Drugs for Hypertension - 2020 ISH Guidelines - PDF

Drugs for Hypertension Module 05: Cardiovascular Pathology John Jhason J. Cabigon, MD, DPCOM, DPASMAP | Asynchronous TABLE OF CONTENTS I. HYPERTENSION................................................................................ 1 A. DIAGNOSIS.........................................................

Drugs for Hypertension Module 05: Cardiovascular Pathology John Jhason J. Cabigon, MD, DPCOM, DPASMAP | Asynchronous TABLE OF CONTENTS I. HYPERTENSION................................................................................ 1 A. DIAGNOSIS................................................................................... 1 II. ANTIHYPERTENSIVE AGENTS........................................................... 3 A. DIURETICS.................................................................................... 3 B. SYMPATHOPLEGIC DRUGS............................................................3 C. DIRECT VASODILATORS.................................................................4 D. RAA INHIBITORS...........................................................................5 III. CLINICAL APPLICATION................................................................... 6 A. THERAPEUTIC OBJECTIVES...........................................................6 B. THERAPY...................................................................................... 7 C. HYPERTENSIVE EMERGENCIES..................................................... 7 D. ESH/ESC KEY MESSAGES.............................................................. 7 E. FOLLOW UP.................................................................................. 9 QUESTIONS......................................................................................... 9 ANSWER KEY..................................................................................... 10 RATIONALE........................................................................................10 LEARNING OBJECTIVES 1. Diagnose hypertension 2. Discuss the rationale for treating hypertension 3. Describe the classes of anti-hypertensives, their indications of use and their side effects 4. Recommend lifestyle modifications I. HYPERTENSION Nice to know! ● If a patient asks why they should take HPN medication even if they do not feel any symptoms, the simple answer is to prevent the aforementioned complications A. DIAGNOSIS ● According to JNC on the diagnosis of HPN ○ Depends on measurement of BP and NOT on symptoms reported by patients ○ HPN is usually asymptomatic until overt end damage is imminent or has already occurred ▸ Important especially for patients who do not take antihypertensives since they do not report any symptoms ▸ It might be too late if we wait for the patient to experience symptoms before administering medications ● 2020 International Society of Hypertension (ISH) ○ Systolic blood pressure (SBP) in office or clinic is ≥140 mmHg and/or their diastolic blood pressure ( DBP) is ≥90 mmHg ▸ Requires only one of the two values to be considered HPN ○ Usually requires 2-3 office visits at 1-4 weeks intervals (depending on BP levels) to confirm the diagnosis ○ Diagnosis can be confirmed in a single visit ▸ If BP ≥180/110 mmHg and there is evidence of CVD – E.g., History of heart attack or MI CLASSIFICATION OF HPN Take Note! ● The lecture is based on Evidence-Based Guideline for the Management of High Blood Pressure in Adults from several sources including ○ The European Society of Hypertension and European Society of Cardiology (ESH/ESC 2018) ○ The American College of Cardiology and American Heart Association (ACC/AHA 2017) ○ Report from the Panel Members Appointed to the Eighth Joint National Council (JNC 8 2014) ○ 2020 International Society of Hypertension ● The Philippines Society of Hypertension has announced that they will be releasing a guideline in 2020 but has yet to do so as of the time of recording ● Most common cardiovascular disease ● Why do we have to treat Hypertension (HPN)? ○ According to the Joint National Council (JNC): ▸ Sustained arterial HPN damages the blood vessels in the kidney, heart, and brain ○ According to the European Guidelines (ESH/ESC): ▸ An increase in office BP bears an independent continuous relationship with the incidence of several cardiovascular events – Stroke, MI, sudden death, heart failure, and Peripheral Artery Disease (PAD) as well as End-Stage Renal Disease (ESRD) ▸ This is true at all ages and all ethnic groups ● Effective pharmacological lower of BP has been shown to prevent damage to blood vessels and to subsequently reduce morbidity and mortality rates YL6:05.04 2020 International Society of Hypertension Figure 1. Classification of hypertension based on office BP measurement Figure 1 ● High-normal BP patients do not experience HPN ○ Serves as a warning sign ○ In previous guidelines, this range was called pre-HPN which calls for lifestyle changes ○ If patient does not change their lifestyle, it will lead to Grade 1 HPN ● Anti-hypertensive medication is given when the patient reaches Grade 1 HPN ● Doctors can also prescribe patients in the high-normal BP category antihypertensives given compelling indications ○ Increased CV risk even if BP is within high-normal range TG13: Abad Santos, Ahalajal, Alba, Bernardo, Binobo, Cai, Dy, Gamboa, Pacis, Rejuso, Tan CG06: Abangan, David, Del Corro, Layug, Mendoza, J., Mendoza, R., Ng, Santiago, Santos, Tseng, Uy, Villavicencio 1 ESC/ESH vs. ACC/AHA Hypertension Guidelines ○ Should instead be followed up with lifestyle modification Masked Hypertension ● Condition wherein the patient has normal BP during doctor’s visits, but has elevated BP at home ○ Reverse of white coat hypertension ● HPN diagnosis needs confirmation with repeated office and out-of-office BP measurements ● Risk of CV events is similar to those with sustained hypertension ○ May require drug treatment Nice to Know! ● Dr. Cabigon advises his patients to record their BP measurements in a notebook twice a day ○ During their next visit, Doc will check their measurements to confirm if there is white coat or masked hypertension Figure 2. European vs. American HPN guidelines ● Ranges of each category are almost the same for both European and American guidelines ● The international guidelines more closely follow the European guideline compared to the American guideline ○ In the American guideline, a SBP of 130 mmHg is already considered Stage 1, whereas in European or international guidelines this value is still high-normal ● Despite the differences in nomenclature, the principle of therapy will be the same ○ Anti-hypertensives will be started at SBP of 140 mmHg ▸ Grade 1 for European ▸ Grade 2 for American ○ Lifestyle modifications may be started at SBP of 130 mmHg ○ If there is presence of CV risk, anti-hypertensives may be started at SBP of 130 mmHg ▸ High-normal for European ▸ Grade 1 for American CRITERIA FOR HPN ETIOLOGY OF HPN ● If you are the first doctor to address a patient’s HPN, you must: ○ Request battery of tests to rule out specific causes of HPN ▸ Most common result: patient is normal ○ Check if there are complications already ● Specific cause of HPN can only be established in 10-15% of patients (Katzung) ● Essential HPN: hypertension where there is no specific cause identified ● Usually multifactorial ○ Genetics ○ Psychological stress ○ Environmental factors ○ Dietary factors NORMAL REGULATION OF BLOOD PRESSURE 𝐵𝑃 = (𝐶𝑂)(𝑃𝑉𝑅) Equation 1. Formula for Arterial Blood Pressure ● Where: ○ BP = Blood Pressure ○ CO = Cardiac Output ○ PVR = Peripheral Vascular Resistance 𝐶𝑂 = (𝑆𝑉)(𝐻𝑅) Equation 2. Formula for Cardiac Output ● Where: ○ CO = Cardiac Output ○ SV = Stroke Volume ○ HR = Heart Rate Equation 1 and Equation 2 Figure 3. Criteria for HPN based on Office-, Ambulatory (ABPM)-, and Home Blood Pressure Measurement (HBPM) ● The ISH defines hypertension based on the following: ○ Office BP measurement ▸ BP measured in the doctor’s office/clinic ○ Ambulatory BP measurement (ABPM) ○ Home BP measurement (HBPM) ▸ BP measured at home ● In practice, you will encounter patients with hypertensive BP in front of the doctor, but with normal HBPM ○ Figure 3 takes into account White Coat HPN and Masked HPN ● Equation 1 ○ Tells us the factors that affect blood pressure ○ Cardiac Output (CO) and Peripheral Vascular Resistance (PVR) are directly proportional to Blood Pressure (BP) ● Equation 2 ○ Cardiac Output (CO) is directly proportional to Stroke Volume (SV) and Heart Rate (HR) ● So to treat HPN, you can target the factors that affect BP: ○ Decrease CO → Decreased BP ○ Decrease PVR → Decreased BP ○ Decrease HR → Decreased BP White Coat Hypertension Site Controlling CO and PVR ● Condition wherein patient has elevated BP during doctor’s visits ● HPN diagnosis needs confirmation with repeated office and out-of-office BP measurements ● Drug treatment may not be prescribed if their total CV risk is low and there is no hypertension-mediated organ damage (HMOD) ○ Examples of HMOD: ▸ Left ventricular hypertrophy ▸ Moderate to severe chronic kidney disease YL6:05.04 Drugs for Hypertension ● Arterioles ○ Vasoconstriction: increase PVR → increase BP ○ Vasodilation: decrease PVR → decrease BP ○ To treat HPN: use vasodilators ● Post-capillary venules or Capacitance vessels ○ Increase venous return → increase in CO → increase in BP ○ To treat HPN: decrease venous return to decrease CO, leading to a decrease in BP 2 ▸ E.g. Diuresis: increasing urine output will decrease actual blood volume ● Heart ○ Heart rate is a major factor in determining BP ○ Increase in HR → increase in CO → increase in BP ○ To treat HPN: Decrease HR ● Kidney (RAAS) ○ Regulates the volume of intravascular fluid through the Renin-Angiotensin-Aldosterone System (RAAS) ▸ One major normal effect of this system is to increase BP ▸ It increases BP through angiotensin and aldosterone ○ Angiotensin: angio- (blood vessel) + -tensin (tense/constrict) ▸ Will produce vasoconstriction ○ Aldosterone: hormone that promotes sodium retention ▸ Recall: Where sodium goes, water follows ▸ Sodium retention → water retention → more blood volume → increase in CO → increase in BP ○ To treat HPN: Block renin, angiotensin, or aldosterone Active Recall Box 1. T/F: The diagnosis of hypertension is based solely on the symptoms reported by patients. 2. T/F: Despite normal HBPM, a hypertension diagnosis is immediately warranted for a patient with elevated BP during a doctor’s visit 3. The kidney regulates the volume of intravascular fluid through what system? Answers: 1F, 2F, 3 Renin-Angiotensin-Aldosterone System (RAAS) Rationale: 1F: According to the JNC guidelines, the diagnosis of HPN depends on the measurement of the patient’s BP, not on their reported symptoms; 2F: HPN diagnosis needs confirmation with repeated office and out-of-office BP measurements II. ANTIHYPERTENSIVE AGENTS ● Diuretics ○ From the word “diuresis” meaning to increase in excretion of urine, thus depleting sodium and blood volume ● Sympathoplegic agents ○ Drugs that block the sympathetic nervous system ○ Effective antihypertensives ○ Decrease PVR and increase venous pooling ▸ Recall: Sympathetic Nervous System (“fight or flight”) – Increase HR and BP – By blocking this system, you can decrease BP by promoting a decrease in vasoconstriction and decreasing HR ● Direct vasodilators ○ Relaxes vascular smooth muscles ● Renin-Angiotensin-Aldosterone (RAA) inhibitors ○ Decrease PVR and blood volume ○ Recall: Drugs that block the RAAS can be effective hypertensives Table 1. Classification of Antihypertensive Drugs (05.04, 2026) Drug Class Diuretics Effects A. DIURETICS THIAZIDE DIURETICS ● Suffix: -thiazide ○ Example: Hydrochlorothiazide Mechanism of Action ● Promotes sodium, potassium, and water secretion in the distal convoluted tubules → ↓ blood volume ● Long term use will ↓peripheral vascular resistance (PVR) Side Effects ● Hyponatremia and hypokalemia are expected ○ These drugs promote sodium and potassium excretion ● Hypomagnesemia ● Hypercalcemia ○ Because of the efflux of sodium, it will now create an electrical gradient, thus promoting the reabsorption of calcium ● Metabolic Alkalosis ○ Diuretic effect will lead to fluid contraction, which will lead to metabolic alkalosis ● Hyperuricemia ○ Secretion of thiazides will be with the use of the same organic acid transporter as uric acid ▸ Thus, they will be competing for the same transporter ○ As thiazide diuretics will be secreted out of the body, uric acid will remain ● Hyperlipidemia ○ Not that well understood ● Hyperglycemia ○ Due to decrease in insulin secretion because of hypokalemia Contraindications ● Gout Usual Dose ● In combination: 12.5 mg OD [ESH/ESC Statement] Thiazide Diuretics ● It has also been argued that diuretics such as chlorthalidone or indapamide should be used in preference to conventional thiazide diuretics, such as hydrochlorothiazide ● But no recommendation can be given to favour a particular diuretic agent (due to limited number of trials) ● In fact, hydrochlorothiazide is still readily available ○ It is usually a part of a single pill combination antihypertensive Deplete sodium Sympathoplegic agents Decrease HR and vasoconstriction (decreases PVR an increases venous pooling) Direct vasodilators Relaxes vascular smooth muscle RAA inhibitors Decrease PVR and blood volume ● The different mechanisms of the drug classifications permit the combination of drugs ○ Drugs with the same mechanisms of action should NOT be combined because side effects may be compounded despite being more efficacious YL6:05.04 ○ For combining antihypertensives, they should be from different classes ● NSAIDs (except aspirin) and decongestants may increase BP, thus may blunt the effect of antihypertensives ○ Decongestants are vasoconstrictors and will directly negate the effects of antihypertensives ○ NSAIDS are also known to negate the effects of antihypertensives ▸ Exception: Aspirin (an original NSAID) which is considered to be a cardioprotectant Drugs for Hypertension B. SYMPATHOPLEGIC DRUGS ● ● ● ● β-blocker receptors α-1-receptor blockers Centrally-acting α2 agonists Others (rarely used) ○ Ganglion-blocking agents (very toxic) ○ Adrenergic neuron-blocking agents (e.g., Guanadrel, Guanethidine, Reserpine) Take note! ● Recall gesture mnemonic ● α-vessels-pupils and β1- β2-Peace 3 ○ α-receptors - blood vessels ; pupils ○ β-receptors - β1 heart (accelerates) ○ β2 bronchioles (dilation); Peace β-BLOCKERS (BB) ● Suffix: -olol ● Examples ○ Propranolol: non-selectively blocks both β1 and β2 ○ Metoprolol and Atenolol: cardio-selective blocker Mechanism of Action ● Decrease sympathetic influence on the heart by blocking βreceptors ○ Lowers heart rate Side Effects ● ● ● ● ● ● Major side effect: Bradycardia Heart blocks May mask hypoglycemia Impotence Rebound tachycardia Hypertension on withdrawal Contraindications ● Asthma/COPD ○ Propranolol is a non-selective β-blocker ○ Recall: β2 stimulation causes bronchodilation which is helpful for those with Asthma or COPD ● Heart blocks ○ Due to bradycardia adverse effect ● Terazosin: 1 mg OD-BID CENTRALLY-ACTING α2 AGONISTS ● Examples: ○ Clonidine ▸ Trade name: Catapres ▸ Usually placed under the tongue ○ Methyldopa ▸ Pregnancy category B drug – Pregnancy category A and B are considered safe for pregnant patients Mechanism of Action ● Acts on the α-receptors in the medulla of the brain → inhibits adrenergic outflow from the brainstem → decrease BP ○ α2 will be centrally-activated, which will inhibit adrenergic outflow, thus decreasing BP Side Effects ● Sedation ● Bradycardia ○ In patients with SA nodal abnormality ● Dry mouth ○ Usually in clonidine ● Rebound hypertension ○ After abrupt withdrawal ○ Clonidine is given ▸ For hypertensive urgencies only ▸ Not as maintenance medication Usual Dose ● Clonidine: 150 mcg BID ● Methyldopa: 250 mg BID β-BLOCKER: BABol CENTRALLY-ACTING α2 AGONISTS: ABS-CBM ABS-CBN is channel 2 (pertaining to α2 agonists) Beta-blockers Asthma Bradycardia ol (ending suffix) Usual Dose ● Propranolol: 40 mg BID ● Metoprolol: 50mg OD-BID ● Atenolol: 50mg OD A2 (α2) agonists Bradycardia Sedation Clonidine B - category of pregnancy of: Methyldopa C. DIRECT VASODILATORS [ESH/ESC Statement] β-blockers ● “2006 meta-analysis reported that β-blockers may be inferior to some – but not all – other drug classes for some outcomes ○ Worse than calcium antagonists (but not diuretics and RAS blockers) for total mortality and CV events ○ Worse than calcium antagonists and RAS blockers for stroke” α1-BLOCKERS ● Suffix: -zosin ● Examples: ○ Prazosin ○ Terazosin CALCIUM CHANNEL BLOCKERS: DIHYDROPYRIDINES Mechanism of Action ● Blocks α1-receptors that leads to vasodilation ○ Vasodilation leads to decrease in total peripheral resistance Side Effects ● Orthostatic hypotension ○ Especially on the first dose ● Other vasodilatory effects: ○ Palpitations ○ Headache Usual Dose ● Prazosin: 2 mg BID-TID YL6:05.04 ● Calcium channel blockers ○ Dihydropyridines ○ Non-dihydropyridines ● Other vasodilators (for severe hypertension) ○ Hydralazine ○ Minoxidil ○ Sodium Nitroprusside ○ Diazoxide ○ Fenoldam Drugs for Hypertension ● Suffix: -dipine ● Examples: ○ Amlodipine ○ Felodipine Mechanism of Action ● Blocks calcium channels in arteriolar smooth muscles → arterial vasodilation ● Calcium is important for muscle contraction ○ Blocking calcium channels will relax muscles Side Effects ● Vasodilation causes: ○ Headache due to expansion of cranial vessels ○ Flushing 4 ○ Orthostatic hypotension ○ Peripheral edema ● Reflex tachycardia Contraindications ● Patients with Congestive Heart Failure (CHF) ○ Contraindicated due to peripheral edema (so as not to add to edema caused by congestion) Usual Dose ● Amlodipine: 5 mg OD ● Felodipine: 5 mg OD Figure 4. Hypertrichosis secondary to minoxidil administration CALCIUM CHANNEL BLOCKERS: NON-DIHYDROPYRIDINES ● Suffix: will NOT end in -dipine ○ As compared to dihydropyridines ● Examples: ○ Diltiazem ○ Verapamil Mechanism of Action ● Blocks calcium channels in arteriolar smooth muscles → arterial vasodilation ○ Similar to dihydropyridines ● Slows AV nodal conduction → reduces heart rate (HR) Side Effects ● Vasodilation effects ○ Headache ○ Flushing ○ Orthostatic hypotension ○ Peripheral edema ● Bradycardia ● Heart blocks ● Sodium nitroprusside ○ Drug of choice in management of hypertensive crisis ● Diazoxide (for severe cases) ● Fenoldam (for severe cases) D. RAA INHIBITORS ● Types of RAA inhibitors: ○ Angiotensin-converting enzyme (ACE) inhibitors ○ Angiotensin II receptor blockers (ARBs) ○ Direct renin inhibitors ○ Aldosterone receptor-blockers ACE INHIBITORS ● Suffix: -pril ● E.g., Captopril, Enalapril Mechanism of Action ● Recall: ○ Angiotensin, especially angiotensin II, is a potent vasoconstrictor ○ ACE converts angiotensin I to angiotensin II ● Inhibition of ACE → Decreased angiotensin II synthesis → arteriolar vasodilation Side Effects Contraindications ● Depressed left ventricle (LV) function ● Heart failure ● Heart blocks Usual Dose ● Diltiazem: 120 mg OD ● Verapamil: 120 mg OD DIRECT VASODILATORS: Calcium Channel Blockers - CVd CVD Calcium channel blockers (dihydropyridines) Vasodilation effects -Dipine ending suffix (Amlodipine, Felodipine) Calcium channel blockers (non-dihydropyridines) Verapamil Diltiazem ● Dry cough and angioedema ○ Due to bradykinin and substance P production ● Hyperkalemia ○ Blocked angiotensin II → blocked aldosterone → hyperkalemia ● Rhinorrhea ● Proteinuria Contraindications ● Patients with hyperkalemia ● Pregnancy ○ ACE inhibitors are under pregnancy category D ● Bilateral renal artery stenosis (leads to acute renal failure) ○ Angiotensin constricts the efferent arteriole to maintain the high vascular resistance ▸ Ensures adequate glomerular pressure and filtration in bilateral renal artery stenosis ○ ACE inhibitors inhibit this mechanism, producing azotemia Usual Dose OTHER VASODILATORS ● Hydralazine ○ For severe HPN ○ Side effects: fluid retention and lupus-like syndrome (e.g., arthralgia, lymphadenopathy, rash, fever) ● Minoxidil ○ For severe HPN and renal insufficiency ○ Side effects: significant fluid retention and hypertrichosis ▸ Hypertrichosis (a.k.a. werewolf syndrome): abnormal amount of hair growth in the body ○ Marketed as a tropical preparation and shampoo for hair regrowth ● Captopril: 25 mg BID ● Enalapril: 5 mg OD-BID RAA INHIBITORS – ACE INHIBITORS: A-pril Cough or A-pril CAP ACE inhibitors -pril ending suffix (Captopril, Enalapril) Cough Angioedema Potassium (hyperkalemia) ARBS ● E.g., Losartan YL6:05.04 Drugs for Hypertension 5 Mechanism of Action ● Blocks the binding of angiotensin II to smooth muscle receptors → arteriolar vasodilation Mechanism of Action ● Promote sodium and water excretion in the collecting duct renal tubules Side Effects ● Similar to ACE inhibitors: ○ Cough and angioedema (remarkably less) ○ Hyperkalemia Side Effects ● Hyperkalemia ○ Due to potassium-sparing effect ● Gynecomastia and impotence Contraindications ● Hyperkalemia ● Pregnancy (category D in 2nd & 3rd trimester) ● Bilateral renal artery stenosis (leads to acute renal failure) Usual Dose ● Losartan: 50 mg OD-BID Usual Dose ● Spironolactone: 25 mg OD RAA INHIBITORS – ALDOSTERONE RECEPTOR-BLOCKERS: SPIRO-SPARING SPIROnolactone: Potassium-SPARING diuretic, leading to hyperkalemia [ESH/ESC Statement] ACE Inhibitors and ARBs ● “Among the well known ancillary properties of ACE inhibitors and angiotensin receptor blockers are their peculiar effectiveness in reducing proteinuria ● Several RCT [randomized clinical trials] have clearly indicated that RAS blockade is more effective in reducing albuminuria than either placebo or other antihypertensive agents in diabetic nephropathy, non-diabetic nephropathy, and patients with CVD” ARBS ● E.g., Aliskiren ● Currently not in use ○ Studies provide contradictory results regarding safety and benefits ○ A large-scale trial was stopped because, in patients at high risk of CV and renal events, there was a higher incidence of: ▸ Adverse events ▸ Renal complications (end-stage renal disease and renal death) ▸ Hyperkalemia ▸ Hypotension Mechanism of Action ● Blocks the entire RAAS ○ Block the binding of renin to the receptor on angiotensinogen → inhibits conversion of angiotensinogen to angiotensin I Side Effects ● Hyperkalemia ● Diarrhea ● Gastroesophageal reflux disease (GERD) Contraindications ● Hyperkalemia ● Pregnancy (category D in 2nd & 3rd trimester) ● Bilateral renal artery stenosis (leads to acute renal failure) Usual Dose ● Aliskiren: 50 mg OD Active Recall Box 1. What is an example of a drug that is a direct renin inhibitor? 2. T/F: Dihydropyridines are vasodilatory, while non-dihydropyridines cause vasoconstriction. 3. T/F: Propranolol, metoprolol, and atenolol are cardio-selective beta blockers. Answers: 1Aliskiren, 2F, 3F Rationale: 2F: Both dihydropyridines and non-dihydropyridines are vasodilatory; 3F: Propranolol non-selectively blocks both β1 and β2 receptors III. CLINICAL APPLICATION A. THERAPEUTIC OBJECTIVES ● To control the blood pressure within 3 months ○ According to the 2020 International Society of Hypertension Global Hypertension Practice Guidelines: ▸ <65 years: BP target <130/80mmHg if tolerated (but still better if >120/70 mmHg) ▸ ≥65 years: BP target <140/90 mmHg if tolerated but consider an individualized BP target in the context of frailty, independence and likely tolerability of treatment ▸ But if drug availability is limited, target BP reduction by at least 20/10 mmHg, ideally to <140/90 mmHg ● Lifestyle modification ○ Salt reduction ○ Healthy diet ○ Healthy drinks ○ Moderation of alcohol consumption ○ Weight reduction ○ Smoking cessation ○ Regular physical exercise ○ Reduce stress and induce mindfulness ○ Complementary, alternative or traditional medicines ○ Reduce exposure to air pollution and cold temperature RAA INHIBITORS – DIRECT RENIN INHIBITORS: Alis(ki)Ren Alis - Inhibit Ren - Renin ARBS ● E.g., Spironolactone ○ A.k.a. potassium-sparing diuretic Take Note! ● In the lecture video, the drug was referred to as “Spirinolactone,” but the correct name of the drug is “Spironolactone” YL6:05.04 Drugs for Hypertension 6 2020 INTERNATIONAL SOCIETY OF HYPERTENSION GUIDELINES Figure 5. Standard drink amounts Figure 5 Figure 7. 2020 International Society of Hypertension therapy guidelines ● For males ○ Not more than 2 standard drinks per day ● For females ○ Not more than 1.5 standard drinks per day ● Binge drinking is still not advised ○ Standard drinks per day is non-transferable to other days ● To assess and identify other CV risk factors or concomitant disorders that may affect prognosis and guide treatment ○ Presence of risk factors will increase the risk in developing cardiovascular events accordingly Figure 7 ● Consider monotherapy in low-risk grade 1 hypertension or in very old (≥80 yrs) or frailer patients ● Consider A + D in post-stroke, very elderly, incipient HF or CCB intolerance ● Consider A+C or C+D in black patients ● Caution spironolactone or other potassium sparing diuretics when estimated GFR <45 ml/min/1.73m2 or K+ >4.5 mmol/L ○ A = ACE-inhibitor or ARB (Angiotensin Receptor Blocker) ○ C = DHP-CCB (Dihydropyridine-Calcium Channel Blocker) ○ D = Thiazide-like diuretic JNC 8 DOSING STRATEGY ● Any of the following options can be done: ○ Start one drug, titrate to maximum dose, and then add a second drug ○ Start one drug and then add a second drug before achieving maximum dose of the initial drug ○ Begin with 2 drugs at the same time, either as 2 separate pills or as a single pill combination ESC/ESH GUIDELINES ● Start with combination, no room for monotherapy ● Simplified drug algorithm ○ ACE or ARB + CCB or Thiazide/Thiazide-like diuretic Figure 6. Simplified classification of hypertension risk according to additional risk factors, hypertension-mediated organ damage (HMOD), and previous disease ● Prevent long term complications including congestive heart failure, stroke, or renal failure ● To minimize the adverse effects of drugs B. THERAPY ● Initiated in a gradual fashion ● Consume drugs daily ○ Should be taken daily regardless of the presence or absence of symptoms ● BP monitoring ● Non-pharmacologic measures C. HYPERTENSIVE EMERGENCIES ● Patients with marked BP elevations and acute target-organ damage ○ E.g., encephalopathy, myocardial infarction, unstable angina, stoke, head trauma, life-threatening, arterial bleeding, or aortic dissection ● Require hospitalization and parenteral drug therapy ● But rapid normalization of BP among chronic hypertensive may lead to cerebral hypoperfusion and brain injury ● BP should be lowered by about 25%, maintaining diastolic blood pressure at no less than 100-110 mmHg ● Subsequently, BP may be reduced to normal using oral meds over several weeks USUAL MEDICATIONS ● Sodium nitroprusside, parenteral calcium channel blockers (like nicardipine), fenoldam, diazoxide, hydralazine, nitroglycerine, labetalol ● Diuretics (like furosemide) are administered to prevent volume expansion that typically occurs during administration of powerful vasodilators HYPERTENSIVE URGENCIES ● Patients with markedly elevated BP, but without acute target organ damage YL6:05.04 Drugs for Hypertension 7 ● Do not require hospitalization, but they should receive immediate combination oral antihypertensive therapy D. ESH/ESC KEY MESSAGES Table 2. Compelling and possible contraindications to the use of antihypertensive drugs Compelling Contraindication Drug Diuretics (thiazides) β-blockers ● Gout ● Asthma ● A-V block (grade 2 or 3) Calcium antagonists (dihydropyridines) ● None ● Metabolic syndrome ● Glucose intolerance ● Pregnancy ● Hypercalcemia ● Hypokalemia ● Metabolic syndrome ● Glucose intolerance ● Athletes and physically active patients ● COPD (except for vasodilator β-blockers) ● Tachyarrhythmia ● Heart failure (HFrEF, class III or IV) ● AV block (grade 2 Calcium antagonists (non-dihydropyridine: or 3, trifascicular verapamil, diltiazem) block) ● Severe LV dysfunction (LV ejection fraction <40%) ● Bradycardia ● Heart failure ACE Inhibitors ARBs Mineralocorticoid receptor antagonists ● Pregnancy ● Previous angioneurotic edema ● Hyperkalemia ● Bilateral renal artery stenosis ● Women of childbearing potential without reliable contraception ● Pregnancy ● Hyperkalemia ● Bilateral renal artery stenosis ● Women of childbearing potential without reliable contraception ● Acute or severe renal failure (eGFR <30 mL/min) ● Hyperkalemia ● The following bullets were emphasized by the lecturer ● Diuretics ○ Compelling contraindication is gout ▸ ​Recall: diuretics produce hyperuricemia ● β-blockers ○ Contraindicated for patients with asthma ▸ Specifically, propranolol, a non-selective β-blocker ○ Contraindicated for patients with A-V block β-blockers produce bradycardia ● Calcium channel antagonists: dihydropyridines Drugs for Hypertension ● ● ● Table 3. Preferred medication in specific conditions ASYMPTOMATIC ORGAN DAMAGE Condition Take Note! YL6:05.04 ● Possible ○ Generally, no compelling contraindications ○ Possibly contraindicated in those with: ▸ Tachyarrhythmia – Since they can cause rebound tachycardia ▸ Heart Failure – Vasodilators can produce edema Calcium antagonists: non-dihydropyridines ○ Produce vasodilation and bradycardia ▸ Dihydropyridines don't have this effect ○ Contraindicated in patients with AV block, severe LV dysfunction, and heart failure ACE Inhibitors ○ Contraindications include: ▸ Pregnancy – Possible contraindications include women of child-bearing potential without reliable contraception ▸ Previousangioneuroticedema ▸ Hyperkalemia ▸ Bilateral Renal Artery Stenosis ARBs ○ Contraindications include: ▸ Pregnancy – Possible contraindications include women of child-bearing potential without reliable contraception ▸ Hyperkalemia ▸ Bilateral Renal Artery Stenosis Mineralocorticoid receptor antagonists ○ Acute or severe renal failure (eGFR <30 mL/min) ○ Hyperkalemia Drug LV hypertrophy ACE inhibitor, calcium antagonist, ARB Asymptomatic atherosclerosis Calcium antagonist, ACE inhibitor Microalbuminuria ACE inhibitor, ARB Renal dysfunction ACE inhibitor, ARB CLINICAL CARDIOVASCULAR EVENT Condition Drug Previous stroke Any agent effectively lowering BP Previous myocardial infarction BB, ACE inhibitor, ARB Angina pectoris BB, calcium antagonist Heart failure Diuretic, BB, ACE inhibitor, ARB, mineralocorticoid receptor antagonists Aortic aneurysm BB Atrial fibrillation, prevention Consider ARB, ACE inhibitor, BB or mineralocorticoid receptor antagonist Atrial fibrillation, ventricular rate control BB, non-dihydropyridine calcium antagonist End-stage renal disease/ proteinuria ACE inhibitor, ARB Peripheral artery disease ACE inhibitor, calcium antagonist OTHER Condition ISH (elderly) Drug Diuretic, calcium antagonist 8 Metabolic syndrome ACE inhibitor, ARB, calcium antagonist Diabetes mellitus ACE inhibitor, ARB Pregnancy Methyldopa, BB, calcium antagonist Blacks Diuretic, calcium antagonist Take Note! ● The following bullets were emphasized by the lecturer ● LV hypertrophy ○ Use of first-line medications ▸ ACE inhibitors, calcium antagonists, ARBs ● Renal dysfunction and related symptoms (e.g., microalbuminuria) ○ Use of ACE inhibitors, ARBs ● Clinical CV events ○ Addition of β-blockers if there’s value in decreasing the heart rate and eventually, heart workload ● End-stage renal disease or proteinuria ○ Use of ACE inhibitors and ARB ● Peripheral artery disease and atherosclerosis ○ Use of calcium antagonists and ACE inhibitors ● Other conditions ○ Diabetes mellitus: ACE inhibitors, ARBs ○ Pregnancy: methyldopa, BBs, calcium antagonists E. FOLLOW UP ● Once antihypertensive drug therapy is initiated, most patients should return for follow-up and adjustment of medications ○ Monthly intervals until the BP goal is reached ● More frequent visits will be necessary for patients with stage 2 hypertension or for patients with complicating comorbid conditions ○ If the case is more complicated or more side effects are expected, ask the patients to return after a week or two to monitor the initial effects of the medications ● After the BP is at goal and stable, follow-up visits can be at 3 to 6 month intervals Review Questions from the lecture 1. Controls hypertension, except: a. Aspirin (Aspilets) b. Captopril (Capoten) c. Nifedipine (Calcibloc) d. Propranolol (Inderal) 2. An antihypertensive (β-blocker) that induces bronchospasms, thus contraindicated among patients with asthma. a. Amphetamines b. Propranolol c. Metoprolol d. Prazosin 3. A hypertensive patient complained of persistent cough. What antihypertensive can produce this symptom? a. ACE inhibitor b. β-blocker c. Calcium channel blocker d. Diuretic 4. What is the most common side effect of calcium channel blockers, as well as other vasodilators? a. Bronchospasm b. Headache c. Hypertension d. Tachycardia 5. Edgar is a known hypertensive. He was started on Metoprolol 50 mg BID. The common side effect of this drug is _____. a. Bradycardia b. Cough c. Fluid and electrolyte imbalance YL6:05.04 Drugs for Hypertension d. Headache 6. The following should be done before giving antihypertensives, EXCEPT: a. Caution client to change position slowly b. Instruct the patient to report adverse reactions c. Maintain high sodium diet d. Monitor vital signs, especially BP ANSWERS: 1A, 2B, 3A, 4B, 5A, 6C RATIONALE: 1. A. Aspirin (Aspilets). Aspirin (“the original NSAID”), for CV indications, is used as an antiplatelet to prevent blood clotting. Captopril is an ACE inhibitor. Nifedipine is a dihydropyridine (calcium channel blocker). Propranolol is a β-blocker. 2. B. Propranolol. It is a non-selective β-blocker that causes bronchospasm and is contraindicated in patients with asthma. 3. A. ACE inhibitor. Recall our memory aid: A-pril cough. 4. B. Headache. Common side effects of vasodilators are headache, orthostatic hypotension, flushing, and peripheral edema. 5. A. Bradycardia. Bradycardia is a common side effect of β-blocker. Recall our memory aid BABol. 6. C. Maintain a high sodium diet. Recall nonpharmacologic measures. Active Recall Box 1. T/F: Therapeutic goals for HPN include controlling BP within 6 months. 2. Which of the following classes of drugs are contraindicated in pregnancy? A. ACE inhibitors B. ARBs C. Both A and B D. NOTA Answers: 1F, 2C Rationale: 1F: Therapeutic goals for HPN include controlling BP within 3 months QUICK REVIEW QUESTIONS 1. Upon requesting for tests to rule out causes of HPN, the most common result is that the patient is likely hypertensive. Hypertension that is brought about by various causes is known as Essential Hypertension. A. Only Statement 1 is true B. Only Statement 2 is true C. Both statements are true D. Both statements are false 2. T/F: Sympathomimetic drugs can decrease blood pressure by decreasing heart rate and causing vasoconstriction. 3. The following are side effects of thiazide diuretics except: A. Hyperlipidemia B. Hypernatremia C. Hyperuricemia D. Hyperglycemia 4. Non-dihydropyridines work by blocking calcium channels in arteriolar smooth muscles, causing vasodilation. Due to this, side effects such as tachycardia and heart blocks may be experienced. A. Only statement 1 is true B. Only statement 2 is true C. Both statements are true D. Both statements are false 5. What drug's mechanism of action is to promote sodium and water excretion in the collecting duct renal tubules? A. ACE Inhibitors B. ARBs C. Calcium antagonists 9 D. Diuretics 6. Captopril and Enalapril are examples of ACE inhibitors. Side effects of these drugs include wet cough and hypokalemia. A. Only statement 1 is true B. Only statement 2 is true C. Both statements are true D. Both statements are false 7. Lifestyle modifications to help with hypertension include the following, EXCEPT: A. Healthy diet B. Regular physical exercise C. Alcohol cessation D. Smoking cessation 8. A patient presents with markedly elevated BP but does not show signs of acute, targeted organ damage. Which of the following should be done in this scenario? A. Hospitalize the patient and constantly monitor their vitals B. Start parenteral hypertensive drug therapy C. Give patient immediate combination oral hypertensive drug therapy and send them home D. NOTA 9. Park Jae-Eun consults with you regarding his family’s history of hypertension. Upon checking his BP, you note a systolic blood pressure of 132 and a diastolic blood pressure of 84. Given that the upper limit of normal BP is 129/84, what will be your course of action as a physician? A. Advise him to adopt a more active lifestyle so his BP remains within normal limits B. Prescribe him hypertensives to control his BP C. Both A & B D. NOTA 10. T/F. A patient can take diuretics even if they have gout. REFERENCES 💻 Cabigon, J.J., MD, DPCOM, DPASMAP (2021, November 11). Drugs For Hypertension. [Lecture video]. REQUIRED ● 📖 Katzung, Bertram G.. (2018). Basic & clinical pharmacology (14th). New York: McGraw-Hill. ● 📄 ASMPH 2026. 05.04: Drugs for Hypertension by Cabigon, J.J., MD, DPCOM, DPASMAP SUPPLEMENTARY ● Concerns and Feedback form: http://bit.ly/YL6CFF2027 How’s My Transing? form: https://bit.ly/2027YL6HMT Mid-Semester Evaluation form: https://bit.ly/2027YL6MidSem End-of-Semester Evaluation form: https://bit.ly/2027YL6EndofSem Errata Points Trackers: https://bit.ly/YL62027EPT YL6 TransMap: https://bit.ly/2027YL6TransMap ANSWER KEY 1D, 2F, 3B, 4A, 5B, 6A, 7C, 8C, 9A, 10F RATIONALE 1. D. Both statements are false. Upon requesting for tests to rule out causes of HPN, the most common result is likely normal. Essential hypertension is HPN where no specific cause can be found or identified. 2. False. Sympathoplegic drugs are used as antihypertensives because they decrease heart rate and cause vasoconstriction, not sympathomimetic drugs. 3. B. Hypernatremia. Thiazide diuretics promote sodium excretion, and thus, the expected side effect is hyponatremia, not hypernatremia. 4. A. Only statement 1 is true. Non-dihydropyridines reduce heart rate, causing bradycardia as a side effect and not tachycardia. 5. B. ARBs. They have the mechanism of action of promoting sodium and water excretion in the collecting duct renal tubules. 6. A. Only statement 1 is true. Side effects of ACE inhibitors include a dry cough and hyperkalemia, not wet cough and hypokalemia. 7. C. Alcohol cessation. Lifestyle modifications include moderation of alcohol consumption rather than the complete cessation of alcohol consumption. 8. C. Give patient immediate combination oral hypertensive drug therapy and send them home. Markedly elevated BP without acute targeted organ damage is indicative of a hypertensive urgency, which does not require hospitalization but does require immediate combination oral antihypertensive therapy. 9. A. Advise him to adopt a more active lifestyle so his BP remains within normal limits. A blood pressure of 136/84 is under the high-normal BP category which does not require the prescription of antihypertensives. 10. False. A compelling contraindication of diuretics is gout because diuretics produce hyperuricemia. YL6:05.04 Drugs for Hypertension 10