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Yr 3 - Pharmacology > Drugs - CVS New > Flashcards

Drugs - CVS New Flashcards

1
Q

Give the 4 pharmacological agents used in the management of heart failure

A

ABAL

  • ACEi - ramipril
  • Beta blockers - bisoprolol
  • Aldosterone antagonist e.g. spironolactone
  • Loop diuretic e.g. furosemide
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2
Q

How do ACEi and ARBs affect potassium levels?

A

Can cause hyperkalaemia

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3
Q

How do aldosterone antagonists affect potassium levels?

A

Can cause hyperkalaemia

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4
Q

How can beta blockers improve prognosis in HF?

A
  • Blocks effect of catecholamines:
    • Enhanced levels of catecholamines resulting from activation of SNS in HF
    • Long-term stimulation of catecholamines becomes harmful (necrosis etc), contributing to progression of HF
  • Prevents arrhythmias
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5
Q

What is the main contraindication for beta blockers?

A

Asthma

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6
Q

What is Ivabradine? Indication?

A

Ivabradine is used to treat adults who have chronic heart failure to reduce their risk of hospitalisation for worsening heart failure.

Only effect is to slow heart rate down (reduces HR via a different mechanism to beta blockers)

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7
Q

What is the usual choice of VTE prophylaxis in hospital if there are any thrombotic risk factors provided the patient is not at risk of bleeding?

A

LMWH:

Dalteparin 5000 units daily or enoxaparin 40mg SC daily prescribed at a ‘prophylactic dose’

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8
Q

Give 5 indications for ACEi

A
  1. HTN (1st or 2nd line)
  2. Chronic heart failure (1st line)
  3. Ischaemic heart disease
  4. Diabetic nephropathy
  5. CKD with proteinuria
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9
Q

How are ACEi effective in CKD?

A

Dilates efferent glomerular arteriole → reduces intraglomerular pressure → slows progression of CKD

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10
Q

Mechanism of ACEi?

A
  1. Blocks conversion of angiotensin I → II
  2. Reduces aldosterone level
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11
Q

Effect of aldosterone on sodium & potassium?

A

Causes reabsorption of sodium and excretion of potassium

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12
Q

What class are drug are mainly responsible for causing angioedema?

A

ACEi

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13
Q

Contraindications of ACEi?

A
  • Renal artery stenosis
  • AKI
  • Pregnant/breastfeeding
  • Hypersensitivity
  • Angioedema (hereditary, idiopathic, or ACE inhibitor associated)
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14
Q

Why are ACEi/ARBs contraindicated in renal artery stenosis?

A

Cause/worsen renal failure particularly in those with renal artery stenosis who rely on constriction of efferent glomerular arteriole to maintain glomerular filtration.

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15
Q

Combination of ACEi/ARBs and spironolactone can cause what?

A

Hyperkalaemia

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16
Q

Combination of NSAIDs and ACEi/ARBs increase the risk of what?

A

Nephrotoxicity

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17
Q

What 2 biochemical changes should be measured when taking ACEi?

A

Serum creatinine and serum potassium

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18
Q

After initiation of ramipril, what would you expect to see in regard to creatinine & potassium?

A

After initiation of ramipril, you would expect to see an insignificant rise in serum creatinine and potassium

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19
Q

A rise of what in serum creatinine and potassium is acceptable when taking ACEi?

A

Increase in serum creatinine of 30% from baseline and increase in potassium of up to 5.5mmol/L are acceptable → after this, stop

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20
Q

Give 5 indications for ARBs

A

They are an alternative to ACEi:

  1. HTN (1st or 2nd line)
  2. Chronic heart failure (1st line)
  3. Ischaemic heart disease
  4. Diabetic nephropathy
  5. CKD with proteinuria
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21
Q

What class of anti-arrhythmic are beta blockers?

A

Class II

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22
Q

Give 5 indications for beta blockers

A
  1. Chronic heart failure
  2. Ischaemic heart disease
  3. AF
  4. Supraventricular tachycardia
  5. Hypertension
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23
Q

How are beta blockers effective in IHD?

A

improve symptoms and prognosis associated with angina and ACS

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24
Q

Beta blockers should only be used in which patients with supraventricular tachycardia?

A

as an option in patients without circulatory compromise to restore sinus rhythm

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25
Q

Are B1 or B2 adrenoceptors located in the heart?

A

B1

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26
Q

Where are B2 adrenoceptors located?

A

In the smooth muscle of the blood vessels and airways

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27
Q

Define ionotropy

A

Force of contraction

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28
Q

Define chronotropy

A

Speed of conduction

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29
Q

Mechanism of beta blockers in the management of IHD?

A
  • By blocking the effect of catecholamines at B1 receptors – beta blockers reduce force of contraction (negative inotropic effect) and speed of conduction (negative chronotropic effect) through AV node
  • This relieves myocardial ischaemia by reducing cardiac work and oxygen demand, and increasing myocardial perfusion
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30
Q

Mechanism of beta blockers in HF?

A

Improve prognosis in heart failure (‘cardioprotective’) by protecting heart from chronic sympathetic stimulation

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31
Q

Mechanism of beta blockers in AF?

A
  • They slow the ventricular rate in AF by prolonging the refractory period of the AV node
  • May also terminate SVT if this is due to a self-perpetuating (re-entry) circuit that takes in the AV node
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32
Q

Mechanism of beta blockers in HTN?

A

Beta blockers lower BP by many methods, one of which is reducing the renin secretion from the kidney which blocks the formation of angiotensin II

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33
Q

Side effects of beta blockers?

A
  • Bradycardia
  • Dizziness, syncope, confusion
  • Fatigue
  • Cold extremities
  • Headache
  • GI upset
  • Sleep disturbance & nightmares
  • Impotence in men
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34
Q

Contraindications for beta blockers?

A
  • Asthma – can cause life-threatening bronchospasm by blocking B2 receptors in airways
  • Hypotension
  • Bradycardia
  • Heart block
  • Diabetes
  • Peripheral vascular disease - can cause constriction of peripheral circulation
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35
Q

Why are beta blockers contraindicated in diabetes?

A

may mask signs of hypoglycaemia (e.g. increased HR)

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36
Q

Which beta blocker is mainly B1 selective?

A

Bisoprolol

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37
Q

Which beta blocker is relatively non-selective?

A

Propanolol

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38
Q

Why should beta blockers not be given with non-dihydropyridine calcium channel blockers (e.g. verapamil, diltiazem)

A

can cause HF, bradycardia and even asystole

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39
Q

Indications for loop diuretics?

A
  • For relief of breathlessness in acute pulmonary oedema in conjunction with oxygen and nitrates (e.g. due to CKD, LVF)
  • For symptomatic treatment of fluid overload in:
    • Chronic heart failure
    • Other oedematous states e.g. due to renal disease or liver failure, where they may be given in combination with other diuretics
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40
Q

What transporter do loop diuretics inhibit?

A

The Na+/K+/2Cl- co-transporter in the ascending loop of Henle

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41
Q

What is the Na+/K+/2Cl- co-transporter responsible for?

A

This protein is responsible for reabsorbing sodium, potassium, and chloride ions from the tubular lumen into the epithelial cell – water then follows by osmosis

(inhibition of this by loop diuretics)

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42
Q

Effect of loop diuretics on potassium levels?

A

Can cause hypokalaemia

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43
Q

Effect of loop diuretics on blood vessels?

A
  • In addition, loop diuretics have a direct effect on blood vessels – cause dilatation of capacitance veins
  • In acute HF, this reduces preload and improves contractile function of the ‘overstretched’ heart muscle
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44
Q

How do loop diuretics affect electrolytes?

A

Hyponatraemia, hypokalaemia, hypochloraemia, hypocalcaemia and hypomagnesaemia due to increased urinary excretion

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45
Q

How do loop diuretics affect acid base balance?

A

Lead to metabolic alkalosis

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46
Q

Why do loop diuretics cause metabolic alkalosis

A

Due to increased excretion of chloride in proportion to bicarbonate.

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47
Q

How do loop diuretics affect the ears? Why?

A

Hearing loss & tinnitus (ototoxic) at higher doses – a similar Na+/K+/2Cl- co-transporter is responsible for regulating endolymph composition in the inner ear

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48
Q

Side effects of loop diuretics?

A
  1. Dehydration & hypotension
  2. Low electrolyte state
  3. Hearing loss & tinnitus
  4. Worsening/increased risk of gout
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49
Q

Why can loop diuretics increase risk of developing gout?

A

This may happen because diuretics increase urination, which reduces the amount of fluid in your body (dehydration is risk factor for gout)

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50
Q

Give some contraindications for loop diuretics

A
  • Hypovolaemia
  • Hypokalaemia
  • Hyponatraemia
  • Loop diuretics
  • Gout
  • Hepatic encephalopathy
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51
Q

Why are loop diuretics contraindicated in hepatic encephalopathy?

A

Hypokalemia and metabolic alkalosis are considered precipitating factors for hepatic encephalopathy

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52
Q

What 3 main drugs can loop diuretics interact with?

A
  1. Lithium
  2. Digoxin
  3. Aminoglycosides
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53
Q

How can loop diuretics interact with lithium?

A

Lithium levels are increased due to reduced excretion

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54
Q

How can loop diuretics interact with digoxin?

A

Risk of digoxin toxicity may be increased due to diuretic-associated hypokalaemia

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55
Q

How can loop diuretics interact with aminoglycosides?

A

Can increase nephrotoxicity and ototoxicity of aminoglycosides

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56
Q

How should the initial dose of loop diuretics be prescribed in acute pulmonary oedema?

A

IV

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57
Q

What is Hypochloraemic alkalosis?

A

This is alkalosis resulting from either a) low chloride intake or b) excess chloride wasting

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58
Q

Give 2 examples of thiazide diuretics

A
  1. Bendroflumethiazide (thiazide)

2. Indapamide (thiazide-like

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59
Q

Indications for thiazide diuretics?

A
  • As an alternative 1st line treatment for hypertension where a calcium channel blocker would otherwise be used but is unsuitable (e.g. due to oedema) or there are features of HF
  • Add-on treatment for hypertension in patients whose BP is not adequately controlled by a CCB + ACEi/ARB
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60
Q

What transporter do thiazide diuretics inhibit?

A

Na+/Cl- co-transporter in the distal convoluted tubule

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61
Q

Function of the Na+/Cl- cotransporter in the kidney?

A

Reabsorbing sodium and chloride ions (thiazide diuretics inhibit this)

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62
Q

How do thiazide diuretics affect sodium & potassium levels?

A

Sodium - hyponatraemia

Potassium - hypokalaemia

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63
Q

Side effects of thiazide diuretics?

A
  • Dehydration (dry mouth, thirsty) & increased urination
  • Hyponatraemia
  • Hypokalaemia (can lead to arrhythmias)
  • Postural hypotension
  • May increase plasma glucose (may unmask T2DM), LDLs and triglycerides
  • Impotence in men
  • Gout
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64
Q

How can thiazide diuretics lead to gout?

A

Thiazide diuretics are associated with elevated serum uric acid (SUA) levels

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65
Q

3 main contraindications for thiazide diuretics?

A
  • Hypokalaemia
  • Hyponatraemia
  • Gout
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66
Q

How can NSAIDs interact with diuretics?

A

NSAIDs may block the antihypertensive effects of thiazide and loop diuretics, beta-adrenergic blockers, alpha-adrenergic blockers, and angiotensin-converting enzyme inhibitors.

No interactions have been reported with centrally acting alpha agonists or the calcium channel blockers

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67
Q

Why should thiazide & loop diuretics not be combined?

A

Can cause hypokalaemia +/- hypotension

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68
Q

Why is the combination of a thiazide diuretic and an ACEi/ARB useful in clinical practice?

A

One of the main side effects of thiazides is hypokalaemia, while one of the main side effects of ACEi and ARBs is hyperkalaemia. Moreover, these drug classes have a synergistic BP lowering effect: thiazides tend to activate the RAAS while ACEi/ARBs block it. Consequently, the combination of a thiazide and an ACEi/ARB is very useful in practice to both improve BP control and maintain neutral potassium balance.

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69
Q

Give 2 examples of aldosterone antagonists

A
  1. Spironolactone
  2. Eplerenone
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70
Q

In which situations is spironolactone indicated as the 1st line diuretic?

A

Ascites and oedema due to liver cirrhosis

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71
Q

Give some indications for aldosterone antagonists

A
  • Ascites and oedema due to liver cirrhosis – spironolactone is 1st line diuretic
  • Chronic heart failure – of at least moderate severity or airing within 1 month of MI, usually as an addition to a beta-blocker and an ACEi/ARB
  • Primary hypoaldosteronism (Conn’s syndrome)
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72
Q

What is conn’s syndrome?

A

Conn’s syndrome is a rare health problem that occurs when the adrenal glands make too much aldosterone (1ary hyperaldosteronism)

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73
Q

Diuretic effect of aldosterone antagonists?

A

Only weak diuretics when used alone. Cause retention of potassium so are given with thiazide/loop diuretics as more effective alternative to potassium supplement.

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74
Q

Effect of aldosterone on the kidney?

A
  • Aldosterone is a mineralocorticoid that is produced in the adrenal cortex – it acts on mineralocorticoid receptors in the distal tubules of the kidney to increase the activity of luminal epithelial Na+ channels:
  • This increases reabsorption of water and sodium → elevates BP with corresponding increase in potassium excretion
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75
Q

Side effects of aldosterone antagonists?

A
  • Hyperkalaemia
  • Gynaecomastia - can affect patient adherence
  • Irregular periods & breast tenderness (boys & girls)
  • Can cause severe liver impairment & jaundice
  • Are a cause of Steven-Johnson syndrome (T cell mediated hypersensitivity reaction) that causes a bullous skin eruption
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76
Q

Which aldosterone antagonist causes gynaecomastia? Which doesn’t?

A

Spironolactone causes gynaecomastia due to anti-androgen effects i.e. decreases testosterone.

Eplerenone is less likely to cause endocrine side effects (as has a lower affinity for androgen receptors and no affinity for progesterone)

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77
Q

Contraindications for aldosterone antagonists?

A
  • Severe renal impairment
  • Hyperkalaemia
  • Addison’s disease (aldosterone deficient)
  • Pregnancy & breastfeeding – can cross the placenta and appear in breast milk
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78
Q

What should be monitored during treatment with aldosterone antagonists?

A
  • Monitor renal function due to risk of renal impairment
  • Monitor K+ levels due to risk of hyperkalaemia
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79
Q

What class of anti-arrhythmics are CCBs?

A

Class IV

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80
Q

CCBs can broadly be divided into what two classes?

A
  1. Dihydropyridines
  2. Non-dihydropyridines
81
Q

Give 2 examples of dihydropyridine CCBs

A
  1. Amlodipine
  2. Felodipine
82
Q

Give 2 examples of non-dihydropyridine CCBs

A
  1. Diltiazem
  2. Verapamil
83
Q

What do dihydropyridine CCBs (e.g. amlodipine) preferentially act upon? What is their main use?

A

Preferentially acts upon vascular smooth muscle so is typically used as an anti-hypertensive rather than an anti-arrhythmic

84
Q

What do non-dihydropyridine CCBs (e.g. diltiazem, verpamil) preferentially act upon? What is their main use?

A

More active on calcium channels in cardiac tissue so typically used for anti-arrhythmic properties than other CCBs

85
Q

Which CCB is the most cardioselective?

A

Verapamil

86
Q

Give some indications for CCBs

A
  • Amlodipine → 1st or 2nd line treatment of hypertension, to reduce risk of stroke, MI and death from CVS disease
  • All CCBs can be used to control the symptoms in people with stable angina (beta blockers are main alternative)
  • Diltiazem and verapamil are used to control cardiac rate in people with supraventricular arrythmias (e.g. atrial fibrillation, atrial flutter, supraventricular tachycardia)
87
Q

Mechanism of CCBs?

A
  • CCBs decrease Ca2+ entry into vascular and cardiac cells, reducing intracellular calcium concentration – this causes relaxation and vasodilation in arterial smooth muscle, lowering arterial pressure
  • In the heart, CCBs:
    • Reduce myocardial contractility
    • Suppress cardiac conduction across the AV node  this slows ventricular rate
    • Reduced contractility, rate & afterload reduces myocardial oxygen demand, preventing angina
88
Q

Side effects of CCBs?

A
  • Ankle swelling
  • Flushing
  • Headache
  • Palpitations
89
Q

Contraindications of CCBs?

A
  • Bradycardia
  • Heart failure
  • Poor LV function – can precipitate or worsen HF
  • AV nodal conduction delay – may provoke complete heart block
90
Q

Why should non-dihydropyridine CCBs (verapamil, diltiazem) not be prescribed with beta blockers?

A

Both exert negative ionotropic and chronotropic effects which can cause HF, bradycardia and asystole

91
Q

Give an example of a short-acting nitrate

A

Glyceryl trinitrate

92
Q

Give an example of a long-acting nitrate

A

Isosorbide mononitrate

93
Q

Indication of GTN?

A

used in the treatment of acute angina and chest pain associated with ACS

94
Q

Indication of isosorbide mononitrate?

A

Long-acting nitrates (isosorbide mononitrate) are used for prophylaxis of angina where a beta-blocker and/or CCB are insufficient/not tolerated

95
Q

When are IV nitrates indicated?

A

IV nitrates used in treatment of pulmonary oedema, usually in combination with furosemide and oxygen

96
Q

Mechanism of nitrates?

A

Nitrates are converted to nitric oxide (NO) which increases cGMP synthesis and reduces intracellular Ca2+ in vascular smooth muscle cells, causing them to relax

97
Q

Sustained use of nitrates can lead to tolerance with reduced symptom relief despite continued use. How can this be minimised?

A

This can be minimised by careful timing of doses to avoid significant nitrate exposure overnight, when it tends not to be needed

98
Q

Why are nitrates contraindicated in severe aortic stenosis?

A

As heart is unable to increase cardiac output sufficiently through the narrowed heart valve to maintain pressure in the now dilated vasculature

99
Q

In ACS, how are nitrates given?

A

GTN given as an infusion

100
Q

Give 3 indications for statins

A
  • 1aryprevention of CVS events
  • 2ary prevention of CVS events
  • 1aryhyperlipidaemia
101
Q

What can happen if statins are taken with P450 enzyme inhibitors e.g. amiodarone, diltiazem, itraconazole, macrolides and protease inhibitors?

A

This leads to accumulation of statins which can increase risk of adverse effects (e.g. muscle problems)

102
Q

Why should grapefruit be avoided when taking statins?

A

Enzyme inhibitor - can increase side effects

103
Q

What blood tests are needed before and after initiation of statins?

A
  • Lipid profile
  • LFTs
  • TFTs
104
Q

Side effects of statins?

A
  • Headaches
  • GI upset
  • Muscle effects:
    • Myalgia (muscle aches)
    • Myopathy
    • Rhabdomyolysis (serious)
  • Can cause rise in liver enzymes (e.g. ALT)
  • Can cause drug induced hepatitis
105
Q

Why should LFTs be monitored with statins?

A

Can cause hepatitis - a rise in ALT up to 3x the upper limit of normal may be acceptable

106
Q

Why should TFTs be checked before starting statins?

A

Hypothyroidism is a reversible cause of hyperlipidaemia so should be corrected before reassessing the need for a statin. Hypothyroidism also increases the risk of myositis with statins.

107
Q

Give some indications for aspirin

A
  1. Treatment of ACS and acute ischaemic stroke
  2. Long term 2ary prevention of thrombotic arterial events in patients with CVS, cerebrovascular and PAD (e.g. post stroke, post MI)
108
Q

How is aspirin useful in treating ACS and acute ischaemic stroke?

A

rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality

109
Q

Are arterial clots rich in fibrin or platelets?

A

Platelets

110
Q

MOA of aspirin?

A

Aspirin irreversibly inhibits COX to reduce the production of thromboxane A2 from arachidonic acid (pro-aggregatory) → this reduces platelet aggregation and risk of arterial occlusion

111
Q

Describe the dose at which aspirin takes effect and how long it lasts

A

Antiplatelet effect of aspirin occurs at low doses and lasts for a lifetime of a platelet (120 days) so only wears off as new platelets are made

112
Q

Give some side effects of aspirin

A
  • Bleeding
  • GI irritation
  • Peptic ulceration & haemorrhage
113
Q

In regular high-dose therapy, what can aspirin cause?

A

Tinnitus

114
Q

Why should aspirin not be given to patients <16 y/o?

A

Risk of Reye’s syndrome

115
Q

What is Reye’s syndrome?

A

A rare disorder that causes brain and liver damage. It normally occurs soon after recovery from a viral infection (e.g. chickenpox) and leads to hypoglycaemia, increased urea levels and prolonged prothrombin time (risk of bleeding).

116
Q

Give some contraindications of aspirin

A
  • Children <16 y/o
  • Hypersensitivity
  • 3rd trimester of pregnancy (high doses)
  • Peptic ulceration
  • Gout
117
Q

Why is high dose aspirin contraindicated in 3rd trimester of pregnancy?

A

Taking higher doses of aspirin during the third trimester increases the risk of the premature closure of a vessel in the foetus’ heart (ductus arteriosus) due to inhibition of prostaglandins.

118
Q

Describe the relationship between aspirin and gout

A

Aspirin can raised uric acid levels which can a) trigger gout attack, b) intensify gout attack, c) cause development of gout

119
Q

Main interaction of aspirin?

A

May increase risk of bleeding if combined with other antiplatelets or anticoagulants

120
Q

What should long-term aspirin be prescribed alongside?

A

Gastroprotection (e.g. omeprazole)

121
Q

Aspirin is not licensed for 1ary prevention of CVS disease (i.e. in patients who have not previously had an event). Why?

A

As potential benefits are offset by increased risk of serious bleeding.

122
Q

Reversal agent of aspirin?

A

No reversal agents – irreversible effect (lasts 4-5 days)

123
Q

What is Reye’s syndrome normally preceded by?

A

It normally occurs soon after recovery from a viral infection (e.g. chickenpox)

124
Q

Give 2 examples of ADP-receptor antagonists

A
  1. Ticagrelor
  2. Clopidogrel
125
Q

Give some indications for ADP-receptor antagonists

A
  • Treatment of ACS (usually in combination with aspirin)
  • Long-term 2ary prevention of thrombotic arterial events
  • Prevent occlusion of coronary artery stents (usually in combination with aspirin)
126
Q

Mechanism of ticagrelor & clopidogrel?

A
  • These drugs prevent platelet aggregation and reduce risk of arterial occlusion by binding irreversibly to adenosine diphosphate (ADP) receptors (P2Y12 type) on surface of platelets
  • This process is independent of COX pathway, so actions are synergistic with those of aspirin
127
Q

Define synergy

A

The interaction of two substances, or other agents to produce a combined effect greater than the sum of their separate effects.

128
Q

Give some side effects of ADP-receptor antagonists

A
  • Bleeding
  • GI upset
  • Thrombocytopenia (rare)
129
Q

Give some contraindications to ADP-receptor antagonists

A
  • Active bleeding
  • May need to be stopped 7 days before elective surgery
  • Renal & hepatic impairment
130
Q

Clopidogrel is a prodrug. What does this mean?

A

requires metabolism by P450 system to its active form

131
Q

Interactions of clopidogrel & ticagrelor?

A
  • Efficacy may be reduced by P450 enzyme inhibitors by inhibiting its activation e.g. omeprazole, ciprofloxacin, erythromycin, some antifungals, some SSRIs
  • Co-prescription with other antiplatelets, anticoagulants or NSAIDs increases risk of bleeding
132
Q

Give 2 major indications for warfarin

A
  1. VTE → treatment & prevention of recurrence (DOACs are an alternative)
  2. Prevention of arterial embolism in patients with AF or prosthetic heart valves
133
Q

Treatment with warfarin is lifelong in what type of prosthetic heart valves?

A

Mechanical

134
Q

Treatment with warfarin is short-term in what type of prosthetic heart valves?

A

Tissue valve replacement

135
Q

Warfarin requires initial concomitant therapy with what? Why?

A

Initial concomitant therapy with heparin is required as it takes several days for anticoagulation with warfarin to be fully established (warfarin is initially pro-thrombotic)

136
Q

What is venous and intracardiac clot formation driven by?

A

the coagulation cascade (while arterial thrombosis is more a phenomenon of platelet activation)

137
Q

What is the coagulation cascade?

A

The coagulation cascade is an amplification reaction between clotting factors that generates a fibrin clot

138
Q

Mechanism of warfarin?

A

Warfarin inhibits hepatic production of vitamin K-dependent coagulation factors (10, 9, 7, 2) by inhibiting vitamin KO reductase (enzyme responsible for restoring vitamin K to its reduced form)

139
Q

What are the vitamin K dependent clotting factors?

A

10, 9, 7, 2

140
Q

What enzyme does warfarin inhibit?

A

Vitamin KO reductase

141
Q

Side effects of warfarin?

A
  • Bleeding (e.g. intracerebral haemorrhage after minor head injury)
  • Can cause coumarin induced skin necrosis
  • Spontaneous bleeding e.g. epistaxis
142
Q

What is coumarin induced skin necrosis?

A

Skin and subcutaneous tissue necrosis occur due to acquired protein C deficiency following treatment with vitamin K anticoagulant

143
Q

What is the reversal agent for warfarin?

A

Phytomenadione (vitamin K1) or prothrombin complex concentrate (PCC)

144
Q

Contraindications to warfarin?

A
  • Immediate risk of haemorrhage e.g. trauma, surgery
  • Pregnancy
  • Malignancy
  • Caution in liver disease (risk of overtoxicity)
  • Haemorrhagic stroke
  • Bleeding
145
Q

Interaction between warfarin and NSAIDs?

A
  • NSAIDs displace warfarin from plasma albumin – potentiates effects
  • NSAIDs inhibit platelet function

These both cause an increased risk of bleeding

146
Q

Metabolism of warfarin?

A

P450 system

147
Q

Give some examples of P450 enzyme inhibitors

A
  • Clarithromycin/erythromycin
  • Ciprofloxacin
  • Amiodarone
  • Oral contraceptives
  • St John’s Wort
148
Q

Give some examples of P450 enzyme inducers

A
  • Phenytoin
  • Carbamazepine
  • Alcohol
  • Allopurinol
  • SSRIs
149
Q

How can Abx interact with warfarin?

A

Can increase the effect of warfarin by killing gut flora that synthesise vitamin K (usually not a clinical problem)

150
Q

What does INR represent?

A

international nationalised ratio is a measure of how long it takes your blood to clot

151
Q

Give some examples of heparin

A
  • Enoxaparin
  • Dalteparin
152
Q

Give 3 major indications for heparin

A
  1. 1ary prevention of VTE in hospital inpatients
  2. ACS → used with antiplatelets to reduce clot progression
  3. Given alongside initiation of warfarin
153
Q

MOA of UFH vs LMWH heparin?

A

Enhances anticoagulant effect of antithrombin (AT) that inactivates clotting factors IIa (thrombin) and Xa:

  • LMWH → more specific for Xa
  • UFH → acts on both IIa and Xa
154
Q

What is fondaparinux?

A

A synthetic anticoagulant

155
Q

MOA of fondaparinux?

A

Mimics the sequence of the binding site of heparin to AT and is very specific for Xa

156
Q

Reversal agent for heparin?

A

Protamine (effective for UFH, less effective for LMWH and no effect against fondaparinux)

157
Q

Reversal agent for fondaparinux?

A

none

158
Q

What is the pharmacological agent & dose of choice for VTE prophylaxis in hospital inpatients?

A

Heparin 5000 units SC daily

159
Q

What should be monitored when taking heparin?

A

Platelet count due to risk of HIT

160
Q

Why is warfarin initially pro-thrombotic?

A

due to initial inhibition of natural anticoagulants (protein C and S) before its effect on clotting factors II, VII, IX, X

161
Q

Give 2 major indications for DOACs

A
  • VTE → treatment & prevention of recurrence (2ary prevention)
  • Atrial fibrillation → prevent stroke & systemic embolism in patients with non-valvular AF who have at least one risk factor
162
Q

What is valvular AF?

A

Seen in people who have a heart valve disorder or a prosthetic heart valve

163
Q

What is non-valvular AF?

A

Caused by other things such as hypertension or stress.

164
Q

General mechanism of DOACs?

A

DOACs act on the final common pathway of the coagulation cascade, comprising factor X, thrombin, and fibrin without having to bind to antithrombin.

All DOACs therefore inhibit fibrin formation, preventing clot formation or extension in the veins and heart

165
Q

Which DOACs inhibit factor Xa? What does this prevent?

A

Rivaroxaban, apixaban, edoxaban

Inhibition of Xa prevents conversion of prothrombin to thrombin

166
Q

Which DOACs inhibit factor IIa? What does this prevent?

A

Dabigatran

Inhibition of IIa prevents conversion of fibrinogen to fibrin

167
Q

describe the risk of bleeding in DOACs vs warfarin

A

Risk of intracranial haemorrhage and major bleeding is less with DOACs than with warfarin BUT risk of GI bleeding is greater

168
Q

Contraindications for DOACs?

A
  • Active, clinically significant bleeding
  • Risk factors for major bleeding e.g. peptic ulceration, cancer, recent surgery or trauma
  • P450 metabolism and excreted in urine & faeces – dose reduction required in hepatic or renal disease
169
Q

How will phenytoin affect the anticoagulant effect of DOACs?

A

Phenytoin is an enzyme inducer → reduces anticoagulant effect

170
Q

How will rifampicin affect the anticoagulant effect of DOACs?

A

Rifampicin is an enzyme inducer → reduces anticoagulant effect

171
Q

How will macrolides affect the anticoagulant effect of DOACs?

A

Macrolides are enzyme inhibitors → increase anticoagulant effect

172
Q

How will fluconazole affect the anticoagulant effect of DOACs?

A

Fluconazole is an enzyme inhibitor → increase anticoagulant effect

173
Q

Why are DOACs preferred over heparin in outpatient treatment/prevention of VTE?

A

Taken orally - no need for SC injections

174
Q

What class of drug is digoxin?

A

Cardiac glyoside

175
Q

Give 2 indications for digoxin

A
  1. Atrial fibrillation or atrial flutter → rate control
  2. Severe heart failure
176
Q

Digoxin can be used for rate control (to reduce ventricular rate) in AF and atrial flutter. What drugs are typically used before this?

A

Beta blocker (bisoprolol) or CCB (verapamil or diltiazem).

Digoxin only used if beta blocker and CCB contraindicated.

177
Q

Digoxin is indicated in which patients with HF?

A

Digoxin is an option in patients who are already taking an ACEi, beta blocker and either an aldosterone antagonist or ARB

It is used at an earlier stage in patients with co-existing AF

178
Q

Define chronotropic effects

A

Those that change the heart rate

179
Q

Define ionotropic effects

A

Those that change the contractility of the heart

180
Q

Describe the chronotropic and ionotropic effects of digoxin

A

Positively ionotropic → increases contractility of heart

Negatively chronotropic → reduces HR

181
Q

Describe the mechanism of digoxin in the management of AF

A

its therapeutic effect arises mainly via an indirect pathway that increases vagal (parasympathetic) tone – this reduces conduction at the AV node which reduces the ventricular rate

182
Q

Describe the mechanism of digoxin in the management of HF

A

it has a direct effect on myocytes through inhibition of Na+/K+-ATPase pumps, causing increased intracellular Na+ and increased intracellular Ca2+ → this increases contractility

183
Q

Give some side effects of digoxin

A
  • Bradycardia
  • GI upset
  • Rash
  • Dizziness
  • Visual disturbance
  • Digoxin is proarrhythmic and has a low therapeutic index – risk of toxicity
  • Digoxin toxicity – arrhythmias, delirium
184
Q

What is digoxin toxicity treated with?

A

Digibind/Digifab

185
Q

Give some contraindications of digoxin

A
  • Second degree heart block
  • Intermittent complete heart block
  • Ventricular arrythmias
  • Renal failure
  • Hypokalaemia, hypomagnesaemia, hypercalcaemia
186
Q

Why is digoxin contraindicated in AV block?

A

Can worsen conduction abnormalities

187
Q

Which electrolyte abnormalities is digoxin contraindicated in? Why?

A

Hypokalaemia, hypomagnesaemia, hypercalcaemia

Increases risk of toxicity → Digoxin competes with potassium to bind the Na+/K+ ATPase pump so when serum potassium levels are low, competition is reduced, and the effects of digoxin are enhanced

188
Q

Which drugs can increase the risk of digoxin toxicity?

A

Loop & thiazide diuretics – can increase risk of digoxin toxicity by cause hypokalaemia

189
Q

How is digoxin metabolisd/eliminated?

A

Excreted by the kidneys without metabolism by the liver

190
Q

Why is digoxin contraindicated in renal failure?

A
  • Excreted by the kidneys without metabolism by the liver
  • In kidney failure, the body is unable to eliminate digoxin, causing levels to accumulate (digoxin toxicity)
191
Q

What is the main indication of amiodarone?

A

Cardiac arrest → VF or pulseless VT

192
Q

Half life of amiodarone?

A

58 days so loading dose is often required

193
Q

What class of drug is amiodarone?

A

Class III anti-arrythmic

194
Q

Give some side effects of chronic amiodarone use

A
  • Pneumonitis
  • Hepatitis
  • Skin – photosensitivity and grey discolouration
  • Thyroid abnormalities – due to iodine content and structural similarities to thyroid hormone
195
Q

Amiodarone increases plasma concentrations of which 3 drugs?

A

Increases plasma concentrations of digoxin, diltiazem and verapamil – this may increase risk of bradycardia, AV block and HF

196
Q

Indication for adenosine?

A
  • EMERGENCIES
  • Used to terminate supraventricular tachycardias
197
Q

Half life of adenosine?

A

10 seconds → given via infusion with large-calibre cannula due to short half-life

198
Q

Side effects of adenosine?

A

Bradycardia and even asystole – due to interfering with functions of AV and SA node

199
Q

What feeling is typically described by patients given adenosine?

A

Deeply unpleasant sensation for patient, said to feel like a ‘sinking feeling in the chest’ often accompanied by breathlessness and a sense of ‘impending doom’ (feeling only brief)

Yr 3 - Pharmacology (18 decks)

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