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Flashcards in CVS Deck (261):
1

How does the sympathetic nervous system regulate cardiac function?

At the SA node, NA binds B1 to increase pacemaker current
At the AV node, NA binds B1 to increase calcium current and hence conduction velocity

2

How does the parasympathetic nervous system regulate cardiac function?

At the SA node, ACh binds M receptors to slow depolarisation by opening potassium channels and inhibiting sodium channels form opening
At the AV node, ACh binds M receptors to decrease conduction velocity

3

Summarise the effect the SNS and PNS has on cardiac function.

SNS - increase pacemaker current and conduction velocity

PNS - slows depolarisation and decreases conduction velocity

4

What changes occur with increased BP?

Baroreceptors activate PNS to inhibit SA firing rate, inhibiting SNS from inducing vasoconstriction

5

What changes occur with decreased BP?

Baroreceptors activate SNS to increase SA firing rate, increase vasoconstriction, increase venous return and increase cardiac output (hence increasing BP)

6

What are the 3 types of heart failure?

Acute left ventricular failure
Cardiogenic shock
Chronic heart failure

7

Describe acute left ventricular failure

Where there is inadequate output leading to pulmonary oedema, reflex contraction (which increases venous return hence exacerbating the issue)

8

What is the treatment goal for acute left ventricular failure and what treatments are used to achieve this goal?

To reduce venous return using loop diuretics, GTN, and opioids

9

Describe cardiogenic shock

Where there is sudden impairment to left ventricular systole, impairing organ perfusion

10

What is the treatment goal for cardiogenic shock and what treatments are used to achieve this goal?

Resuscitation, dobutamine to increase tissue perfusion

11

Describe chronic heart failure

Where there is myocardium disease due to excess load because of e.g. IHD, valve dysfunction, HTN

12

What is the treatment goal for chronic heart failure and what treatments are used to achieve this goal?

Reduce compensatory mechanisms and increase CO using ACEI, diuretics, beta-blockers and digoxin

13

Outline the mechanism of cardiac contraction

Action potential arrives at sodium channel, opening the channel and allowing sodium influx. This causes further membrane depolarisation, opening calcium channels and causing calcium influx. The increased calcium concentration inside the cytoplasm causes calcium-induced calcium release from the SR, causing myofibre contraction.

14

Describe the mechanism of action of digoxin

Inhibits Na+/K+ ATPase, causing less sodium to leave the cell, ultimately slowing down the Na+/Ca2+ exchanger, causing the concentration of calcium inside the cell to remain high, allowing more calcium to enter the SR causing a stronger contraction next time (increasing contractility)

15

Describe the mechanism of action of dobutamine

Beta-1 agonist, activates ACy, increasing the concentration of cAMP, activating PKA causing calcium channels to open, increasing contractility, and stimulating the calcium pump to allow more calcium to enter the SR. Also inhibits Na+/K+ ATPase, increasing concentration of calcium in the cell, increasing contractility.

16

Describe the mechanism of action of enoximone

PDE inhibitor, increases concentration of cAMP, activating PKA, causing calcium channels to open and increasing contractility, allowing more calcium to enter the SR, and inhibiting the Na+/K+ ATPase, increasing the concentration of calcium inside the cell, increasing contractility

17

What class of drug is digoxin?

Cardiac glycoside

18

How does digoxin cause arrhythmia?

More calcium in the cell, more calcium-induced calcium release, more spontaneous contraction

19

What are the indications for digoxin?

Symptomatic relief in heart failure
Supraventricular arrhythmia

20

Describe the PK of digoxin

Fp.o. ~75%
T1/2 ~40h
Vd ~640L/70kg (binds Na+/K+ ATPase in skeletal muscle)
Eliminated through p-GP

21

Describe the ADRs of digoxin

Arrhythmia, nausea, vomiting, fatigue, confusion, impaired coloured vision

22

What are the cautions for digoxin?

Hypokalaemia (digoxin binds with more affinity in the absence of potassium)
Hypothyroidism (reduced GFR -> increased toxicity)
Elderly (reduced GFR)

23

What are the contraindications to the use of digoxin?

Heart block, as digoxin inhibits AV node conduction

24

What interactions are associated with digoxin?

Diuretics (hypokalaemia)
Verapamil, quinidine, amiodarone (displace digoxin from tissue binding sites -> reduced Vd)
Antibiotics (increase Fp.o)
Beta-blockers (inhibit AV conduction and decrease contractility)
CCBs (decrease contractility)
p-GP inhibitors (reduce elimination)

25

Describe the two forms of IHD and give example of each

Chronic arterial disease e.g. stable angina
Acute coronary syndromes e.g. unstable angina, NSTEMI and STEMI

26

Describe how stable angina occurs

Where there is partial vessel block.
Exertion causes the oxygen demand to exceed the supply due to the reduced blood flow, resulting in chest pain radiating to arm and jaw, however this pain resolves on rest

27

Describe how unstable angina occurs

Where the plaque ruptures, causing platelet aggregation and thrombus formation hence blocking the vessel further. This results with pain at rest

28

Describe how an NSTEMI occurs

Coronary artery still not fully blocked so some tissue perfusion remains. This results in a small area of tissue death
(NSTEMI = non-ST elevated myocardial infarction)

29

Describe how a STEMI occurs

Where there is complete occlusion leading to a large area of tissue death
(STEMI = ST-elevated myocardial infarction)

30

Describe the mechanism of action of organic nitrates

NO activates guanylate cyclase, increasing the concentration of cGMP, activating PKG, resulting in vasodilation

31

What are the indications of organic nitrates?

Angina
Left ventricular failure

32

Describe the PK of organic nitrates

Glyceryl trinitrate - t1/2 ~5mins, sublingual, buccal, transdermal, i.v.
Isosorbide mononitrate - slower onset, low first pass metabolism, t1/2 ~ 5h
Isosorbide dinitrate - extensive first pass metabolism to mononitrate (active)

33

What are the ADRs of nitrates?

Dizziness, headache, flushing, tolerance

34

What interactions are associated with nitrates?

Diuretics
Hypotensive drugs
Drugs affecting CO
Drugs causing vasodilation
PDE inhibitors
Heparin

35

What cautions are associated with nitrates?

Pregnancy (affects placental blood flow)

36

What are the contraindications of nitrates?

Hypotension
Hypovolaemia
Hypersensitivity

37

What is the mechanism of action of beta-blockers?

Block beta2-receptor, increasing the concentration of cAMP, block the phosphorylation of MLCK, causing vasodilation

38

What are the indications for beta-blockers?

Prophylactic treatment of stable angina, HTN, MI, arrhythmia, HF, anxiety

39

Describe the ADRs of beta-blockers

Bronchoconstriction, bradycardia, reduced cardiac contractility, erectile dysfunction, sleep disturbances

40

Describe the cautions associated with beta-blockers

Pregnancy, avoid suddenly stopping therapy, can mask signs of hypoglycaemia, diabetes

41

What are the contraindications associated with beta-blockers?

Asthma, heart block, uncontrolled HF, bradycardia, hypotension, prolong QT(sotalol)

42

What interactions are associated with beta-blockers?

Verapamil (asystole)
Reduced renal/hepatic perfusion

43

Describe the mechanism of action of the dihydropyridines

Have only vascular effects:
Arteriolar dilation - lower resistance, lower workload, lower oxygen demand
Coronary artery dilation - reduced vasospasm, improved oxygen supply

44

Describe the mechanism of action of verapamil and diltiazem

Vascular and cardiac effects:
Arteriolar dilation - lower resistance, workloads and oxygen demand
Coronary artery dilation - reduced vasospasm and improved oxygen supply
Reduced rate and cardiac contractility: lower workload and lower oxygen demand

45

What are the indications for dihydropyridines?

HTN
Stable angina prophylaxis

46

What ADRs are associated with the dihydropyridines?

Flushing, headache, oedema, reflex tachycardia, increased contractility

47

What cautions are associated with the dihydropyridines?

HF (amlodipine and felodipine preferred)
Pregnancy

48

What contraindications are associated with the use of dihydropyridines?

Breast feeding, unstable angina, 1 month after MI

49

What interactions are associated with the use of dihydropyridines?

Drugs that cause hypotension
Grapefruit juice
Ciclosporin and digoxin (inhibit renal secretion by p-GP)

50

What are the indications for use of diltiazem?

HTN
Stable angina prophylaxis

51

What ADRs are associated with diltiazem?

Bradycardia (inhibits AV node conduction)
Teratogenic

52

What cautions surround the use of diltiazem?

Hepatic and renal failure

53

What are the contraindications for the use of diltiazem?

Breast feeding
Pregnancy
HF
AV block

54

What interactions are associated with diltiazem?

Hypotensive drugs
Beta-blockers (asystole)
Propranolol
Ciclosporin (inhibits CYP3A4 metabolism)
Digoxin (inhibits renal secretion by p-GP)

55

What are the indications for use of verapamil?

Supraventricular tachycardia
HTN, stable angina prophylaxis

56

What ADRs are associated with verapamil?

Bradycardia
Hypotension
Constipation

57

What cautions surround the use of verapamil?

Hepatic impairment

58

What are the contraindications for the use of verapamil?

Breastfeeding
Pregnancy
HF
AV block

59

What interactions are associated with the use of verapamil?

Hypotensive drugs
Beta-blockers
Ciclosporin and digoxin
Grapefruit juice

60

What class of drug is nicorandil?

Potassium channel opener

61

What are the indications for nicorandil?

Stable angina
Nitrate tolerance (its an NO donor)

62

What ADRs are associated with nicorandil?

Headache, flushing, reflex tachycardia

63

What caution are associated with the use of nicorandil?

Hypovolaemia

64

What are the contraindications for the use of nicorandil?

Cardiogenic shock, hypotension

65

What interactions are associated with the use of nicorandil?

Sildenafil (slower turnover of cGMP -> hypotension)

66

What is the mechanism of action of nicorandil?

Open potassium channels causing hyperpolarisation of calcium channels thus closing them, decreasing concentration of calcium in the cell, leading to vasodilation

67

Describe the mechanism of action of loop diuretics

Inhibit NKCC2, inhibiting sodium and water reabsorption

68

What are the indications for loop diuretics?

Oedema, HTN, hypercalcaemia, hyperkalaemia, hyponatraemia

69

Describe the PK of loop diuretics

Furosemide t1/2~1h
Bumetanide t1/2~1.5h
Torasemide t1/2~3h
Highly protein bound
Secreted into proximal tubule

70

What ADRs are associated with loop diuretics?

Hypokalaemia, sulpha allergy, hypotension, hypocalcaemia, hypomagnesaemia, hyperuricaemia and gout, ototoxicity

71

What cautions are associated with the use of loop diuretics?

Gout
Diabetes

72

What are the contraindications for use of loop diuretics?

Hypokalaemia, hypovolaemia, pregnancy

73

What interactions are associated with loop diuretics?

Aminoglycoside antibiotics (ototoxicity)
Cardiac glycosides (arrhythmia)
NSAIDs
Lithium

74

Describe the mechanism of action of thiazides and thiazide-like diuretics

Inhibit NCC1, inhibiting Sodium and water reabsorption

75

What are the indications for use of thiazides?

Mild oedema, HTN, diabetes insipidus

76

Describe the PK of thiazides

Bendroflumethazide t1/2~6h
Indapamide t1/2~16h
Metolazone t1/2~4h
Plasma protein bound

77

Which thiazide/thiazide-like diuretic is preferred in advanced renal failure?

Metolazone

78

What ADRs are associated with the use of thiazides?

Hypokalaemia, nocturia, hypotension, hyponatraemia, hypomagnesaemia, decreased calcium excretion, impotence

79

What can hypokalaemia lead to?

Arrhythmia, encephalopathy, diabetes mellitus, fatigue and lethargy

80

How is hypokalaemia treated?

Potassium sparing diuretics
Potassium supplement
Diet - bananas

81

What cautions are associated with he use of thiazides?

Gout
Diabetes

82

What interactions are associated with thiazides?

Sulfonylureas
Antiarrhythmic agents that prolong QT
Cardiac glycosides
NSAIDs

83

Describe the mechanism of action of potassium sparing diuretics

Amiloride - inhibit ENaC, inhibiting sodium and water reabsorption

Spironolactone and eplerenone - block aldosterone receptor, inhibiting the expression of ENaC

84

What are the indications for the use of potassium sparing diuretics?

Conserving potassium
Concomitant digoxin therapy
Secondary hyperaldosteronism
Elderly

85

What ADRs are associated with potassium sparing diuretics?

Hyperkalaemia
Metabolic acidosis
Spironolactone - impotence, gynaecomastia, menstrual cycle irregularities

86

What interactions are associated with potassium sparing diuretics?

NSAIDs (impair renal function and cause hyperkalaemia)

87

Describe the mechanism of action of alpha-blockers

Block alpha-1 receptor, inhibiting activation of Gq, inhibiting vasoconstriction
Relax arteriolar resistance vessels and dilate venous capacitance

88

What class of drug is doxazosin?

Alpha-blocker

89

What are the indications for the use of alpha-blockers?

HTN
BPH

90

What ADRs are associated with alpha-blockers?

Postural hypotension
Reflex tachycardia (palpitations)
Lethargy
Dizziness
Headache

91

What cautions are associated with the use of alpha-blockers?

Pregnancy
HF

92

What are the contraindications for the use of alpha-blockers?

Incontinence

93

What interactions are associated with alpha-blockers?

Diuretics and beta-blockers (potentiate hypotensive effect)

94

Describe the mechanism of action of alpha-agonists

Activate alpha-2 receptor, inhibiting sympathetic output from CNA by inhibiting NA release, inhibiting vasoconstriction

95

What is the mechanism of action of ACE inhibitors?

Prevent conversion of angiotensin I to angiotensin II by inhibiting Angiotensin Converting Enzyme (ACE)
Inhibits vasoconstriction and aldosterone release caused by angiotensin II and reduces metabolism of bradykinin

96

What are the indications for the use of ACEIs?

HTN, HF, MI, diabetic nephropathy

97

What ADRs are associated with the use of ACEIs?

Hypotension, hyperkalaemia, persistent dry cough, rash

98

What cautions are associated with the use of ACEIs?

Hepatic insufficiency

99

What contraindications are associated with the use of ACEIs?

Reduced renal perfusion
Pregnancy

100

What interactions are associated with ACEIs?

Hypotensive drugs
Potassium sparing diuretics (hyperkalaemia)
NSAIDs (reduced GFR)

101

What is the mechanism of action of ARBs?

Block Angiotensin 1 receptor (AT1), blocking angiotensin 2 from causing vasoconstriction

102

What are the indications for use of ARBs?

HTN
Prevention of diabetic nephropathy

103

What ADRs are associated with ARBs?

Headache, dizziness, fatigue

104

What cautions are associated with the use of ARBs?

Renal insufficiency

105

What are the contraindications for the use of ARBs?

Pregnancy

106

What interactions are associated with ARBs?

Hypotensive drugs
Potassium sparing diuretics (hyperkalaemia)
NSAIDs

107

What are the 3 classes of arrhythmia?

Supraventricular
Ventricular
Heart block

108

Describe supraventricular arrhythmias

Where the origin is in the SA, AV nodes or atria
Can result in sinus tachycardia/bradycardia (due to altered SA firing), AT (due to an alternative SA pacemaker), atrial flutter, AF (due to re-entry impulses in the atrium)

109

Describe ventricular arrhythmias

Origin in ventricles
VT, VF (due to re-entry impulses)

110

What are the treatment goals for arrhythmias?

Restore normal cardiac rhythm
Prevent recurrence of arrhythmia
Prevent more severe arrhythmia
Deal with haemodynamic consequences

111

What are the general actions of anti-arrhythmic drugs?

Alter the baseline/threshold potential in SA cells
Alter the rate of phase 4 repolarisation
Alter the baseline/threshold potential in contractile cells
Alter the duration of action potential (by altering the refractory period)

112

Give an example of a class Ia anti-arrhythmic

Disopyramide

113

Describe the mechanism of action of class Ia anti-arrhythmics

Block sodium channels thus slowing phase 0 and decreasing conduction velocity
Block potassium channels thus prolonging repolarisation and increasing the refractory period
Block parasympathetic inhibition of AV node

114

What are the indications of Class Ia anti-arrhythmics?

VT following MI

115

What ADRs are associated with class Ia anti-arrhythmics?

Negative inotrope
Dry mouth, urinary retention, blurred vision, constipation

116

What cautions surround the class Ia anti-arrhythmics?

Pregnancy

117

What are the contraindications for the use of disopyramide?

HF

118

What interactions are associated with disopyramide?

Prolong QT (sotalol etc.)
Negative inotrope (beta-blockers etc.)

119

Give an example of a class Ib anti-arrhythmic

Lidocaine

120

What are the indications for the use of lidocaine?

VT, local anaesthesia

121

What ADRs are associated with lidocaine?

Nausea, vomiting, drowsiness, convulsions

122

What is the mechanism of action of lidocaine?

Block open and refractory sodium channels, shortening the action potential

123

What cautions are associated with the use of lidocaine?

Hepatic impairment, HF

124

What are the contraindications for the use of lidocaine?

AV block

125

What interactions are associated with the use of lidocaine?

Diuretics (hypokalaemia predisposes to arrhythmia)

126

Give an example of a class Ic anti-arrhythmic

Flecainide

127

What is the mechanism of action of felcaininde?

Sodium channel blocker, slows conduction in all cardiac tissue, suppresses premature ventricular contraction and increases PR and QRS intervals

128

What are the indications for the use of flecainide?

AF and AT

129

What ADRs are associated with the use of flecainide?

Negative inotrope, lightheadedness, arrhythmia

130

What cautions are associated with the use of flecainide?

Heart block
Pregnancy
Hepatic insufficiency

131

What are the contraindications for the use of flecainide?

HF, previous MI

132

What interactions are associated with flecainide?

Diuretics (risk of arrhythmia due to hypokalaemia)
Amiodarone
Fluoxetine
Negative inotropes

133

Give an example of a class II anti-arrhythmic

Atenolol

134

What is the mechanism of action of class II anti-arrhythmics?

Block beta-receptors, inhibit pacemaker and slows pacemaker current, prolong repolarisation

135

What are the indications for the use of class II anti-arrhythmics?

Supraventricular arrhythmia e.g. AF

136

Give an example of a class III anti-arrhythmic

Amiodarone

137

Describe the mechanism of action of amiodarone

Blocks potassium channels to prolong repolarisation, increases refractory period (reduced re-entry)

138

What are the indications for the use of amiodarone?

Arrhythmia

139

What cautions surround the use of amiodarone?

Bolus i.v. In HF

140

What are the contraindications for the use of amiodarone?

Bradycardia
Heart block
Iodine sensitivity
Pregnancy
Breastfeeding

141

What ADRs are associated with the use of amiodarone?

Pulmonary fibrosis, visual halo (deposits of lipofuscin of cornea), sensitivity to sunlight, grey skin discolouration, hyperthyroidism

142

What interactions are associated with amiodarone?

CYP3A4 substrate, inhibits metabolism of warfarin
Inhibits renal excretion of digoxin by p-GP
Prolong QT

143

Give an example of a class IV anti-arrhythmic

Verapamil/diltiazem

144

Describe the mechanism of action of class IV anti-arrhythmics

CCBs, slows SA rate, slows phase 0 in AV node

145

What type of arrhythmia are CCBs used to treat?

Re-entrant, e.g. supraventricular tachycardia, that involve the AV node

146

Describe the structure of lipoproteins

Hydrophobic core consisting of cholesterol and TAG
Surface monolayer of phospholipid
Apolipoprotein on surface

147

Outline the transport of lipids

Lipids get broken down into triglycerides and cholesterol and combine with bile to make a micelle, which then gets packaged into chylomicrons containing ApoB48 protein on the surface. They also obtain an ApoCII protein from HDL which is a ligand for lipoprotein lipase, which breaks down 50% into free fatty acids that go to the muscle. The other 50% is present as a remnant that exchanges its ApoCII for ApoE from HDL, allowing VLDL to be taken up into the liver by LDL-R. LDL containing ApoB100 becomes oxidised LDL in blood vessels leading to atherosclerosis.

148

What are the three different types of hyperlipidaemia?

Hypercholesterolaemia
Hypertriglyceridaemia
Mixed hyperlipidaemia

149

Describe the mechanism of action of statins

Inhibit HMG CoA Reductase, prevent synthesis of cholesterol so concentration of cholesterol decreases, switching on SREBP, which up-regulates the LDL-R, increasing LDL uptake thus decreasing plasma cholesterol concentration

150

What are the indications for use of statins?

Occlusive arterial disorders
Coronary heart disease
Patients at risk of atherosclerosis even if asymptomatic (diabetics >40, FH)

151

Describe the metabolism of statins

CYP3A4 - simvastatin and atorvastatin
CYP2C9 - fluvastatin
Renal - pravastatin and rosuvastatin

152

What ADRs are associated with statins?

Myopathy progressing to rhabdomyolysis

153

What cautions surround the use of statins?

Risk of myopathy (risk increased by renal insufficiency, co-treatment with fibrates or ciclosporin)

154

What are the contraindications for the use of statins?

Liver disease
Pregnancy
Breastfeeding

155

What interactions are associated with the use of statins?

Warfarin
CYPs
Fibrates

156

Describe the mechanism of action of bile acid binding resins

Decrease reabsorption of bile, increased bile synthesis, reduced liver cholesterol, switched on SREBP, increased expression of LDL-R, reduced plasma cholesterol

157

Give an example of a bile acid binding resin

Cholestyramine and colestipol

158

What are the indications for the use of bile acid binding resins?

Patients in which statins are insufficient on own or contraindicated

159

What ADRs are associated with bile acid binding resins?

Constipation, bloating, flatulence

160

What cautions surround the use of bile acid binding resins?

May also bind vitamin A, D, and K thus supplements Amy be necessary
May also bind drugs e.g. warfarin, digoxin, statins, thiazides, aspirin, so give other drug 1h before or 4h after the resin

161

What is the mechanism of action of ezetimibe?

Inhibit NPC1L1 to inhibit transport of cholesterol across the intestinal brush border, decreasing the concentration of cholesterol in chylomicrons, the liver, VLDL and LDL, thus switching on SREBP, up regulating the LDL-R and reducing plasma cholesterol

162

What are the indications of ezetimibe?

Hypercholesterolaemia
Used with statin or on own if statin now appropriate

163

What cautions surround the use of ezetimibe?

Hepatic impairment

164

What are the contraindications for the use of ezetimibe?

Breastfeeding

165

What ADRs are associated with ezetimibe?

Diarrhoea, abdominal pain

166

What interactions are associated with ezetimibe?

Fibrates

167

Describe the mechanism of action of fibrates

Activate PPAR-alpha, decrease plasma triglyceride by increasing lipoprotein lipase, fatty acid uptake and oxidation, and increase HDL, increasing LDL clearance

168

Give an example of a fibrate

Bezafibrate

169

What are the indications for the use of fibrates?

Hypercholesterolaemia where statin unsuccessful or inappropriate
Hypertriglyceridaemia

170

What cautions surround the use of fibrates?

Myotoxicity especially in patients with renal disease
Displaces warfarin from plasma proteins

171

What are the contraindications for the use of fibrates?

Hepatic and renal impairment
Pregnancy
Breastfeeding

172

What ADRs are associated with fibrates?

Nausea, abdominal discomfort, anorexia, myopathy

173

What interactions are associated with fibrates?

Statins
Warfarin
Ezetimibe

174

Give an example of a PCSK9 inhibitor

Alirocumab and evolucumab

175

What is the mechanism of action of PCSK9 inhibitors?

Inhibit PCSK9 which increases the number of LDL-Rs thus promoting LDL clearance

176

Describe the mechanism of action of nicotinic acid

Precursor of NADP
Increases HDL
Decreases lipolysis in adipose tissue, decreased flux of FFA to liver, reduced production of VLDL thus decreases LDL and triglycerides

177

What is the indication for use of nicotinic acid?

Hyperlipidaemia with statin or if statin not tolerated
Hypertriglyceridaemia

178

What ADRs are associated with nicotinic acid?

Flushing and pruritus (PG release and vasodilation - treat with aspirin)
Diarrhoea, nausea, vomiting
Hyperuricaemia (inhibits uric acid secretion -> may cause gout))
Reduced insulin sensitivity (may cause diabetes)

179

What cautions are associated with the use of nicotinic acid?

Unstable angina
MI
Diabetes
Gout

180

What are the contraindications for the use of nicotinic acid?

Arterial bleeding
Peptic ulcer disease
Breast feeding

181

What are the three causes of thrombosis?

Endothelial injury
Abnormal blood flow
Hypercoagulability

182

Describe an arterial thrombosis

More platelet rich
Can result in a stroke or MI
Risk factors include smoking, diabetes, BP, weight and cholesterol
Treatment involves reducing risk factors and the use of antiplatelet drugs

183

Describe a venous thrombosis

More fibrin rich
Can result in a DVT or PE
Risk factors include genetic predisposition and slow blood flow
Treatment involves anticoagulants

184

Describe the mechanism of action of aspirin

Inhibits COX1 by acetylation, inhibiting PG synthesis in platelets which inhibits TxA2 synthesis, inhibiting aggregation

185

What are the indications for the use of aspirin?

Primary and secondary prevention of thromboembolism in atherosclerotic disease: angina, MI, stroke, peripheral vascular disease
Analgesia, anti-inflammatory for rheumatoid arthritis

186

What ADRs are associated with aspirin?

Haemorrhage
Hypersensitivity

187

What are the cautions and contraindications for aspirin?

Risk of bleeding
Asthma
Renal insufficiency

188

What interactions are associated with aspirin?

Anticoagulants
Antiplatelets
NSAIDs
Diuretics (antagonise effect)

189

Give an example of a PDE inhibitor

Dipyridamole

190

What is the mechanism of action of dipyridamole?

PDE inhibitor, promotes activation of PKA which inhibit platelet activation
Inhibits reuptake of adenosine into platelets

191

What are the indications for use of dipyridamole?

Prevention of embolism from prosthetic heart valve with warfarin
Prevention of vessel block in patients with ischaemic stroke with aspirin

192

What ADRs are associated with dipyridamole?

Bleeding, headache, diarrhoea, facial flushing

193

What cautions surround the use of dipyridamole?

Risk of bleeding

194

What interactions are associated with dipyridamole?

Anticoagulants

195

Give an example of an ADP receptor antagonist

Clopidogrel

196

What is the mechanism of action of clopidogrel?

Inhibits P2Y which inhibits the inhibition of ACy, increasing the concentration of cAMP, activating PKA which inhibits GP-IIbIIIa, inhibiting platelet activation

197

What ADRs are associated with clopidogrel?

Haemorrhage
Abdominal pain
Nausea

198

What cautions surround the use of clopidogrel?

Risk of bleeding

199

What are the contraindications for the use of clopidogrel?

Active bleeding
Breastfeeding

200

What interactions are associated with clopidogrel?

Aspirin
Antiplatelets
Warfarin

201

Give an example of a GP-IIbIIIa antagonist

Eptifibatide, abciximab, tirofiban

202

What is the mechanism of action of GP-IIbIIIa antagonists?

Inhibit end-point of platelet aggregation

203

What ADRs are associated with GP-IIbIIIa antagonists?

Haemorrhage

204

What cautions surround the use of GP-IIbIIIa antagonists?

Risk of bleeding or active bleeding

205

What are the contraindications for the use of GP-IIbIIIa antagonists?

Recent abnormal bleeding or stroke

206

What is the mechanism of action of heparin?

Inhibit clotting factors IX, Xa, XIa, XIIa and thrombin by catalysing irreversible binding of anti-thrombin III

207

What ADRs are associated with heparin?

Haemorrhage
Thrombocytopenia

208

What are the contraindications for the use of heparin?

Haemophilia
Thrombocytopenia
Severe hepatic disease

209

What interactions are associated with heparin?

Increase risk of bleeding
NSAIDs

210

What is the mechanism of action of warfarin?

Inhibit vitamin K reductase, preventing reduction of vitamin K which prevents the carboxylation of clotting factors, preventing clot formation

211

What ADRs are associated with warfarin?

Haemorrhage

212

What are the contraindications for the use of warfarin?

Pregnancy
Peptic ulcer

213

What interactions are associated with warfarin?

NSAIDs (displace from plasma proteins)
Antibiotics
CYP2C9 (inhibitors - amiodarone, cimetidine, clopidogrel, fluconazole, fluoxetine, inducers-barbiturates, carbamazepine, phenytoin, alcohol)

214

Give an example of a thrombin inhibitor

Dabigatran

215

What is the mechanism of action of dabigatran?

Thrombin inhibitor

216

What ADRs are associated with the use of dabigatran?

Bleeding

217

What cautions surround the use of dabigatran?

Assess renal function before use and annually

218

What are the contraindications for the use of dabigatran?

Active bleeding/risk of bleeding

219

What interactions are associated with dabigatran?

Anticoagulants

220

Give and example of a factor Xa inhibitor

Rivaroxaban

221

What ADRs are associated with rivaroxaban?

Bleeding

222

What cautions surround the use of rivaroxaban?

Renal impairment
Risk of bleeding

223

What are the contraindications for the use of rivaroxaban?

Active bleeding

224

What interactions are associated with rivaroxaban?

Anticoagulants

225

Name the 4 different fibrinolytic agents

Late please
Relteplase
Tenecteplase
Streptokinase

226

What ADRs are associated with fibrinolytic agents?

Haemorrhage
Streptokinase generates bradykinin => hypotension
Allergy to streptokinase

227

What are the contraindications for the use of fibrinolytic agents?

Previously received streptokinase

228

Define normal BP

90-120/60-80mmHg

229

Define the two classifications of HTN

Primary (essential) - no know identifiable cause
Secondary - underlying cause known

230

What is essential HTN associated with?

Stress response, race, age, heredity, socioeconomic background

231

What can secondary HTN be caused by?

Renal disease, endocrine disease, vascular disease, pregnancy, drugs

232

Outline the pathophysiology of HTN

Arterial BP -CO+TPR
Increased HR/stroke volume = increased CO (also increased by SNS)
Vasoconstriction (arteriosclerosis, atherosclerosis, increased blood viscosity) = increased TPR (decreased by PNS)

233

A patient has a clinic BP of >140/90 and an ABPM of over 135/85, what stage of HTN do they have?

Stage 1

234

A patient has a clinic BP >160/100 and an ABPM of over 150/95, what stage of HTN do they have?

Stage 2

235

A patient’s SBP is >180 and DBP is>110, what stage of HTN do they have?

Severe (stage 3)

236

What are the long-term consequences of HTN?

ESKD, CVD, arteriosclerosis, retinopathy, stroke

237

What is first line treatment for a patient over 40 years old with stage 1 HTN and no other risk factors?

Lifestyle interventions including weight loss, healthy diet, increasing exercise, reducing salt, smoking cessation, decreasing alcohol, decreasing caffeine

238

What is first line treatment for someone who is under 80, with stage 1 HTN and renal disease?

Antihypertensives

239

What are the risk factors that mean someone gets offered antihypertensives first-line?

Target organ damage
Established CVD
Renal disease
Diabetes
10y CVD risk of ≥20%
Stage 2 HTN

240

What is the BP target for someone under 80?

140/90

241

What is the BP target for someone over 80?

150/90

242

What is the BP target for someone with diabetes?

140/80

243

What is the BP target for someone with diabetes and retinopathy/nephropathy/neuropathy?

130/80

244

Define gestational HTN

New HTN occurring after 20 weeks gestational age without significant proteinuria

245

Define pre-eclampsia

Gestational HTN with significant proteinuria

246

What are the symptoms of pre-eclampsia?

Severe headaches, visual disturbances, new epigastric pain (persistent), nausea, vomiting, sudden swelling of face and extremities

247

What is HTN in pregnancy defined as being?

Single DBP reading of ≥90mmHg on two or more occasions more than 4h apart AND/OR a single DBP reading of >110mmHg

248

What is first line treatment for someone with type 1 diabetes and a BP reading of ≥135/85mmHg?

Antihypertensives

249

What is the threshold BP for starting antihypertensives in someone with type 1 diabetes and albuminuria and 2 or more features of metabolic syndrome (obesity, insulin resistance, tiredness)?

≥130/80mmHg

250

What are the BP reading for someone with postural hypotension?

Lying/sitting = 120/76mmHg
Standing = 97/60mmHg

251

Define heart failure

A failure to meet normal perfusion demands of the body or where perfusion needs can only be met by an elevated filling pressure

252

Describe the compensatory mechanisms that kick in when the heart fails as a pump

RAAS - sodium and water retention and vasoconstriction -> increased TPR
SNS - muscle stretches -> remodelling

253

What are natriuretic peptides?

Hormones released by the blood stream in response to the body’s increased ventricular wall stress, myocardial damage and volume overload

254

Define the normal, suspect HF and high levels of BNP and NT-proBNP

Normal: BNP<100pg/mL NT-proBNP<400pg/mL
Suspect HF: BNP 100-400pg/mL NT-proBNP 400-2000pg/mL
High - refer: BNP >400pg/mL NT-proBNP >2000pg/mL

255

What are the main underlying causes of HF?

Myocardial dysfunction
Volume overload
Pressure overload
Impaired filling
Arrhythmias
High output

256

Describe the changes in ejection fraction

Normal >50%
LVSD <45%
Symptoms <35%
Thrombosis <10%

257

Outline the signs and symptoms of HF

SOB, swelling of feet and legs, chronic lack of energy, orthopnoea, hepatomegaly=>ascites, cough with frothy sputum, increased urination at night, confusion and/or impaired memory, arrhythmias, raised JVP, presence of a third heart sound, reduced exercise tolerance

258

Outline the NYHA classification of heart failure

Class I - no limitations
Class II - ordinary activity=symptoms
Class III - less than ordinary activity = symtpoms
Class IV - symptoms at rest

259

What lifestyle interventions can be recommended to someone with HF?

Avoid excessive alcohol intake (=> dilated cardiomyopathy)
Smoking cessation
Low intensity exercise
Decrease salt to <6g per day
Daily weight monitoring

260

What invasive procedures are available for someone with HF?

Cardiac resynchronisation therapy with pacing (CRT-P)
Implantable cardioverter defibrillators (ICDs)
Coronary revascularisation
Cardiac transplantation
Assisted ventilation

261

What are the desirable lipid ranges?

TC <5mmol/L
LDL <3mmol/L
HLD >1.2mmol/L (F), >1mmol/L (M)
Triglycerides <1.7mmol/L