Prescribing Pearls for the Primary Care Provider

Educational Objectives

The goal of this program is to improve pharmacologic management of patients with hypertension, skin disorders, and gastroesophageal reflux disease. After hearing and assimilating this program, the clinician will be better able to:

1. Optimize treatment of hypertension based on patient age, ethnicity, and risk factors.
2. Prescribe a multiple-antihypertensive regimen for patients with persistent high blood pressure.
3. Counsel patients with hypertension about medications and herbal supplements that may increase blood pressure.
4. Avoid tolerance induction and tachyphylaxis in patients using topical steroids.
5. Plan an appropriate course of treatment for patients with chronic gastroesophageal reflux disease.

Summary

Hypertension

Hypertension medications: the majority of the blood pressure (BP)-lowering action of a medication is obtained at the initial dose; increasing the dose to the maximum allowed confers a modest incremental reduction in BP; calcium channel blockers may be an exception, as they have a linear effect with higher doses, but doubling the initial dose does not double the effect; if a patient is not yet at their goal BP, the question arises whether to increase the dose or add a second medication; the speaker suggests titrating the medication up to the highest dose if a patient is close to the BP goal (ie, ≤10 mm Hg of the goal systolic BP); a different medication should be added if BP needs to be lowered by >10 mm Hg; a synergistic effect is seen when taking ≥2 antihypertensive medications; fewer adverse effects are seen with lower doses of 2 medications than with the highest dose of a single medication

Recommendations from the 8th Joint National Committee (JNC 8): 2 medications should be started at the same time (either as separate pills or as a single combination pill) when the average systolic BP is >160 mm Hg or >20 mm Hg above goal, or the diastolic BP is >100 mm Hg or >10 mm Hg above goal

Testing prior to starting medication: obtain a baseline metabolic panel (BMP) to check kidney function and electrolyte status; check lipids, hemoglobin A1C, and thyroid-stimulating hormone to assess for comorbid conditions that may affect the medication choice; BMP should be obtained every 6 mo, although annual testing may be acceptable for younger patients without major medical issues and with good kidney function; BMP should be checked more frequently (eg, every 3 mo) for patients with multiple comorbid conditions (eg, heart disease, diabetes, chronic kidney disease [CKD]); obtain baseline electrocardiography before initiating therapy to check for left ventricular hypertrophy, heart block, arrhythmia, and prior myocardial infarction (MI)

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs): used for primary hypertension, left ventricular systolic dysfunction, congestive heart failure (CHF), history of MI, diabetes, and CKD; they are also used as monotherapy for young patients; because of the risk for fetotoxicity, these are not recommended for women of childbearing age, especially if they desire pregnancy or are not using reliable contraception

Elevations in creatinine: BMP should be obtained before and ≈2 to 3 wk after starting therapy; creatinine may temporarily increase by 15% to 20% because of the decreased glomerular filtration rate (GFR) and reduced intraglomerular pressure; this can happen with any antihypertensive medication but occurs most frequently with this class; discontinuation of the medication is not necessary because this does not represent acute kidney injury

Hyperkalemia: relatively common; if potassium levels are borderline high, continue the medication and monitor closely; if levels are extremely high, stop the medication or decrease the dose; later, a diuretic can be added to lower potassium levels; patients with CKD are at highest risk for hyperkalemia; increased creatinine and hyperkalemia occur with both ACEs and ARBs, so switching from one to the other does not solve the problem

Adverse effects of ACE inhibitors: dry cough is most common; angioedema can also occur but is rarer; if these develop, switch to an ARB; the dry cough typically occurs within the first few weeks of use, but it may occur after ≥6 mo of use; cough is more common in women and in individuals of Chinese ethnicity; Black individuals have a higher risk for angioedema than the rest of the US population; ACE inhibitors are often used first because they are older drugs with more studies on their efficacy and are typically covered by insurance, but studies are showing that ARBs have a lower side effect profile with equal efficacy; the speaker recommends ARBs for Chinese women, Black individuals, and patients prone to cough (eg, chronic asthma, chronic obstructive pulmonary disease, allergic rhinitis, bronchiectasis); ARBs can also cause cough and angioedema, but it is much less likely

Concomitant use of ACE inhibitors and ARBs: not recommended; data show no improvement in outcomes and an increase in adverse effects

Thiazide diuretics: include hydrochlorothiazide (HCTZ), indapamide, and chlorthalidone (the latter 2 are thiazide-like diuretics); obtain a BMP at baseline and 2 to 3 wk after starting therapy; diuretics are associated with metabolic adverse effects, eg, hypokalemia and hyponatremia (most common), hyperuricemia, hyperglycemia, hyperlipidemia, hypomagnesemia, and hypercalcemia; these metabolic effects are often dose-dependent; the speaker does not always check magnesium and uric acid, except uric acid in patients with gout (he typically avoids diuretics for patients with gout); a major side effect is increased urination, although this can be an advantage for patients prone to volume overload; this effect often normalizes after ≈1 mo of treatment; in general, it is recommended to take diuretics in the morning

Doses and BP-lowering effect: most of the effect is obtained at the starting dose, with increases in dose leading to small incremental improvements in BP and higher incidence of side effects and metabolic adverse effects

Comparison of drugs: chlorthalidone and indapamide are more potent than HCTZ because they have much longer half-lives; duration of action is <12 hr for HCTZ, >24 hr for chlorthalidone, and between 12 and 24 hr for indapamide; 12.5 mg of chlorthalidone is equivalent to ≈25 mg of HCTZ in terms of BP reduction; chlorthalidone is better studied; however, regional practices, physician experience, and tradition affect prescribing practices, favoring HCTZ; in addition, HCTZ comes in fixed-dose combination pills; another advantage of HCTZ is that it causes less hypokalemia and is available in 12.5-mg and 25-mg tablets (chlorthalidone is available only in 25-mg tablets); patients with inadequate BP control on HCTZ who do not want to add a medication can switch to chlorthalidone or indapamide

Medication combinations: combining thiazide diuretics with an ACE, ARB, or spironolactone, which increase potassium levels, can mitigate the hypokalemia associated with thiazides; avoid thiazide diuretics if the creatinine level is >1.8 mg/dL or GFR is <20 mL/min (they become ineffective)

Furosemide (Lasix): loop diuretics are not generally used as the main antihypertensive because of their short half-life and prevalence of electrolyte disturbances; furosemide lasts for 6 hr; loop diuretics can be used for patients prone to fluid overload (eg, CHF, severe CKD)

Calcium channel blockers (CCBs): are divided into dihydropyridines (DHPs) and non-dihydropyridines (non-DHPs) based on their predominant physiologic effects; DHPs are predominantly vasodilators and have limited chronotropic and ionotropic effects; non-DHPs are less potent vasodilators and have a slowing effect on cardiac contractility and conduction; therefore, DHPs are preferred for primary hypertension; DHPs end with “pine” suffix (eg, amlodipine, isradipine, nifedipine, nicardipine), and the most commonly used non-DHPs are verapamil and diltiazem

Adverse effects: with DHPs, headache, lightheadedness, flushing, and dose-dependent peripheral edema (seen in 20%-30% of patients and more commonly in women) are most common; to reduce edema, decrease the dose, add an ACE or ARB (venous dilation reduces transcapillary pressure), or switch to non-DHPs or another class of medication; use non-DHPs for patients who experience adverse effects with DHPs; the cardiac depressive effects of non-DHPs are advantageous for patients with cardiac arrhythmias or tachycardia with atrial fibrillation; DHP and non-DHP agents are useful for patients with chronic stable angina; non-DHPs can cause dose-dependent constipation (affects ≤25% of patients), bradycardia, and worsening cardiac output; non-DHPs are contraindicated in patients who are taking beta blockers or have heart failure with a reduced ejection fraction, sick sinus syndrome, or second- or third-degree atrioventricular block; chronic use of DHP or non-DHP agents can cause gingival hyperplasia

Beta blockers: decades ago, these were used as first-line or second-line therapy for primary hypertension; currently, they are considered third- or fourth-line agents; they are typically used after an MI or for patients with systolic heart failure, stable angina, or a predisposition to tachyarrhythmias; abrupt withdrawal of the medication can lead to increased sympathetic activity (more common with short-acting beta blockers), which can lead to accelerated angina, MI, or sudden death; for agents with a short half-life (which typically require twice-daily administration, eg, propranolol, metoprolol tartrate, carvedilol), initially decrease to daily use for 1 wk, then every other day for 1 wk, and then discontinue; for those with a longer half-life (eg, atenolol, metoprolol succinate, nadolol) reduce to a half dose for ≈1 wk, then a half dose every other day for ≈1 wk, then stop

Selection of an antihypertensive medication among different populations

Gout: avoid thiazide diuretics, loop diuretics, or beta blockers because they can increase uric acid levels; CCBs are preferred because they appear to have urate-lowering properties; the ARB losartan has a uricosuric effect

Patients <50 yr of age: ACE inhibitors and ARBs are generally used, but the fetotoxic effects are a concern for women of childbearing age

Black patients: thiazide diuretics and CCBs are good first-line options

Patients >60 yr of age: thiazide diuretics or CCBs (especially DHPs) are recommended

Diabetes: start with an ACE inhibitor or ARB; thiazide diuretics and CCBs may be considered; many patients with diabetes have resistant hypertension and may require 3 agents

Proteinuric CKD: ACE inhibitors or ARBs are recommended

Congestive heart failure: beta blockers, ACE inhibitors, or ARBs are recommended

Prior MI: beta blockers and ACE inhibitors or ARBs are recommended

Chronic atrial fibrillation: beta blockers and non-DHPs are preferred; however, combining these agents may result in excessive slowing of the heart rate

Benign prostatic hyperplasia: nonselective alpha-blockers are recommended, eg, terazosin and doxazosin; newer-generation alpha blockers (eg, tamsulosin [Flomax]) have minimal BP-lowering effects because they are selective for the prostate and bladder

Benign essential tremor: beta blockers are recommended

Chronic migraine: beta blockers and non-DHPs are recommended

Raynaud phenomenon: DHPs are a good option

Depression: beta blockers may worsen depression (controversial); avoid central alpha-2 agonists

Prone to hyponatremia or hypokalemia: avoid diuretics

Glucose intolerance: avoid diuretics until diabetes develops

Bronchospastic conditions (eg, asthma): avoid nonselective beta blockers

Erectile dysfunction: avoid beta blockers

Heart block (greater than first degree): avoid beta blockers and non-DHPs

Patients taking lithium: diuretics can reduce renal clearance; ACE inhibitors (and likely ARBs and spironolactone) can increase steady-state lithium levels

Pregnant or contemplating pregnancy: transition to methyldopa, nifedipine, or labetalol

Osteoporosis: thiazide diuretics help preserve hip and spine bone mineral density

Kidney stones: consider thiazide diuretics because they reduce renal excretion of calcium

Medications that increase BP: regular use of nonsteroidal anti-inflammatory drugs or high doses of aspirin can raise BP and interact with antihypertensive medication to reduce effectiveness; other medications that can increase BP include some psychiatric medications, eg, duloxetine (Cymbalta), venlafaxine (Effexor), monoamine oxidase inhibitors, tricyclic antidepressants, fluoxetine (Prozac), and bupropion (Wellbutrin); estrogen-containing contraceptives (eg, pills, patches, vaginal rings); decongestants, eg, phenylephrine and pseudoephedrine; medications for attention deficit hyperactivity disorder, eg, methylphenidate (Concerta, Ritalin), amphetamine-dextroamphetamine (Adderall), and lisdexamfetamine (Vyvanse); high doses of caffeine; herbal products (eg, Arnica, Ephedra, ginseng, and licorice); immunosuppressants (eg, tacrolimus, cyclosporin); and chronic use of steroids, eg, prednisone

Skin Disorders

Topical steroids: classified based on potency (group 1 is the highest, group 7 is the lowest); optimal class to use is determined by type, anatomic location, and severity of skin condition; using the appropriate formulation improves efficacy and adherence

Creams: most commonly prescribed; made of water, oils, chemicals, and preservatives; chemicals can irritate the skin in individuals with severe pre-existing inflammation

Ointments: made of petroleum oil with little or no water; they usually do not contain preservatives and thus are more soothing, less irritating, and more potent (even within the same class) because they are more occlusive; they are greasy but are good for areas with thick, irritated, or inflamed skin; patients can wrap the area in plastic wrap at night to avoid getting the ointment on clothes or bedding

Gels: made of water and propylene glycol (synthetic alcohol); they dry quickly but can sting due to the alcohol content; they are good to use in areas that are wet, sweaty, or hairy (drying effect)

Solutions, foams, and lotions: best used for the scalp; foams can be sprayed at the base of the hair

Impregnated tape: can be used on itchy areas to occlude the skin and form a barrier to prevent patients from scratching; formulations are expensive

Dental paste: has a thick and sticky consistency; it can be used to help heal aphthous ulcers (canker sores)

Steroid atrophy: requires ≥2 wk of use and may take ≥2 mo to develop with some potencies and anatomic areas; higher potency increases the risk but is more appropriate for severe conditions or thicker skin (the potency can be decreased later); starting with too low of a potency does not resolve the condition and prolongs steroid use; the strength percentage is not an accurate gauge of the potency

Antifungal creams: common fungal infections include tinea corporis, tinea cruris, and tinea pedis; these are typically caused by dermatophytes and are treated with azoles (eg, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole), allylamines (eg, naftifine, terbinafine), butenafine, tolnaftate, or ciclopirox; many are available over the counter; nystatin is not recommended for dermatophyte infections; however, it is used for candidal infections (eg, diaper dermatitis); oral solutions can be used for thrush

Antifungal-steroid combinations: useful when the diagnosis is not clear or to calm severe inflammation and itchiness associated with a fungal infection; the speaker recommends against using premixed creams, eg, betamethasone-clotrimazole (Lotrisone); the antifungal likely needs to be used for several weeks or indefinitely for prevention, and long-term use of betamethasone can cause steroid atrophy; use steroid with a potency class ≥4 when mixing with an antifungal medication

Gastrointestinal (GI) Medications for Gastroesophageal Reflux Disease (GERD), Gastritis, Dyspepsia, Peptic Ulcer Disease

Proton pump inhibitors (PPIs) vs histamine 2 (H2) blockers: PPIs — more potent acid suppressors; take several days to initiate acid suppression and ≈5 days for optimal efficacy (acid reduction of ≈66%); not useful for as-needed dosing; H2 blockers — work quickly and are better for patients who only need occasional dosing; they may not be effective when used long term; when taken regularly, H2 blockers can cause tachyphylaxis (diminishing response to regular use), although this does not occur in all patients

Prescribing considerations: dosing — PPIs work best on an empty stomach and should be taken 30 to 60 min before eating; most patients only require once daily dosing, but those who require more symptom relief can take PPIs twice daily; for patients having breakthrough symptoms, an H2 blocker can be added to the PPI; avoid taking them together (they can counteract each other); take the PPI before breakfast and the H2 blocker before bed; rebound hypersecretion — may develop after abruptly stopping a PPI (may also occur with H2 blockers); typically occurs after >6 mo of PPI use but can happen after 2 mo of use; reported in >60% of patients; when discontinuing, taper the dose over 3 to 4 wk; if rebound symptoms occur, add an H2 blocker or antacid for several weeks

Long-term adverse effects of PPIs: H2 blockers are safe for long-term use and are available without a prescription; however, PPIs have safety concerns, including potentially significant drug interactions

Drug interactions: the presence of an interaction with clopidogrel is controversial, as some research suggests that PPIs decrease its efficacy; pantoprazole is thought to be the safest PPI to use with clopidogrel; omeprazole and esomeprazole are thought to have more interactions with clopidogrel; PPIs can decrease the absorption of protease inhibitors used for HIV and are contraindicated in patients taking rilpivirine; atazanavir should not be used when the PPI equivalent dose is >20 mg daily of omeprazole; PPIs can delay methotrexate elimination, potentially leading to toxicity (dose of methotrexate may need to be reduced)

Vitamin and mineral absorption: long-term use of PPIs can decrease absorption of magnesium, vitamin B12, and iron; consider checking magnesium, vitamin B12, and ferritin levels twice yearly, especially if the patient is taking a diuretic; PPIs can increase fracture risk because decreased acid may increase the gastric pH and decrease absorption of calcium; consider supplementing with calcium citrate instead of calcium carbonate

Infectious illness: the increased gastric pH with PPIs may result in more bacterial growth, which may increase risk for pneumonia and COVID-19 (associations may also be due to confounding variables); chronic PPI use also increases risk for Clostridioides difficile infection and diarrhea; discontinue PPIs ≥2 wk before a Helicobacter pylori stool or breath test to decrease the risk for a false-negative result (discontinuing H2 blockers is more controversial; some clinicians advise stopping ≈2 days before testing)

Adverse effects of H2 blockers: the speaker advises avoiding cimetidine (Tagamet) because it is least effective and has the most drug interactions; men can develop gynecomastia and impotency; ranitidine (Zantac) is currently off the market because of NDMA contamination; the most common H2 blockers in current use are famotidine (Zantac 360) and nizatidine

Readings

Carey R, Whelton P. New wrinkles in hypertension management 2022. Curr Opin Cardiol. 2022; 37 (4): 317-325. doi: 10.1097/HCO.0000000000000980. View article; Chen C, Hung C, Chiang C, et al. Pulmonary arterial hypertension in the elderly population. J Chin Med Assoc. 2022; 85 (1): 18-23. doi: 10.1097/JCMA.0000000000000658. View article; Georgianos P, Agarwal R. Management of hypertension in advanced kidney disease. Curr Opin Nephrol Hypertens. 2022; 31 (4): 374-379. doi: 10.1097/MNH.0000000000000812. View article; Matok I, Gorodischer R, Koren G, et al. The safety of H₂-blockers use during pregnancy. J Clin Pharmacol. 2010; 50 (1): 81-87. doi: 10.1177/0091270009350483. View article; Nicola AM, Albuquerque P, Paes HC, et al. Antifungal drugs: New insights in research & development. Pharmacol Ther. 2019; 195 21-38. doi: 10.1016/j.pharmthera.2018.10.008 View article; Sahoo AK, Mahajan R. Management of tinea corporis, tinea cruris, and tinea pedis. Indian Dermatol Online J. 2016; 7 (2): 77-86. doi: 10.4103/2229-5178.178099. View article; Schubert ML. Gastric acid secretion. Curr Opin Gastroenterol. 2016; 32 (6): 452-460. doi: 10.1097/MOG.0000000000000308. View article; Taylor D, Chen Y, Hanlon J, et al. 376 persistent GERD symptoms despite PPI treatment - prevalence and patient characteristics: Results from a cross-sectional patient survey. The American Journal of Gastroenterology. 2019; 114 S220-S220. doi: 10.14309/01.ajg.0000591036.97478.93. View article; Tita A, Szychowski J, Boggess K, et al. Treatment for mild chronic hypertension during pregnancy. Obstetrical & Gynecological Survey. 2022; 77 (11): 634-636. doi: 10.1097/01.ogx.0000899456.24100.71 View article; Yadlapati R, Gyawali PC, Pandolfino JE. AGA clinical practice update on the personalized approach to the evaluation and management of GERD: Expert review. Clin Gastroenterol Hepatol. 2022; 20 (5): 984-994e1. doi: 10.1016/j.cgh.2022.01.025. View article.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Lee was recorded exclusively for Audio Digest. Audio Digest thanks Dr. Lee for his cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 2.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 2.00 CE contact hours.

Lecture ID:

FP710201

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.