Lecture 24 - Antihypertensives

Front 1

Why is hypertension important?

Back 1

Strong Correlation of Hypertension and Cardiovascular Morbidity and Mortality

Front 2

What is primary hypertension?

Back 2

Hypertension with No Known Cause

Front 3

What is secondary hypertension?

Back 3

Hypertension with an Identifiable Cause

Front 4

What is the prevalence of primary hypertension?

Back 4

90 - 95%

Front 5

What is the prevalence of secondary hypertension?

Back 5

5 - 10%

Front 6

What are some of the known causes of secondary hypertension?

Back 6

Phaeochromocytoma (Tumour of Adrenals)
Narrowing of Aorta (Coarctation)
Renal Artery Stenosis
Chronic Renal Disease

Front 7

What is a normal systolic/diastolic blood pressure?

Back 7

< 120 mmHg; < 80 mmHg

Front 8

What is the target systolic/diastolic blood pressure for people with uncomplicated hypertension?

Back 8

< 140/90 mmHg; High Normal

Front 9

What is the target systolic/diastolic blood pressure for people coronary heart disease, stroke, transient ischaemic attack, diabetes, chronic kidney disease, or proteinuria
(300 - 1000mg/day)?

Back 9

< 130/80 mmHg;

Front 10

What is the target systolic/diastolic blood pressure for people with proteinuria > 1000mg/day?

Back 10

< 125/75 mmHg; Normal

Front 11

What trend is seen with indigenous population in terms of cardiovascular disease?

Back 11

Higher Rates of CVD; 3x Higher in Aboriginal and Torres Strait Islanders

Front 12

What should determine treatment decisions in uncomplicated hypertension?

Back 12

Absolute Risk

Front 13

What does absolute risk examine?

Back 13

Both Cardiovascular Risk and Blood Pressure

Front 14

Which categories of blood pressure should always be treated?

Back 14

Grade 3 (Severe); > 180, > 110
Isolated Systolic Hypertension; > 140, < 90

Front 15

Which categories of blood pressure require assessment of absolute CV risk?

Back 15

Grade 1 (Mild); 140-159, 90-99
Grade 2 (Moderate); 160-179, 100-109

Front 16

When should antihypertensives be started in conjunction with lifestyle changes?

Back 16

Grade 3 (Severe)
Isolated Systolic Hypertension with Widening Pulse Pressure
Evidence of End Organ Damage (< Grade 3)
Consider in Aboriginal and Torres Strait Islander People with Hypertension

Front 17

Why should hypertension be treated?

Back 17

Lowering of Systolic and Diastolic Pressure Reduces the Risk of CV Events and Stroke

Front 18

What is the approach to treating hypertension?

Back 18

Stepped Approach with Lifestyle Changes; using low doses of several drugs, adding new medications until target blood pressure is achieved thereby minimising adverse events and maximising patient compliance.

Front 19

What are the lifestyle changes recommended in hypertension?

Back 19

Weight Loss
Salt Restriction (4 - 5mmHg Reduction)
Limiting Alcohol (2 - 4mmHg Reduction)
Exercise (4 - 9mmHg Reduction)

Front 20

What is RAAS?

Back 20

Renin-Angiotensin-Aldosterone System

Front 21

What stimulates the release of renin?

Back 21

Fall in Blood Pressure (Hypotension)
Fall in Circulating Volume (Hypovolaemia)
Sodium Depletion

Front 22

What cells is renin released from? Where are they located?

Back 22

Granular Cells; Juxtaglomerular Apparatus in Kidney

Front 23

What is the function of renin?

Back 23

Catalyses of Angiotensin I Production from Angiotensinogen; leading to
Production of Angiotensin II

Front 24

What is the function of Angiotensin II?

Back 24

Vasoconstrictor
Anti-Natriuretic Peptide (Cause Salt Retention)
Stimulates Aldosterone (Anti-Natriuretic/Antidiuretic)
Hypertrophogenic Agent (Vascular Growth)

Front 25

What is the common suffix of ACE Inhibitors?

Back 25

‘-pril’, i.e. captopril, enalapril

Front 26

What is the mechanism of action of ACE Inhibitors?

Back 26

Competitive Inhibition of Angiotensin Converting Enzyme (ACE) in the RAAS System

Front 27

Where is ACE found in the body?

Back 27

The Lungs

Front 28

What are the contraindications for ACE Inhibitors?

Back 28

Bilateral Renal Stenosis (GFR Maintained by Angiotensin II)
Pregnancy (Foetal Toxicity)
Hyperkalaemia (Leads to K+ Retention - Reduced Aldosterone)

Front 29

What are the pharmacological effects of ACE Inhibitors?

Back 29

Small Reduction of BP in Normal Patients
Great Reduction of BP in Hypertensive Patients
Reduction of Cardiac Load and Arterial Pressure

Front 30

Which areas of the vascular system are more sensitive to angiotensin II?

Back 30

Vascular Beds of Heart, Brain and Kidney

Front 31

Where are ACEIs excreted?

Back 31

Renal

Front 32

Why does hyperkalaemia occur with treatment with ACE Inhibitors?

Back 32

Inhibition of Aldosterone Secretion; Retention of Potassium, Loss of Sodium

Front 33

What are the adverse effects of ACE inhibitors?

Back 33

Dry Cough (Most Common)
First Dose Hypotension

Front 34

What are the adverse effects of ACE inhibitors at higher doses?

Back 34

Taste Disturbances
Angioneurotic Oedema
Neutropenia (Captopril > Others)

Front 35

What is the reason for development of a dry cough with ACE Inhibitors?

Back 35

Accumulation of Bradykinin (Normally Degraded by ACE)

Front 36

Which drugs interact with ACE Inhibitor?

Back 36

NSAIDs
Potassium Supplements (e.g. SPAN-K, SLOW-K)
Potassium Sparing Diuretics (e.g. amiloride)

Front 37

What is the effect of interaction of NSAIDs and ACE Inhibitors?

Back 37

Reduces Effectiveness of ACE Inhibitors

Front 38

What is the effect of interaction of Potassium Supplements and ACE Inhibitors?

Back 38

Hyperkalaemia

Front 39

What is the effect of interaction of Potassium Sparing Diuretics and ACE Inhibitors?

Back 39

Hyperkalaemia

Front 40

What are ARBs?

Back 40

Angiotensin II Receptor Blockers (ARBs); Angiotensin II Receptor Antagonists

Front 41

What are Angiotensin II Receptor Antagonists also known as?

Back 41

‘Sartans’, or ARBs

Front 42

What is the mechanism of action of Angiotensin II Receptor Antagonists?

Back 42

Competitive Antagonism of the Angiotensin AT1 Receptor

Front 43

What is the common suffix of ARBs?

Back 43

‘-sartan’, i.e. candesartan, irbesartan, eprosartan, telmisartan

Front 44

What are the advantages of ARBs over ACEIs?

Back 44

No Cough
Cleared by Hepatic Metabolism (ACEIs Renal)

Front 45

What are the contraindications for ARBs?

Back 45

Bilateral Renal Stenosis (GFR Maintained by Angiotensin II)

Pregnancy (Foetal Toxicity)

Hyperkalaemia (Reduced Aldosterone)

Note: Same as ACE Inhibitors

Front 46

Why were the β-Adrenoceptor Antagonists Developed?

Back 46

Reduce Rate and Force of Contraction in Angina

Front 47

Where are β1 Receptors Found? What is their purpose?

Back 47

Heart and Kidney; Increase Heart Rate (Chronotropic) & Force of Contraction (Inotropic)

Front 48

Where are β2 Receptors Found? What is their purpose?

Back 48

Lungs, Liver and Arterial SMC; Mediate Vasodilation and Bronchodilation

Front 49

Where are β3 Receptors Found? What is their purpose?

Back 49

Adipose Tissue; Mediate Lipolysis

Front 50

What is the mechanism of action of β-Adrenoceptor Antagonists?

Back 50

Unknown; but though to include:
Reduction of Cardiac Output
Inhibition of Renin Release
Reduced Sympathetic Activity

Front 51

Which type of β-Adrenoceptor Antagonist is preferable?

Back 51

‘Cardioselective’, i.e. atenolol, metoprolol, bisoprolol

Front 52

Which β-Adrenoceptor Antagonists have partial agonist activity?

Back 52

Oxprenolol and Pindolol

Front 53

Which β-Adrenoceptor Antagonists also have α1 antagonism?

Back 53

Carvedilol and Labetalol

Front 54

What is the effect of β-Adrenoceptor Antagonists with partial agonist activity?

Back 54

Increased Resting Heart Rate
Reduction with Exercise

Front 55

What is the effect of β-Adrenoceptor Antagonists that also have α1 antagonism?

Back 55

Vasodilation

Front 56

What are the indications for β-Adrenoceptor Antagonists?

Back 56

Myocardial Infarction
Hypertension with either Angina or Heart Failure

Front 57

Are β-Adrenoceptor Antagonists tolerated better or worse than other classes?

Back 57

Less Well-Tolerated

Front 58

What are the adverse effects of β-Adrenoceptor Antagonists?

Back 58

Cold Hands and Feet
Tiredness and Muscle Fatigue
Bad Dreams
Mask Sympathetic Reponses to Hypoglycaemia (Diabetes)

Front 59

What are the contraindications of β-Adrenoceptor Antagonists?

Back 59

Asthmatic and COPD Patients
Cardiac Depression
Intermittent Claudication
Raynaud’s Syndrome
Athletes and Physically Active Patients

Front 60

Why would you not use β-Adrenoceptor Antagonists in asthmatic and COPD patients?

Back 60

Non-Selective Blockers, i.e. propranolol, can lead bronchoconstriction

Cardioselective Blockers at higher doses decrease selectivity and have a similar effect

Front 61

What is a CCB?

Back 61

Calcium Channel Blocker

Front 62

What type of calcium channel do CCBs target?

Back 62

L-Type; Voltage-Gated Calcium (CaV1) Channels

Front 63

What can leads to increased calcium levels in the smooth muscle cell?

Back 63

Depolarisation of the Cell
Receptor Regulated Channel
Agonist Operated Channel

Front 64

What are the three types of CCBs?

Back 64

Dihydropyridines
Phenylalkylamines
Benzothiazepines

Front 65

What is the selectivity of dihydropyridines?

Back 65

Selective for CaV Channels in Smooth Muscle of Blood Cells

Front 66

What is the selectivity of phenylalkylamines?

Back 66

Cardioselective

Front 67

What is the selectivity of benzothiazepines?

Back 67

Non-Selective

Front 68

What is an example of a dihydropyridines?

Back 68

Amlodipine, Felodipine, Nifedipine

Front 69

What is an example of a phenylalkylamines?

Back 69

Verapamil

Front 70

What is an example of a benzothiazepines?

Back 70

Diltiazem

Front 71

What are dihydropyridines mainly used for?

Back 71

Antihypertensives

Front 72

What are phenylalkylamines mainly used for?

Back 72

Antiarrhythmics

Front 73

What are benzothiazepines mainly used for?

Back 73

Antianginal

Front 74

What is the difference of amlodipine and nifedipine?

Back 74

Amlodipine: Long Acting, Once Daily Dose
Nifedipine: Short Acting, Given as Slow Release

Front 75

What is the effect of administration of dihydropyridines?

Back 75

Selective Block of CaV Channels in Smooth Muscle of Blood Cells; leads to
Decreased Blood Pressure via Vasodilation (Decreases Peripheral Resistance)

Front 76

Which calcium channel blocker can cause reflex tachycardia? Why?

Back 76

Dihydropyridines; may affect the baroreceptor leading to sympathetic discharge

Front 77

What is the effect of administration of phenylalkylamines on HR and SV?

Back 77

Decreases both HR and SV

Front 78

What is the effect of administration of benzothiazepines on HR and SV?

Back 78

Little or No Change in Heart Rate

Front 79

Why are calcium channel blockers used to treat hypertension?

Back 79

High Compliance
No Renin Stimulation
Rarely Cause Postural Hypotension
Opposite Side Effects to β-Blockers (often used in combination)

Front 80

Why are calcium channel blockers often used in combination with β-Blockers?

Back 80

Side Effect Profile is Exact Opposite of β-Blockers

Front 81

What conditions are calcium channel blockers contraindicated in?

Back 81

Acute Myocardial Infarction
Heart Failure (high doses)
Bradycardia (esp. verapamil)

Front 82

Which drug is especially contraindicated in bradycardia?

Back 82

Verapamil; a phenylalkylamines

Front 83

What are the adverse drug reactions of calcium channel blockers?

Back 83

Flushing, Headache, and Ankle Oedema (Short Acting Dihydropyridines)
Bradycardia and Heart Block (Verapamil and Diltiazem)
Constipation (Verapamil)

Front 84

Which CCBs may cause flushing, headache, and ankle oedema? Why?

Back 84

Short Acting Dihydropyridines; Vasodilation

Front 85

Which CCBs may cause bradycardia, and heart block?

Back 85

Verapamil and Diltiazem

Front 86

Which CCB may cause constipation? Why?

Back 86

Verapamil; Effects on GIT Nerves and Smooth Muscle

Front 87

Which antihypertensive drug is used commonly in the first line treatment of mild-moderate hypertension in elderly patients?

Back 87

Thiazide Diuretics

Front 88

How are side effects avoided with thiazide diuretics?

Back 88

Low Doses

Front 89

What conditions benefit from use of thiazide diuretics?

Back 89

Reduction of Stroke
Reduction of Myocardial Infarction

Front 90

When should thiazide diuretics be administered? Why?

Back 90

Morning; Avoid Nocturnal Diuresis

Front 91

Which patients should be monitored when using thiazide diuretics?

Back 91

Patients with Gout, or History of Hypoglycaemia

Front 92

Where do thiazide diuretics act?

Back 92

Distal Convoluted Tubule on the Na+/Cl- Symporter

Front 93

Can the use of thiazides cause hypokalaemia? Why?

Back 93

Yes; Excess Na+ Exchanged in Collecting Tubule

Front 94

What is the effect of thiazide diuretic administration?

Back 94

Initial Decrease in Blood Pressure
Inhibition of Agonist-Induced Vasoconstriction via Calcium Desensitisation in SMCs

Front 95

What are the adverse drug reactions associated with thiazide diuretics?

Back 95

Gout (particular with high doses)
Hypokalaemia, Hyponatraemia; and
Impotence

Front 96

What conditions do not cause problems with normal doses of thiazide diuretics?

Back 96

Diabetes
Hypercholesterolemia

Front 97

What are the two types of direct-acting vasodilators?

Back 97

Hydralazine
Monoxidil

Front 98

What are the indications for direct-acting vasodilators?

Back 98

Resistant Forms and Emergencies

Front 99

What is the major limitation of direct-acting vasodilators?

Back 99

Reflex Tachycardia

Front 100

Where does hydralazine act?

Back 100

Mainly on the Arterioles

Front 101

What is the mechanism of action of hydralazine?

Back 101

Inhibition of Ca2+ release from the SR

Front 102

What is the effect of hydralazine?

Back 102

Reduction of Blood Pressure and Peripheral Resistance but Produces Fluid Retention

Front 103

Why would hydralazine be administered with a β-Blocker?

Back 103

In response to the reduction in peripheral resistance, both tachycardia and increased cardiac output may develop as a reflex response.

Front 104

How is hydralazine administered?

Back 104

Slow IV Injection in Hypertensive Crisis

Front 105

Where does minoxidil act?

Back 105

Mainly on the Arterioles

Front 106

What is the mechanism of action of minoxidil?

Back 106

Hyperpolarisation of Cell; by
Opening K+ATP Channels; and
Closure of CaV Channels

Front 107

What can be administered with minoxidil to reduce salt and water retention?

Back 107

Loop Diuretic

Front 108

What can be administered with minoxidil to reduce risk of reflex tachycardia?

Back 108

β-Blocker

Front 109

How is minoxidil administered?

Back 109

Oral Administration

Front 110

What are the indications for minoxidil?

Back 110

Severe Hypertension Unresponsive to Standard Therapy

Front 111

What is minoxidil also used for, other than severe hypertension?

Back 111

Topical Administration for Male-Pattern Baldness (Alopecia Androgenetica)

Front 112

What are examples of α-Adrenoceptor Antagonists?

Back 112

Doxazosin and Prazosin

Front 113

Which receptor do α-Adrenoceptor Antagonists act on?

Back 113

α1-Adrenoceptor

Front 114

What is the mechanism of action of α-Adrenoceptor Antagonists?

Back 114

α1-Adrenoceptor Antagonism; leads to
Inhibition of Vascular Smooth Muscle Contraction in Arteries; causing
Vasodilation and Decreases Blood Pressure

Front 115

Are α-Adrenoceptor Antagonists indicated as an initial therapy?

Back 115

No

Front 116

What condition can be treated simultaneously with hypertension by doxazosin?

Back 116

Benign Prostatic Hypertrophy

Front 117

What are the adverse drug reactions of α-Adrenoceptor Antagonists?

Back 117

First Dose Hypotension
Orthostatic Hypotension (Dizziness)
Dry Mouth (α1 causes increased salivary secretion)
Headache

Front 118

What are the three types of centrally acting agents for hypertension?

Back 118

Methyldopa
Clonidine
Moxonidine

Front 119

What is the main indication for methyldopa in hypertension?

Back 119

Hypertension of Pregnancy

Front 120

What is the mechanism of action of methyldopa?

Back 120

Decarboxylation in the CNS to α-methylnoradrenaline, which is thought to stimulate α2 adrenoceptors resulting in a reduction in sympathetic tone and a fall in blood pressure;
It may also have a role as a false neurotransmitter, and have some inhibitory actions on plasma renin activity.

Front 121

What are the adverse drug reactions of methyldopa?

Back 121

Sedation and Drowsiness
Dry Mouth and Nasal Congestion
Orthostatic Hypertension

Front 122

What is the main indication for clonidine in hypertension?

Back 122

Used in Hypertension due to Head Trauma, or Headache

Front 123

How is clonidine administered in hypertension?

Back 123

IV Injection

Front 124

What is the mechanism of action of clonidine?

Back 124

Stimulates the α2 Adrenoceptors; and
Central Imidazoline Receptors; leading to
Reduced Sympathetic Tone

Front 125

What is the mechanism of action of moxonidine?

Back 125

Stimulates the Central Imidazoline Receptors; leading to Reduced Sympathetic Tone

Front 126

How is moxonidine administered in hypertension? How Often?

Back 126

Oral Administration; Once Daily

Front 127

What is the advantage of use of moxonidine compared to clonidine?

Back 127

Less Drowsiness

Front 128

What are the drugs of choice for ‘young’ individuals (< 55 years)

Back 128

ACE Inhibitors; or
AT1 Receptor Blockers

Front 129

What are the drugs of choice for ‘elderly’ individuals (> 55 years)

Back 129

CCB (amlodipine); or
Diuretics (thiazide)

Front 130

What are the major reasons for the development of resistant hypertension?

Back 130

Compliance Failure
Renovascular Disease
Conn’s Syndrome
White Coat Hypertension

Front 131

What are HMG-CoA Reductase Inhibitors also known as?

Back 131

‘Statins’

Front 132

When are ‘statins’ recommended in hypertension?

Back 132

‘High Risk’ Hypertensive Patients

Front 133

What constitutes a ‘high risk’ hypertensive patient?

Back 133

Established Atherosclerotic Disease; or
At Least 3 of the Certain Criteria (i.e. male, > 55 years, smoker, T2D, family history, etc)

Front 134

What can induce/aggravate hypertension?

Back 134

Prescription Drugs: i.e. NSAIDs, Corticosteroids, EPO, MAOIs
Others: Excessive Liquorice, Stimulants, Excessive Salt or Alcohol Use, Sleep Apnoea