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Blood Pressure Management - Comprehensive Clinical Guide

1. Classification

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2. BP Targets

• Most adults: < 130/80 mm Hg (standard clinical measurement)
• High-risk adults using standardized measurement protocols (e.g., SPRINT-like): < 120 mm Hg systolic - trials show reduced cardiovascular mortality even in patients ≥75 years, including frail elderly who are not institutionalized
• Diabetes: < 130/80 mm Hg; consider < 120/80 mm Hg in those at high CV risk but low medication risk
• CKD (KDIGO 2021): SBP < 130 mm Hg; ACEi/ARB preferred
• Elderly (≥65 years): Same targets apply, but start drugs at low doses; monitor for orthostatic hypotension; use ambulatory or home BP monitoring to avoid overtreatment

Key nuance: Standard office BP readings are on average ~10 mm Hg higher than standardized protocol readings. A clinical target of < 130 mm Hg approximately corresponds to a SPRINT-protocol target of < 120 mm Hg. - Goldman-Cecil Medicine, p. 755

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3. Non-Pharmacological (Lifestyle) Therapy

• Weight loss - reducing BMI in overweight/obese patients
• Sodium restriction - lowers BP in salt-sensitive patients
• DASH diet
• Alcohol limitation - < 20 g/day in women, < 40 g/day in men
• Regular aerobic exercise
• Smoking cessation (reduces overall CV risk)
• Renal denervation - evidence supports use in well-defined resistant hypertension
• Bariatric surgery - can normalize BP in grossly obese individuals

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4. First-Line Drug Classes

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5. Treatment Algorithm

Step-by-Step Approach:

• ACEi or ARB + CCB or thiazide diuretic
• Prefer combination for Stage 2 (BP > 20/10 mm Hg above target) - Grade I, Level C
• Monotherapy reasonable for Stage 1 (BP goal < 130/80 mm Hg) - Grade IIa, Level C
• Consider monotherapy in low-risk grade 1 (SBP < 150), very old (≥80 years), or frail patients

• ACEi or ARB + CCB + thiazide/thiazide-like diuretic

• Add spironolactone 25-50 mg once daily (most evidence)
• Alternatives: other diuretics, alpha-blocker, or beta-blocker
• Consider specialist referral

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6. Compelling Indications - Drug Choice by Condition

ACEi + ARB combination must be avoided - minimal added BP lowering with high risk of renal impairment and hyperkalemia. - Goldman-Cecil Medicine

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7. Key Drug Notes

• ARNI (sacubitril/valsartan): Established in HFrEF; effective 24-hour BP lowering including nocturnal BP; superior to ARB alone - potential role in hypertension
• SGLT2 inhibitors (empagliflozin, dapagliflozin): BP lowering via natriuresis; contributes to CV and renal outcome benefits

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8. Hypertensive Emergency vs. Urgency

• CCBs: Nicardipine, clevidipine
• Nitric oxide vasodilators: Sodium nitroprusside, nitroglycerin
• Adrenergic blockers: Labetalol, esmolol, phentolamine
• Vasodilator: Hydralazine
• Dopamine agonist: Fenoldopam

Initial goal is a controlled reduction - not rapid normalization, which risks hypoperfusion of target organs. - Lippincott Pharmacology

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9. Special Populations

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10. Drug Interactions to Know

• NSAIDs (except sulindac, celecoxib): Raise BP; impair kidney function
• Acetaminophen: Can also raise BP via unknown mechanism
• Verapamil/diltiazem + statins: Significant CYP3A4 inhibition; reduce statin dose
• Grapefruit + DHP CCBs (not amlodipine): Up to 24-hour increase in drug levels
• ACEi/ARB + K+-sparing diuretics: High hyperkalemia risk
• Iron + methyldopa: Reduces methyldopa absorption by ~50%

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2025 Guideline Update

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Diabetes Mellitus (DM) Medications - Comprehensive Guide

Diagnosis Recap

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Drug Classes at a Glance

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1. Biguanides - Metformin

• No hypoglycemia risk
• Weight neutral or modest weight loss
• Cheap, widely available
• Proven CV safety (UKPDS)
• Well-established safety profile

• GI side effects (nausea, diarrhea) - take with food, titrate slowly
• Lactic acidosis (rare, primarily in renal/hepatic failure)
• Vitamin B12 deficiency with long-term use - monitor levels

• eGFR < 30 mL/min (use with caution 30-45)
• Active liver disease
• Contrast dye administration (hold temporarily)
• Excessive alcohol use

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2. Sulfonylureas

• First-gen (rarely used): Tolbutamide, chlorpropamide
• Second-gen (preferred): Glipizide, glimepiride, glyburide

• Glipizide and glimepiride preferred over glyburide in elderly and CKD (glyburide has active metabolites → accumulation → prolonged hypoglycemia)
• Most common cause of hypoglycemia among oral agents
• Weight gain occurs
• Metabolized by liver; excreted by kidney

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3. Meglitinides

• Repaglinide - stronger, also reduces FPG
• Nateglinide - primarily postprandial effect

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4. Thiazolidinediones (TZDs / Glitazones)

• Fluid retention / edema (3-4%; up to 15% with insulin)
• Heart failure - contraindicated in NYHA class III-IV
• Weight gain
• Bone fractures (especially in women)
• Bladder cancer risk with pioglitazone (inconsistent data, ongoing monitoring)
• Check LFTs before initiation; avoid if ALT > 2.5x ULN

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5. DPP-4 Inhibitors ("Gliptins")

• Sitagliptin: reduce dose for eGFR < 45
• Saxagliptin: reduce for eGFR < 45; also ↑ HF risk
• Alogliptin: reduce for eGFR < 60; potential liver risk
• Linagliptin: No renal dose adjustment (biliary excretion) - preferred in CKD

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6. GLP-1 Receptor Agonists

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7. SGLT2 Inhibitors ("Flozins")

• Heart failure: Reduced HF hospitalization in both HFrEF and HFpEF
• CKD: Delays progression (CREDENCE, DAPA-CKD trials)
• CV outcomes: Reduced MACE in high-risk patients (EMPA-REG, CANVAS, DECLARE)

• Higher CV/CKD risk or HF: Strong recommendation FOR SGLT2 inhibitors
• Moderate risk: Weak recommendation in favor
• Lower risk: Weak recommendation against

• Canagliflozin: 100-300 mg daily (avoid if eGFR < 30)
• Dapagliflozin: 10 mg daily (5 mg in hepatic failure)
• Empagliflozin: 10-25 mg daily

• Genitourinary infections (UTIs, candidal vulvovaginitis)
• Euglycemic DKA (especially Type 1; not approved for T1DM due to this risk)
• Volume depletion / hypotension
• Fournier's gangrene (rare)
• Canagliflozin: ↑ risk of lower limb amputations and fractures

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8. α-Glucosidase Inhibitors

• Acarbose: 50 mg twice daily, titrate to 100 mg TID
• Miglitol: 25 mg TID, titrate to 50-100 mg TID

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9. Insulin

Profiles

Key Insulin Concepts

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10. Other Agents

• Mimics amylin (co-secreted with insulin)
• ↓ postprandial glucose, glucagon, and gastric emptying
• Used as adjunct to insulin in T1DM and T2DM

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Treatment Algorithm for Type 2 DM

Lifestyle modification + Metformin (if no contraindication)
        │
        ├── ASCVD/HF/CKD present?
        │       → Add GLP-1 RA or SGLT2i (evidence-based, organ-protective)
        │
        ├── Need more glucose lowering?
        │       → Add second agent from complementary class
        │
        ├── HbA1c still above target?
        │       → Triple therapy or add basal insulin
        │
        └── Insulin required?
                → Basal insulin first; add prandial if needed

• Higher CV/CKD/HF risk: Strong recommendation for SGLT2i or GLP-1 RA
• Tirzepatide: Weakly recommended in those with obesity across all risk levels

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Glycemic Targets (ADA)

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Special Situations

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