5 - Hypertension and Heart Failure

Question 1

define hypertension, and explain pathophys briefly

Answer 1

hypertension is a long term elevation in BP above normal that will lead to end organ damage and heart failure

an elevated BP will go on to cause
the vasculature will hypertrophy and thicken - increasing TPR and decrease compliance long term

this can cause renal damage, peripheral vascular disease, vasuclar dimentia, retionopahtys and LVH - heart failure

Question 2

1st step of treatment is ?

Answer 2

recommend lifestyle changes

Question 3

how do we diagnose hypertension - general idea, not specifics

Answer 3

Sitting, relaxed and arm is supported
• Both arms, >15 mmHg difference repeat measurement and use arm with higher reading
• Measurements over period of visits +/- ABPM/HBPM

• Aim – target BP and reduced CVD risk
• 140/90 < 80 years old inc. type II diabetes
• 150/90 > 80 years old
• 135/85 type 1 diabetes

Question 4

outline the staging of hypertension

Answer 4

120/80 mmHg “desired” – minimise CVD risk

• Stage 1 hypertension
Clinic blood pressure ranging from 140/90 mmHg to 159/99 mmHg

• Stage 2 hypertension
Clinic blood pressure of 160/100 mmHg or higher but less than 180/120 mmHg

• Stage 3 or severe hypertension
Clinic sbp of 180 mmHg or higher or clinic dbp of 120 mmHg or higher.

Question 5

what is prehypertension ?

what are some of the recommend advice and changes ?

Answer 5

>120/80 <140/90 mmHg
• Promotion of regular exercise
• Modified healthy/balanced diet
• Reduction in stress and increased relaxation
• Limited/reduced alcohol intake
• Discourage excessive caffeine consumption
• Smoking cessation
• Reduction in dietary sodium
• Contribute to CVD risk reduction

Question 6

what are the primary hypertension therapeutic agents ?

Answer 6

• Angiotensin converting enzyme (ACE) inhibitors
(ACEi)

Angiotensin (AT1)receptor blockers (ARBs)

• Calcium channel blockers (CCBs)
• Diuretics – thiazide and thiazide-like

Question 7

outline/draw the RAAS system, including where enzymes are made - use this to show where some of the drugs target

Answer 7

do it, then check against lec 5 - slide 17

Question 8

outline how an ACEi works and the resulting effects it has

Answer 8

ACE - luminal surface of capillary endothelial cells, predominantly in the lungs
• ACE catalyses conversion of angiotensin-I to potent active vasoconstrictor angiotensin-II

• AT1 receptor subtype typical of classic angiotensin-II actions
- vasoconstriction, stimulation of aldosterone, cardiac and vascular muscle cell growth and vasopressin (ADH) release from posterior pituitary

Limit the conversion of Angiotensin-I to Angiotensin-II by inhibiting circulating and tissue ACE
• A reduction in Angiotensin-II effects, resulting in
• vasodilation (↓ PVR →↓afterload)
• reduction in aldosterone release (↑Na + H2O exc.)
• reduced vasopressin (ADH) release (↑ H2O exc.)
• reduced cell growth and proliferation

• Bradykinin also a substrate for ACE
• Use of ACEi therefore potentiates bradykinin
- vasodilatation via NOS/NO and PGI2
→ ACEi vasodilation in low-renin hypertensives

Question 9

what are the side effects of an ACEi

what are the contraindications

Answer 9

Hypotension!
Dry cough (10-15% - BK association)
hyperkalaemia (low aldosterone ↑ K+)

renal failure (esp. renal artery stenosis where constriction of efferent arteriole needed)
AKD,
DONT TAKE - pregnant or breastfeeding - CKD
angioedema (BK more common in black population)

Question 10

what are important DDI’s ?

Answer 10

↑K+ drugs
NSAIDs,
other antihypertensive agent

Question 11

what are the two key ACEis

Answer 11

Lisinopril

Ramipril

the Prils

Question 12

outline how ARB’s work (angiotension receptor blockers/antangonists)

Answer 12

AT1 and AT2 receptors - AT1 important in relation to
cardiovascular regulation

• no effect on bradykinin - less effective in low-renin hypertensives
↓ ↓ dry cough and angioedema

• Directly targeting AT1 receptors - more effective at inhibiting Ang-II mediated vasoconstriction

Question 13

contraindications and DDI’s of ARB’s

Answer 13

X Renal artery stenosis, AKD, pregnancy, breastfeeding, (CKD - caution)

Δ ↑K+ drugs, NSAIDs, other antihypertensive agents

Question 14

name the two key ARB’s

Answer 14

Candesartan

Losartan

the sartans

Question 15

outline how CCB’s (calcium chanel blockers work)

Answer 15

LTCCs allow inward Ca2+ flux into cells – voltage
operated calcium channel (VOCC)
• Expressed throughout the body - inc. vascular
smooth muscle cells AND cardiac myocytes plus SA
and AV node

• CCBs target calcium initiated smooth muscle
contraction (in hypertension) - block ca entering smooth muscle - less contractile force and hence vasodilation of vessels

• 3 classes of CCB interact with different sites on (α1)
subunit of VOCC - selectivity for vascular smooth muscle or myocardium

Question 16

what are the types of CCBs

when are they 1st choice over ACEi

Answer 16

• dihydropyridines
• non-dihyropyridine - phenylalkylamines and benzothiazapines
• dihydropyridines selective for peripheral vasculature, little chronotropic or inotropic effects (first line CCB for hypertension)
• Phenylalkyamine depresses SA node and slows AV conduction, negative inotropy - targets MYOCARDIUM
• Benzothiazapines - bit of both effects

CCBs – primary choice antihypertensive in low renin patients

Question 17

what are the dihydropyridine class of CCB’s

name the three drugs

Side Effects

contras and DDI’s

Answer 17

amlodipine, nifedipine, nimodipine

the idipines

• Amlodipine has long half life others tend to be shorter
• Nimodipine selectivity for cerebral vasculature (sub arachnoid haemorrhage)

side effects: Ankle swelling, flushing, headaches (vasodilation)
Palpitations (compensatory tachycardia)

X Unstable angina, severe aortic stenosis - they need the higher TPR
Δ amlodipine + simvastatin (increased effect of statin), other antihypertensive agents

Question 18

name the key benzothiazapine

Answer 18

diltiazem

Question 19

outline the phenylalkylamines

one key drug
role and cases used for
side effects
contras + DDI’s

Answer 19

Verapamil

Class IV anti-arrhythmic agent/prolongs the action potential/effective refractory period

• Less peripheral vasodilatation, negative chronotropic and inotropic effects
• Used for: Arrhythmia, angina, (hypertension)

• Constipation, bradycardia (i.v.), heart block and cardiac failure

• X Poor LV function (caution), AV nodal conduction delay
• Δ β-blockers (cardiologist only), other antihypertensive and antiarrhythmic agents

Question 20

outline the phenylalkylamines

two key drug
role
side effects
contras + DDI’s

Answer 20

thiazide - bendroflumethiazide
thiazide like - indapamide

• Inhibit N+/Cl- co-transporter in DCT
↓Na+ and H2O (RAAS compensates)

• Useful over CCB in oedema

• Hypokalaemia, hyponatraemia, hyperuricemia, arrhythmia
• ↑ glucose (especially with beta-blockers)
• ↑ cholesterol and triglyceride

X Hypokalaemia, hyponatraemia, gout,
Δ NSAIDs, ↑K+ drugs (monitoring)

Question 21

describe the approach to treating primary hypertension

Answer 21

look at the diagram on lec 5 slide 28 - this is KEY ! so do it

Question 22

why use ACEi or ARB for type 2 diabetics - the two pronged approach

Answer 22

↓ Diabetic nephropathy and CKD with proteinuria
dilation of efferent glomerular arteriole

So called “two pronged” approach
↓PVR→↓BP and dilation of efferent glomerular arteriole

→ reduced intraglomerular pressure – good for type II diabetes

Question 23

what do we give extra if a patient is at stage 4 resistant hypertension ?

do DDI’s and Contras

Answer 23

• Spironolactone – aldosterone receptor antagonist
• X Hyperkalaemia, Addison’s
• Δ ↑K+ drugs inc. ACEi and ARBs (monitoring)

• α and β blockers if high K+

Question 24

outline B blockers

3 key drug
mechanism
side effects
contras + DDI’s

Answer 24

labetalol, bisoprolol, metoprolol - lols

Decrease sympathetic tone by blocking NAd and reducing myocardial contraction → ↓ CO
↓ renin secretion β1

Bronchospasm, heart block, Raynaud’s (cold hands), lethargy, impotence
• Mask tachycardia – sign of insulin induced hypoglycaemia

X Asthma, (COPD), haemodynamic instability, hepatic failure (dose monitoring)
Δ non-dihydropyridine CCB – verapamil and diltiazem – asystole!

Question 25

outline a blockers

key drug
role
side effects
contras + DDI’s

Answer 25

doxazosin

Selective antagonism of α-1 adrenoceptors
• Reduce peripheral vascular resistance

• Urinary tract inc. bladder neck and prostate - BPH (tamsulosin)
• Relatively safe in renal disease
• Postural hypotension………dizziness, syncope, headache and fatigue
• X postural hypotension
• Δ (dihydropyridine CCBs - oedema)

Question 26

outline heart failure and its postivie feedback loop of damage

symptoms

treatment of heart failure - what drugs are used when

Answer 26

symptoms - exercise intolerance, dyspnoea, fatigue (swelling)

for treatment look at slide 35
genreal idea

• diuretics (furosemide)
• ACEi - lisinopril, ramipril

and BB - bisoprolol

add and MRA - spironolactone

ARB IF ACEi contra - Candesartan, losartan

the aim is reduce preload, sympathetic stim, and blood volume

if LV w/rEF - correct underlying cause - ie eat less salt, drink less liquids