CVS Flashcards
1
Q
How does the sympathetic nervous system regulate cardiac function?
A
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
Q
How does the parasympathetic nervous system regulate cardiac function?
A
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
Q
Summarise the effect the SNS and PNS has on cardiac function.
A
SNS - increase pacemaker current and conduction velocity
PNS - slows depolarisation and decreases conduction velocity
4
Q
What changes occur with increased BP?
A
Baroreceptors activate PNS to inhibit SA firing rate, inhibiting SNS from inducing vasoconstriction
5
Q
What changes occur with decreased BP?
A
Baroreceptors activate SNS to increase SA firing rate, increase vasoconstriction, increase venous return and increase cardiac output (hence increasing BP)
6
Q
What are the 3 types of heart failure?
A
Acute left ventricular failure
Cardiogenic shock
Chronic heart failure
7
Q
Describe acute left ventricular failure
A
Where there is inadequate output leading to pulmonary oedema, reflex contraction (which increases venous return hence exacerbating the issue)
8
Q
What is the treatment goal for acute left ventricular failure and what treatments are used to achieve this goal?
A
To reduce venous return using loop diuretics, GTN, and opioids
9
Q
Describe cardiogenic shock
A
Where there is sudden impairment to left ventricular systole, impairing organ perfusion
10
Q
What is the treatment goal for cardiogenic shock and what treatments are used to achieve this goal?
A
Resuscitation, dobutamine to increase tissue perfusion
11
Q
Describe chronic heart failure
A
Where there is myocardium disease due to excess load because of e.g. IHD, valve dysfunction, HTN
12
Q
What is the treatment goal for chronic heart failure and what treatments are used to achieve this goal?
A
Reduce compensatory mechanisms and increase CO using ACEI, diuretics, beta-blockers and digoxin
13
Q
Outline the mechanism of cardiac contraction
A
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
Q
Describe the mechanism of action of digoxin
A
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
Q
Describe the mechanism of action of dobutamine
A
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
Q
Describe the mechanism of action of enoximone
A
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
Q
What class of drug is digoxin?
A
Cardiac glycoside
18
Q
How does digoxin cause arrhythmia?
A
More calcium in the cell, more calcium-induced calcium release, more spontaneous contraction
19
Q
What are the indications for digoxin?
A
Symptomatic relief in heart failure
Supraventricular arrhythmia
20
Q
Describe the PK of digoxin
A
Fp.o. ~75%
T1/2 ~40h
Vd ~640L/70kg (binds Na+/K+ ATPase in skeletal muscle)
Eliminated through p-GP
21
Q
Describe the ADRs of digoxin
A
Arrhythmia, nausea, vomiting, fatigue, confusion, impaired coloured vision
22
Q
What are the cautions for digoxin?
A
Hypokalaemia (digoxin binds with more affinity in the absence of potassium)
Hypothyroidism (reduced GFR -> increased toxicity)
Elderly (reduced GFR)
23
Q
What are the contraindications to the use of digoxin?
A
Heart block, as digoxin inhibits AV node conduction
24
Q
What interactions are associated with digoxin?
A
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
