CPT5 - Hypertension & Heart Failure

Question 1

Overview of autonomic sympathetic activity and RAAS

Sympathetic Activity x3
Reduced Renal Blood Flow x5
Reduced GFR
Autacoids

Answer 1

1. ) Sympathetic Activity
   - a-1 –> vasoconstriction –> ↑ preload and TPR
   - ß-1 in heart –> ↑HR and SV –> ↑CO
   - ß-1 in kidney –> ↑renin –> activation of RAAS
2. ) Reduced Renal Blood Flow - ↑renin –> ↑AngII which:
   - stimulates sympathetic activity
   - stimulates aldosterone secretion
   - stimulates NaCl/water reabsorption (+aldosterone)
   - causes efferent arteriole vasoconstriction
   - stimulates ADH secretion –> water reabsorption
3. ) Reduced GFR - caused by reduced RBF
   - leads to ↑Na/water retention –> ↑BV –> ↑CO
4. ) Autacoids - local vasoactive hormones
   - inc. bradykinin and NO

Question 2

Diagnosis of hypertension

Measuring BP x3
Overcoming White Coat Hypertension x2
Diagnosing Hypertension x3
Staging Hypertension x4

Answer 2

1. ) Measuring BP - best practice
   - sitting, relaxed, and arm is supported
   - use arm with higher reading
   - repeat 2x if >15mmHg difference
2. ) Overcoming White Coat Hypertension
   - ambulatory BP (ABPM) measures for 24hrs
   - home monitoring (HBPM) so stress free
   - patients should take BP readings a few hours after taking the medication
3. ) Diagnosing Hypertension - where you start treatment
   - >140/90 if < 80 years (inc type II diabetes)
   - >150/90 if > 80 years
   - >135/85 if type 1 diabetes
4. ) Staging Hypertension - +20/10
   - pre-hypertension: 120-140/80-90
   - stage 1: >140/90, stage 2: >160/100, 3: >180/110

Question 3

NICE step-wise guidelines of treating primary hypertension

4 Steps
Target Blood Pressure

Answer 3

1. ) Step 1 - ACEi/ARB in <55 non-blacks
   - if >55 or black (any age), use CCB (less renin levels)
   - anyone w/ type II diabetes is given an ACEi/ARB
2. ) Step 2 - CCB or thiazide-like diuretics
   - others are given an ACEi/ARB or thiazide-like diuretic

3.) Step 3 - ACEi/ARB + CCB + thiazide-like diuretic

4. ) Step 4 - resistant hypertension
   - low dose spironolactone if serum K+ is < 4.5 mM
   - a/ß-blocker (carvediol, BB) if serum K+ is >4.5 mM
5. ) Target Blood Pressure
   - <140/90 if < 80 years old
   - <150/90 if >80 years old

Question 4

Using ACEi and ARBs to treat hypertension

Drug Names (ACEi x2, ARBs x2)
Mechanism
Independent AngII Production
Side Effects x6
Contraindications x5
Cautions x3

Answer 4

1. ) Drug Names
   - ACEi - lisinopril and ramipril
   - ARBs - candesartan and lorsartan
2. ) Mechanism
   - ACEi prevents formation of AngII and breakdown of bradykinin
   - ARBs block AT1 receptors AngII primarily acts on
3. ) Independent AngII Production - chymases can produce AngII from AngI without the need for ACE
   - this makes ARBs more effective
4. ) Side-Effects - hypotension
   - dry cough and angioedema: ↑bradykinin (ACEi)
   - hyperkalemia: ↓aldosterone
   - renal failure in renal artery stenosis: efferent arteriole cannot constrict
   - nephrotoxic
5. ) Contraindications
   - pregnancy, breastfeeding (ARBs)
   - AKI, CKD, renal artery stenosis

6.) Caution - ↑K+ drugs, NSAIDs, other anti-hypertensives
- a small rise in creatinine (<20%) is expected when starting an ACEi or ARB, the drug should be continued and measurements repeated in one week

Question 5

Why ACEi/ARBs are first-line for all patients with type 2 diabetes (2 reasons)

Intraglomerular Pressure

Answer 5

Reduced Intraglomerular Pressure - ↓BP and dilation of efferent glomerular arteriole
- good for type II diabetes

Reduced chance of diabetic nephropathy and CKD w/ proteinuria

Question 6

Using dihydropyridine CCBs to treat hypertension

Drug Names x3
Mechanism
Side-Effects x4
Contraindications x2
Caution x2

Answer 6

1.) Drug Names - amlodipine, nifedipine, nimodipine

2. ) Mechanism - prevents Ca2+ influx through VOCC
   - selective for vasculature so prevents vasoconstriction
   - nimodipine is selective for cerebral vasculature so is used in a subarachnoid haemorrhage
3. ) Side-Effects - due to vasodilation
   - ankle swelling (can add diuretic if doesn’t resolve)
   - flushing, headaches
   - palpitations (compensatory tachycardia)
4. ) Contraindications
   - unstable angina and severe aortic stenosis
   - protein leakage (check ACR, albumin:creatinine)
5. ) Caution
   - amlodipine + simvastatin (↑effect of statin)
   - other anti-hypertensive agents

Question 7

Using non-dihydropyridine CCBs to treat hypertension

Drug Names x2
Mechanism
Side Effects x4
Contraindications x2
Caution x3

Answer 7

1. ) Drug Names - verapamil and diltiazem
   - verapamil is a phenylalkylamine
   - diltiazem is a benzothiazapine which sits in between other CCB classes
2. ) Mechanism - prevents Ca2+ influx through VOCC
   - selective for the heart so reduces HR and SV
   - causes some coronary and peripheral vasodilation
   - class IV anti-arrhythmic drug so is also used for arrhythmia and angina
3. ) Side-Effects
   - bradycardia (IV), heart block, cardiac failure
   - constipation
4. ) Contraindications
   - poor LV function, AV nodal conduction delay

5.) Caution - beta blockers, other antihypertensive and antiarrhythmic drugs

Question 8

Using thiazide/thiazide-like diuretics to treat hypertension

Drug Names x2
Mechanism
Side-Effects x7
Contraindications x3
Caution x2

Answer 8

1. ) Drug Names - bendroflumethiazide, indapamide
   - bendroflumethiazide (thiazide)
   - indapamide (thiazide-like)
2. ) Mechanism - inhibits Na-Cl symporter in DCT
   - reduces Na/water retention
3. ) Side-Effects
   - ↓K+, ↓Na+, ↑urea (hyperuricemia), ↑glucose
   - ↑cholesterol (LDL) and triglycerides
   - arrhythmia
4. ) Contraindications
   - hypokalaemia, hyponatraemia, gout
5. ) Caution
   - NSAIDs, ↓K+ drugs

Question 10

Using beta-adrenoceptor blockers to treat resistant hypertension

Drug Names x3
Mechanism 
Gestational Hypertension
Side Effects x7
Contraindications x3
Caution

Answer 10

1. ) Drug Names
   - labetalol,
   - bisoprolol (cardio-selective)
   - metoprolol
   - carvediol
2. ) Mechanism - blocks ß-1 adrenoceptors
   - ↓myocardial contraction –> ↓CO –> ↓renin secretion
3. ) Gestational Hypertension - IV labetalol
   - first line treatment of hypertension in pregnancy
4. ) Side Effects
   - heart block, cold hands, lethargy, impotence (ED)
   - bronchospasm (ß-2 adrenoceptor)
   - insulin resistance, ß-blockers mask the signs of hypoglycaemia (e.g. sweating, tachycardia)

5.) Contraindications
- asthma/COPD
- hepatic failure
- haemodynamic instability

6. ) Caution - use of non-dihydropyridine CCBs
   - can cause asystole

Question 11

Using beta-adrenoceptor blockers to treat resistant hypertension

Drug Names x3
Mechanism 
Gestational Hypertension
Side Effects x7
Contraindications x3
Caution

Answer 11

1. ) Drug Names
   - labetalol,
   - bisoprolol (cardio-selective)
   - metoprolol
   - carvediol
2. ) Mechanism - blocks ß-1 adrenoceptors
   - ↓myocardial contraction –> ↓CO –> ↓renin secretion
3. ) Gestational Hypertension - IV labetalol
   - first line treatment of hypertension in pregnancy
4. ) Side Effects
   - heart block, cold hands, lethargy, impotence
   - bronchospasm (ß-2 adrenoceptor)
   - insulin resistance, ß-blockers mask the signs of hypoglycaemia (e.g. sweating, tachycardia)

5.) Contraindications
- asthma/COPD (bronchospasm)
- hepatic failure, haemodynamic instability
- peripheral vascular disease e.g. ischaemic leg ulcers

6. ) Caution - use of non-dihydropyridine CCBs
   - can cause asystole

Question 12

Using alpha-adrenoceptor blockers to treat resistant hypertension

Drug Name
Mechanism
Side Effects x5
Contraindication
Caution

Answer 12

1.) Drug Name - doxazosin

2. ) Mechanism - selective a-1 adrenoceptor blocker
   - ↓TPR –> ↓preload –> ↓CO –> ↓renin release
3. ) Side Effects - postural hypotension, headache, dizziness, syncope, fatigue
4. ) Contraindications - postural hypotension
5. ) Caution - use of dihydropyridine CCBs
   - can cause oedema

Question 12

NICE step-wise guidlines of managing heart failure

First Line Treatment
HFpEF 
HFrEF 
Third Line Treatment
Non-Pharmacological Management

Answer 12

1. ) First Line Treatment - diuretics (e.g furosemide)
   - manages congestive symptoms and fluid retention
   - furosemide (IV if severely overloaded)
   - bumetanide (oral)
   - bendroflumethiazide can be added
2. ) HFpEF (>45%)- manage co-morbidities:
   - hypertension, atrial fibrillation, IHDs, diabetes
3. HFrEF (<45%) - medication
   - ACEi OR ARB, hydralazine and isosorbide mononitrate if intolerant to both
   - BB e.g. bisoprolol if BP>100 and resting HR >60 (ivabradine if contraindicated)
   - sacubitril/valsartan (EF <35%) as addition to ACEi/ARB
   - spironolactone if symptoms continue (↑ life expectancy in heart failure)
4. ) Third Line Treatment - personalised exercise-based cardiac rehabilitation program unless unstable condition
   - pacemaker if LBBB (CRT or ICD)
5. ) Non-Pharmacological Management
   - salt and fluid restriction