Hypertension

Question 1

What are the treatment targets of HTN?
(for both general and special populations)

(taken from NUH Guide)

Answer 1

General:
* < 140/90 mmHg in patients aged < 80 years
* < 150/90 mmHg in patients aged ≥ 80 years (do not decrease diastolic BP to < 60 mmHg)
Special Populations:
* < 140/80 mmHg for patients with diabetes mellitus
≤ 130/80 mmHg in patients with proteinuria (with/without diabetes)
* < 150/100 mmHg in pregnant patients without target organ damage (do not decrease diastolic BP to < 80 mmHg)
* < 140/90 mmHg in pregnant patients with target organ damage
* < 220/120 mmHg during 1st 24hrs of acute stroke (lower with care by 10-15%) (lower by 10/5 mmHg if BP > 140/90 mmHg after acute phase of stroke)

Question 2

List 5 risk factors for CVD

Answer 2

• Smoking
• High BP (Grade 1/2 HTN)
• Age (≥ 55 in men, ≥ 65 in women)
• Family History of premature HTN (≤ 55 in men, ≤ 65 in women)
• Dyslipidemia: Total Cholesterol > 6.2mmol/L (240 mg/dL), Triglycerides > 1.7 mmol/L (150 mg/dL), HDL < 1.0mmol/L (40 mg/dL), LDL > 4.1mmol/L (160 mg/dL)
• Diabetes Mellitus
• Obesity

Question 3

What are some lifestyle modifications / non-pharmacological management of HTN?

Answer 3

• Restrict salt intake (5 - 6g daily)
• Increase consumption of vegetables, fruits, low-fat dietary products
• Decrease intake of saturated and total fats
• Reduce weight to BMI < 23 kg/m3 and waist circumference < 90 cm in men, < 80 cm in women
• Do at least 30 min of moderate dynamic exercise (5-7 days per week)
• Quit smoking
• Reduce alcohol intake (< 2 standard drinks/day for men, < 1 standard drink/day for women)

Note: recommend lifestyle changes to all hypertensive pts, and in pts with high normal BP. HOWEVER, drug tx should not be delayed without reason beyond 3-6 months if indicated.

Question 4

When initiating tx, aim for BP control within ____ months

1 drug ≈____mmHg

Answer 4

3 months

10/5mmHg

Question 5

Recommended follow-up intervals

(taken from NUH Guide)

Answer 5

6 months:
* Good BP control AND no complications

3-4 months:
* Good BP AND elderly/ has complications (e.g. IHD, CVA, renal impairment)
* Adherent to tx AND with or without complications/ comorbidities AND stable but sub-optimal control related to individual targets for BP, HbA1C, cholesterol over past 4-6 months

2 weeks:
* ACEi / ARB initiation or up-titration (test K and Cr)
* Poor BP control AND requires titraiton of meds

Question 6

What first-line and add-on HTN drugs are preferrably indicated in pts with these comorbidities / compelling indications:
1. DM
2. Chronic kidney disease/ proteinuria
3. HF
4. Isolated systolic HTN (older persons)
5. MI or AF
6. Recurrent stroke prevention
7. Pregnancy
8. BPH

Looking at the 4 main HTN drug classes: ACEi / ARB, BB, CCB, Diuretics

Good to rationalise in your head the reasons for the use of these drugs!

Answer 6

1. ACEi (preferred if proteinuric) / ARB, add-on CCB, diuretics
2. ACEi / ARB
3. ACEi / ARB, diuretics
4. Diuretics, long-acitng CCB
5. BB, add-on ACEi / ARB (LV dysfunction)
6. Diuretic, ACEi
7. Methyldopa, nifedipine, labetalol
8. Prazosin

Question 7

What HTN drugs are contraindicated in pts with these comorbidities:
1. Asthma / bronchospasm
2. HF or 2°/3° heart block
3. Gout
4. Bilateral renal artery stenosis
5. DM
5. Pregnancy / breastfeeding

Looking at the 4 main HTN drug classes: ACEi / ARB, BB, CCB, Diuretics

Good to rationalise in your head the reasons for the avoidance of these drugs!

Answer 7

1. BB (prevents bronchodilation due to bronchial beta-2 receptors. Beta-1 selectivity is not absolute, and may diminish at higher doses, so there’s still that risk for selective BBs)
2. BB, diltiazem/ verapamil
3. Diuretic
4. ACEi, ARB
5. BB (mask signs of hypoglycemia e.g. tachycardia, palpitations, tremors)
6. ACEi, ARB, diuretic

Question 8

List 4 common antihypertensive combinations that should be avoided/ not used and why?

Answer 8

1. BB + ACEi / ARB -> does not produce synergistic BP reduction
2. ACEi + ARB -> decreases GFR in CKD pts
3. BB + non-DHP CCB -> increased risk of bradycardia and/or atrioventricular block, since both classes have negative inotropic and chronotropic effects
4. BB + Diuretic -> increases risk of developing DM

Question 9

When should you substitute another HTN drug from a different class instead of increasing the dose of the first drug?

Answer 9

When no/ limited response or was poorly-tolerated

Question 10

When should you add-on a second agent from a different class?

Answer 10

When inadequate response (fail to achieve target BP) but well tolerated

Add-on diuretic first if not already used

Question 11

MoA of ACEi

Taken from ACE Guidelines Dec 2023, to update to that in formulary

Answer 11

Inhibits formation of angiotensin II
-> increases vasodilation

Question 12

MoA of ARB

Taken from ACE Guidelines Dec 2023, to update to that in formulary

Answer 12

Blocks type 1 angiotension II receptors
-> prevents vascular contraction

Question 13

Common and max doses of ACEis:
1. Lisinopril
2. Enalapril
3. Captopril

Taken from NUH Guide
Order is in ascending order of cost

Answer 13

1. 5-40mg OD, max 40mg/day
2. 5-20mg BD, max 40mg/day
3. 12.5-25mg TDS, max 150mg/day

Strengths available
1. Lisinopril: 5, 10, 20mg tablets
2. Enalapril: 5, 10, 20mg tablets
3. Captopril: 12.5, 25mg tablets

Question 14

Renal dose adjustments for ACEis:
1. Lisinopril
2. Enalapril
3. Captopril

Taken from ACE Guidelines Dec 2023 and UTD

Answer 14

Lisinopril
* CrCl 10-30: initial 2.5-5mg OD
* CrCl <10: initial 2.5mg OD
* HD: 2.5mg OD, administer post HD on dialysis days
* PD: 2.5mg OD

Enalapril
* CrCl 10-30: initial 2.5mg/day in 1-2 divided doses, max 20mg/day
* CrCl <10: initial 1.25mg OD or 2.5mg every other day, max 10mg/day
* HD: dialyzable, 2.5mg 3 times weekly post HD, max 10mg OD
* PD: dialyzable, dose as in CrCl <10

Captopril
* CrCl 10-50: 75% of normal dose Q12-18h, max 50mg Q12h
* CrCl <10: 50% of normal dose Q24h, max 50mg Q24h
* HD: administer usual dose Q24hr, administer after post HD on dialysis days, max 50mg Q24h
* PD: administer usual dose Q24h, max 50mg Q24h

Question 15

Hepatic dose adj for ACEis
1. Lisinopril
2. Enalapril
3. Captopril

Answer 15

No dose adj needed

Question 16

Common and max doses of ARBs:
1. Losartan
2. Telmisartan
3. Irbesartan
4. Candesartan
5. Valsartan

Taken from NUH Guide
Order is in ascending order of cost

Answer 16

1. 25-100mg OD, max 100mg/day
2. 40-80mg OD, max 80mg/day
3. 150-300mg OD, max 300mg/day
4. 8-16mg OD, max 32mg/day
5. 40-160mg OD, max 320mg/day

Strengths available
1. Lorsartan: 50, 100mg tablets
2. Telmisartan: 40, 80mg tablets
3. Irbesartan: 150, 300mg tablets
4. Candesartan: 8mg tablets
5. Valsartan: 80, 160mg tablets

Question 17

Renal dose adjustments for ARBs:
1. Losartan
2. Telmisartan
3. Irbesartan
4. Candesartan
5. Valsartan

Taken from ACE Guidelines Dec 2023 and UTD

Answer 17

1. CrCl <20: initial 25mg OD, poorly dialyzed so no dose adj needed for HD and PD
2. no dose adj needed, poor dialyzed so no dose adj needed for HD and PD
3. no dose adj needed, poor dialyzed so no dose adj needed for HD and PD
4. CrCl ≤30: initial 4mg OD, max 16mg/day, not significantly dialyzed but follow CrCl≤30 dose for HD and PD
5. no dose adj needed, poor dialyzed so no dose adj needed for HD and PD

Question 18

Hepatic dose adjustments for ARBs:
1. Losartan
2. Telmisartan
3. Irbesartan
4. Candesartan
5. Valsartan

Taken from UTD

Answer 18

1. Mild to moderate hepatic impairment: initial 25mg OD
2. Hepatic impairment: initial 40mg OD
3. no dose adj needed
4. Moderate to severe hepatic impairment (child-Pugh class B, C): initial 4-8mg OD
5. no dose adj neeeded

Question 19

ADRs of ACEi / ARB

Answer 19

• Severe hypotension
• Acute renal failure
• Hyperkalemia
• Angioedema and dry cough (less in ARB)

Question 20

Use with caution / C/Is of ACEi / ARB

Answer 20

Pregnancy / breastfeeding, bilateral renal artery stenosis
for ACEi only: idiopathic / hereditary angioedema

Question 21

Monitoring parameters of ACEi / ARBs (include what and when to monitor/ follow-up)

Answer 21

Moniter K and Cr Q2-4 weeks
* before initiation
* after initiation
* after dose up-tiration

Once stable, monitor at least once every 12 months

Question 22

MoA of CCB

Taken from ACE Guidelines Dec 2023, to update to that in formulary

Answer 22

Prevents calcium from entering the cells of the heart and arteries
-> reduces contraciton of arteries
-> allows vasodilation

Question 23

Common and max doses of CCBs:
1. Amlodipine
2. Nifedipine LA
3. Diltiazem tablets
4. Diltiazem SR capsules

Taken from NUH Guide
Order is in ascending order of cost

Answer 23

1. 2.5-10mg OD, max 10mg/day
2. 30-90mg OD, max 120mg/day
3. 30-60mg TDS, max 360mg/day
4. 90-200mg OD, max 360mg/day

Strengths available
1. Amlodipine: 5, 10mg tablets
2. Nifedipine LA: 30, 60mg tablets
3. Diltiazem tablets: 30, 60mg tablets
4. Diltiazem SR capsules: 90, 100, 200mg capsules

Question 24

Renal dose adjustments for CCBs
1. Amlodipine
2. Nifedipine LA
3. Diltiazem

Taken from ACE Guidelines Dec 2023

Answer 24

No dose adj needeed

HD, PD: poorly dialyzed, no dose adj needed

Question 25

Hepatic dose adjustments for CCBs 1. Amlodipine 2. Nifedipine LA 3. Diltiazem ## Footnote Taken fron UTD

Answer 25

1. initial 2.5mg OD 2. No dose adj needed, CL is reduced in pts with cirrhosis so monitor closely for ADRs and consider dose adj 3. No dose adj needed, Half life is increased in pts with cirrhosis so monitor closely for ADRs and consider dose adj

Question 26

ADRs of CCBs ## Footnote Taken from NUH Guide and UTD

Answer 26

Peripheral oedema, flushing diltiazem: hepatotoxicity, bradycardia , cutaneous hypersensitivity reactions

Question 27

Use with caution / C/Is of CCBs

Answer 27

Caution: * pts with HF. If to use, amlodipine is the preferred choice * DHP: hepatic impairment * non-DHP: heart block, LV dysfunction, hepatic impairment C/Is * Diltiazem: sick sinus syndrome, 2°/3° heart block, acute MI, pulmonary congestion For non-DHP, avoid abrupt discontinuation

Question 28

MoA of diuretics ## Footnote Taken from ACE Guidelines Dec 2023, to update to that in formulary

Answer 28

Reduces sodium reabsorption at different sites in the nephron -> increases urinary sodium and water loss

Question 29

Common and max doses of diuretics: 1. Hydrochlorothiazide 2. Indapamide tablets 3. Indapamide SR tablets ## Footnote Taken from NUH Guide Order is in ascending order of cost

Answer 29

1. 12.5-25 OD, max 50mg/day 2. 2.5-5mg OD, max 5mg/day 3. 1.5mg OD, max 1.5mg/day ## Footnote **Strengths available** 1. Hydrochlorothiazide: 25mg tablets 2. Indapamide: 2.5mg tablets, SR 1.5mg tablets

Question 30

Renal dose adjustments for diuretics: 1. Hydrochlorothiazide 2. Indapamide ## Footnote Taken from ACE Guidelines Dec 2023

Answer 30

Hydrochlorothiazide * Use with caution in renal impairment * CrCL <10: use not recommended due to lack of efficacy * HD, PD: use not recommended due to lack of efficacy Indapamide * CrCL <30: contraindicated * HD, PDL not significantly dialyzable, no dose adj needed

Question 31

Hepatic dose adjustments for diuretics 1. Hydrochlorothiazide 2. Indapamide

Answer 31

No dose adj needed

Question 32

ADRs of diuretics

Answer 32

* Hypokalaemia (more likely for doses ≥25mg OD) * Hyponatremia * Hypercalcemia * Increased urination * Increased uric acid production * Hyperglycaemia

Question 33

Use with caution / C/Is of diuretics

Answer 33

Caution: risk of sqaumous cell carcinoma, DM, gout C/I * Hydrochlorothiazide: pregnancy, renal decompensation, anuria * Indapamide: sulphonamides allergy, severe renal disease (ineffective)

Question 34

Monitoring parameters of diuretics (include what and when to monitor/ follow-up)

Answer 34

Monitor K and Na levels Q2-4 weeks * before initiation * after initiation * after dose up-titration Once stable, monitor at least once every 12 months

Question 35

MoA of BBs ## Footnote Taken from ACE Guidelines Dec 2023, to update to that in formulary

Answer 35

Blocks neurotransmitters in norepinephrine and epinephrine from binding to receptors

Question 36

Common and max doses of BBs: 1. Atenolol 2. Bisoprolol 3. Carvedilol 4. Metoprolol ## Footnote Taken from NUH Guide Order is in ascending order of cost

Answer 36

1. 25-100mg OD, max 100mg/day 2. 1.25-10mg OD, max 20mg/day 3. 3.125 OD - 25mg BD, max 50mg/day 4. 25 BD - 50mg TDS, max 400mg/day ## Footnote **Strengths available** 1. Atenolol: 50, 100mg tablets 2. Bisoprolol: 2.5, 5mg tablets 3. Carvedilol: 6.25, 25mg tablets 4. Metoprolol: 50, 100mg tablets

Question 37

Renal dose adjustments for BBs: 1. Atenolol 2. Bisoprolol 3. Carvedilol 4. Metoprolol ## Footnote Taken from ACE Guidelines Dec 2023 and UTD

Answer 37

Atenolol * CrCl <50: reduce daily dose by 50% *(12.5-50mg OD, max 50mg/day)* * CrCl<25, reduce daily dose by 75% *(6.25-25mg OD, max 25mg/day)* * HD: moderately dialyzed, initial 25-50mg OD, administer post HD on dialysis days * PD: not significantly dialyzed, max 25mg/day Bisoprolol * CrCl <20: 1.25-2.5mg OD, max 10mg/day * HD: moderately dialyzed, initial 1.25-2.5mg OD, max 10mg/day, administer post HD on dialysis days * PDL slightly dialyzable, initial 1.25-2.5mg OD, max 10mg/day Carvedilol and metoprolol: no dose adj needed. No dose adj needed for HD and PD

Question 38

Hepatic dose adjustments for BBs 1. Atenolol 2. Bisoprolol 3. Carvedilol 4. Metoprolol ## Footnote Taken from UTD

Answer 38

1. no dose adj needed 2. hepatitis, cirrhosis: initial 2.5mg OD 3. Severe impairment: use is contraindicated 4. No specific dose adj, but consider intiating with reduced doses and gradual dosage titration due to extensive hepatic metabolism

Question 39

ADRs of BBs

Answer 39

* Hypotension * Masking of hypoglycemia * Bronchospasm (esp non-selective) * AV node block, bradycardia

Question 40

Use with caution / C/Is of BBs ## Footnote Taken from NUH Guide

Answer 40

C/Is * Asthma * Sinus node dysfunction * Pregnancy * DM * Uncompensated HF * Heart block greater than 1° Avoid uprubt discontinuation

Question 41

What are the differences between cardioselective and non-selective BBs? In what conditions are one preferred over the other? ## Footnote Taken from ACE Guidelines Dec 2023

Answer 41

Cardioselective: * e.g. Atenolol, bisoprolol, metoprolol, nebivolol * APrimarily targets only beta-1 receptors in the heart * Have more favourable SE profile * Less likely to cause constriciton of airways * Preferred for pts with respiratory diseases, and for management of CHD, chronic HF, acute coronary syndrome, and some arrhthymias Non-selective * e.g. Propranolol, carvedilol * Targets both beta-1 and beta-2 receptors throughout the body, hence can cause more SEs beyond the heart * Preferred for pts who require tx for migraine prveention, essential tremor, or portal HTN in cirrhosis ## Footnote Note that beta-1 selectivity is not absolute, however, and may diminish at higher doses

Question 42

Common and max dose of spironolactone **(mineralocorticoid receptor antagonist, MRA)** ## Footnote Taken from NUH Guide

Answer 42

25mg OD, max 50mg/day ## Footnote **Strength available** Spironolactone 25mg tablets

Question 43

Renal dose adjustments for spironolactone **(mineralocorticoid receptor antagonist, MRA)** ## Footnote Taken from UTD

Answer 43

**For HF only ** * eGFR >50 mL/minute/1.73 m2: No initial dosage adjustment necessary * eGFR 30 to 50 mL/minute/1.73 m2: Initial: 12.5 mg once daily or every other day; may double the dose every 4 weeks if serum potassium remains <5 mEq/L and kidney function is stable, up to a maximum target dose of 25 mg/day * eGFR <30 mL/minute/1.73 m2: Use not recommended; heart failure clinical trials excluded patients with serum creatinine ≥2.5 mg/dL For HD and PD, not routinely recommended, though unlikely to be significantly dialyzed given high degree of protein binding. Initial 12.5mg OD or every other day From NUH Guide: should usually be restricted to pts with eGFR≥ 45ml/min and plasma K concentration of ≤4.5mmol/L

Question 44

Hepatic dose adjustments for spironolactone ## Footnote Taken from UTD

Answer 44

No dose adj needed

Question 45

ADRs of spironolactone ## Footnote Taken form NUH Guide

Answer 45

* Gynecomastia/ breast tendernss * Impotence in man * Menstrual irregularities in women * Hyperkalemia, esp when taken tgt with ACEi/ARBs

Question 46

Use with caution / C/Is of spironolactone ## Footnote Taken from UTD

Answer 46

Caution: fluid/ electrolyte imbalance C/Is: severe kidney impairment (eGFR<30ml/min), anuria, pregnancy, breastfeeding

Question 47

Monitoring parameters of spironolactone ## Footnote Taken from NUH Guide and UTD

Answer 47

Monitor electrolytes (K) and eGFR soon after initiation (1w, then again 2-4w later), and at least annually thereafter

Question 48

Common and max dose of hydralazine **(vasodilator)** ## Footnote Taken from NUH Guide

Answer 48

10-50mg TDS, max 300mg/day ## Footnote **Strengths available ** Hydralazine 10, 25, 50mg tablets

Question 49

Renal dose adjustments for hydralazine **(vasodilator)** ## Footnote Taken from UTD

Answer 49

GFR<10ml/min, HD, PD: administer usual dose every 8-12hrs

Question 50

Hepatic dose adjustments for hydralazine ## Footnote Taken from UTD

Answer 50

No dose adj provided However, note that hydralazine undergoes extensive hepatic metabolism

Question 51

ADRs of hydralazine ## Footnote Taken from NUG Guide and UTD

Answer 51

Lupus-like syndrome (more likely with larger dose, longer duration) Tachycardia, flushing, peripheral oedema

Question 52

Use with caution / C/Is of hydralazine ## Footnote Taken fron NUH Guide and UTD

Answer 52

C/I: Mitral valve rheumatic heart disease, coronary artery disease, idiopathic systemic lupus erythematosus and related diseases, severe tachycardia

Question 53

Common and max dose of prazosin **(alpha blocker)** ## Footnote Taken from NUH Guide

Answer 53

0.5-1mg TDS, max 20mg/day ## Footnote **Strength available** Prazosin 1mg tablet

Question 54

Renal dose adjustment of prazosin **(alpha blocker)** ## Footnote Taken from UTD

Answer 54

* eGFR <60 mL/minute/1.73 m2: low doses, titrate cautiously * HD, PD: unlikely to be dialyzed (highly protein bound), no adj needed

Question 55

Hepatic dose adjustments for prozasin ## Footnote Taken from UTD

Answer 55

No dose adj provided

Question 56

ADRs of prazosin ## Footnote Taken from NUH Guide and UTD

Answer 56

Orthostatic hypotension, floppy iris syndrome Fatigue, edema, priapism, CNS depression

Question 57

Use of caution / C/Is of prazosin ## Footnote Taken from UTD

Answer 57

Cateract surgery pts, HF

Question 58

From **BEERs Criteria**, avoid use of prazosin in HTN because:

Answer 58

* Non-selective peripheral alpha-1 blocker * High risk of orthostatic hypotension and associated harms, especially in older adults; not recommended as routine treatment for hypertension * Alternative agents have superior risk/benefit profile.

Question 59

Common and max dose of methyldopa **(centrally acting agent)** ## Footnote Taken from NUH Guide

Answer 59

125-500mg TDS, max 3000mg/day ## Footnote **Strength available** Methyldopa 250mg tablets

Question 60

Renal dose adjustment of methyldopa **(centrally acting agent)** ## Footnote Taken from UTD

Answer 60

* CrCl >50 mL/minute: Administer Q8h * CrCl 10 to 50 mL/minute: Administer Q8-12h * CrCl <10 mL/minute: Administer Q12-24h * HD: Moderately dialyzable, administer after hemodialysis on dialysis days * PD: Administer Q12-24h

Question 61

Hepatic dose adjustments for methyldopa ## Footnote Taken from UTD

Answer 61

No dose adj provided. C/I in active/acute hepatic diseasee

Question 62

ADRs of methyldopa ## Footnote Taken from UTD

Answer 62

Edema, hepatotoxicity + more ## Footnote sry i sianz to do, someone help fill

Question 63

Use with caution / C/Is of methyldopa ## Footnote Taken from NUH Guide and UTD

Answer 63

C/Is: acute liver disease, current MAOi therapy

Question 64

Resistant hypertension is defined as:

Answer 64

BP that remains above goal despite concurrent use of three antihypertensive agents of different classes at **optimal/ best tolerated doses**, one of which should be a **diuretic**

Question 65

What are the possible causes of resistant hypertension?

Answer 65

* Non-adherence ot medication * "White coat" effect * Wrong cuff size * Lifestyle factors (obesity/ large weight gain, excessive alcohol consumption, high alcohol intake) * Chronic intake of vasopressor / sodium-retaining drugs (sympathomimetics, nasal decongestants, oral contraceptives, NSAIDs) * Obstructive sleep apnoea * Chronic pain * Secondary hypertension * Advanced end-organ damage (e.g. renal impairment)

Question 66

Pharmacological and non-pharmacological measures for resistant hypertension

Answer 66

Pharmacological: * Add-on low dose spironolactone * If intolerant to spironolactone, add-on further diuretic therapy like higher dose thiazide/ thiazide-like diuretic, or loop diuretic for pts with renal impairment (GFR ≤30ml/min) * Or add-on bisoprolol Non-pharmacological: * Check and reinforce adherence to medication / diet / lifestyle measures (esp reduction of sodium intake) * Address any drug interactions and associated medical problems, if present