTRA)

∙Asthma, EIB, allergic rhinitis ∙montelukast (Singulair), zafirlukast (Accolate), zileuton (Zyflo) ∙MOA: selectively antagonizes leukotriene receptor CysLT-1, blocking activation of cellular activity associated with inflammatory processes and smooth muscle contraction in the airways and similar effects associated with allergic rhinitis in the nasal passages ∙SE: headache, dizziness, abdominal pain, increased LFTs, upper respiratory infections, sinusitis, and pharyngitis. ∙Key Points: dosed based on age and not weight.

Short Acting Muscarinic Antagonist (SAMA) / Short Acting β2 Agonist (SABA)

∙COPD ∙ipratropium/albuterol (Combivent) ∙MOA: activates β2 adrenergic receptors and at the same time, antagonizes muscarinic receptors, causing airway smooth muscle relaxation and bronchodilation ∙SIG: 1 INH QID; max 6 INH QD ∙SE: bitter taste, dry mouth, cough, tremor, palpitations, ↓K, ↑BG ∙Key points: ・caution with narrow-angle glaucoma or with urinary retention. ・ensure proper inhaler technique

Long Acting Muscarinic Antagonist (LAMA): tiotropium bromide (Spiriva)

∙COPD ∙provide modest improvements in asthma exacerbations and are reserved in patients with uncontrolled asthma despite being on an ICS-LABA. ∙MOA: similar to SAMA but longer ∙t 1/2 = several days ∙Metabolism: Hydrolysis, CYP450 Oxidation, Glutathione Conjugation ∙Bulkier ester which provides greater metabolic stability ∙SIG: inhale the contents of 1 capsule (2P) via Handihaler; 2P QD (Respimat) ∙SE: same as SAMA

Long Acting Muscarinic Antagonist (LAMA) / Long Acting β2 Agonist (LABA) / Inhaled Corticosteroid (ICS)

∙COPD ∙umeclidinium/vilanterol/fluticasone (Trelegy Ellipta) ∙MOA: 1. Blocks muscarinic receptors that are involved in contraction of smooth muscles in the lungs, causing airway to relax. 2. activates β2 receptors in the airways, causing them to relax 3. inhibiting inflammatory cell activity and reducing the release of inflammatory mediators to keep airways open ∙SE: nasopharyngitis, HA, URTI, pneumonia (rare, but serious SE)

Long Acting Muscarinic Antagonist (LAMA): umeclidium bromide [w/ vilanterol (Anoro Ellipta)]

∙COPD (maintenance) ∙MOA: antagonizes muscarinic receptors causing airway smooth muscle relaxation and bronchodilation, while a LABA activates beta-2 adrenergic receptors causing airway smooth muscle relaxation and bronchodilation. ∙DOA: > 24 hours ∙SIG: QD ∙negligible oral absorption ∙t 1/2 = 11 hours ∙Metabolism: CYP2D6 - O-dealkylation, hydroxylation; extensive metabolism

Long Acting Muscarinic Antagonist (LAMA): aclidinium bromide (Tudorza)

∙COPD (maintenance) ∙MOA: same as tiotropium ∙SIG: BID ∙t 1/2 = 5 to 8 hours ∙limited oral absorption ∙Metabolism: extensive hydrolysis for the drug that is systematically absorbed (despite the bulky ester ➡ lipophilic)

β-blockers

∙CV indications such as HTN, HF, angina (1st line for chronic stable angina), AF. ∙Other indications: migraine prophylaxis, glaucoma, performance anxiety, sx of hyperthyroidism, familial palsy and tremors ∙MOA: competitively inhibit NE and Epi from binding onto β-adrenergic receptors leading to a ↓ HR and contractility. ***Remember: NE and Epi are endogenous hormones that normally bind to β-adrenergic receptors in ❤️ muscles → ↑ in HR and contractility ∙non-selective β-antagonists: block both β1- and β2-receptors ・propranolol (Inderal), sotalol (Betapace), pindolol (Visken)**, timolol (Timoptic) **pindolol has intrinsic sympathomimetic activity (ISA) that is associated with less resting bradycardia and less peripheral vasoconstriction (meaning they also stimulate β-adrenergic receptors, mimicking the effects of NE and EPI) ∙selective β1 (cardioselective)-antagonists: more selective to β1, although this selectivity can be lost when doses are pushed. **MANBABE** ・metoprolol (Toprol XL, Lopressor) ・atenolol (Tenormin) ・nebivolol (Bystolic)* ・bisoprolol ・acebutolol (Sectral)** ・betaxolol ・esmolol (Brevibloc) *nebivolol has one isomer that is β1 selective, and the other isomer promotes endothelial NO-dependent vasorelaxation. **acebutolol has ISA just like pindolol ∙non-selective ⍺1- and β-receptor blocker and/or partial agonist: in addition to blocking β1- and β2-receptors, they block ⍺1-receptors that contribute to blood vessel dilating effects ・carvedilol (Coreg) ・labetatol (Normodyne) ∙SIG: (see image) ∙SE: ↓HR, fatigue/dizziness, ↓ exercise tolerance (caution with asthma/COPD), mask hypoglycemia (except sweating and hunger) ∙Key points: do not abruptly stop taking β-blockers. if pt wants it off, they either have to taper off over 1 to 2 weeks to avoid rebound hypertension, or recommend medical attention.

Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors

∙CVD prevention; as an adjunct to diet, alone or in combination with other lipid lowering therapies (i.e. simvastatin, ezetimibe) for tx of adults with primary hyperlipidemia to reduce LDL-C ∙evolocumab (Repatha) ∙MOA: inhibiting PCSK9 from binding to LDL receptors which result in an ↑ LDL-R → ↑ liver capacity to remove LDL-C ∙SIG: SW Q2-4wk ∙SE: nasopharyngitis, URTI, influenza, back pain, and injection site rxns ∙Key points: ・3rd line LDL lowering agent ・C/I in pts with serious hypersensitivity to Repatha ・can lower LDL-C by 60% in pts on statin therapy ・clinical benefits = ↓ rates of stroke or MI

GLP-1 Analogs: liraglutide (Victoza), exenatide (Byetta IR; Bydureon ER), dulaglutide (Trulicity), semaglutide (Ozempic)

∙Glucagon-like Peptide (GLP) ∙T2DM ∙MOA: ・GLP (or incretin) is a type of hormone that is commonly found in the gut. It gets released during meals and travels to the pancreas to cause an increase in glucose-dependent insulin secretion. In T2DM, this process is becomes blunted or absent. ・GLP-1 Agonists are incretin mimetics that bind to and activate GLP-1 receptors in the pancreas increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and promoting fullness (satiety) resulting in weight loss. ∙SE: (decreases over time): nausea, diarrhea, HA; hypoglycemia, injection site irritation, pancreatitis (rare, but severe), weight loss ∙BBW: risk of thyroid C-cell tumors → avoid if personal or family hx of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome ∙Key Points: ・rotate sites (stomach area, upper thigh, of back of the arm) with each injection. ・Never share GLP-1 Analog pens between patients ・Keep refrigerated and stable at room temp once out of the fridge ・monitor A1C every 3 months (while not at goal); 6 months (if at goal) ・Assess frequency of hypoglycemia ・Avoid: CrCl < 30 ml/min (exenatide IR) and eGFR < 45 ml/min (exenatide ER), gastroparesis, acute pancreatitis ・(liraglutide): should be used during pregnancy ONLY IF the potential benefits justifies the potential risk to the fetus ・not recommended in patients with hx of drug-induced immune-mediated thrombocytopenia from exenatide products ・avoid in patients with diabetic retinopathy complications with a history of diabetic retinopathy (dulaglutide) ・avoid in patients with acute gallbladder disease

Calcium Channel Blockers (CCBs): Non-dihydropyridines (Non-DHPs)

∙HTN and angina ∙diltiazem (Cardizem, Dilacor, Tiazac), verapamil (Calan, Veralan) ∙MOA: inhibits the transmembrane influx of calcium ions in blood vessels and myocardium leading to dilation of the main coronary and systemic arteries. This leads to decreased myocardial contractility, decreased peripheral arterial resistance, and improved oxygen delivery to the myocardial tissue. ∙SIG: (see image) ∙SE: light-headedness upon initiation, edema, HA, nausea, (-) CYP3A4, ↓HR, constipation (verapamil), gingival hyperplasia, arrhythmias ∙Key points: ・monitor HR, BP, electrolytes, and ECG ・Non-DHPs are more selective for cardiac muscle cells, and thus are more potent negative inotropes than DHP CCBs. ・C/I 2°/3° AV block, systolic HF (ok in diastolic HF), acute MI and pulmonary congestion documented by xray or admission ・do not start or ↑ if HR <55 to 60, ↓ or stop if HR <50

Diuretics

∙HTN, CHF, edema ∙MOA: promote diuresis to expel extra Na+ and H2O from the body ∙Diuretic Sites of Action: Proximal DT, Ascending Loop of Henle, Distal CT, and Collecting Ducts ∙5 types: Loop, Osmotics, Thiazides, Carbon Anhydrase Inhibitors, Aldosterone and Na+ channel blockers

Diuretics: Thiazides

∙HTN, edema ∙MOA: decreases the reabsorption by blocking Na+/Cl- symporter in distal convoluted tubule of nephrons, causing an increased excretion of Na+ and Cl- as well as yielding diuresis. ∙chlorthalidone (preferred tx for HTN), hydrochlorothiazide (aka HCTZ) (Hydrodiuril), indapamide (Lozol), metolazone (Zaroxolyn) ∙SIG: (see image) ∙SE: lightheadedness, increased urination frequency, increased sensitivity to sunlight, ↓K, ↓Na, ↓Mg, ↑Ca, ↑ uric acid, ↑ glucose ∙Key Points: ・Avoid NSAIDS → ↑Na+ retention and a vasoconstrictive effect ・Watch for signs of dehydration and/or electrolyte imbalance ・Assess for changes in electrolytes, renal function (necessary for Thiazide diuretic efficacy and safety), and lipids regularly (may cause TG and LDL ↑) ・C/I: patients who are anuria as well as who are on lithium (reduces renal clearance of lithium and add a high risk of lithium toxicity), and Sulfanomide-derived drugs should be avoided. ・It may precipitate hyperuricemia and acute gout in certain patients ・Possibility of exacerbation or activation of SLE ・Use with caution in patients who have impaired hepatic function or progressive liver disease (chlorthalidone) ・It can cause idiosyncratic reactions such as acute myopia and secondary angle-closure glaucoma (HCTZ)

Diuretics: Potassium (K+)-sparing

∙HTN, edema, CHF ∙most commonly used in combination with Thiazide diuretics ∙amiloride, eplerenone (Inspra)*, spironolactone (Aldactone)*, triamterene (Dyrenium) ∙MOA: ・inhibits epithelial cell sodium channels (ENaC) in the collecting duct of nephrons. This inhibition of sodium reabsorption causes decreased potassium excretion. ENaC inhibition produces a weak diuretic effect and does not significantly lower blood pressure alone. ・aldosterone receptor blocker* ∙SIG: (see image for amiloride and triamterene); eplerenone: 50-100 mg once or in 2 divided doses daily; spironolactone: 25-100 mg once daily ∙SE: dizziness, nausea, diarrhea, rash, photosensitivity, ↑K+, gynecomastia (in spironolactone), breast tenderness (in spironolactone), impotence and menstrual irregularities (in spironolactone) ∙Key Points: ・Always take in the morning to avoid nocturia ・Avoid NSAIDs and lithium ・Avoid using salt-substituents in diet ・Assess for changes in K+ levels and renal function regularly ・Use extreme caution with drugs that can cause increased serum potassium levels such as ACEIs, ARBs, heparin, NSAIDs, etc. if unavoidable (monitor serum potassium frequently). ・C/I in patients with: ・anuria ・severe or progressive kidney disease or dysfunction, with the possible exception of nephrosis ・severe hepatic disease ・pre-existing elevated serum K+ ・development of hyperkalemia ・dietary potassium supplements, potassium salts or potassium-containing salt substitutes ・concomitant use w/ other K-sparing agents ・DM and metabolic or respiratory acidosis (amiloride) ・Addison's Disease (spironolactone) ・renal impairment with CrCl ≤ 30 ml/min (or < 50ml/min for HTN) (eplerenone) ・who are using strong CYP3A inhibitors

Calcium Channel Blockers (CCBs): Dihydropyridines (DHP)

∙HTN; CAD, angina ∙MOA: inhibits the transmembrane influx of calcium ions into vascular smooth muscle (primarily) and cardiac muscle, causing peripheral arterial vasodilation. This leads to reduced peripheral vascular resistance and reduced blood pressure. Therefore, it only acts on peripheral vasculature (no effect on AV node)--they are more selective for vascular smooth muscle, and thus more potent vasodilators than non-DHP CCBs. ∙DIPINE: felodipine (Plendil), amlodipine (Norvasc), nifedipine (Procardia XL) →→FAN ∙SIG: (see image) ∙SE: HA/flushing, reflex tachycardia (↑HR), ankle oedema, gingival hyperplasia, hypotension ∙Key points: ・Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily. ・monitor pts with bradycardia, hypotension and edema

GLP-1 Analogs: semaglutide (Ozempic)

∙Initial Dosing: 0.25 mg subcutaneously once weekly for 4 weeks ・After 4 weeks of 0.25 mg weekly, increase to 0.5 mg weekly ・If additional glycemic control is needed after at least 4 weeks of 0.5 mg weekly, the dosage may be increased to 1 mg weekly ・If additional glycemic control is needed after at least 4 weeks of 1 mg weekly, the dosage may be increased to 2 mg weekly ∙Max Dosing: 2 mg weekly The dose of 0.25 mg weekly is not intended for glycemic control and is being used to limit gastrointestinal symptoms during initial titration

GLP-1 Analogs: dulaglutide (Trulicity)

∙Initial Dosing: 0.75 mg subcutaneously once weekly ・Dosage should be adjusted according to clinical response ・Increase to 1.5 mg weekly for added glycemic control ・If additional glycemic control is needed, increase the dosage in 1.5 mg increments after at least 4 weeks on the current dosage ∙Max Dosing: 4.5 mg weekly

Opioid Analgesics

∙MOA: a natural or semisynthetic full opioid agonist that binds to opioid receptors (primarily mu-opioid receptors) blocking transmission of nociceptive signals and inhibiting other pain pathways to provide pain relief ∙The primary therapeutic action is analgesia, however, this agent also exhibits dose-related degrees of anxiolysis, euphoria, sedation, respiratory depression, and gastrointestinal system smooth muscle contraction. ∙SE: remember MORPHINES M: Myosis O: Orthostatic Hypotension R: Respiratory depression P: Pruritis/rash H: Hypotension I: Inability to go (constipation) N: Nausea E: Euphoria S: Sedation ∙Precautions/Warnings (BBW): ・take lowest effective dose for shortest possible duration ・For chronic opioid therapy, assess benefits vs. risks within 1-4 weeks after initiation/dose increase and at least every 3 months thereafter; screen for signs of opioid misuse, development of opioid use disorder. Monitor pain severity and assess efficacy of therapeutic regimen ・may require regular use of stimulant laxatives if constipation occurs with continued use (a disorder called Opioid-induced Constipation). ・initiate low dose in patients with renal/hepatic impairments ・avoid excessive grapefruit juice consumption (it inhibits CYP3A4 and can ↑ plasma concentrations of oxycodone) ・(Morphine): C/I with concurrent use of MAOIs or use of MAOIs within the last 14 days as well as an increased risked of seizure in pts with seizure disorders ・do not drink alcohol or take other drugs that may cause drowsiness like other opioids, benzodiazepines, and other CNS-depressing agents due to increased risk of CNS/respiratory depression ∙Tolerance develops with prolonged use of an opioid agent, making higher doses/stronger agents potentially required to achieve the same analgesic effect ・Withdrawal occurs with rapid dose reduction or sudden discontinuation after prolonged opioid use--don't abruptly discontinue after taking it for a few weeks or more. slowly taper down to avoid uncomfortable, potentially dangerous withdrawal symptoms. ・Opioid withdrawal symptoms include: opioid drug craving, anxiety, and restlessness to a major syndrome that may include uncontrolled pain, flu-like symptoms, abdominal and muscle cramps, tachycardia, vomiting, sweating, and suicide. ・highly addictive and can be dangerously habit-forming. pt should consult with their healthcare provider if they feel their current regimen is inadequate for symptom control ・can cause opioid overdose. patients/caregivers should be aware of symptoms and proper use of naloxone. opioid overdose sxs include: unresponsiveness, slow or irregular heartbeat, constricted pupils, pale skin, blue-ing lips or finger nails, slowed HR. Call 911 immediately and give naloxone if OD has occured. If available, doses of naloxone should be given every 2-3 minutes until the person wakes up or emergency personnel arrive. Naloxone wears off after 30-90 minutes (opioids stay in the body longer) so it is important to stay with the person until medical personnel arrive or they are able to be transported to a hospital. ・Pregnancy/Lactation: ・prolonged use of opioids during pregnancy may cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts ・opioid analgesics can be present in human milk, so infants exposed to opioids through breastmilk should be monitored for excess sedation and respiratory depression withdrawal symptoms can occur in breastfed infant when maternal administration of opioid analgesic is stopped or when breast-feeding is stopped

Smoking Cessation: bupropion HCL SR 150 mg (Zyban)

∙MOA: unknown; however, it is a weak reuptake inhibitor of norepinephrine and dopamine. Does not inhibit the reuptake of serotonin and does not inhibit monoamine oxidase. ∙begin 1 week PRIOR to quit date (it is recommended to set a target quit date within the first 2 weeks of treatment) ∙Initial dosing: 150 mg once daily AM x 3 days, then 150 mg BID x 7-12 weeks with minimum 8-hr interval between doses. ∙Max dosing: 300 mg/day If treatment is not achieved after 7 to 12 weeks, d/c bupropion and reassess. ∙SE: xerostomia, insomnia, HA, tinnitus, agitation, tremors/seizures, weight loss, blurred vision, constipation, n/v, ↑HR ∙BBW: d/c if patient has agitation or suicidal ideation (especially young adults) ∙C/I: seizure disorder, hx of anorexia/bulimia, MAOI within 14 days, use w/ linezolid or IV methylene blue, abrupt d/c of EtOH, BZD, barbiturates, antiepileptics ∙use caution with underlying psych disorders; avoid use in pilots, air traffic controllers, commercial truckers, bus drivers ∙Pregnancy Cat C

Insulin: intermediate (Basal)

∙NPH (Novolin N; Humulin N) ∙Onset: 2 to 4 hr ∙Peak: 4 to 10 hr ∙Duration: 10 to 16 hr ∙Stability: Novolin N (vials): 31 days; Humulin (vials): 42 days Novolin N (pens): 14 days; Humulin (pens): 14 days

Smoking Cessation: NRT-Patch

∙Nicoderm CQ, Habitrol ∙>10 cigs/day: use 21 mg patch/day for 6 weeks, then 14 mg patch/day for 2 weeks, then 7 mg patch/day for 2 weeks ∙≤10 cigs/day: use 14 mg patch/day for 6 weeks, then 7 mg patch/day for 2 weeks ∙Apply 24 hour patch upon waking; if sleep disrupted, may remove patch at bedtim ∙Remove before MRI **PATCH HIGHEST ADHERENCE RATE** ∙Pregnancy Cat D ∙Duration: 8 to 10 weeks

Smoking Cessation: NRT-Lozenge

∙Nicorette, Nicorette Mini ∙1st cig ≤ 30 min after waking up → use 4mg lozenge ∙1st cig > 30 min after waking up → use 2 mg lozenge ∙Schedule: Max 20 lozenges/day; Min 9 lozenges/day ・Weeks 1 to 6: 1 lozenge Q1-2H ・Weeks 7 to 9: 1 lozenge Q2-4H ・Weeks 10 to 12: 1 lozenge Q4-8H ∙Dissolve in mouth, do not chew ∙Takes 20 to 30 mins to dissolve ∙Pregnancy Cat C ∙Duration: up to 3 months

Smoking Cessation: NRT-Gum

∙Nicorette, Nicorette Starter Kit, Nicorelief, Thrive ∙≥25 cigs/day → use 4 mg ∙<25 cigs/day → use 2 mg ∙Schedule: Max 24 pieces/day ・Weeks 1 to 6: 1 pc Q1-2H ・Weeks 7 to 9: 1 pc Q2-4H ・Weeks 10 to 12: 1 pc Q4-8H ∙chew gum slowly until "peppery" or "flavored" taste emerges, then "park" in between cheek and gums to facilitate nicotine absorption through oral mucosa ∙gum should be intermittently chewed and parked for about 30 min or until taste or tingle goes away ∙Pregnancy Cat C ∙Duration: up to 3 months

Smoking Cessation: NRT-Inhaler

∙Nicotrol Inhaler ∙Use 6 to 16 cartridges daily (use 1 cartridge Q1-2H initially); taper frequency of use over 6 to 12 weeks ∙Avoid: bronchospastic disorder ∙Frequent, continuous puffing for 20 min with each cartridge. Once cartridge opens it is good for one day. Peak effect within 15 mins. ∙Clean mouthpiece with soap and water regularly ∙Pregnancy Cat D ∙Duration: up to 6 months

Smoking Cessation: NRT-Nasal Spray

∙Nicotrol NS ∙Initiate with 1 to 2 doses Q1H (min 8 doses/hr) → ↑PRN ∙Max 5 doses/hr or 40 doses/day ∙Note: 1 dose = 2 sprays (1 spray in each nostril) ∙Do not sniff, swallow or inhale through the nose (irritating effect) ∙Spray is best delivered with head tilted slightly back ∙Avoid in severe reactive airway disease, chronic nasal disorder ∙Mimics nicotine the most: highest dependence potential ∙Pregnancy Cat D ∙Duration: up to 3 months

Usual DOAC dosing for DVT prophylaxis (hip/knee replacement)

∙Pradaxa: 110 mg on 1st day, then 220 mg QD (Hip x28-35 days; Knee x6-10 days) ∙Xarelto: 10 mg QD (Hip x35 days; Knee x12 days) ;Acutely ill: 10 mg QD x31-39 days ∙Eliquis: 2.5 mg BID (Hip x35 days; Knee x12 days)

Usual DOACs dosing for AF

∙Pradaxa: 150 mg BID ∙Xarelto: 20 mg QD WM ∙Eliquis: 5 mg BID

Renal adjusted dose for AF with DOACs

∙Pradaxa: CrCl 15 to 30 or CrCl 30 to 50 w/ dronedarone or ketoconazole (PO): 75 mg BID (Avoid P-gp inhibitor if CrCl < 30. Per ACCP, C/I in CrCl < 30) ∙Xarelto: CrCl 15 to 50: 15 mg QD WF (Avoid if CrCl <15; consider Eliquis or warfarin) ∙Eliquis: 2.5 mg BID if ≥ 2 of the following: ・≥ 80 yo, ≤60 kg, SCr ≥ 1.5 (preferred NOAC* in ESRD/dialysis) *NOAC: new oral anticoagulant*

Usual DOAC dosing for DVT Tx

∙Pradaxa: start after 5 days of IV Anticoag: 150 mg BID ∙Xarelto: 15 mg BID WF x 21 days, then 20 mg QD WF ∙Eliquis: 10 mg BID x 7 days, then 5 mg BID

SGLT2-Inhibitor: canaglifozin (Invokana), empagliflozin (Jardiance)

∙Sodium Glucose co-transporter 2 Inhibitor ∙T2DM ∙risk reduction of hospitalizations for HF patients with T2DM ∙MOA: SGLT2 proteins are located in the proximal convoluted tubules of the kidneys and are responsible for 90% of glucose reabsorption. SGLT2-inhibitors work by inhibiting SGLT-2 leading to decrease reabsorption of glucose and an increase in its excretion in the urine. ∙SIG: take in the morning before first meal of the day ・canaglifozin: 100 mg QAM (max 300 mg/day) ・empaglifozin: 10 mg QAM (max 25 mg/day) ∙SE: hypotension, genital mycotic infection, ↑ urination, ↑K, renal insufficiency, ↑LDL-C ***Remember HULKY*** H: hyperkalemia; hypotension U: UTI L: loss of weight K: ketoacidosis Y: yeast infections (genital) ∙BBW: ↑ risk of lower limb amputation (canagliflozin) ∙Key Points: ・check A1C every 3 months (while not at goal); 6 months (if at goal) ・monitory blood glucose closely d/t the risk of hypoglycemia when used in combination with sulfonylureas and insulin ・limit 100 mg/day of canaglifozin if eGFR 30 to < 60 ml/min; initiation is not recommended if eGFR is < 30 ml/min (renal impairment) ・avoid in patients with severe hepatic impairment (canagliflozin) ・use of empagliflozin for glycemic control in patients without established cardiovascular disease or cardiovascular risk factors is not recommended when eGFR < 30 mL/min. ・C/I: dialysis; hypersensitivity to the drug ingredient ・watch out for s/sx dehydration (dizziness, lightheadedness, and thirst) ・Fournier's gangrene (rare, but serious life-threatening necrotizing infection in the genital or perineal area. if suspected, D/C canagliflozin right away and start tx immediately with broad spectrum abx)

Insulin(s)

∙T1DM, T2DM, Gestational Diabetes ∙MOA: a hormone produce by β-cells in the pancreas, works to regulate the metabolism of carbohydrates (simple sugars), protein, and fats by promoting the absorption and storage of glucose from the blood into liver, fat, and skeletal muscle cells to be used as energy. A combination of basal (long-acting) and bolus (short-acting) insulin replicates the physiologic insulin. ∙Basal: Suppress BG production between meals and overnight ∙Bolus: Covers ↑BG following a meal ∙Grouped according to how fast they work in the body: ・rapid (last 2 to 5 hours) and short-acting (last 4 to 8 hours) insulin help reduce blood sugar at meal times ・intermediate (last 12 to 16 hours) and long-acting (last 12 to 24 hours) insulin help manage blood sugar throughout the day ・ultra-long acting last 48 hours ∙SE: ***Remember WILD*** W: weight gain I: injection site reaction L: low blood sugar (hypoglycemia) D: drop in K+ ∙Key Points: ・inject the exact dose of insulin as prescribed subcutaneously into the abdomen (preferred), upper arms, thighs, or buttocks. count to 5 seconds before pulling out the needle. dispose needles into the sharps container and do not share needles. rotate injection sites every 1 to 2 weeks. ・when mixing insulins, always draw up the clear insulin (regular or rapid-acting insulin) before the cloudy insulin (NPH). Insulin glargine and insulin detemir should not be mixed with any of other insulins. ***Remember: We prefer CLEAR days over CLOUDY DAYS*** ・store unopened insulin vials or pens in the refrigerator. ・check A1C every 3 months (while not at goal) or 6 months (if at goal) ・watch for sxs of hypoglycemia (fatigue, hunger, increased anxiety, dizziness, palpitations). high risk of level 2 hypoglycemia; consider prescribing glucagon.

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: sitagliptin (Januvia), linagliptin (Tradjenta)

∙T2DM ∙MOA: a dipeptidyl peptidase-4 (DPP-4) inhibitor, which is believed to exert its actions in patients with type 2 diabetes mellitus by slowing the inactivation of incretin hormones (e.g. GLP-1 and GIP). These hormones are rapidly inactivated by the enzyme, DPP-4. By increasing and prolonging active incretin levels, DPP-4 inhibitors increase insulin release and decrease glucagon levels in the circulation in a glucose-dependent manner. ∙Benefits: no weight gain ∙SIG: Take with or without food. Sitagliptin: Recommended Dosing: 100 mg by mouth once daily Max Dosing: 100 mg daily Linagliptin: Recommended Dosing: 5 mg by mouth once daily Max Dosing: 5 mg daily ∙SE: UTI, HA, rash, nasopharyngitis/URTI ∙Key Points: ・(sitagliptin): If eGFR ranges between 30 mL/min to < 45 mL/min, limit dose to 50 mg once daily; If eGFR <30 mL/min or in patients on dialysis, limit dose to 25 mg once daily. May be administered without regard to the timing of dialysis. ・(linagliptin): no renal adjustments needed ・potential increased risk of pancreatitis and heart failure ・increased risk of hypoglycemia when used in combination with SFUs and insulin

Sulfonylureas (SFUs): glyburide (Diabeta, Micronase, Glynase), glipizide (Glucotrol), glimepiride (Amaryl)

∙T2DM ∙MOA: stimulates insulin secretion from pancreatic β cells. ∙2nd generation SFUs: glyburide, glipizide, glimepiride ∙SIG: Glyburide: Standard tablets (Diabeta) ∙Initial Dosing: 2.5-5 mg PO QD with breakfast or first main meal ・Elderly patients and those with renal or hepatic insufficiency may be initiated on 1.25 mg daily ・Dosage should be adjusted according to clinical response ・Generally, up to 2.5 mg increments at weekly intervals as needed ・Doses greater than 10 mg daily may be better tolerated as two divided doses ∙Max Dosing: 20 mg daily (as single or divided doses) Micronized tablets (Glynase) ∙Initial Dosing: 1.5-3 mg PO QD with breakfast or first main meal ・Elderly patients and those with renal or hepatic insufficiency may be initiated on 0.75 mg daily ・Dosage should be adjusted according to clinical response ・Generally, up to 1.5 mg increments at weekly intervals as needed ・Doses greater than 6 mg daily may be better tolerated as two divided doses ∙Max Dosing: 12 mg daily (as single or divided doses) Glipizide: Immediate-release tablet ∙Initial Dosing: 5 mg PO QD 30 minutes prior to breakfast ・Elderly patients and those with liver disease may be initiated on 2.5 mg daily ・Dosage should be adjusted according to clinical response ・Generally, in 2.5 - 5 mg increments every several days as needed ・Doses greater than 15 mg daily should be divided and given before meals ∙Max Dosing: 40 mg daily (in divided doses) Extended-release tablet ∙Initial Dosing: 5 mg PO QD with breakfast (or first main meal) ・Elderly patients and those with liver disease may be initiated on 2.5 mg daily ・Dosage should be adjusted according to clinical response ∙Max Dosing: 20 mg daily Glimepiride ・Initial Dosing: 1-2 mg by mouth once daily with breakfast or first main meal ・Elderly patients and those with renal impairment should be initiated on 1 mg daily ・Dosage should be adjusted according to clinical response ・Generally, in 1-2 mg increments every 1-2 weeks as needed ∙Max Dosing: 8 mg daily ∙SE: nausea, heartburn, weight gain ***Remember SLG, Sulfonylureas Lowers Glucose*** S: Stomach upset (nausea/vomiting) L: Lowers BG G: Gain weight ∙Key Points: ・C/I in patients with T1DM, DKA, use with bosentan (glyburride), sulfa allergy ・use extreme caution in elderly patients (glyburide) (Beers Criteria) ・use in patients with severe hepatic or renal impairment (esp. glipizide which requires renal adjustments), and pregnant women ・glyburide has the highest risk of hypoglycemia in renal impairment and makes your blood to glide down too much ・monitor BG in frequent intervals (2 to 4 x/d) as directed by doctor ・avoid long-acting SFUs (i.e. glyburide) in pt ≥ 60 y.o. and CrCl < 50 d/t ↑ risk of hypoglycemia

Biguanides: metformin (Glucophage)

∙T2DM; (off-label): Gestational Diabetes, Polycystic Ovary Syndrome (PCOS) ∙MOA: decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease. ∙Benefits: no weight gain; ↓ Hepatic glucose production, ↓ glucose absorption from the gut, ↑ glucose uptake by cells in the body ∙SIG: Take each dose with a meal Adult dosing for Immediate-release tablet: Initial Dosing: 500 mg PO BID (or 850 mg once daily) with meals ・Dosage should be adjusted according to clinical response ・Increase in 500 mg increments weekly, or 850 mg increments every 2 weeks ・Max 2550 mg daily ・Doses above 2000 mg daily may be better tolerated if given in 3 divided doses Max Dosing: 2550 mg daily (in divided doses) Adult dosing for Extended-release tablet: Initial Dosing: 500 mg PO QD with evening meal ・Dosage should be adjusted according to clinical response ・Increase in 500 mg increments weekly ・Max 2000 mg daily (with evening meal) ・If glycemic control is not achieved with 2000 mg once daily, consider a trial of 1000 mg twice daily Max Dosing: 2000 mg daily (in single or divided doses) Adult dosing for Oral solution: Metformin oral solution has a concentration of 100 mg/mL (500 mg/5 mL). Initial Dosing: 500 mg PO BID (or 850 mg once daily) with meals ・Dosage should be adjusted according to clinical response ・Increase in 500 mg increments weekly, or 850 mg increments every 2 weeks ・Max 2550 mg daily ・Doses above 2000 mg daily may be better tolerated if given in 3 divided doses Max Dosing: 2550 mg daily (in divided doses) Pediatric (≥ 10 y.o.) dosing for IR tablets: Initial Dosing: 500 mg PO BID ・Dosage should be adjusted according to clinical response ・Increase in 500 mg increments weekly ・Max 2000 mg daily Max Dosing: 2000 mg daily (in divided doses) Pediatric (≥ 10 y.o) dosing Oral solution: Metformin oral solution has a concentration of 100 mg/mL (500 mg/5 mL). Initial Dosing: 500 mg PO BID ・Dosage should be adjusted according to clinical response ・Increase in 500 mg increments weekly ・Max 2000 mg daily Max Dosing: 2000 mg daily (in divided doses) ∙SE: initial stomach upset and/or diarrhea, hypoglycemia, lactic acidosis (rare), B12 deficiency; ***Remember BRAG*** B: B12 deficiency R: Renal dosing required A: Acidosis (lactic) G: GI disturbances (abdominal pain, flatulence, cramping) ∙Key Points: ・C/I: not recommended for patients with renal impairment (eGFR 30 - 45 ml/min) ・C/I: not recommended for patients with hepatic impairment due to lactic acidosis ・C/I: excessive EtOH intake → lactic acidosis ・concomitant use of ranolazine 1000 mg BID and metformin results in increased plasma levels of metformin. When ranolazine 1000 mg BID is co-administered with metformin, metformin dose should not exceed 1700 mg/day. Monitor blood glucose levels and risks associated with high exposures of metformin. Note: Metformin exposure was not significantly increased when given with ranolazine 500 mg BID ・check A1C every 3 months (while not at goal) or 6 months (if at goal) ・monitor renal function and B12 levels ・assess frequency of hypoglycemia ・C/I in patients with acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma

Thiazolidinediones (TZDs): pioglitazone (Actos), rosiglitazone (Avandia)

∙T2DM; as an adjunct diet and exercise to improve glycemic control in adults with T2DM ∙MOA: agonizes peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptors causing increased peripheral insulin sensitivity. PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and the liver. ∙The decreased insulin resistance results in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower A1C values. This class of medication depends on the presence of insulin for its MOA. ∙Benefits: good lipid profile (Actos: ↑HDL, ↓TG); ↑ insulin sensitivity, ↑ glucose uptake in muscles and fat, ↓ glucose production in the liver ∙SIG: QD with food (Liver function tests should be obtained prior to starting therapy.) Initial Dosing: 15-30 mg PO QD ・An initial dose of 15 mg daily is recommended in patients with congestive heart failure (NYHA class I or II) ・Dosage should be adjusted according to clinical response ・Titrate in 15 mg increments to a max daily dose of 45 mg Max Dosing: 45 mg QD ∙SE: weight gain, fluid retention, URTI, HA, mild anemia, ↑AST/ALT (rare), ↑ fracture risk ***Remember HUGE Heart*** H: Hypoglycemia U: URTI G: Gain weight E: Edema, peripheral Heart failure exacerbation ∙Key Points: DDI: coadministration of gemfibrozil (strong CYP2C8 inhibitor) and pioglitazone increases the exposure of pioglitazone by 3-fold. Therefore, the maximum recommended dose of pioglitazone is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors; CYP2C8 inducers, such as rifampin, may significantly reduce the exposure (AUC) of pioglitazone. Therefore, if an inducer of CYP2C8 is started or stopped during treatment with pioglitazone, changes in diabetes tx may be needed based on clinical response without exceeding the maximum recommended daily dose of 45 mg for pioglitazone. ・check A1C every 3 months (while not at goal) and 6 months (if at goal) ・assess hypoglycemia frequency ・routinely check for weight gain and edema ・educate patients that it may take several weeks for the onset of effects to show ・monitor blood glucose in frequent intervals (2 to 4 times a day) as directed by doctor ・pioglitazone has cardiovascular benefits (e.g. stroke, heart attacks) and may improve lipid levels ・BBW: avoid Class III/IV HF, ↑ risk of MI (rosiglitazone), ↑ risk of bladder cancer (pioglitazone)

Opioid Analgesic: tramadol

∙Ultram ∙Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate (tablet, solution) ∙Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate (extended release tablet, extended release capsule) ∙MOA: a synthetic mu (µ)-opioid agonist and a weak inhibitor of NE and serotonin reuptake. Tramadol is metabolized via CYP2D6 to the active metabolite, M1, which is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in mu-opioid binding. It works for analgesia by blocking transmission of nociceptive signals and inhibiting other pain pathways. (In short, it is a central acting analgesic that have dual mechanism of action that includes partially binding to central mu-receptors to produce analgesic effects (less affinity to opioids, and inhibiting serotonin (5-HT) and NE uptake in the CNS to provide pain relief) The primary therapeutic action is analgesia, however, this agent also exhibits dose-related degrees of anxiolysis, euphoria, sedation, respiratory depression, and gastrointestinal system smooth muscle contraction. ∙SIG: (IR): Initial Dosing: For patients not requiring rapid analgesic onset: ・Start with 25 mg by mouth daily ・Titrate in increments of separate 25 mg doses every 3 days to reach 100 mg/day (25 mg four times daily) ・Thereafter, may increase by 50 mg every 3 days to reach 200 mg/day (50 mg four times daily) ・After titration, may give 50-100 mg Q4-6H PRN (max 400 mg/day) For patients requiring rapid analgesic onset: ・50-100 mg Q4-6H PRN (max 400 mg/day) Max Dosing: 400 mg/day (80 mL of oral solution) Dose reduction or discontinuation: In physically opioid-dependent patients, initiate taper in small decrements (no more than 10-25% of TDD) at 2-4 week intervals ・Monitor for pain management, withdrawal symptoms, and mood changes (ER): Initial Dosing: 100 mg by mouth once daily. This is also the recommended initial dosing for those converting from other opioids ・Discontinue all other around-the-clock opioids upon initiation of tramadol ER Converting from tramadol IR products: ・Calculate the 24-hour total daily IR dose ・Round down to the next lower 100 mg increment of the ER tablet or ER capsule ・ER dosing has limited flexibility - some patients may not be able to convert to ER tramadol Dose titration: titrate by 100 mg increments every 5 days Max Dosing: 300 mg/day Dose reduction or discontinuation: In physically opioid-dependent patients, initiate taper in small decrements (no more than 10-25% of TDD) at 2-4 week intervals ・Monitor for pain management, withdrawal symptoms, and mood changes ∙SE: drowsiness/sedation, upset stomach or nausea (IR), constipation, itching, rash, xerostomia, increased body temp, or sweating, hyponatremia, hypoglycemia ∙Key Points: ・Avoid use in CYP2D6 ultra-rapid metabolizers (toxicity risk) especially in children; caution with initiation of CYP2D6 inducers or discontinuation of concurrent CYP2D6 inhibitors ・risk of serotonin syndrome when used with serotonergic drugs ・increased risk of seizure, and suicidal ideation ・C/I in younger children < 12 y.o. ・C/I in pts who are currently using MAOIs or use within the last 14 days

Smoking Cessation: varenicline (Chantix)

∙a partial nicotine agonist ∙aid to smoking cessation treatment ∙MOA: ・binds with high affinity and selectivity at alpha-4 beta-2 neuronal nicotinic acetylcholine receptors. ・produces agonist activity at these receptors, while simultaneously preventing nicotine binding and subsequent stimulation of the central nervous mesolimbic dopamine system (proposed reinforcement and reward mechanism of smoking). ∙SIG: The patient should set a date to stop smoking. Begin varenicline dosing one week before this date. Alternatively, the patient can begin varenicline dosing and then quit smoking between days 8 and 35 of treatment. ・Initial Titration Dosing: ・Days 1-3: 0.5 mg by mouth once daily ・Days 4-7: 0.5 mg by mouth twice daily ・Day 8 to end of treatment: 1 mg by mouth twice daily ・Maintenance Dosing: 1 mg by mouth twice daily ・Patients should be treated with varenicline for 12 weeks. ・For patients who have successfully stopped smoking at the end of 12 weeks, an additional course of 12 weeks treatment is recommended to further increase the likelihood of long-term abstinence ∙SE: n/v, insomnia, abnormal dreams, HA, constipation, Stevens-Johnson Syndrome (rare, but serious skin rxn), angioedema ∙BBW: d/c if pt has agitation, suicidal ideation or seizure disorder ∙Key Points: ・limit or avoid drinking alcohol while on this medication ・report any changes in mood or behavior ・assess efficacy and tolerance periodically ・adjunctive therapy with NRT not recommended due to increase SE ・Pregnancy Cat C ・Treatment Considerations: ・For patients who are sure that they are not able or willing to quit abruptly, consider a gradual approach to quitting smoking with varenicline. Patients should begin varenicline dosing and reduce smoking by 50% from baseline within the first four weeks, by an additional 50% in the next four weeks, and continue reducing with the goal of reaching complete abstinence by 12 weeks. Continue varenicline treatment for an additional 12 weeks, for a total of 24 weeks of treatment. Encourage patients to attempt quitting sooner if they feel ready. ・Patients who are motivated to quit, and who did not succeed in stopping smoking during prior varenicline therapy for reasons other than intolerability due to adverse events or who relapsed after treatment, should be encouraged to make another attempt with varenicline once factors contributing to the failed attempt have been identified and addressed.

P2Y12 Inhibitors

∙acute coronary syndrome or hx of MI (heart attack) ∙carotid artery stenting ∙Irreversible platelet inhibitor: clopidogrel (Plavix), prasugrel (Effient) ∙Reversible platelet inhibitor: Ticagrelor (Brilinta) ∙MOA: stop platelets (cells that begin the process of clot formation) from aggregating or sticking together by inhibiting P2Y12 component of adenosine diphosphate (ADP) receptors that mediate platelet activation ∙SE: bleeding/bruising, rash/pruritus, abdominal pain (dyspepsia, diarrhea), HA ***Remember BRAH*** ∙Key Points: ・take with or without food, but may administer with food to help with stomach upset ・notify healthcare provider prior to surgical or dental procedure as these drugs are recommended to be held prior to reduce the risk of bleeding ・report any s/sxs of unusual bleeding or bruising, dark and tarry stools, or blood in the urine

Hematinics: cyanacobalamin

∙aka Vit B12 ∙Vit B 12 deficiency ∙MOA: a coenzyme needed for various metabolic functions including fat and carbohydrate metabolism, protein synthesis, cell replication and hematopoiesis. A deficiency of B12 leads to lack of DNA synthesis and presents clinically as macrocytic anemia or hyperhomocysteinemia ∙B12 injections are recommended as first-line for patients with severe deficiency or neurological sxs ∙natural sources of B12: eggs, dairy, salmon, meat ∙S/Sxs of B12 deficiency: fatigue, memory issues, numbness/tingling, weight loss ∙SE: hypersensitivity to the ingredient, pain on injection site (IV formulation), HA, infection, rash ***Remember PAIR*** ∙Key Points: ・take on an empty stomach to increase oral absorption ・it may require several weeks for maximum effect ・avoid EtOH as it inhibits the absorption of B12

Anticoagulants

∙aka blood thinners ∙used to prevent coagulation (or clotting) of blood

Hematinics: folic acid

∙aka vit B9, responsible for healthy cell growth including those found inside of the skin tissues as well as hair and nails ∙megaloblastic and macrocytic anemias due to folate deficiency ∙MOA: a necessary for the formation of several coenzymes in many metabolic systems, particularly purine and pyrimidine synthesis (rate-limiting step in DNA synthesis) and the production of RBCs. ∙SIG: 1 mg (1000 mcg) QD ∙foods that are high in folic acid: broccoli, green leafy vegetables, avocado, beans, peas, lentils, beets ∙SE: flushing, bronchospasm (airway narrows), malaise (rare), skin rash ***Remember FAMS*** ∙Key Points: ・take with or without food ・may take several weeks for maximum effect ・monitor hematocrit, reticulocyte count, vitamin B12, folate and iron levels ・avoid EtOH as it inhibits the absorption of B9

Insulin: rapid-acting (Bolus)

∙aspart (Novolog), lispro (Humalog), glulisine (Apidra) ∙Onset: 5 to 15 min ∙Peak: 0.5 to 1.5 hr ∙Duration: 3 to 5 hours ∙Stability: vial and pens: 28 days ∙For U-100: 1 ml = 100 units of insulin ∙For U-500: 1 ml = 500 units of insulin

Short Acting Muscarinic Antagonist (SAMA)

∙commonly used with SABA for acute asthma exacerbations; COPD ∙ipratropium (Atrovent) ∙MOA: inhibits ACh from binding onto muscarinic receptors on airway smooth muscle cells (hence why they are called anticholinergics) leading to bronchodilation ∙SIG: 2P QID ∙t 1/2 = ~2 hours ∙SE: dry mouth, URTI, nasopharyngitis, sinusitis

Insulin: ultra long-acting (Basal)

∙degludec (Tresiba) ∙Onset: 1 hr ∙Peak: 9 hr ∙Duration: 42 hr ∙Stability: 56 days (pen)

Insulin: long-acting (Basal)

∙glargine (Lantus, Toujeo, Basaglar), detemir (levemir) ∙Onset: Lantus: 3 to 4 hrs Toujeo: 6 hrs Basaglar: 1 to 2 hrs detemir: 2 hrs ∙Peak: Lantus: no peak Toujeo: no peak Basaglar: no peak detemir: ~flat ∙Duration: Lantus: 24 hr Toujeo: 24 hr Basaglar: 24 hr detemir: 14 to 24 hr ∙Stability: Vials and pens Lantus: 28 days Toujeo: 28 days Basaglar (pen): 28 days detemir (pen): 42 days

HMG-CoA Inhibitors

∙hypercholesterolemia/hyperlipidemia ∙1st line LDL lowering agents ∙simvastatin (Zocor), lovastatin (Mevacor), fluvastatin (Lescol), atorvastatin (Lipitor), pravastatin (Pravachol), rosuvastatin (Crestor) ∙MOA: inhibits cholesterol synthesis in the liver by blocking the enzyme HMG-CoA reductase, which prevents the conversion of HMG-Coa to mevalonate. This is the RLS in cholesterol synthesis. ∙SIG: QPM or QHS with or without food due to short half-life (Zocor, Pravachol, Lescol); anytime of the day with or without food (rest of statins) ∙SE: HMG-CoA H: hepatoxicity/HA M: myalgia/myopathy G: GI effects (diarrhea, flatulence) C: CPK increase A: avoid in pregnancy (category X) ∙Key points: ・avoid grapefruit and grapefruit juice ・use of statins with fibrates and niacin products with ≥ 1 gram increases the risk of myopathies (rhabdomyolysis). ・since cholesterol is synthesize at night, statins with short half-life should be taken at bedtime to maximize their effects. ・consider stopping statins in older adults with life expectancy <1 year, dementia, frailty, or multiple comorbidities ・CI: active liver disease (unexplained ↑ LFTs), pregancy and breastfeeding ・monitor LFTs, lipid panel and sx of myopathy (muscle weakness, cramping)

Angiotensin Receptor Blockers (ARBs)

∙hypertension ∙losartan (Cozaar), valsartan (Diovan), olmesartan (Benicar), candesartan (Atacand) ∙MOA: blocks angiotensin II from binding to the angiotensin II (AT1) receptors in many tissues (e.g., vascular smooth muscle, adrenal gland), preventing subsequent vasoconstriction and aldosterone secretion. ∙SIG: (see image) ∙SE: ↑K+, ↑SCr (creatinine serum), angioedema ∙Key points: ・avoid in pregnancy ・do not combine with ACEIs or aliskiren in pts with DM ・do not use w/in 36 hours of Entresto

Angiotensin-Converting Enzyme (ACE) Inhibitors

∙hypertension, HF ∙lisinopril (Zestril, Prinivil), ramipril (Altace), enalapril (Vasotec), benazepril (Lotensin) ∙MOA: inhibits the ACE from converting Angiotensin I to Angiotensin II, resulting in vasodilation and a reduction in BP. ∙SIG: (see image) ∙SE: (ACE Inhibitors = ACE Cards = TOP CARD) T = teratogenic O = orthostatic hypotension P = K+ increase C = cough (dry) A = angioedema R = renal impairment D = dizziness ∙Key Points: ・monitor K+ levels, creatinine levels, and hypersensitivity rxns ・take w/ or w/o food at the same time everyday ・avoid K+ supplements or K+ containing substitutes ・seek medical help if facial or lip swelling occurs ・BBW: pregnancy or breastfeeding, Hx of bilateral renal stenosis, angioedema, use w/ aliskiren in pt's w/ DM, use w/n 36 hrs of Entresto

Fibrates

∙hypertriglyceridemia ∙gemfibrozil (Lopid), fenofibrate (Tricor, Lofibra) ∙MOA: activates Peroxisome Proliferator Activated Receptor-⍺ (PPAR-⍺) → ↑ lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein CIII ∙SIG: Take 30 mins AC (AM and PM) ∙SE: gallstones, myopathy, hepatotoxicity, ↑ LDL when TG is high ∙Key Points: ・C/I: pts with renal and hepatic impairments, gall bladder disease, concomitant use of gemfibrozil with simvastatin, sulfonylureas (SFUs), niacin, ezetimibe

Hematinics: iron supplements

∙iron-deficiency or iron-deficiency anemia ∙Ferrous sulfate, Ferrous gluconate, Ferrous fumarate ∙MOA: RBC use a molecule called hemoglobin to carry oxygen to the body's tissues. To make hemoglobin, cells need iron to build a component called heme. When iron stores are low, it can lead to the development of anemia, and iron supplements are given to replace levels. ∙SIG: Ferrous Sulfate: Each 325 mg tablet of ferrous sulfate provides 65 mg of elemental iron. (1 QD) Ferrous Gluconate: Each 240 mg tablet of ferrous sulfate provides 27 mg of elemental iron. (1 QD) Ferrous Fumarate: Each 324 mg tablet of ferrous sulfate provides 106 mg of elemental iron. (1 QD) ∙SE: constipation (dose-related), stomach upset (n/v, diarrhea), abdominal pain, dark stools ***Remember, too much iron can make you constipated and SAD*** ∙Key Points: ・take on an empty stomach for better absorption, however, it can be taken with food to help with stomach upset ・consult with healthcare provider regarding absorption of other medications that may alter if taken with iron ・may cause discoloration of stools and can mask blood in stool if patients are also on an anticoagulant ・avoid in patients with stomach problems, peptic ulcer, enteritis, or ulcerative colitis ・C/I in patients with hemochromatosis and hemolytic anemia ・keep out of reach of children as fatal poisonings have occured with accidental overdosing or iron-containing products in children < 6 yo

Inhaled Corticosteroids (ICS)

∙key controller medications that work by reducing inflammations specifically in the lungs ∙Asthma ∙Generic (Brand): fluticasone (Flovent), budesonide (Pulmicort), beclomethasone (QVAR), ciclesonide (Alvesco), mometasone (Asmanex) ∙MOA: inhibits inflammatory cells and the release of inflammatory mediators by binding onto glucocorticoid receptors to reduce hyperinflammatory cascade that leads to hyperactivity, swelling, and mucus production ∙SIG: 1 to 4 P BID (QVAR, Pulmicort); 1 to 2 P BID (Alvesco, Flovent, Asmanex) ∙SE: HOCUS (Hoarseness, Oral thrush, Cough, URI (rare and often occurs with high doses or long-term use), Sore throat) ∙Key points: Rinse mouth after use to prevent thrush

Non-pharmacological tx approach for T2DM

∙lifestyle: healthy eating, weight control, ↑ physical activity, diabetes education

Muscle Relaxants: cyclobenzaprine (Flexeril)

∙muscle spasm ∙a centrally acting skeletal muscle relaxant with serotonergic and anticholinergic activity. ∙It appears to act primarily at the brain stem to reduce tonic somatic motor activity by influencing both gamma and alpha motor neurons leading to a reduction in muscle spasms, though the mechanism of action is not fully understood. ∙Structurally (see image), cyclobenzaprine is similar to tricyclic antidepressants and also produces anticholinergic effects. ∙SIG: 5 mg TID is generally as effective as 10 mg TID for acute low back pain and has less sedation. ∙SE: drowsiness, xerostomia, fatigue, urinary retention, confusion, dizziness. ***Remember: Cyclobenzaprine can cause BAD Sedation*** B: Blurred vision A: Anticholinergic side effects D: Dry mouth S: Sedating/Somnolence ∙Key Points: ・limit or avoid drinking alcohol or taking other drugs that may cause drowsiness while on this medication ・rise slowly from sitting or lying, may increase risk of falling. ・report any severe symptoms of agitation, profuse sweating, racing heartbeat, dizziness, or hallucinations to provider ・IR: use caution and titrate slowly in pts with mild hepatic impairments; do not use in pts with moderate to severe hepatic impairments. ER: not recommended in patients with hepatic impairments ・avoid in patients who are ≥ 65 y.o. due to anticholinergic effects, sedation, increased risk fall/fracture, and efficacy (Beers Criteria) ・use caution in patients with urinary retention, angle-closure glaucoma, increased IOP due to high anticholinergic effects ・avoid use in patients with arrhythmia or cardiac conduction abnormalities ・C/I with concomitant use of MAOIs or use within the last 14 days, and pts with hyperthyroidism

Muscle Relaxants: tizanidine (Zanaflex)

∙muscle spasticity ∙a centrally acting alpha-2 adrenergic receptor agonist that reduces spasticity by increasing presynaptic inhibition of motor neurons. Agonism of alpha-2 receptor causes reduction of Glutamate, an excitatory amino acid responsible for neuronal firing that leads to muscle spasms. Tizanidine may also potentiate the action of glycine (an inhibitory neurotransmitter). It is structurally similar to clonidine (see image). ∙SIG: Initial Dosing: 2 mg PO Q6-8H PRN ・Maximum of 3 doses in 24 hours ・May gradually increase in 2-4 mg increments at each dose, at 1-4 day intervals between dose increases Max Dosing: 36 mg/day Maximum studied single dose is 16 mg Discontinuation: When discontinuing tizanidine in patients who have been receiving high doses of (20-36 mg/day) for long periods of time (≥ 9 weeks) OR those who may be on concomitant narcotics, decrease slowly (2-4 mg per day) to reduce the risks of withdrawal, rebound hypertension, tachycardia, and hypertonia. ∙SE: (because of it's similar structure to clonidine, it causes similar SE--low BP, bradycardia, dizziness, hypotension) ***Remember BASH M*** B: Bradycardia A: Asthenia (physical weakness/lack of energy) S: Sedation/dizziness H: Hepatotoxicity M: Mouth dryness ∙Key Points: ・use caution in patients with renal insufficiency (creatinine clearance < 25 mL/min), as clearance is reduced by more than 50%. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. ・use caution in patients with any hepatic impairment. In these patients, during titration, the individual doses should be reduced. If higher doses are required, individual doses rather than dosing frequency should be increased. ・monitor bp in those on antihypertensives or at risk of hypotension ・monitor liver function at baseline and 1 month after max dose is achieved ・withdrawal may occur upon abrupt discontinuation--slowly decrease dose after a few months of continued use at higher doses ・C/I with strong CYP1A2 inhibitors (i.e. ciprofloxacin, fluvoxamine); risk of severe hypotension, bradycardia, drowsiness ・rare, potential risk of hepatotoxicity

Opioid Analgesics: morphine

∙natural full opioid agonist ∙Roxanol (IR); MS Contin, Kadian (ER) ∙Management of acute and chronic pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate (immediate release formulations) ∙Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate (extended release formulations) ∙SIG: ∙Use the lowest effective dose for the shortest possible duration; for acute pain, a few days or less are often adequate. ∙Extended-release/long-acting opioid dosing should be scheduled and not be used intermittently/as needed ・IR dosing: Using morphine as the first opioid analgesic (opioid-naïve or non-tolerant patients): Initial Dosing: (Tablet) 15-30 mg PO Q4H PRN. Do not use morphine sulfate tablet in pediatric patients weighing < 50 kg (Solution) 10-20 mg by mouth Q4H PRN ・ER tablet dosing: Opioid-naïve or non-tolerant patients: Note: morphine sulfate ER (e.g., MS Contin) 100 and 200 mg tablets, a single dose > 60 mg, or TDD > 120 mg are only for patients who tolerate an opioid of comparable potency Initial Dosing: (Opioid-naïve) 15 mg PO Q8-12H (Opioid non-tolerant) 15 mg PO Q12H. Any higher starting doses in non-tolerant patients may cause fatal respiratory depression ・ER capsules dosing (once or twice daily; Kadian and generics) Opioid non-tolerant patients: Note: morphine sulfate ER (e.g., Kadian) 100 and 200 mg capsules, a single dose > 60 mg, or TDD > 120 mg are only for patients who tolerate an opioid of comparable potency Note: do not use morphine sulfate ER capsule (Kadian) as an initial opioid treatment in opioid-naïve patients Initial Dosing: 30 mg PO Q24H. Any higher starting doses in non-tolerant patients may cause fatal respiratory depression ・ER capsules dosing (once daily formulations) Opioid-naïve or non-tolerant patients: Note: morphine sulfate ER 90 and 120 mg once-daily capsules are only for patients who tolerate an opioid of comparable potency Initial Dosing: 30 mg PO Q24H. Any higher starting doses in non-tolerant patients may cause fatal respiratory depression Pediatric Dosing (IR formulation): Tablet Note: do not use morphine sulfate tablet in pediatric patients weighing less than 50 kg Initial Dosing (in those weighing ≥ 50kg): 15 mg PO Q4H PRN Max Dosing: NTE 30 mg as an initial dose Solution (≥ 2 years) Note: only use 2 mg/mL or 4 mg/mL concentrations in pediatric patients Initial Dosing: 0.15-0.3 mg/kg PO Q4H PRN Max Dosing: NTE 20 mg as an initial dose Refer to the following steps for accurate dose measurement: ・Multiply actual body weight (kg) by the recommended dose (0.15-0.3 mg/kg) ・Convert the calculated dose (mg) to volume (mL) using the concentration of the product (mg/mL) ・Round the resulting volume (mL) ・If < 1 mL, round to the nearest 0.1 mL ・If > 1 mL, round to the nearest 0.2 mL ・Convert the rounded volume to the final dose (mg) to be dispensed using the concentration of the product ・Both the calculated final dose and volume should be on prescription ∙Initiate morphine with lower usage than usual and titrate slowly in patients with renal failure and Cirrhosis. ∙if currently taking a CNS depressant, initiate morphine ER tablet with the lowest possible dose (15 mg Q12H) ∙for precautions/warnings, see Opioid Analgesics flashcard.

Muscle Relaxants: methocarbamol (Robaxin)

∙painful musculoskeletal conditions ∙MOA: not well understood but is thought to be related to its sedative effects caused by general central CNS depression. Its effects are possibly mediated through inhibition of acetylcholinesterase. It does not directly act on muscle, motor end plates or nerve fibers. ∙SIG: Initial Dosing: 1500 mg PO QID ・Three 500 mg tablets OR two 750 mg tablets per dose ・Generally, 6 g/day recommended for the first 48-72 hours ・For severe conditions, 8 g/day may be considered ・Thereafter, the dose may be reduced to approximately 4 g/day Maintenance Dosing: Two 500 mg tablets (1000 mg) QID OR One 750 mg tablet Q4H OR Two 750 mg tablets (1500 mg) TID ∙SE: HA, nausea/vomiting, insomnia, drowsiness, dizziness, hypotension, dark green/brown discoloration of urine, Myasthenia Gravis ***Remember: SAILS*** S: Stomach upset (nausea/vomiting) A: Aching head (HA) I: Insomnia L: Low BP (hypotension) S: Sedated State ∙Key Points: ・Take with (if stomach upset occurs) or without food ・Limit or avoid drinking alcohol or taking other drugs that may cause drowsiness while using this medication ・avoid in patients who are ≥ 65 y.o. due to anticholinergic effects, sedation, increased risk fall/fracture, and efficacy (Beers Criteria) ・may exacerbate Myasthenia Gravis symptoms (it inhibits pyridostigmine bromide, so use caution in patients with MG receiving AchE agents)

Muscle Relaxants: carisoprodol (Soma)

∙painful musculoskeletal conditions ∙a controlled substance (CIV) ∙a centrally acting skeletal muscle relaxant whose mechanism of action is not well understood, but is thought to exert its effect through sedative and analgesic effects. Carisoprodol is metabolized by CYP2C19 to meprobamate, which is barbiturate-like, has anxiolytic and sedative properties, and is known to exert action on GABA-A receptors. ∙SIG: may take with or without food. Recommended Dosing: 250-350 mg by mouth three times a day and at bedtime Note: recommended maximum duration of therapy is 2-3 weeks ∙SE: drowsiness, dizziness, HA, vertigo ∙Key Points: ・avoid drinking alcohol or taking other drugs that may cause drowsiness or sedation while on this medication ・do not abruptly discontinue after taking this medication regularly for a few weeks or more; slowly decrease dose to avoid withdrawal symptoms ・can be become addictive ・avoid use in elderly patients (≥65 y.o.) due to anticholinergic effects, sedation, increased fall/fracture risk, and efficacy (Beers Criteria) ・use caution CYP2C19 poor/rapid metabolizers and in use with CYP2C19 inducers/inhibitors ・C/I in patients with hx of acute intermittent porphyria

Give non-pharmacological ways in order to lower BP

∙reduce Na intake ∙aerobic exercise 150 mins/week ∙DASH diet

Insulin: short-acting (Bolus)

∙regular (Novolin R, Humulin R) ∙Onset: 0.5 to 1 hr ∙Peak: 2 to 3 hr ∙Duration: 5 to 8 hr ∙Stability: Novolin R (vials): 31 days; Humulin R (vials) 42 days

Methylxanthines

∙reversible airflow obstruction sx ∙theophylline (Theo-Dur, Theo-24 Elixophyllin, Theochron) ∙MOA: blocks PDE resulting in bronchodilation and mild anti-inflammatory effects. 1. blocks (acts as a competitive non-selective) PDE, causing an ↑ intracellular cAMP and cGMP levels which results in bronchial smooth muscle relaxation, pulmonary vasodilation, diuresis, CNS stimulation and cardiac stimulation. 2. a nonselective adenosine receptor antagonist that acts on A1, A2, and A3 with almost the same affinity, which possibly explains theophylline's cardiac effects. Adenosine-mediated channels also increase the contraction force of diaphragmatic muscles by enhancing their calcium uptake. ∙SIG: dosed by IBW; Therapeutic range (5 to 15 mcg/ml) ∙SE: nausea, headache, tachycardia, insomnia, tremor, and nervousness, arrhythmias, confusion, seizures ∙Key points: ・decline usage due to the greater efficacy use of ICS and β2-agonists, and due to numerous DDI and side effects associated with it. ・caution with CVD, hyperTSH, PUD, seizures ・NTI: 10 to 20 mcg/ml which would require frequent lab draws to monitor blood levels

Smoking Cessation: Nicotine Replacement Therapy (NRT)

∙smoking cessation aid ∙MOA: a plant alkaloid, found in the tobacco plant, and an addictive central nervous system stimulant. Nicotine acts as an agonist at the nicotinic cholinergic receptors in the autonomic ganglia, at neuromuscular junctions, and in the adrenal medulla and the brain. Nicotine's CNS-stimulating activities may be mediated through the release of several neurotransmitters, including acetylcholine, beta-endorphin, dopamine, norepinephrine, serotonin, and ACTH. As a result, peripheral vasoconstriction, tachycardia, and elevated blood pressure may be observed with nicotine intake. Nicotine can be used therapeutically to help with smoking cessation. ∙OTC Formulations: gums, lozenges, patches ∙Rx Formulations: nasal spray, inhaler ∙SE: HA, dizziness, dyspepsia ∙C/I: recent MI (≤2 wks), arrhythmia, severe or worsening angina ∙Key Points: ・assess efficacy and tolerance periodically ・monitor BP and HR ・For Gum/Lozenge/Inhaler: Acidic beverages (coffee, juices, soft drinks) interfere with buccal absorption of nicotine. Avoid food or beverage for 15 mins before use, water is okay. ・For Gum/Lozenge/Patch: • Recent (<2 weeks) myocardial infarction • Serious underlying arrhythmias • Serious or worsening angina pectoris • Pregnancy and/or breastfeeding • Adolescents (<18 years of age) • Temporomandibular joint disease (gum only) ・For Nasal Spray: All above OTC nicotine precautions PLUS • underlying chronic nasal disorders • severe reactive airway disease ・For Inhaler: All above OTC nicotine precautions PLUS • underlying bronchospastic disease

Systemic Corticosteroids

∙speeds recovery and prognosis recurrent exacerbations; COPD ∙prednisone (Deltasone), methylprednisolone (Medrol), dexamethasone (Decadron) ∙MOA: suppress histamine and prostaglandins; can inhibit immune system to reduce inflammation ∙SIG: 40 mg/day x 5D ∙SE: Short-term SE (< 1 mo)* vs Long-term SE ・Psychiatric (mood changes*) ・Round face, buffalo hump ・Eyes (glaucoma, cataracts) ・Diabetes (↑BG*) ・Neutrophila (↑WBC*) ・Immunosuppression, insomnia* ・Stomach (GI upset*, ulcer) ・Osteoporosis, obesity ・Na+/H2O retention* (↑BP) ・Electrolytes (↑Na+/↓K+) ∙other SE: hirsutism (in ♀); amenorrhea; growth retardation, weight gain* ∙Key Points: AVOID live vaccine x 1 mo after d/c if on high-dose systemic steroid (20 mg/day prednisone equivalent) for > 2 weeks

Direct Oral Anticoagulants (DOACs)

∙stroke prevention in nonvalvular atrial fibrillation or flutter ∙tx and prevention of DVT or pulmonary embolism ∙prophylaxis after hip or knee replacement surgery ∙preferred over warfarin in the treatment of blood clots due to a more favorable safety profile, fewer drug and food interactions, and no regular blood testing required. ∙types of DOACs: ・Direct Thrombin Inhibitor: dabigatran (Pradaxa) ・Factor Xa Inhibitor: rivaroxaban (Xarelto), apixaban (Eliquis) ∙MOA: ・the process by which blood clots form is complex and is referred to as the coagulation cascade. ・apixaban and rivaroxaban are factor Xa inhibitors that work by directly inhibiting factor Xa in the intrinsic and extrinsic coagulation pathway leading to inhibition of platelet activation and fibrin clot formation. (TIP: the generic names hint at their MOA as factor Xa inhibitors--apixaban, rivaroxaban) ・dabigatran is a prodrug that works by directly inhibiting thrombin ∙SE: bleeding, anemia, dyspepsia--abdominal pain (dabigatran) ***Remember BAD*** ∙Key Points: ・C/I in active bleeding and in patients with mechanical heart valve(s) ・premature discontinuation can increase risk of thrombotic events ・BBW: pt receiving neuraxial anesthesia or spinal puncture due to risk of hematomas ・avoid in patients with severe hepatic impairment ・take with or without food except for rivaroxaban which should be administered with food (evening meal) if doses ≥ 15 mg for optimal absorption ・notify healthcare provider prior to surgical or dental procedures as these drugs need to be held for 24 to 48 hours prior ・report any s/sxs of bleeding such us unusual bleeding or bruising, dark and tarry stools, or blood in urine.

Opioid Analgesics: fentanyl

∙synthetic full opioid agonist ∙Duragesic ∙Management of pain in opioid-tolerant patients, severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate ∙SIG: Use the lowest effective dose for the shortest possible duration (Fentanyl patches are extended-release dosage formulations and should never be used for intermittent pain use or in those who are opioid naive. Whether treating acute or chronic pain with an opioid analgesic, use of the lowest effective dose for the shortest possible duration is recommended to mitigate risk of severe adverse effects and opioid use disorder (addiction, dependence, etc).) ・Adult dosing for severe pain: Discontinue all other around-the-clock opioid drugs when fentanyl patch therapy is initiated. Each fentanyl patch is worn continuously for up to 72 hours: ・Do not increase transdermal fentanyl dose for the first time until at least 3 days after the initial application. ・After a dose change, it may take up to 6 days for fentanyl levels to reach equilibrium ・Therefore, evaluate for further titration no less than two 3-day applications ・Base dosage increments on the daily dosage of supplementary opioids ・Use the following ratio: 45 mg/24hr oral morphine to 12 mcg/hr transdermal fentanyl A small number of adult patients may require Q48H dosing interval: ・Consider only if adequate pain control cannot be achieved using Q72H interval ・Consider dose increase before changing dosing intervals Discontinuation If converting to another opioid, remove patch and titrate the new opioid based on patient response ・17 or more hours after patch removal required for 50% decrease in serum fentanyl level ・Do NOT convert fentanyl dosing to another opioid. ・If discontinuing and not converting to another opioid, gradual reduction required Example: 50% reduction every 6 days. ・Pediatric dosing for severe pain: Discontinue all other around-the-clock opioid drugs when fentanyl patch therapy is initiated. Each fentanyl patch is worn continuously for up to 72 hours: ・Do not increase transdermal fentanyl dose for the first time until at least 3 days after the initial application ・After a dose change, it may take up to 6 days for fentanyl levels to reach equilibrium ・Therefore, evaluate for further titration no less than two 3-day applications ・Base dosage increments on the daily dosage of supplementary opioids ・Use the following ratio: 45 mg/24hr oral morphine to 12 mcg/hr transdermal fentanyl A small number of adult patients may require Q48H dosing interval: ・Consider only if adequate pain control cannot be achieved using Q72H interval ・Consider dose increase before changing dosing intervals Discontinuation If converting to another opioid, remove patch and titrate the new opioid based on patient response ・17 or more hours after patch removal required for 50% decrease in serum fentanyl level ・Do NOT convert fentanyl dosing to another opioid. ・If discontinuing and not converting to another opioid, gradual reduction required Example: 50% reduction every 6 days ∙SE: drowsiness/sedation, constipation, sweating, xerostomia, fatigue, loss of appetite, application site redness/irritation ∙Key Points: ・do not apply heat to patch site; do not partake in rigorous activity that significantly elevates body temperature; contact provider if having fever ・Keep out of reach of children and pets; used patches still contain potentially lethal amounts of fentanyl; dispose patch in toilet immediately after use ・Do not drink alcohol or take other drugs that may cause drowsiness while using this medication, unless under provider supervision ・Do not abruptly discontinue after taking regularly for a few weeks or more ・This medication is addictive and has abuse potential; store medication in a safe place to prevent theft or inappropriate use ・Caution for accidental opioid overdose; patients/caregivers should be aware of symptoms and proper use of naloxone (the life-saving reversal agent) ・Avoid using fentanyl patches in patients with severe renal and hepatic impairments; start with one-half of the usual dose for patient with mild to moderate renal and hepatic impairments. ・C/I in patients who are not opioid-tolerant ・may cause serotonin syndrome with concomitant use with serotonergic drugs ∙for other precautions/warnings, see Opioid Analgesics flashcard.

Opioid Analgesics: oxycodone IR

∙synthetic full opioid agonist ∙Oxy IR, Roxicodone ∙Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate (immediate release formulations) ∙SIG: Using oxycodone as the first opioid analgesic Initial Dosing: 5-15 mg PO Q4-6H PRN ・For chronic pain, doses should be given ATC to prevent reoccurrence of pain rather than PRN after the pain has occurred ・For severe chronic pain, doses should be given Q4-6H (not PRN) on a regularly scheduled basis ・May take with food if upset stomach or nausea occurs; avoid high-fat meals near doses. ∙SE: drowsiness/sedation, constipation, fatigue, HA, dizziness, or sweating, severe hypotension ∙Initiate Oxycodone with lower dosage than usual in patients with renal and hepatic impairment ∙for precautions/warnings, see Opioid Analgesics flashcard.

Opioid Analgesics: oxycodone ER

∙synthetic full opioid agonist ∙Oxycontin, Xtampza** ∙Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate (extended release formulations) ∙SIG: For Opioid non-tolerant patients Note: oxycodone ER 60 and 80 mg tablets, a single dose > 40 mg, or TDD > 80 mg are only for patients who tolerate an opioid of comparable potency Initial Dosing: 10 mg PO Q12H. Any higher starting dose in non-tolerant patients may cause fatal respiratory depression ER capsule Note: oxycodone ER capsule (Xtampza) is formulated with base oxycodone; other oral oxycodone formulations are based on oxycodone HCl 10 mg Oxycodone HCl = 9 mg base Oxycodone (ER cap) 15 mg Oxycodone HCl = 13.5 mg base Oxycodone (ER capsule) 20 mg Oxycodone HCl = 18 mg base Oxycodone (ER capsule) 30 mg Oxycodone HCl = 27 mg base Oxycodone (ER capsule) 40 mg Oxycodone HCl = 36 mg base Oxycodone (ER capsule) For Opioid non-tolerant patients (including opioid-naïve patients): Note: single dose of oxycodone ER capsule > 36 mg, or TDD > 72 mg are only for patients who tolerate an opioid of comparable potency Initial Dosing: 9 mg PO Q12H with food. Any higher starting dose in non-tolerant patients may cause fatal respiratory depression For Pediatric Dosing: use of oxycodone ER tablet in pediatric patients is only approved for: ・≥ 11 years of age ・Already receiving and tolerating opioids for at least 5 consecutive days ・Min 20 mg/day of oxycodone (or equivalent) for the 2 days immediately preceding the initiation of oxycodone ER tablet ・i.e., not appropriate for pediatric patients requiring < 20 mg TDD of oxycodone. Discontinue all other ATC opioids upon initiation of oxycodone ER tablet. For Geriatric Dosing: initiate at one-third to one-half of the recommended starting dose in debilitated and opioid-naive geriatric patients ∙ER tablets: May take with food if upset stomach or nausea occurs ∙ER capsules: Take with food; if desired, contents may be sprinkled over soft foods or in a gastrostomy or nasogastric feeding tube (**Food affects the absorption of oxycodone extended-release capsules (Xtampza); doses should be taken with food to ensure consistent plasma drug levels**). ∙SE: drowsiness/sedation, constipation, fatigue, HA, dizziness, or sweating, severe hypotension ∙Initiate Oxycontin at one-third to one-half of the recommended starting dose. ∙ if currently taking a CNS depressant, initiate oxycodone ER tablet at one-third to one-half of the recommended starting dose ∙for precautions/warnings, see Opioid Analgesics flashcard.

Opioid Analgesic: oxycodone/APAP

∙synthetic full opioid agonist ∙Percocet, Roxicet, Endocet ∙Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate ∙see Hydrocodone/APAP for MOA of APAP. ∙SIG: (see image) Take doses only as often as directed; do not use more frequently than prescribed. Do not use in combination with other products containing APAP. May take with food if upset stomach or nausea occurs. ∙for precautions/warnings, see Opioid Analgesics flashcard.

Opioid Analgesics: hydrocodone/APAP

∙synthetic full opioid agonist ∙Vicodin, Norco, Lortab ∙Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate ∙APAP aka Acetaminophen: ・MOA: not well defined; Its antipyretic and analgesic activity are thought to result from inhibition of prostaglandin synthesis and release in the central nervous system. Inhibition of the nitric oxide (NO) pathway via action on neurotransmitter receptors, such as N-methyl-D-aspartate (NMDA) and substance P, also may result in elevation of the pain threshold. ∙SIG: (see image) Take doses only as often as directed; do not use more frequently than prescribed. Do not use in combination with other products containing APAP. May take with food if upset stomach or nausea occurs. ∙SE: drowsiness/sedation, constipation, fatigue, HA, dizziness, or sweating ∙for precautions/warnings, see Opioid Analgesics flashcard.

Vitamin K Antagonist

∙warfarin (Coumadin) ∙used to treat and prevent blood clots or thrombosis; often prescribed to reduce the risks of stroke and transient ischemic attack (TIA) in atrial fibrillation or flutter. ∙DVT or pulmonary embolism ∙MOA: it prevents the formation of blood clots by suppressing the body's production of vitamin-K-dependent factors that are essential to the clotting process. It suppresses this process through inhibition of vitamin K epoxide reductase (VKOR), an enzyme responsible for converting vitamin K epoxide to the reduced form of vitamin K needed in the production of vitamin K dependent clotting factors. Warfarin decreases clotting factors II, VII, IX, and X, and protein C and S. ***Remember 2 + 7 is 9, not 10*** ∙Antidote for warfarin: Vit. K ∙SE: bleeding, skin necrosis (rare), purple toe syndrome (rare) ∙Key Points: ・take warfarin at the same time every day (preferrably in the evening) ・ACC may contact the pt to change dose during the day depending on lab results; if a miss dose occur, take it as soon as you remember. if it's almost time for the next dose, do not take the missed dose, and return to normal dosing schedule. DO NOT take a double dose to make up for the missed dose. Inform ACC of your missed dosed ・has many DDI and food interactions, report to healthcare provider if there are any medication or diet changes (CYP3A4 inhibitors ↑ INR; CYP3A4 inducers ↓ INR. **severe interactions with CYP3A4 may warrant an empiric decrease/increase of initial Warfarin dose** ・avoid cranberry products, and keep Vitamin K consumption in diet consistent (dark green leafy vegetables) as high Vitamin K intake counteracts the effects of the drug ・report any s/sxs of unusual bleeding or bruising, black tarry or coffee ground stools, or blood in the urine ・avoid EtOH, ASA, and other salicylates (ibuprofen, etc); for fever or pain, use APAP instead ・blood levels (INRs) are required for monitoring warfarin's effectiveness and to decrease risks of bleeding. The higher the INR, the thinner the blood and higher risk for bleed. The lower the INR, the thicker the blood and higher risk for clotting.

Long Acting Beta 2 Agonists: indacaterol (Arcapta)

∙β2 partial agonist ∙COPD ∙SIG: 1 cap QD via Neohaler ∙DOA: 24 hours ∙Bulky, highly lipophillic N group ∙must be combined with ICS

Long Acting Beta 2 Agonists: olodaterol (Striverdi)

∙β2 partial agonist ∙COPD ∙Sig: 2 puffs QD ∙DOA: 24 hours ∙similar to formoterol but no stereocenters ➡ no diastereomers

Short Acting Beta 2 Agonists (SABA)

∙β2 selective agonists ∙Asthma, EIB ∙Generic (Brand): albuterol [(Ventolin, ProAir, Proventil) S-enantiomer]; levalbuterol [(Xopenex) R-enantiomer] ∙MOA: binds to β2- receptors in the lungs, causing bronchial smooth muscle relaxation and bronchodilation. Activation of β2-receptors causes an ↑ in cAMP which leads to a ↓ in Ca2+ release. Since Ca2+ plays a big role contraction, a ↓ in Ca2+ leads to a ↓ in contraction of airway smooth muscles and bronchodilation. ∙SIG: 1-2 puffs q4-6h prn; for EIB, can be taken 15 minutes before exercise ∙SE: tremors, tachycardia (palpitations), nervousness, cough, hyperglycemia, hypokalemia ∙DOA: 3 to 6 hours ∙Key Points: -used as rescue medications to provide quick relief. Regular daily used is not recommended. -ensure proper inhaler technique

Long Acting Beta 2 Agonists (LABA) or w/ ICS: formoterol (Foradil) or fomorterol/budesonide (Symbicort)

∙β2 selective full agonists ∙Asthma/COPD ∙SIG: BID ∙DOA: 12 hours ∙used as R,R and S,S racemate → R,R is ~1000x more active than the S,S enantiomer ∙must be combined with ICS

Long Acting Beta 2 Agonists: arformoterol (Brovana)

∙β2 selective full agonists ∙COPD ∙SIG: BID ∙an R,R enantiomer of formoterol, which makes is more potent. ∙No COMT, No MAO ∙must be combined with ICS

Long Acting Beta 2 Agonists (LABA) or w/ ICS: vilanterol trifenatate/umeclidinium (Anoro Ellipta) or vilanterol/fluticasone (Breo Ellipta)

∙β2 selective partial agonists ∙Asthma/COPD ∙DOA: 24 hours ∙single R-enantiomer ∙Key points: must be combined with ICS

Long Acting Beta 2 Agonists (LABA) or w/ ICS: salmeterol xinafoate (Serevent) or salmeterol/fluticasone (Advair)

∙β2 selective partial agonists ∙preferred long-term controller for moderate/severe persistent asthma when used with ICS ∙Asthma/COPD ∙MOA: works just like SABA but longer ∙SIG: BID ∙SE: same as SABA ∙DOA: 12 hours ∙Key Points: -should NOT be used as a monotherapy due to an ↑ risk of asthma related deaths (BBW) -- must use with ICS in treating asthma -what makes them long acting: No COMT, No MAO, high lipophilicity and extended substituent on N lead to prolonged and selective binding to a second non-polar domain on the β2 receptor. -greater bronchiol tissue penetration which leads to ↓ clearance from lungs

DPI counseling points

・Do not open the device until you are ready to use it. • Never open or swallow the capsule - always use it with its matching DPI ・Do not shake the DPI. ・Do not use a holding chamber or spacer with a DPI. ・With most DPIs, the mouthpiece should be pointed up or held horizontal when using in order to not dump the medication after loading. ・Rinse your mouth after using, if instructed by your physician. ・Multi-dose devices have an indicator to alert you to the number of doses remaining, or when the device is almost empty. ・General instructions are that you should not allow your DPI to get wet. The mouthpiece should be wiped regularly with a clean, dry cloth. ・Inhaling the dry powder may cause some people to cough; talk with your doctor if this happens.