phamacological management of essential hypertension - revision guide

Phamacological Management of Essential Hypertension

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Introduction• This resource is a revision guide of the drugs used to treat

essential hypertension• The first part of the resource summarises the key points of the

subject, including which drugs should be used and when, as well as their cautions, contraindications and side effects

• The second part of the resource will provide questions for self assessment

• This resource is a summary only, it does not contain all the information available

• This resource aims to set out the important information in a easy to understand and easy to learn format. The key points that will be useful in a clinical situation will be highlighted

• Do not feel that you have to do everything in one session, if you are tired then take a break and come back at another time

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Contents• Introduction• Treatment overview• ACE inhibitors• ARBs• Calcium Channel Blockers• Diuretics• Beta blockers• Alpha adrenoreceptor blockers• Methyldopa• Questions

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Why Learn About Hypertension?

• Hypertension is common– In the UK, about half of people over 65, and about 1

in 4 middle aged adults, have high blood pressure

• At least 1 in 20 adults have blood pressure of 160/100 mmHg or above

• High blood pressure is a risk factor for developing a cardiovascular disease (heart attack or stroke), and kidney damage

Previous Contents Next

Introduction to Hypertension• The aim of treating hypertension is to reduce the patient’s blood

pressure in order to reduce their risk of cardiovascular disease.

• It is important to remember lifestyle changes that decrease blood pressure and decrease cardiovascular risk in the absence of a reduction in blood pressure. These should be discussed with the patient before pharmacological treatment is started.

• Remember that you will be treating asymptomatic patients and that treatment will be long term, it is therefore important to consider a patient’s quality of life and how it will be affected by the adverse effects of the treatment.


• Hypertension is defined as a blood pressure of over 140/90mmHg

• Blood pressure should be measured on three separate occasions

• Patients should be offered drug treatment if: – They have a blood pressure >160/100mmHg or– They have an isolated systolic hypertension (>160mmHg) or– They have a blood pressure >140/90mmHg and:

• 10 year CVD risk of at least 20% or• Existing CVD or target organ damage

• The aim of treatment it to reduce blood pressure to <140/90mmHg


• Treatment choice is based on British Hypertension Society guidelines and NICE recommendations.

• First line treatment is to start the patient on one of:Angiotensin Converting Enzyme (ACE) InhibitorAngiotensin II receptor Blocker (ARB) Calcium Channel Blocker Diuretic

• Drugs can be combined if treatment with one drug does not achieve the target reduction (see next page)

• Additional drugs used for hypertension include beta blockers, alpha adrenoreceptor blockers and centrally acting drugs such as methyldopa


Guidelines For Treatment

Previous

Contents

Next Guidelines from NICE and BHS

ACE Inhibitors• Inhibit conversion of angiotensin I to angiotensin II

(Affects RAAS see next slide for diagram of RAAS)

• Examples of drugs in group:– Captopril, Lisinopril, Ramipril, Perindopril

• Uses:– Hypertension – Prevention of cardiac remodelling following MI – Treatment and prevention of diabetic nephropathy – Treatment of heart failure


• Contraindicated in pregnancy, caution when prescribing to female patients of childbearing age

• Avoid in patients with renovascular disease as can cause renal impairment

• A small deterioration in renal function is often seen on starting these drugs

• Can get first dose hypotension due to vasodilatation (more common in patients with fixed cardiac output)

• If possible stop diuretics 2 days before starting ACE inhibitors


ACE Inhibitors – cautions and contraindications (CIs)

• Commonly causes a dry cough due to inhibition of bradykinin metabolism

• Cause hyperkalaemia (caution when prescribing with potassium sparing diuretics)

• ACE inhibitors are a good choice for treating hypertension in diabetics as they treat and prevent diabetic nephropathy

• Hypersensitivity to ACE inhibitors occurs rarely and is characterised by angio-oedema

• Do not give with NSAIDs


ACE Inhibitors – Side effects

Angiotensin Receptor Blockers (ARBs)

• Antagonists of the angiotensin II receptor

• Angiotensin II receptors are classified into two subtypes – AT1 and AT2, AT1 receptors mediate all of the classical pharmacological effects of angiotensin II. ARBs block AT1

• Example of drugs in group:– Losartan, Candesartan, Eprosartan, Irbesartan, Olmesartan,

Telmisartan

• Uses:– Hypertension– Treatment and prevention of diabetic nephropathy– Treatment of heart failure


• Similar to ACE inhibitors but do not cause dry cough, therefore major use is in patients who are unable to tolerate ACE inhibitors due to a dry cough

• Contraindicated in pregnancy

• Avoid in patients with renovascular disease

• A small deterioration in renal function is often seen on starting these drugs


ARBs – cautions and CIs

• Can cause first dose hypotension

• If possible stop diuretics 2 days before starting ARB

• Good choice in patient with diabetes

• Can cause hyperkalaemia

• Hypersensitivity can occur, but is rare

• Do not give with NSAIDs


ARBs – Side effects

Calcium Channel Blockers• Inhibit influx of calcium into cells

• Reduce myocardial contractility, depress formation and propagation of electrical impulses within the heart, decrease coronary and systemic vascular tone

• There are 3 groups of calcium channel blocker, they have differential effects on the heart and peripheral vasculature– Dihydropyridines – peripheral vasculature– Phenylalkylamines – heart– Benzthiazepines – heart and peripheral vasculature


Dihydropyridines• Affect peripheral vasculature more than heart

• Examples of drugs in this group:– Amlodpipine, Felopdipine, Lacidipine, Nicardipine,

Nifedipine, Nimodipine

• Uses:– Treatment of hypertension– Prophylaxis of angina– Prophylaxis of migraine (unlicensed) – Prevention and treatment of neurological ischaemia

following SAH (subarachnoid haemorrhage)


• Avoid in pregnancy and breastfeeding

• Do not use for one month after an MI, do not use in unstable angina

• Give as modified release formulation to avoid exaggerated fall in BP

• Cause flushing, headache and peripheral oedema as a result of vasodilatation

• Patients should avoid grapefruit juice as it increases metabolism of the drugs


Dihydropyridines – cautions, CIs, side effects

Phenylalkylamines (verapamil)• Affect heart more than peripheral vasculature

• Uses:– Prevention of SVT (supraventricular tachycardia)– Treatment of hypertension– Prophylaxis of angina

• Although verapamil can be used to treat hypertension and angina, there are more appropriate choices for these indications


• Take care in pregnancy and breastfeeding (no clear evidence of harm)

• Avoid in patients with known left ventricular impairment or heart failure as they are negatively inotropic

• Slows cardiac conduction – avoid in 2nd and 3rd degree heart block

• Do not give with beta blockers

• Can cause hypotension

• Long term treatment can result in gynaecomastia


Phenylalkylamines – cautions, CIs, side effects

Benzthiazepines (diltiazem)

• Affect both the heart and peripheral vasculature

• Uses:– Prophylaxis of angina– Treatment of hypertension


• Avoid in pregnancy and breastfeeding

• Avoid in patients with heart failure as negatively inotropic

• Avoid in patients with 2nd or 3rd degree heart block

• Adverse effects - vasodilatation (flushing, headache, peripheral oedema)

• Can cause hypotension

• Be careful when prescribing with beta blockers as there is a risk of significant reduction in cardiac output


Benzthiazepines – cautions, CIs, side effects

Diuretics• Thiazide diuretics, potassium sparing diuretics and

spironolactone are used to treat hypertension. They all work in the distal convoluted tubule

• The antihypertensive effect of diuretics is not related directly to their diuretic potency, but instead the BP lowering action appears to depend upon more subtle alterations to the contractile responses of vascular smooth muscle

• Lower initial doses of diuretics should be used in the elderly because they are particularly susceptible to the side effects


Thiazide and Thiazide-like diuretics• Thiazide = Bendroflumethiazide, Chlorothiazide,

Hydrochlorothiazide• Thiazide like = Chlortalidone, Indapamide, Metolazone, Xipamide

• Can cause hypokalaemia

• In hepatic failure hypokalaemia can precipitate encephalopathy

• Can precipitate gout (thiazides interfere with the excretion of uric acid)

• Can precipitate DM type II (diabetes mellitus) or worsen glucose control in DM

• Do not use in pregnancy


• Can cause increased plasma lipid concentrations, rashes and erectile impotence

• Ensure patient is not hypovolaemic before starting diuretic therapy

• Ineffective in people with poor renal function because they act from within the tubular lumen

• Low doses of thiazides are as effective as high doses in the treatment of hypertension and cause fewer side effects


Thiazide diuretics – cautions, CIs, side effects

Potassium sparing diuretics• Examples of drugs in group;

– Amiloride, Triamterene

• Inhibit the Na+ channels in the apical membrane of the late distal tubule and collecting duct

• Although they have diuretic action, their main use is in combination with thiazide or loop diuretics in order to conserve potassium


• Hypersensitivity reactions can occur but are uncommon

• Triamterene can cause folate deficiency

• Do not use in patients with renal insufficiency because they are at risk of hyperkalaemia

• Risk of hyperkalaemia when prescribed with – ACE-I, ARBs, ciclosporin, NSAIDs, trimethroprim, potassium supplements


K+ sparing diuretics – cautions, CIs, side effects

Spironolactone• Aldosterone receptor antagonist• Not used as first line therapy for hypertension• Avoid in severe renal insufficiency• Avoid in pregnancy and breast feeding• Avoid in Addison’s disease• Do not combine with other potassium sparing

diuretics• Can cause painful gynaecomastia in men and

breast enlargement in women


Beta blockers • Beta blockers are no longer used as a first line therapy

in the treatment of hypertension, see: http://www.nice.org.uk/nicemedia/pdf/cg034quickrefguide.pdf pages 8 and 9

• Examples of drugs in group:– Propanolol, Atenolol, Bisoprolol, Metaprolol, Sotalol

• Beta1 specific blockers are relatively cardioselective but still cause bronchoconstriction, all beta blockers are contraindicated in asthma


http://www.nice.org.uk/nicemedia/pdf/cg034quickrefguide.pdf

• Do not give to patients with acute or unstable angina

• Can mask the physiological signs of hypoglycaemia

• Avoid in pregnancy unless absolutely necessary

• Do not stop treatment suddenly, rebound symptoms can be severe

• Common adverse effects are cold limbs and peripheries and a feeling of tiredness

• Can cause sleep disturbance and nightmares, erectile impotence

• Sotalol occasionally causes life threatening ventricular arrhythmias


Beta Blockers – cautions, CIs, side effects

Alpha1 adrenoreceptor blockers• Act via selective blockade of peripheral alpha1

adrenoreceptors to produce vasodilator effects

• Not widely used first line treatments

• Examples of drugs in group:– Prazosin, Doxazosin

• Associated with first dose hypotensive effect, accompanied by reflex cardioacceleration and palpitations, risk of vasovagal collapse


Treatment of hypertension during pregnancy

• Methyldopa

• Beta blockers safe in 3rd trimester

• Modified release nifedipine also used


Methyldopa• Centrally active antihypertensive drug, acts on central

alpha 2 adrenoreceptors to reduce sympathetic outflow

• Usually reserved for treatment of hypertension during pregnancy

• Avoid in liver disease• Do not give to patients with depression, porphyria or

phaeochromocytoma• Do not stop suddenly as can cause rebound hypertension• Adverse effects – sedation and tiredness, dry mouth,

diarrhoea


QUESTIONS


Questions• There are 20 questions in this session

• They are designed to help you test your knowledge of material that has been covered

• Click on an answer to see if it is correct• Keep a record of your score

• If you are unsure why something is correct or incorrect go back to the relevant section, you can navigate back to the question you were on by going to

Contents Questions choose the question number

NextPrevious Contents

QuestionsQ1 Q6Q2 Q7Q3 Q8Q4 Q9Q5 Q10

Q11 Q16Q12 Q17Q13 Q18Q14 Q19Q15 Q20

Start Questions

Question 1

Which of these drugs is a beta blocker?

RamiprilNifedipineAtenolol

RAMIPRIL

INCORRECT

Ramipril is an ACE inhibitor

Back to Question 1 Beta Blockers

NIFEDIPINE

INCORRECT

Nifedipine is a calcium channel blocker

Beta Blockers Back to Question 1

ATENOLOL

CORRECT

This is a beta blocker

Next Question

Question 2

Which of these drugs does not cause hypokalaemia?

LisoniprilIndapamideBisoprolol

LISONIPRIL

INCORRECT

Lisonipril is an ACE-inhibitor, it can cause hypokalaemia

Back to Question 2 ACE-Inhibitors

INDAPAMIDE

INCORRECT

Indapamide is a thiazide-like diuretic, it can cause hypokalaemia

Diuretics

Back to Question 2

BISOPROLOL

CORRECT

Bisoprolol is a beta blocker, it does not cause hypokalaemia

Next Question

Question 3

Which of these is the best choice for treating hypertension in diabetic patients?

PerindoprilMetolazone

Atenolol

PERINDOPRIL

CORRECT

This is an ACE-inhibitor, it can be used to treat and prevent diabetic nephropathy

and is a good choice for diabetic patients

Next Question

METALAZONE

INCORRECT

Metalazone is a thiazide-like diuretic, these drugs can precipitate type II diabetes mellitus or worsen glucose control in

diabetes

Back to Question 3 Diuretics

ATENOLOL

INCORRECT

Atenolol is a beta blocker, it can mask the physiological responses to hypoglycaemia, they

are not contraindicated in diabetes, but they should not be given to patients who have

frequent episodes of hypoglycaemia

Beta Blockers Back to Question 3

Question 4

Which of these groups of calcium channel blockers does nifedipine belong to?

PhenylalkylaminesDihydropyridinesBenzthiazepines

PHENYLALKYLAMINES

INCORRECT

Verapamil is an example of a drug in this group

Back to Question 4 Calcium Channel Blockers

DIHYDROPYRIDINES

CORRECT

Drugs in this group tend to have the suffix ‘-ine’

Next Question

BENZATHIAZEPINES

INCORRECT

Diltiazem is an example of a drug in this group

Calcium Channel BlockersBack to Question 4

Question 5

Which of these is a calcium channel blocker?

DiltiazemDigoxin

Doxazosin

DILTIAZEM

CORRECT

Diltiazem is a calcium channel blocker

Next Question

DIGOXIN

INCORRECT

Digoxin is a cardiac glycoside, it is used as an antiarrhythmic drug and in the

treatment of heart failure

Back to Question 5 Calcium Channel Blockers

DOXAZOSIN

INCORRECT

Doxazosin is an alpha1 receptor blocker


Question 6

Which of these is safe to use during pregnancy?

CaptoprilMethyldopa

Bendroflumethiazide

CAPTOPRIL

INCORRECT

Captopril is an ACE inhibitor, ACE inhibitors can cause birth defects

Back to Question 6 ACE-Inhibitors

METHYLDOPA

CORRECT

Methyldopa is the first choice drug for hypertension during pregnancy

Next Question

BENDROFLUMETHIAZIDE

INCORRECT

Bendroflumethiazide is a thiazide diuretic, it can cause neonatal thrombocytopenia if

given during pregnancy

Diuretics

Back to Question 6

Question 7

Which of these is used to treat hypertension?

AmiodaroneAdenosineAmlodipine

AMIODARONE

INCORRECT

Amiodarone is an antiarrhythmic drug, it is not used to treat hypertension

Back to Question 7Contents

ADENOSINE

INCORRECT

Adenosine is an antiarrhthymic drug which is an antagonist at the purine A2 receptors, it is not

used to treat hypertension

ContentsBack to Question 7

AMLODIPINE

CORRECT

Amlodipine is a calcium channel blocker, it is used as a first line treatment of

hypertension

Next Question

Question 8

ARBs do not cause a dry cough

TRUEFALSE

TRUE

CORRECT

ARBs do not cause a dry cough, ACE inhibitors cause a dry cough because they inhibit

bradykinin metabolism, ARBs do not inhibit bradykinin metabolism, they are used for

patients who are intolerant to ACE-inhibitors because of the dry cough

Next Question

FALSE

INCORRECT

ARBs do not cause a dry cough, ACE inhibitors cause a dry cough because they inhibit

bradykinin metabolism, ARBs do not inhibit bradykinin metabolism, they are used for

patients who are intolerant to ACE-inhibitors because of the dry cough

ARBs

Next Question

Question 9

ARBs block AT2 receptors

TRUEFALSE

TRUE

INCORRECT

ARBs block AT1 receptors. AT1 receptors mediate all the classical pharmacological

effects of angiotensin II, the functional role of AT2 receptors in unclear

Next Question

ARBs

FALSE

CORRECT

ARBs block AT1 receptors. AT1 receptors mediate all the classical pharmacological

effects of angiotensin II, the functional role of AT2 receptors in unclear

Next Question

Question 10

The correct definition of hypertension is:

A blood pressure > 135/85mmHgA blood pressure > 140/90mmHg

A blood pressure > 160/100mmHg

135/85mmHg

INCORRECT

If you are unsure why this is incorrect then see the introductory slide on hypertension or follow

this link:http://www.nice.org.uk/nicemedia/pdf/

cg034quickrefguide.pdfBack to Question 10

Introduction

140/90mmHg

CORRECT

Hypertension is defined by WHO as a blood pressure >140/90mmHg

Next Question

160/100mmHg

INCORRECT

This is the blood pressure at which drug therapy should be considered with a 10 year

cardiovascular risk of less than 20% and no cardiovascular or target organ damage

IntroductionBack to Question 10

Question 11

Which of these is not a contraindication for ACE-inhibitors?

Renovascular diseasePregnancy

Diabetes Mellitus

RENOVASCULAR DISEASE

INCORRECT

ACE-inhibitors can cause severe renal impairment in patients with renovascular

disease

Back to Question 11ACE-Inhibitors

PREGNANCY

INCORRECT

ACE-inhibitors can cause birth defects and are contraindicated in pregnancy

ACE-Inhibitors

Back to Question 11

DIABETES MELLITUS

CORRECT

ACE-inhibitors can be used to treat and prevent diabetic nephropathy in Type 1

Diabetes Mellitus

Next Question

Question 12

Thiazide diuretics are the first choice for patients with renal impairment

TRUEFALSE

TRUE

INCORRECT

Thiazides are ineffective in patients with poor renal function as they work from

within the tubular lumen

Next Question

Diuretics

FALSE

CORRECT

Thiazides are ineffective in patients with poor renal function as they work from

within the tubular lumen

Next Question

Question 13

Which of these is an alpha1 adrenoreceptor blocker?

DoxazosinMetaprololNimodipine

DOXAZOSIN

CORRECT

Doxazosin is an alpha1 adrenoreceptor blocker

Next Question

METAPROLOL

INCORRECT

Metaprolol is a beta blocker

Back to Question 13Alpha Receptor Blockers

NIMODIPINE

INCORRECT

Nimodipine is a calcium channel blocker

Alpha Receptor BlockersBack to Question 13

Question 14

Cardioselective beta blockers cause bronchoconstriction and should not be

used in patients with asthma

TRUEFALSE

TRUE

CORRECT

Cardioselective beta blockers are only relatively selective (they still have some effect on other receptors) and still cause

bronchoconstriction

Next Question

FALSE

INCORRECT

Cardioselective beta blockers are only relatively selective (they still have some effect on other receptors) and still cause

bronchoconstriction

Next Question

Beta Blockers

Question 15

Which of these is not a first line treatment for hypertension?

PropanololRamipril

Felodipine

PROPANOLOL

CORRECT

This is a beta blocker. Beta blockers are no longer used as a first line treatment for hypertension, for more information see:http://www.nice.org.uk/nicemedia/pdf/

cg034quickrefguide.pdf

Next Question

RAMIPRIL

INCORRECT

Ramipril is an ACE inhibitor, it is often used as a first line treatment for hypertension


FELODIPINE

INCORRECT

Felodipine is a calcium channel blocker, it is often used as a first line treatment for

hypertension


Question 16

Which of these is an ACE-inhibitor?

DoxazosinCaptoprilAmiloride

DOXAZOSIN

INCORRECT

Doxazosin is an alpha adrenoreceptor blocker


CAPTOPRIL

CORRECT

This is an ACE-inhibitor, ACE-inhibitors tend to have the suffix ‘-pril’

Next Question

AMILORIDE

INCORRECT

Amiloride is a potassium sparing diuretic

ACE-Inhibitors

Back to Question 16

Question 17

Diltiazem blocks calcium channels in both cardiac and skeletal muscle

TRUEFALSE

TRUE

INCORRECT

Diltiazem blocks calcium channels in cardiac and smooth muscle but not in skeletal

muscle

Next Question

Calcium Channel Blockers

FALSE

CORRECT

Diltiazem blocks calcium channels in cardiac and smooth muscle but not in skeletal

muscle

Next Question

Question 18

Thiazide diuretics cause:

HypokalaemiaHypocalcaemiaHypouricaemia

HYPOKALAEMIA

CORRECT

Thaizide diuretics cause an increased urinary loss of potassium which can lead

to hypokalaemia

Next Question

HYPOCALCAEMIA

INCORRECT

Hypercalcaemia is a rare adverse effect of thiazide diuretics resulting from reduced

renal excretion of calcium

Back to Question 18Diuretics

HYPOURICAEMIA

INCORRECT

Thiazide diuretics interfere with the excretion of uric acid and can cause hyperuricaemia

Diuretics

Back to Question 18

Question 19

Which of these drugs should not be taken with grapefruit juice?

VerapamilSpironolactone

Nifedipine

VERAPAMIL

INCORRECT

This is not one of verpamil’s drug interactions

Back to Question 19Calcium Channel Blockers

SPIRONOLACTONE

INCORRECT

This is not one of Spironolactone’s drug interactions

Diuretics

Back to Question 19

NIFEDIPINE

CORRECT

Grapefruit juice affects the metabolism of dihydropyridines (except amlodipine) and

therefore increases the risk of adverse effects

Next Question

Question 20

Increasing the dose of a thiazide diuretic does not cause a greater

decrease in blood pressure

TRUEFALSE

TRUE

CORRECT

Low doses are as effective as higher doses, higher doses have a higher incidence of

adverse effects

Results

FALSE

INCORRECT

Low doses are as effective as higher doses, higher doses have a higher incidence of

adverse effects

Results

Diuretics

Results• Score 0-10 You need to do more revision

• Go back through this guide or read crash course pharmacology

• Score 10-15 Good score, but you could do better, look up the things you struggled with and try again

• Score 15-20 Excellent, well done, now make sure you don’t forget everything

References

References• Lecture Notes on Clinical Pharmacology, 6th

Edition. Reid, Rubin and Whiting. Blackwell Science

• Companion to Pharmacology, 2nd edition. Dale and Dickenson. Churchill Livingstone

• Oxford Handbook of Practical Drug Therapy. Richards and Aronson. Oxford University Press

• British National Formulary, edition 53 March 2007

• http://www.nice.org.uk/nicemedia/pdf/cg034quickrefguide.pdf

End

phamacological management of essential hypertension - revision guide

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