Drugs - CVS New Flashcards
(199 cards)
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
2
Q
How do ACEi and ARBs affect potassium levels?
A
Can cause hyperkalaemia
3
Q
How do aldosterone antagonists affect potassium levels?
A
Can cause hyperkalaemia
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
5
Q
What is the main contraindication for beta blockers?
A
Asthma
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)
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’
8
Q
Give 5 indications for ACEi
A
- HTN (1st or 2nd line)
- Chronic heart failure (1st line)
- Ischaemic heart disease
- Diabetic nephropathy
- CKD with proteinuria
9
Q
How are ACEi effective in CKD?
A
Dilates efferent glomerular arteriole → reduces intraglomerular pressure → slows progression of CKD
10
Q
Mechanism of ACEi?
A
- Blocks conversion of angiotensin I → II
- Reduces aldosterone level
11
Q
Effect of aldosterone on sodium & potassium?
A
Causes reabsorption of sodium and excretion of potassium
12
Q
What class are drug are mainly responsible for causing angioedema?
A
ACEi
13
Q
Contraindications of ACEi?
A
- Renal artery stenosis
- AKI
- Pregnant/breastfeeding
- Hypersensitivity
- Angioedema (hereditary, idiopathic, or ACE inhibitor associated)
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.
15
Q
Combination of ACEi/ARBs and spironolactone can cause what?
A
Hyperkalaemia
16
Q
Combination of NSAIDs and ACEi/ARBs increase the risk of what?
A
Nephrotoxicity
17
Q
What 2 biochemical changes should be measured when taking ACEi?
A
Serum creatinine and serum potassium
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
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
20
Q
Give 5 indications for ARBs
A
They are an alternative to ACEi:
- HTN (1st or 2nd line)
- Chronic heart failure (1st line)
- Ischaemic heart disease
- Diabetic nephropathy
- CKD with proteinuria
21
Q
What class of anti-arrhythmic are beta blockers?
A
Class II
22
Q
Give 5 indications for beta blockers
A
- Chronic heart failure
- Ischaemic heart disease
- AF
- Supraventricular tachycardia
- Hypertension
23
Q
How are beta blockers effective in IHD?
A
improve symptoms and prognosis associated with angina and ACS
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
25
Are B1 or B2 adrenoceptors located in the heart?
B1
26
Where are B2 adrenoceptors located?
In the smooth muscle of the blood vessels and airways
27
Define ionotropy
Force of contraction
28
Define chronotropy
Speed of conduction
29
Mechanism of beta blockers in the management of IHD?
* 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
30
Mechanism of beta blockers in HF?
Improve prognosis in heart failure (‘cardioprotective’) by protecting heart from chronic sympathetic stimulation
31
Mechanism of beta blockers in AF?
* 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
32
Mechanism of beta blockers in HTN?
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
33
Side effects of beta blockers?
* Bradycardia
* Dizziness, syncope, confusion
* Fatigue
* Cold extremities
* Headache
* GI upset
* Sleep disturbance & nightmares
* Impotence in men
34
Contraindications for beta blockers?
* **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
35
Why are beta blockers contraindicated in diabetes?
may mask signs of hypoglycaemia (e.g. increased HR)
36
Which beta blocker is mainly B1 selective?
Bisoprolol
37
Which beta blocker is relatively non-selective?
Propanolol
38
Why should beta blockers not be given with **non-dihydropyridine calcium channel blockers** (e.g. verapamil, diltiazem)
can cause HF, bradycardia and even asystole
39
Indications for loop diuretics?
* 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
40
What transporter do loop diuretics inhibit?
The Na+/K+/2Cl- co-transporter in the ascending loop of Henle
41
What is the **Na+/K+/2Cl- co-transporter** responsible for?
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)
42
Effect of loop diuretics on potassium levels?
Can cause hypokalaemia
43
Effect of loop diuretics on blood vessels?
* 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
44
How do loop diuretics affect electrolytes?
Hyponatraemia, hypokalaemia, hypochloraemia, hypocalcaemia and hypomagnesaemia due to **increased urinary excretion**
45
How do loop diuretics affect acid base balance?
Lead to **metabolic alkalosis**
46
Why do loop diuretics cause metabolic alkalosis
Due to **increased excretion of chloride in proportion to bicarbonate**.
47
How do loop diuretics affect the ears? Why?
**Hearing loss** & **tinnitus** (**ototoxic**) at higher doses – a similar **Na+/K+/2Cl- co-transporter** is responsible for regulating endolymph composition in the inner ear
48
Side effects of loop diuretics?
1. Dehydration & hypotension
2. Low electrolyte state
3. Hearing loss & tinnitus
4. Worsening/increased risk of gout
49
Why can loop diuretics increase risk of developing gout?
This may happen because diuretics increase urination, which reduces the amount of fluid in your body (dehydration is risk factor for gout)
50
Give some contraindications for loop diuretics
* Hypovolaemia
* Hypokalaemia
* Hyponatraemia
* Loop diuretics
* Gout
* Hepatic encephalopathy
51
Why are loop diuretics contraindicated in hepatic encephalopathy?
Hypokalemia and metabolic alkalosis are considered precipitating factors for hepatic encephalopathy
52
What 3 main drugs can loop diuretics interact with?
1. Lithium
2. Digoxin
3. Aminoglycosides
53
How can loop diuretics interact with lithium?
**Lithium** levels are increased due to reduced excretion
54
How can loop diuretics interact with digoxin?
Risk of **digoxin toxicity** may be increased due to diuretic-associated hypokalaemia
55
How can loop diuretics interact with aminoglycosides?
Can increase nephrotoxicity and ototoxicity of **aminoglycosides**
56
How should the initial dose of loop diuretics be prescribed in acute pulmonary oedema?
IV
57
What is ***Hypochloraemic alkalosis?***
This is alkalosis resulting from either a) low chloride intake or b) excess chloride wasting
58
Give 2 examples of thiazide diuretics
1. **Bendroflumethiazide** (thiazide)
**2. Indapamide** (thiazide-like
59
Indications for thiazide diuretics?
* 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
60
What transporter do thiazide diuretics inhibit?
**Na+/Cl- co-transporter** in the **distal convoluted tubule**
61
Function of the Na+/Cl- cotransporter in the kidney?
Reabsorbing sodium and chloride ions (thiazide diuretics inhibit this)
62
How do thiazide diuretics affect sodium & potassium levels?
Sodium - hyponatraemia
Potassium - hypokalaemia
63
Side effects of thiazide diuretics?
* 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
64
How can thiazide diuretics lead to gout?
Thiazide diuretics are associated with elevated serum uric acid (SUA) levels
65
3 main contraindications for thiazide diuretics?
* **Hypokalaemia**
* **Hyponatraemia**
* **Gout**
66
How can NSAIDs interact with diuretics?
**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
67
Why should thiazide & loop diuretics not be combined?
Can cause hypokalaemia +/- hypotension
68
Why is the combination of a thiazide diuretic and an ACEi/ARB useful in clinical practice?
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_.
69
Give 2 examples of aldosterone antagonists
1. Spironolactone
2. Eplerenone
70
In which situations is spironolactone indicated as the **1st line diuretic?**
**Ascites** and **oedema** due to **liver cirrhosis**
71
Give some indications for aldosterone antagonists
* **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)**
72
What is conn's syndrome?
**Conn's syndrome** is a rare health problem that occurs when the adrenal glands make too much aldosterone (1ary hyperaldosteronism)
73
Diuretic effect of aldosterone antagonists?
Only weak diuretics when used alone. Cause retention of potassium so are given with thiazide/loop diuretics as more effective alternative to potassium supplement.
74
Effect of aldosterone on the kidney?
* **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**
75
Side effects of aldosterone antagonists?
* **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
76
Which aldosterone antagonist causes gynaecomastia? Which doesn't?
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)
77
Contraindications for aldosterone antagonists?
* **Severe renal impairment**
* **Hyperkalaemia**
* **Addison’s disease** (aldosterone deficient)
* **Pregnancy & breastfeeding** – can cross the placenta and appear in breast milk
78
What should be monitored during treatment with aldosterone antagonists?
* Monitor renal function due to risk of renal impairment
* Monitor K+ levels due to risk of hyperkalaemia
79
What class of anti-arrhythmics are CCBs?
Class IV
80
CCBs can broadly be divided into what two classes?
1. Dihydropyridines
2. Non-dihydropyridines
81
Give 2 examples of dihydropyridine CCBs
1. Amlodipine
2. Felodipine
82
Give 2 examples of non-dihydropyridine CCBs
1. Diltiazem
2. Verapamil
83
What do dihydropyridine CCBs (e.g. amlodipine) preferentially act upon? What is their main use?
Preferentially acts upon **vascular smooth muscle** so is typically used as an **anti-hypertensive** rather than an anti-arrhythmic
84
What do non-dihydropyridine CCBs (e.g. diltiazem, verpamil) preferentially act upon? What is their main use?
More active on **calcium channels in cardiac** **tissue** so typically used for **anti-arrhythmic properties** than other CCBs
85
Which CCB is the most cardioselective?
Verapamil
86
Give some indications for CCBs
* _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
Mechanism of CCBs?
* 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
Side effects of CCBs?
* Ankle swelling
* Flushing
* Headache
* Palpitations
89
Contraindications of CCBs?
* **Bradycardia**
* **Heart failure**
* **Poor LV function** – can precipitate or worsen HF
* **AV nodal conduction delay** – may provoke complete heart block
90
Why should non-dihydropyridine CCBs (verapamil, diltiazem) not be prescribed with **beta blockers**?
Both exert negative ionotropic and chronotropic effects which can cause HF, bradycardia and asystole
91
Give an example of a **short-acting nitrate**
Glyceryl trinitrate
92
Give an example of a **long-acting nitrate**
**Isosorbide mononitrate**
93
Indication of GTN?
used in the treatment of **acute angina** and chest pain associated with **ACS**
94
Indication of isosorbide mononitrate?
Long-acting nitrates (isosorbide mononitrate) are used for **prophylaxis of angina** where a beta-blocker and/or CCB are insufficient/not tolerated
95
When are IV nitrates indicated?
IV nitrates used in treatment of **pulmonary oedema,** usually in combination with furosemide and oxygen
96
Mechanism of nitrates?
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
Sustained use of nitrates can lead to **tolerance** with reduced symptom relief despite continued use. How can this be minimised?
This can be minimised by careful timing of doses to avoid significant nitrate exposure overnight, when it tends not to be needed
98
Why are nitrates contraindicated in severe aortic stenosis?
As heart is unable to increase cardiac output sufficiently through the narrowed heart valve to maintain pressure in the now dilated vasculature
99
In ACS, how are nitrates given?
GTN given as an infusion
100
Give 3 indications for statins
* **1aryprevention of CVS events**
* **2ary prevention of CVS events**
* **1aryhyperlipidaemia**
101
What can happen if statins are taken with **P450 enzyme inhibitors** e.g. amiodarone, diltiazem, itraconazole, macrolides and protease inhibitors?
This leads to accumulation of statins which can increase risk of adverse effects (e.g. muscle problems)
102
Why should grapefruit be avoided when taking statins?
Enzyme inhibitor - can increase side effects
103
What blood tests are needed before and after initiation of statins?
* Lipid profile
* LFTs
* TFTs
104
Side effects of statins?
* 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
Why should LFTs be monitored with statins?
Can cause hepatitis - a rise in ALT up to 3x the upper limit of normal may be acceptable
106
Why should TFTs be checked before starting statins?
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
Give some indications for aspirin
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
How is aspirin useful in treating ACS and acute ischaemic stroke?
rapid **inhibition of platelet aggregatio**n can prevent or limit arterial thrombosis and reduce subsequent mortality
109
Are **arterial clots** rich in fibrin or platelets?
Platelets
110
MOA of aspirin?
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
Describe the dose at which aspirin takes effect and how long it lasts
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
Give some side effects of aspirin
* Bleeding
* GI irritation
* Peptic ulceration & haemorrhage
113
In regular high-dose therapy, what can aspirin cause?
Tinnitus
114
Why should aspirin not be given to patients \<16 y/o?
Risk of **Reye's syndrome**
115
What is Reye's syndrome?
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
Give some contraindications of aspirin
* Children \<16 y/o
* Hypersensitivity
* 3rd trimester of pregnancy (high doses)
* Peptic ulceration
* Gout
117
Why is high dose aspirin contraindicated in 3rd trimester of pregnancy?
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
Describe the relationship between aspirin and gout
Aspirin can **raised uric acid** levels which can a) trigger gout attack, b) intensify gout attack, c) cause development of gout
119
Main interaction of aspirin?
May increase risk of bleeding if combined with other antiplatelets or anticoagulants
120
What should long-term aspirin be prescribed alongside?
Gastroprotection (e.g. omeprazole)
121
Aspirin is not licensed for **1ary prevention of CVS disease** (i.e. in patients who have not previously had an event). Why?
As potential benefits are offset by increased risk of serious bleeding.
122
Reversal agent of aspirin?
No reversal agents – irreversible effect (lasts 4-5 days)
123
What is Reye's syndrome normally preceded by?
It normally occurs soon after recovery from a viral infection (e.g. chickenpox)
124
Give 2 examples of ADP-receptor antagonists
1. Ticagrelor
2. Clopidogrel
125
Give some indications for ADP-receptor antagonists
* **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
Mechanism of ticagrelor & clopidogrel?
* 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
Define synergy
The interaction of two substances, or other agents to produce a **combined effect greater than the sum of their separate effects.**
128
Give some side effects of ADP-receptor antagonists
* Bleeding
* GI upset
* **Thrombocytopenia** (rare)
129
Give some contraindications to ADP-receptor antagonists
* Active bleeding
* May need to be stopped 7 days before elective surgery
* Renal & hepatic impairment
130
Clopidogrel is a **prodrug**. What does this mean?
requires metabolism by P450 system to its active form
131
Interactions of clopidogrel & ticagrelor?
* 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
Give 2 major indications for warfarin
1. VTE → treatment & prevention of recurrence (DOACs are an alternative)
2. Prevention of arterial embolism in patients with AF or prosthetic heart valves
133
Treatment with warfarin is **lifelong** in what type of prosthetic heart valves?
Mechanical
134
Treatment with warfarin is short-term in what type of prosthetic heart valves?
Tissue valve replacement
135
Warfarin requires initial concomitant therapy with what? Why?
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
What is venous and intracardiac clot formation driven by?
the coagulation cascade (while arterial thrombosis is more a phenomenon of platelet activation)
137
What is the coagulation cascade?
The coagulation cascade is an **amplification** reaction between clotting factors that generates a **_fibrin_** **clot**
138
Mechanism of warfarin?
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
What are the vitamin K dependent clotting factors?
10, 9, 7, 2
140
What enzyme does warfarin inhibit?
Vitamin KO reductase
141
Side effects of warfarin?
* Bleeding (e.g. intracerebral haemorrhage after minor head injury)
* Can cause coumarin induced skin necrosis
* Spontaneous bleeding e.g. epistaxis
142
What is coumarin induced skin necrosis?
Skin and subcutaneous tissue necrosis occur due to **acquired protein C deficiency** following treatment with vitamin K anticoagulant
143
What is the reversal agent for warfarin?
**Phytomenadione** (vitamin K1) or **prothrombin complex concentrate** (PCC)
144
Contraindications to warfarin?
* Immediate risk of haemorrhage e.g. trauma, surgery
* Pregnancy
* Malignancy
* Caution in liver disease (risk of overtoxicity)
* Haemorrhagic stroke
* Bleeding
145
Interaction between warfarin and NSAIDs?
* NSAIDs displace warfarin from plasma albumin – potentiates effects
* NSAIDs inhibit platelet function
These both cause an **increased risk of bleeding**
146
Metabolism of warfarin?
P450 system
147
Give some examples of P450 enzyme **inhibitors**
* Clarithromycin/erythromycin
* Ciprofloxacin
* Amiodarone
* Oral contraceptives
* St John's Wort
148
Give some examples of P450 enzyme **inducers**
* Phenytoin
* Carbamazepine
* Alcohol
* Allopurinol
* SSRIs
149
How can Abx interact with warfarin?
Can **increase** the effect of warfarin by **killing gut flora** that synthesise vitamin K (usually not a clinical problem)
150
What does INR represent?
international nationalised ratio is a measure of how long it takes your blood to clot
151
Give some examples of heparin
* Enoxaparin
* Dalteparin
152
Give 3 major indications for heparin
1. 1ary **_prevention_** of VTE in hospital inpatients
2. ACS → used with antiplatelets to reduce clot progression
3. Given alongside initiation of warfarin
153
MOA of UFH vs LMWH heparin?
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
What is fondaparinux?
A synthetic anticoagulant
155
MOA of fondaparinux?
Mimics the sequence of the binding site of heparin to AT and is very specific for **Xa**
156
Reversal agent for heparin?
Protamine (effective for **UFH**, less effective for LMWH and no effect against fondaparinux)
157
Reversal agent for fondaparinux?
none
158
What is the pharmacological agent & dose of choice for VTE prophylaxis in hospital inpatients?
Heparin 5000 units SC daily
159
What should be monitored when taking heparin?
Platelet count due to risk of HIT
160
Why is warfarin initially pro-thrombotic?
due to initial inhibition of natural anticoagulants (protein C and S) before its effect on clotting factors II, VII, IX, X
161
Give 2 major indications for DOACs
* **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
What is valvular AF?
Seen in people who have a heart valve disorder or a prosthetic heart valve
163
What is non-valvular AF?
Caused by other things such as hypertension or stress.
164
General mechanism of DOACs?
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
Which DOACs inhibit factor Xa? What does this prevent?
Rivaro**x**aban, api**x**aban, edo**x**aban
Inhibition of Xa prevents conversion of **prothrombin** to **thrombin**
166
Which DOACs inhibit factor IIa? What does this prevent?
Dabigatran
Inhibition of IIa prevents conversion of **fibrinogen** to **fibrin**
167
describe the risk of bleeding in DOACs vs warfarin
Risk of intracranial haemorrhage and major bleeding is less with DOACs than with warfarin BUT risk of **GI** bleeding is greater
168
Contraindications for DOACs?
* 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
How will phenytoin affect the anticoagulant effect of DOACs?
Phenytoin is an enzyme inducer → reduces anticoagulant effect
170
How will rifampicin affect the anticoagulant effect of DOACs?
Rifampicin is an enzyme inducer → reduces anticoagulant effect
171
How will macrolides affect the anticoagulant effect of DOACs?
Macrolides are enzyme inhibitors → increase anticoagulant effect
172
How will fluconazole affect the anticoagulant effect of DOACs?
Fluconazole is an enzyme inhibitor → increase anticoagulant effect
173
Why are DOACs preferred over heparin in outpatient treatment/prevention of VTE?
Taken orally - no need for SC injections
174
What class of drug is digoxin?
Cardiac glyoside
175
Give 2 indications for digoxin
1. **Atrial fibrillation** or **atrial flutter** → rate control
2. **Severe heart failure**
176
Digoxin can be used for rate control (to reduce ventricular rate) in AF and atrial flutter. What drugs are typically used before this?
Beta blocker (bisoprolol) or CCB (verapamil or diltiazem).
Digoxin only used if beta blocker and CCB contraindicated.
177
Digoxin is indicated in which patients with HF?
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
Define chronotropic effects
Those that change the heart rate
179
Define ionotropic effects
Those that change the **contractility** of the heart
180
Describe the chronotropic and ionotropic effects of digoxin
Positively ionotropic → increases contractility of heart
Negatively chronotropic → reduces HR
181
Describe the mechanism of digoxin in the management of AF
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
Describe the mechanism of digoxin in the management of HF
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
Give some side effects of digoxin
* Bradycardia
* GI upset
* Rash
* Dizziness
* Visual disturbance
* Digoxin is proarrhythmic and has a low therapeutic index – risk of toxicity
* Digoxin toxicity – arrhythmias, delirium
184
What is digoxin toxicity treated with?
Digibind/Digifab
185
Give some contraindications of digoxin
* Second degree heart block
* Intermittent complete heart block
* Ventricular arrythmias
* **Renal failure**
* Hypokalaemia, hypomagnesaemia, hypercalcaemia
186
Why is digoxin contraindicated in AV block?
Can worsen conduction abnormalities
187
Which electrolyte abnormalities is digoxin contraindicated in? Why?
**Hypokalaemia, hypomagnesaemia, hypercalcaemia**
## Footnote
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
Which drugs can increase the risk of digoxin toxicity?
**Loop** & **thiazide** diuretics – can increase risk of digoxin toxicity by cause **hypokalaemia**
189
How is digoxin metabolisd/eliminated?
Excreted by the kidneys **without** metabolism by the liver
190
Why is digoxin contraindicated in renal failure?
* 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
What is the main indication of amiodarone?
Cardiac arrest → VF or pulseless VT
192
Half life of amiodarone?
58 days so **loading dose** is often required
193
What class of drug is amiodarone?
Class III anti-arrythmic
194
Give some side effects of **chronic** amiodarone use
* Pneumonitis
* Hepatitis
* Skin – photosensitivity and grey discolouration
* Thyroid abnormalities – due to iodine content and structural similarities to thyroid hormone
195
Amiodarone increases plasma concentrations of which 3 drugs?
Increases plasma concentrations of **digoxin, diltiazem** and **verapamil –** this may increase risk of bradycardia, AV block and HF
196
Indication for adenosine?
* EMERGENCIES
* Used to terminate **supraventricular tachycardias**
197
Half life of adenosine?
10 seconds → given via infusion with large-calibre cannula due to short half-life
198
Side effects of adenosine?
**Bradycardia** and even **asystole** – due to interfering with functions of AV and SA node
199
What feeling is typically described by patients given adenosine?
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)
