3.1) Hypertension

Question 1

1. What is blood pressure? Is this uniform throughout the body?

Answer 1

BP is the driving force to perfuse organs with blood (force per unit area acting on vessels)
It is NOT uniform— differs based on position, time and activities

Question 2

What is the equation for mean arterial pressure?

Answer 2

Mean arterial pressure= cardiac output x total peripheral resistance

Question 3

Which systems are responsible for blood pressure regulation?

Answer 3

Autonomic sympathetic activity and Renin-angiotensin-aldosterone system

Question 4

Which endogenous chemicals can be released to modify BP?

Answer 4

Autacoids— bradykinin and nitric oxide—- act on vascular smooth muscle to cause vasodilation.

Question 5

What is the relationship between radius, smooth muscle tone and peripheral resistance?

Answer 5

Radius decreases cause resistance increase.
Smooth muscle tone changes total peripheral resistance.

Question 6

How does an increased peripheral resistance impact on BP?

Answer 6

Increased peripheral resistance increases BP

Question 7

What is hypertension?

Answer 7

High blood pressure
Above 135 ambulatory
Above 140 in clinic

Question 8

What is the importance of reducing BP?

Answer 8

A reduction in both SBP and DBP reduces cardiovascular disease risk.

Question 9

What are some of the different types of hypertension?

Answer 9

Essential/primary/idiopathic- no known cause
Secondary- as a result of other pathology
Pre-hypertension- state preceding hypertension (where prophylaxis is helpful)
Isolated diastolic/systolic hypertension
White coat/clinical hypertension- anxiety of attending practice increases BP

Question 10

How is hypertension staged?

Answer 10

Desired= 120/80mmHg

Stage 1= ranging clinic pressure 140/90- 159/99mmHg
Stage 2= clinic pressure of 160/100 mmHg or higher but less than 180/120mmHg
Stage 3 (severe)= clinical systolic BP of 180 or higher

Question 11

What is prehypertension?
How is this treated?

Answer 11

Between 120/80 and 140/90 mmHg
Treated with promotion of regular exercise, modifications to diet, reduction of stress, reduced alcohol intake, discouraging excessive caffeine, reduction of dietary sodium

Question 12

Which agents can be used to treat primary hypertension?

Answer 12

Angiotensin converting enzyme inhibitors (ACEi)
Angiotensin receptor (AT1) blockers (ARBs)
Calcium channel blockers (CCBs)
Diuretics- thiazide and thiazide-like

Question 13

How does the RAAS system increase BP?

Answer 13

• decrease in renal perfusion detected by macula densa cells of DCT, stimulates release of renin from granular cells.
• renin cleaves angiotensinogen to angiotensin I
• angiotensin I to lungs acted on by ACE to form angiotensin II
  -angiotensin II has actions on: increases sympathetic activity, increases tubular reabsorption of sodium and electrolytes in nephron (absorbs water also- increasing plasma volume), stimulates adrenal cortex to increase aldosterone release (increases expression eNac to reabsorb more), arteriolar vasoconstriction.

Question 14

How do ACEi have an anti-hypertensive effect?

Answer 14

Limit the conversion of angiotensin I to angiotensin II. Therefore, reduced amounts of angiotensin II to have hypertensive effects.

Question 15

Why might ARBs be more effective at controlling hypertension than ACEi?

Answer 15

Angiotensin II can also be produced from angiotensin I independently of ACE via action of chymases. Thus this form of angiotensin II will not be prevented from acting in the case of ACEi.

Question 16

Give examples of ACEi

Answer 16

Lisinopril
Ramipril

Question 17

What are some of the side effects of ACEi agents?

Answer 17

Hypotension
Dry cough— due to potential ion of bradykinin
Hyperkalaemia— lower aldosterone, increases K+
Cause or worsen renal failure
Angioedema

Question 18

Contraindications of ACEi?

Answer 18

Renal artery stenosis
Acute kidney injury
Pregnancy
Chronic kidney disease
Idiopathic angioedema

Question 19

Interactions with ACEi may include?

Answer 19

Hyperkalaemia causing drugs (potentiates)
NSAIDs- disruption to renal function
Other antihypertensive agents— hypotension

Question 20

ARBs target which receptor?

Answer 20

AT1 receptor

Question 21

What are examples of ARBs?

Answer 21

Candesartan
Losartan

Question 22

Do ARBs have an effect on bradykinin?

Answer 22

No—- less likely to have a dry cough or angioedema

Question 23

What are the possible side effects of ARBs?

Answer 23

Hypotension
Hyperkalaemia- low aldosterone, increases K+
Cause or worsen renal failure

Question 24

What are some of the contraindications of ARBs?

Answer 24

Renal artery stenosis
AKD
Pregnancy
CKD

Question 25

Interactions between ARBs and other drugs?

Answer 25

Hyperkalaemia causing drugs NSAIDs- affect renal function Other antihypertensive agents

Question 26

What are the 3 classes of CCBs? What do they all interact with?

Answer 26

Dihydropyridines Non-dihydropyridines- phenylalkylamines and benzothiazepines All interact with different sites on alpha 1 subunits of voltage gated calcium channels. Have different selectivity for vascular smooth muscle or myocardium

Question 27

Which agents fall into the dihydropyridine class? What tissue are these selective for?

Answer 27

Amlodipine Nifedipine Nimodipine Selective for peripheral vasculature

Question 28

What is special about amlodipine in relation to other dihydropyridines?

Answer 28

Has a longer half life

Question 29

Which of the dihydropyridines is selective for cerebral vasculature?

Answer 29

Nimodipine Useful in ischaemic effects of subarachnoid haemorrhage

Question 30

Side effects of dihydropyridines include?

Answer 30

Ankle swelling Flushing Headaches (vasodilation in the cerebral vasculature) Palpitations (compensatory tachycardia)

Question 31

Contraindications of D-CCBs?

Answer 31

Unstable angina Severe aortic stenosis

Question 32

What is a possible DDI of D-CCBs?

Answer 32

Amlodipine and simvastatin —-causes increased effect of statin

Question 33

Phenylalkylamines have what mechanism of action?

Answer 33

Class IV anti-arrhythmic agents- prolongs the action potential to have a negative inotropic and chronotropic effect

Question 34

Which drug is an example of a phenylalkylamine?

Answer 34

Verapamil

Question 35

Side effects of Non-dihydropyridine calcium channel blockers include?

Answer 35

Constipation Bradycardia Heart block Cardiac failure

Question 36

Contraindications of ND-CCBs include?

Answer 36

Poor left ventricular function (caution) AV nodal conduction delay

Question 37

Interactions with ND-CCBs may include?

Answer 37

Beta blockers Other anti hypertensive and anti-arrhythmic agents

Question 38

Diltiazem is an example of which class of agent?

Answer 38

Benzothiazepine Non-dihydropyridine calcium channel blocker

Question 39

What is the mechanism of action of the azide and thiazide- like diuretics?

Answer 39

Inhibit the Na+/Cl- co-transporter in the distal convoluted tubule, reduces sodium and water reabsorption

Question 40

Give examples of thiazide agents

Answer 40

Bendroflumethiazide Indapamide

Question 41

What are some of the side effects of diuretic use?

Answer 41

Hypokalaemia Hyponatraemia Hyperuricaemia (gout) Arrhythmia Increased plasma glucose Increases cholesterol and triglyceride plasma levels

Question 42

What are some of the contraindications to thiazide diuretics?

Answer 42

Patients already experiencing hypokalaemia, hyponatraemia and gout

Question 43

What are some of the DDIs associated with thiazide diuretics?

Answer 43

NSAIDs Hypokalaemia causing drugs ie loop diuretics (electrolyte monitoring required)

Question 44

Which treatments are firstline for individuals aged 55 or less no Afro-Caribbean heritage? Which other demographic also?

Answer 44

ACEi/ARBs Type 2 diabetes mellitus

Question 45

What if firstline for patients aged 55 or over or with an Afro-Caribbean heritage?

Answer 45

CCBs

Question 46

Second line management?

Answer 46

T2DM/under 55= add CCB or thiazide like diuretic Without T2DM/Afro-Caribbean= add ACEi/ARB or thiazide like diuretic

Question 47

Third line management?

Answer 47

ACEi or ARB + CCB + thiazide like diuretic

Question 48

What is resistant hypertension?

Answer 48

Hypertension that persists after step 3 of management. Need to consider patient adherence or secondary cause for hypertension that could control BP once managed

Question 49

What does Step 4 of management involve?

Answer 49

Spironolactone (if patients K+ normal) - could cause hyperkalaemia, gynaecomastia Contraindicated in situations potassium is high or Addisons Instead use alpha and beta blockers or centrally acting drugs ie labetalol to reduce sympathetic outflow

Question 50

Give examples of beta blockers

Answer 50

Labetalol Bisoprolol Metoprolol

Question 51

How do beta blockers work?

Answer 51

Decease sympathetic tone by blocking noradrenaline binding and reducing myocardial contraction (reducing CO)

Question 52

What are some of the side effects of beta blockers?

Answer 52

Brconshospasm Heart block Raynaud’s Lethargy Impotence

Question 53

In what circumstances may beta blockers be contraindicated?

Answer 53

Asthma (beta 2 antagonists), haemodynamic instability, hepatic failure

Question 54

What are some of the DDI that may occur with beta blockers?

Answer 54

ND-CCBs- verapamil and diltiazem can cause asystole

Question 55

Doxasozin is a drug within which class?

Answer 55

Alpha adrenoceptor blocker (antagonist)

Question 56

Which receptors are specifically targeted by alpha blockers? How does this achieve changes to BP?

Answer 56

Alpha 1 receptors Reduce peripheral vascular resistance- act on alpha 1 receptors in smooth vascular muscle.

Question 57

What are some of the side effects of alpha blockers?

Answer 57

Postural hypotension Dizziness Syncope Headache Fatigue

Question 58

In which circumstances are alpha blockers contraindicated?

Answer 58

Postural hypotension

Question 59

Indicate some of the DDIs associated with alpha blockers

Answer 59

D-CCBs- increased risk of oedema