Hypertension

Question 1

High-risk patients include those with:

Answer 1

DM
CKD (eGFR <60 ml/min/1.73 m2 and/or urine albumin: creatinine ratio ≥300 mg/g)
post-renal transplantation
heart failure with reduced or preserved ejection fraction,
known CVD,
peripheral arterial disease,
and/or ≥10% ten year ASCVD risk

Question 2

compensatory responses to anti-HTN:

Answer 2

water& salt retention: hydralazine, alpha blockers, alpha-2 agonist (clinidine, methyldopa)

Tachycardia: alpha-1 blockers, hydralazine, Minoxidil

Question 3

Differences between ACE inhibitors and ARBs:

Answer 3

1. In the heart & kidney; the production of Ang-II may be catalyzed by enzymes other than ACE, such as chymase. The effect of the Ang-II produced by this reaction can be inhibited by the ARBs but not by ACE inhibitors.
2. ACE is a kininase. Thus, inhibiting this enzyme, which normally degrades bradykinin, with an ACE inhibitor leads to increased kinin levels. This is likely responsible for the cough that may be seen with ACE inhibitors (but not with ARBs).
3. By decreasing angiotensin II production, ACE inhibitors reduce the effect of both AT1 and AT2 receptors; only the former are inhibited by the ARBs.

Question 4

Aliskiren

Answer 4

• 1st Renin inhibitor drug.
• Reduces aldosterone through inhibition of Ang-I leading to potassium retention thus causing hyperkalemia.

should not be combined with ACEI or ARBs;due to risk of hyperkalemia

🧪🔬- should be discontinued prior to testing for parathyroid function💊

-Aliskiren, as with other inhibitors of the RAS, should not be used in pregnancy.

Question 5

MOA of vasodilators:

Answer 5

1. D1 receptor activation: Fenoldopam
2. Release of NO: hydralazine, Nitroprusside
3. Opening of K+2 channels and hyperpolarization: Minoxidil
4. Inhibition of calcium influx via L-type channels: CCB

Question 6

unique Se/toxicities associated with anti-HTN drugs:

Answer 6

Minoxidil: leads to hirsutism
Methyldopa: hemolytic anemia through immune induced antibodies
Nitroprusside: cyanide toxicities if infusion >2mcg/kg/min and infusion duration is > 10 minutes
Hydaralazine: lupus-like syndrome for doses >200mg/day
Reserpine: severe psych effects including parkinson’s and depression

Question 7

BP categories include:

Answer 7

Normal: SBP <120 and DBP <80
Elevated (pre-HTN category is no longer used): SBP 120-129 and DBP <80
Stage-1: SBP 130-139 and DBP 80-89
Stage-2: SBP >140 and DBP >90

-Individuals are classified based on highest reading of either SBP or DBP

Question 8

The following diet and lifestyle modifications Are recommended for hypertensive patients;

Answer 8

1) sodium restriction to <1500 mg/d or minimally an absolute reduction of at least 1000 mg/d,
2) increased intake of dietary potassium (3500–5000 mg/d),
3) weight loss if overweight/obese (target ideal body weight or, alternatively, weight loss of at least 1 kg),
4) appropriate physical activity prescription (aerobic or dynamic resistance 90–150 min/week or isometric resistance 3 sessions/week),
5) moderation of alcohol intake (≤2 drinks per day in men, ≤1 per day in women)
6) a healthy DASH-like diet rich in fruits, vegetables, whole grains and low-fat dairy products with reduced saturated and total fat.

Question 9

Treating hypertension with selected co-morbidities drug class:

Answer 9

AF, DM, aortic disease, CKD: ACEI or ARB.

HF (preserved Ejection fraction): diuretics for volume overload.
**Add ACEI or ARB and beta blocker for incremental BP control; also consider angiotensin receptor – neprilysin inhibitor and mineralocorticoid receptor antagonists

HF (reduced ejection fraction), Angina, post MI or ACS: beta blockers. AVOID: Non-DHP calcium antagonists

Secondary stroke prevention: Thiazide, ACEI, ARB or thiazide + ACEI combination. **if previously treated, restart drugs a few days post-event; if not previously treated, start drug treatment a few days post-event if BP ≥140/90.

Valvular heart disease such as: Aortic stenosis (asymptomatic) or Aortic insufficiency: Avoid beta blockers, non-DHP calcium antagonists. Avoid drugs that slow heart rate

Question 10

Prodrugs anti-HTN:

Answer 10

Minoxidil is a prodrug that is converted by sulfation via the sulfotransferase enzyme SULT1A1 to its active form, minoxidil sulfate

Methyldopa is a prodrug that is metabolized into alpha-methyl-noradrenaline (norepinephrine) and acts centrally to decrease the adrenergic neuronal outflow from the brain stem.

Question 11

Race vs. HTN treatment:

Answer 11

African Americans. Accordingly, those without heart failure or CKD who do not meet criteria for two-drug therapy should be initially treated with either a thiazide-type diuretic or calcium antagonist.

• combination > monotherapy in this population.

Question 12

Prototypes of anti-HTN drugs:

Answer 12

CCB: Nifedipine
Beta-blockers: Propranolol (nonselective)
ACEI: Captopril (shorter half life than newer generations)
ARB: Losartan

Question 13

White coat hypertension:

Answer 13

office BP is ≥130/80 mm Hg but out of office (home or daytime ambulatory BP) <130/80 mm Hg after 3 months of diet and lifestyle modification.