What it is:Persistently elevated arterial blood pressure. Mostly silent until it damages something. About 90% is primary (no identifiable cause); under 10% is secondary, usually from CKD or renovascular disease.
Why we treat it:Not to fix a number. To prevent stroke, MI, heart failure, and kidney failure. Risk of premature death tracks with how high the BP is.
The whole algorithm in one line:Classify the BP → check for a compelling indication → if none, pick from the four first-line classes → Stage 1 gets one drug, Stage 2 gets two.
Almost every exam question is really asking one of two things: "what number triggers drug therapy?"or "does this patient have a comorbidity that forces a specific drug?"Get the thresholds and the compelling indications table cold and you've got most of this chapter.
| Category | Systolic | Diastolic | |
|---|---|---|---|
| Normal | <120 | and | <80 |
| Elevated | 120–129 | and | <80 |
| Stage 1 | 130–139 | or | 80–89 |
| Stage 2 | ≥140 | or | ≥90 |
Normal and Elevated use and. Stage 1 and Stage 2 use or. So 135/75 is Stage 1 (systolic qualifies alone) and 125/85 is also Stage 1 (diastolic qualifies alone). When the two numbers disagree, the higher category wins.
| Cause | Clues that point to it |
|---|---|
| CKD / renovascular disease | Most common secondary cause. Abdominal systolic-diastolic bruit suggests renal artery stenosis. Protein, RBCs, casts in urine. |
| Primary aldosteronism | Unexplained hypokalemia → muscle cramps and weakness. Check plasma/urinary aldosterone. |
| Pheochromocytoma | Headaches, sweating, tachycardia, palpitations, orthostatic hypotension. Check plasma norepinephrine and urinary metanephrines. |
| Cushing syndrome | Moon face, buffalo hump, hirsutism, weight gain, polyuria, edema, acne, menstrual irregularity, muscle weakness. |
| Others | Coarctation of the aorta, obstructive sleep apnea, hyperparathyroidism, hyperthyroidism. |
Corticosteroids · estrogens · NSAIDs· amphetamines · cyclosporine · tacrolimus · erythropoietin · venlafaxine. Before you add a fifth antihypertensive, make sure one of these isn't the reason the BP won't budge.
Uncomplicated primary hypertension is asymptomatic. Elevated BP may be the only physical finding. Symptoms, when present, usually belong to a secondary cause or to end-organ damage.
BUN, serum creatinine with eGFR (CKD-EPI creatinine equation), fasting lipid panel, fasting glucose, electrolytes (sodium, potassium, calcium), uric acid, hemoglobin and hematocrit, spot urine albumin-to-creatinine ratio, plus a 12-lead ECG.
It's not just a kidney screen. In diabetes, an ACR ≥30 mg/gflips the patient into "treat like CKD," which means an ACEi or ARB titrated to max tolerated dose instead of any first-line agent. One lab value changes the drug choice.
BP goal for most adults: <130/80 mm Hg.That includes patients with ASCVD, diabetes, or CKD.
| Situation | Start drugs when BP is… | Goal |
|---|---|---|
| Elevated BP or Stage 1, low risk(primary prevention, 10-yr ASCVD risk <10%) | ≥140/90 - lifestyle alone until then | <130/80 |
| Stage 1 or 2 withclinical ASCVD, or 10-yr ASCVD risk ≥10% | ≥130/80 | <130/80 |
| Older ambulatory, community-dwelling | Per risk above | SBP <130 |
| Institutionalized, high disease burden, or limited life expectancy | Individualize | Relaxed SBP <150 (or <140 if tolerated) |
| History of stroke or TIA | >140/90, only after stabilizing post-event | <130/80 |
Two patients both sitting at 134/84 (Stage 1). The one with a 10-year ASCVD risk of 6% gets lifestyle only. The one with prior MI gets lifestyle plus a drug today. Same number, different answer, because risk determines the threshold.
These apply to all patients with elevated BP or Stage 1/2 hypertension, and are the onlyinitial treatment for low-risk Stage 1.
| Intervention | Target |
|---|---|
| Weight loss | If overweight or obese |
| DASH eating plan | Fruits, vegetables, low-fat dairy, reduced saturated fat |
| Sodium reduction | Ideally 1.5 g/day sodium(3.8 g/day sodium chloride) |
| Physical activity | 90–150 min/weekaerobic or dynamic resistance training |
| Alcohol moderation | ≤2 drinks/day men, ≤1 drink/day women |
| Smoking cessation | Doesn't lower BP but cuts CV risk - still push it |
Block angiotensin I → II conversion, also block bradykinin breakdown (hence cough).
Block AT₁ receptor directly. Catch angiotensin II made by chymase too. No cough.
Block voltage-gated Ca channels → vasodilation. DHP vs non-DHP behave very differently.
Chlorthalidone preferred over HCTZ, more potent mg-for-mg.
Evidence suggests they don't reduce CV events as well as the four above when used as initial therapy without a compelling indication. Reserve them for a specific compelling indication(HFrEF, stable ischemic heart disease, post-ACS) or as add-on to a first-line agent. This reversal from older teaching is heavily tested.
Everything else- α₁-blockers, MRAs, central α₂-agonists, direct renin inhibitors, direct arterial vasodilators - is reserved for resistant hypertension or add-on after first-line agents are in place. They either lack outcome evidence or have tolerability problems.
A compelling indication is a comorbidity where trial data support a specific drug class for boththe hypertension and the comorbidity. When one exists, it overrides the generic first-line choice.
| Comorbidity | First choice | Then add |
|---|---|---|
| HFrEF | ACEi or ARB (ARNI preferred over either) | Evidence-based β-blocker (bisoprolol, carvedilol, metoprolol succinate) → then MRA. Diuretic if edema. |
| HFpEF | ACEi or ARB, or β-blocker | Diuretic if edema present. Target symptoms and BP, not mortality - the HFrEF benefits don't transfer. |
| Stable ischemic heart disease | β-blocker(without ISA) - therapy of choice | ACEi or ARB. Long-acting non-DHP CCB is an alternative to β-blocker. DHP CCB as add-on if angina persists. |
| Diabetes | Any first-line agent (ACEi, ARB, CCB, thiazide) if noalbuminuria | If ACR ≥30 mg/g → treat as CKD, use ACEi or ARB at max tolerated dose. β-blocker is useful add-on. |
| CKD | ACEi or ARB- reduces intraglomerular pressure and slows progression | Start low, check SCr soon after starting to avoid AKI from a rapid BP drop. |
| Secondary stroke prevention | Thiazidealone or thiazide + ACEi | Only start after the patient is stabilized post-event. |
| Resistant hypertension | Optimize first-line triple therapy | MRA(spironolactone) - aldosterone excess is common in this setting. Chlorthalidone over HCTZ. |
Kidneys → ACEi/ARB.CKD and albuminuric diabetes both get RAAS blockade because it lowers pressure inside the glomerulus, not just in the artery.
Heart muscle already injured → β-blocker gets promoted.Stable ischemic heart disease and HFrEF are the two places β-blockers move to the front of the line.
ACEi + ARB.No additional CV event reduction, higher risk of renal dysfunction and hypotension. Same goes for ACEi or ARB with a direct renin inhibitor (aliskiren).
| Drug | Usual range (mg/day) | Frequency |
|---|---|---|
| ACE inhibitors | ||
| Lisinopril | 10–40 | 1 |
| Benazepril | 10–40 | 1 or 2 |
| Enalapril | 5–40 | 1 or 2 |
| Ramipril | 2.5–10 | 1 or 2 |
| Quinapril | 10–80 | 1 or 2 |
| Captopril | 12.5–150 | 2 or 3 |
| Fosinopril | 10–40 | 1 |
| Perindopril | 4–16 | 1 |
| Trandolapril | 1–4 | 1 |
| ARBs | ||
| Losartan | 50–100 | 1 or 2 |
| Valsartan | 80–320 | 1 |
| Candesartan | 8–32 | 1 or 2 |
| Irbesartan | 150–300 | 1 |
| Olmesartan | 20–80 | 1 |
| Telmisartan | 20–40 | 1 |
| Azilsartan | 40–80 | 1 |
| CCB - dihydropyridine | ||
| Amlodipine | 2.5–10 | 1 |
| Felodipine | 5–20 | 1 |
| Nifedipine long-acting | 30–90 | 1 |
| Nisoldipine | 10–40 | 1 |
| CCB - nondihydropyridine | ||
| Diltiazem SR / ER | 120–480 / 180–480 | 1 or 2 |
| Verapamil SR | 180–420 | 1 or 2 |
| Verapamil (Verelan PM) | 100–400 | 1 (evening) |
| Thiazide diuretics | ||
| Chlorthalidone(preferred) | 12.5–25 | 1 |
| Hydrochlorothiazide | 12.5–50 | 1 |
| Indapamide | 1.25–2.5 | 1 |
| Metolazone | 2.5–10 | 1 |
| Loop diuretics (only if edema or eGFR <30) | ||
| Furosemide | 20–80 | 1–2 |
| Torsemide | 5–10 | 1 |
| Bumetanide | 0.5–4 | 1–2 |
| MRA / potassium-sparing | ||
| Spironolactone | 25–50 | 1 or 2 |
| Eplerenone | 50–100 | 1 or 2 |
| Triamterene | 50–100 | 1 or 2 |
| Amiloride | 5–10 | 1 or 2 |
| β-blockers (compelling indication or add-on) | ||
| Metoprolol succinate ER | 50–200 | 1 |
| Metoprolol tartrate | 100–200 | 2 |
| Atenolol | 25–100 | 1 or 2 |
| Bisoprolol | 2.5–10 | 1 |
| Nebivolol | 5–20 | 1 |
| Carvedilol | 12.5–50 | 2 |
| Labetalol | 200–800 | 2 |
| Propranolol LA | 80–320 | 1 |
| Alternative agents | ||
| Doxazosin / Terazosin / Prazosin | 1–8 / 1–20 / 2–20 | 1 / 1–2 / 2–3 |
| Aliskiren (direct renin inhibitor) | 150–300 | 1 |
They block conversion of angiotensin I to angiotensin II (a potent vasoconstrictor and aldosterone stimulator), block bradykinin degradation, and stimulate synthesis of vasodilators like prostaglandin E₂ and prostacyclin.
Start low, titrate slowly.Acute hypotension can occur at initiation, especially if sodium- or volume-depleted, in HF exacerbation, very elderly, or already on vasodilators or diuretics. Use half the normal starting dose in those patients.
GFR drops somewhat when you start an ACEi because you've removed angiotensin II's constriction of the efferentarteriole. A modest rise in serum creatinine - absolute increase under about 1 mg/dL- does not warrant stopping. Larger jumps mean reduce or discontinue.
Adverse effects:dry cough in up to 20% (bradykinin-mediated) · hyperkalemia, mainly in CKD or with potassium supplements, potassium-sparing diuretics, MRAs, ARBs, or renin inhibitors · angioedema in <1%, may need drug treatment and sometimes emergent intubation.
Bilateral renal artery stenosis, or unilateral stenosis in a solitary functioning kidney, makes the patient dependent on angiotensin II constricting the efferent arteriole to maintain filtration. Take that away and filtration collapses. Classic contraindication.
Contraindicated in pregnancy- as are ARBs and direct renin inhibitors.
Angiotensin II is made two ways: the classic renin-angiotensin pathway using ACE, and an alternative pathway using enzymes like chymase. ACE inhibitors only block the first. ARBs block the receptor, so they neutralize angiotensin II from either pathway.
They don't touch bradykinin, which is why there's no cough and less angioedema. Note the flip side: some of the antihypertensive benefit of ACE inhibitors may actually come frombradykinin.
All ARBs have similar efficacy with fairly flat dose-response curves, so pushing the dose gains less than adding a CCB or thiazide, which meaningfully increases efficacy.
Adverse effects:low overall. Still can cause renal insufficiency, hyperkalemia, and orthostatic hypotension. Contraindicated in pregnancy. An ARB can generally be used after ACEi-induced angioedema with careful monitoring.
Both block voltage-sensitive calcium channels, reducing calcium entry, relaxing cardiac and vascular smooth muscle. Where they differ matters enormously.
| Dihydropyridines (amlodipine, felodipine, nifedipine) | Nondihydropyridines (verapamil, diltiazem) | |
|---|---|---|
| Main site | Vasculature | Heart |
| Heart rate | Reflex increase(baroreceptor-mediated) | Decrease |
| AV conduction | No effect | Slowed - verapamil more than diltiazem |
| Inotropy | Negative, except amlodipine and felodipine | Negative - verapamil can precipitate HF with borderline reserve |
| Use in SVT | Not effective | Yes |
| Signature side effects | Peripheral edema, flushing, headache, dizziness, gingival hyperplasia | Bradycardia, AV block, HF, peripheral edema, hypotension; verapamil constipation ~7% |
Can rarely increase the frequency, intensity, and duration of angina alongside acute hypotension. Use sustained-release formulations or another dihydropyridine instead.
How they work over time:acutely, diuresis drops plasma volume, stroke volume, and cardiac output, which triggers a compensatory rise in peripheral vascular resistance. With chronic therapy, fluid volume returns close to baseline but peripheral vascular resistance falls below where it started- and that's what sustains the BP reduction. Thiazides also mobilize sodium and water out of arteriolar walls.
Chlorthalidone over HCTZ, especially in resistant hypertension, because it's more potent milligram for milligram.
Loop diureticsare stronger diuretics but weaker antihypertensives. Use them when edema also needs treating, or in severe CKD with eGFR <30where thiazides stop working well.
Potassium-sparing diuretics(triamterene, amiloride) are weak on their own and don't add antihypertensive effect to a thiazide or loop. Their real job is offsetting potassium wasting.
MRAs(spironolactone, eplerenone) are the go-to for resistant hypertensionbecause elevated aldosterone is common there.
Hypo-kalemia, hypo-magnesemia, hyper-calcemia, hyperuricemia, hyperglycemia, dyslipidemia, sexual dysfunction. Calcium goes the opposite direction from the others - that's the one people miss. Loop diuretics flip it: more pronounced hypokalemia and hypocalcemia, less effect on lipids and glucose.
Low-dose therapy (HCTZ 25 mg or chlorthalidone 12.5 mg daily) causes far fewer electrolyte problems. Eplerenone carries higher hyperkalemia risk and is contraindicated in impaired renal function or type 2 diabetes with proteinuria. Spironolactone causes gynecomastia in up to 10%; rare with eplerenone.
| Hypertensive EMERGENCY | Hypertensive URGENCY | |
|---|---|---|
| Definition | Extreme BP elevation withacute or progressing end-organ damage | Extreme BP elevation withoutacute end-organ injury |
| Examples of damage | Papilledema, encephalopathy, acute kidney injury, acute HF or pulmonary edema, aortic dissection, ACS, stroke | None |
| Setting | ICU, IV therapy, continuous monitoring | Outpatient; oral therapy |
| Pace | Controlled, gradual reduction - dropping BP too fast causes ischemia | Over hours to days |
A BP of 210/125 with no symptoms and a normal exam is urgencyand does not need the ICU. A BP of 185/121 with papilledema and rising creatinine is an emergency. The number alone never decides it.
| Parameter | When | Watching for |
|---|---|---|
| Blood pressure | Normal → 1 yr · Elevated or Stage 1 low-risk → 3–6 mo · Stage 1 high-risk or Stage 2 → 1 mo | Reaching goal; over-treatment |
| SCr and potassium | Baseline, then shortly after starting or increasing any ACEi, ARB, MRA, or renin inhibitor | AKI, hyperkalemia |
| Electrolytes on diuretics | Baseline and periodically | Hypokalemia, hypomagnesemia, hyponatremia, hypercalcemia (thiazide) |
| Orthostatic vitals | Older adults, after any titration | Fall risk |
| Uric acid, glucose, lipids | Periodically on thiazides | Metabolic effects |
| Urine ACR, eGFR | Annually, more often in CKD or diabetes | Progression of kidney disease |