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ACEM Primary VIVA > VIVA: Pharmacology - Cardiovascular > Flashcards

VIVA: Pharmacology - Cardiovascular Flashcards

1
Q

What is the mechanism of action of GTN?

A
  1. Taken up by vascular smooth muscle
  2. Denitrited by glutathione-S-transferase to release nitric oxide
  3. NO activates cGMP and reduces intracellular Ca2+, resulting in smooth muscle relaxation and vasodilation

Prostaglandins may be involved

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2
Q

What are the clinical effects of GTN?

A

Beneficial effects:
- Venodilation* -> reduced VR and decreased ventricular preload -> decreased LVEDV, LV wall tension -> reduced myocardial oxygen consumption*
- Vasodilation of epicardial coronary arteries -> increased coronary collateral flow
- Decreased systemic BP*

Adverse effects:
- Hypotension
- Tachycardia
- Headache

*2/3 to pass + 2 adverse effects

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3
Q

What are the indications for GTN use in the ED?

A
  • Angina*
  • Acute coronary syndrome
  • Hypertensive urgencies/emergencies
  • APO
  • Aortic dissection (with B blockade)

*needed to pass + 2 others

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4
Q

What is adenosine and how does it work?

A
  • Naturally-occurring nucleoside*
  • Blocks AV conduction* by activating inward rectifier K+ current (i.e. hyperpolarises the AV node)

*needed to pass

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5
Q

Describe the pharmacokinetics of adenosine

A
  • Short half-life (less than 30secs)*
  • Uptake by endothelial and red cells
  • Less effective in presence of adenosine receptor blockers (e.g. caffeine, theophylline)

*needed to pass

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6
Q

What are the side effects of adenosine?

A

4 to pass:
1. Cardiovascular:
- Chest tightness / burning
- Flushing
- Hypotension
- Arrhythmia
2. Neurological:
- Headache
- Paraesthesias
3. Respiratory:
- Bronchospasm
4. GIT:
- Nausea

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7
Q

What are the possible drug interactions with adenosine?

A

1/3 to pass:
- Theophylline inhibits (adenosine receptor blocker)
- Dipyridamole enhances (adenosine uptake blocker)
- Interactions with other AV nodal blocking drugs

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8
Q

What antiarrhythmic class does amiodarone belong to?

A
  • Class III*
  • Also has class I, II and IV effects

*needed to pass

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9
Q

What are the effects of amiodarone on the heart?

A
  • Increases action potential duration due to blockade of rapid component of delayed K+ current (Ikr)*
  • Chronic use also blocks slow K+ rectifier
  • Prolongs QT* (due to above effects)
  • Blocks inactivated Na+ channels
  • Weak adrenergic and Ca2+ channel blocker

*needed to pass

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10
Q

What other arrhythmias is amiodarone used for?

A

2 to pass:
- AF
- VT
- VF
- Supraventricular (re-entrant/accessory)

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11
Q

What arrhythmias may amiodarone cause?

A

1 to pass:
- TdP (rare, <1%)
- Bradycardia
- Heart block

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12
Q

Describe the pharmacodynamics of digoxin

A
  1. Inhibitor of Na+/K+ ATPase*:
    - Increases intracellular Na+, decreases intracellular K+
    - Increased intracellular Na+ leads to reduced Na+/Ca2+ exchanger activity which leads to increased intracellular Ca2+
    - Increased intracellular Ca2+ causes an increase in contractility (inotropy)
    - Inhibition of Na+/K+ ATPase in vascular smooth muscle causes depolarisation, which causes smooth muscle contraction and vasoconstriction
  2. Electrical effects*:
    - Direct: shortening of action potential, leading to shortened atrial and ventricular refractoriness
    - Increased automaticity of the heart muscle: leads to bigeminy, followed by VT and then VF
  3. Parasympathetic and sympathetic effects:
    - At lower doses, parasympathetic effects (early signs of toxicity = bradycardia, AV block)
    - At higher doses, increased sympathetic effect which may further sensitise the myocardium to automaticity

*needed to pass

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13
Q

What are the non-cardiac symptoms and signs of digoxin toxicity?

A
  1. GIT:
    - Anorexia
    - Nausea and vomiting
    - Diarrhoea
  2. CNS*:
    - Disorientation
    - Hallucinations
    - Yellow/green vision (or some variation of)
    - Chemoreceptor trigger zones

*1 example to pass

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14
Q

What factors may predispose a patient to digoxin toxicity?

A
  1. Electrolyte imbalances*:
    - Hypokalaemia (K+ normally inhibits digoxin binding to the Na+/K+ ATPase)
    - Hypercalcaemia (potentiates digoxin toxicity by increasing the intracellular Ca2+ stores, producing automaticity)
    - Hypomagnesaemia
  2. Drugs that increase digoxin effect*:
    - Amiodarone (by increasing plasma digoxin concentrate)
    - Diltiazem
    - Verapamil
    - Quinidine
    - Macrolide antibiotics (azithromycin, erythromycin, clarithromycin)
    - K+ depleting drugs (including diuretics)
    - Spironolactone
  3. Organ disease:
    - Renal failure (important because of kinetics)
    - Hypothyroidism

*1 example of each to pass

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15
Q

What is digoxin’s mechanism of action in heart failure?

A

Ca2+ accumulation in cells * (due to Na+/K+ block*, increased intracellular Na+ reduces Na+/Ca2+ exchange):
- Increased contraction strength *
- Increased SV/CO per beat (with smaller EDSV, small heart, reduced right heart pressures/volume)
- Slower HR via effects on parasympathetic fibres/AV node, further increasing SV (particularly in AF)

*2/3 to pass

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16
Q

Why are patients in heart failure prone to digoxin toxicity?

A
  1. Poor renal function from low CO*
  2. Potential dehydration and/or other drug interactions* (e.g. ACEI, diuretics, spironolactone, Ca2+ channel blockers)
  3. Potential effects on effective Vd
  4. Low K+ from other heart failure medications, especially diuretics
  5. Poor cardiac reserve/output, altered digoxin handling during acute HF / fluid distribution changes / other major illnesses

*1/2 to pass + 1 other

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17
Q

What are the features of digoxin toxicity?

A
  1. Cardiovascular:
    - Arrhythmias due to increased automaticity and AV block (particularly bradyarrhythmias, but also R-on-T)
    - Severe heart block (particularly if pre-existing block)
    - Worsening HF
    - Hypotension
  2. Metabolic:
    - Hyperkalaemia* (associated strongly with mortality)
  3. GIT:
    - Anorexia
    - Nausea and vomiting
    - Diarrhoea
  4. CNS*:
    - Disorientation
    - Hallucinations
    - Yellow/green vision (or some variation of)
    - Chemoreceptor trigger zones
    - Lethargy, fatigue
    - Headaches
    - Paraesthesias

*1 example to pass

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18
Q

Describe the pharmacodynamics of propranolol that make it useful in thyrotoxicosis

A

Competitive non-selective B-blocker, blocking both B1 and B2 receptors*

Cardiovascular effects:
- Decreased BP
- Decreased HR (especially rate control of AF)
- Negative inotropy and chronotropy
- Decreased catecholamine effects which are prominent in hyperthyroidism

Inhibition of peripheral conversion of thyroxine to triiodothyronine (especially specific to propranolol over other B-blockers)

Also has Na+-channel blocking action (“membrane stabilisation”)

*needed to pass + 2 cardiovascular effects

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19
Q

What are the adverse effects of propranolol?

A
  1. CVS*:
    - Bradycardia
    - Hypotension
    - Worsening CCF
    - Worsening ischaemia in PVD
    - QRS widening and arrhythmias in toxicity
  2. CNS*:
    - Sedation
    - Depression
    - Dreams
    - Coma, seizure, delirium in toxicity
  3. Respiratory*:
    - Worsening asthma/COPD
  4. Other:
    - Decreased exercise tolerance
    - Fatigue
    - Impotence
    - Decreased libido
    - Masks symptoms of hypoglycaemia

*1 example from each

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20
Q

Describe the mechanism of action of verapamil

A
  • Block voltage-gated L-type Ca2+ channels* (a1 subunit) to reduce frequency of opening when depolarised, resulting in decreased transmembrane Ca2+ current* and Ca2+ influx*
  • Decreases AV node conduction and contractility*, thereby reducing CO
  • Also causes vascular smooth muscle relaxation (moreso with dihydropyridines)

*needed to pass

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21
Q

What are the toxic effects of verapamil?

A
  1. Cardiovascular*:
    - Bradycardia
    - AV block
    - Cardiac arrest
    - Heart failure
    - Hypotension
  2. Minor*:
    - Flushing
    - Dizziness
    - Nausea
    - Constipation
    - Peripheral oedema

*3 cardiovascular and 1 minor needed to pass

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22
Q

What antidotes can be used to treat verapamil toxicity?

A

1 to pass:
- IV calcium
- High-dose insulin euglycaemic therapy

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23
Q

What is the mechanism of enalapril?

A

Competitive inhibitor of angiotensin converting enzyme (ACE):
- Blocks conversion of angiotensin I to II*
- Decreases vascular tone* due to prevention of vasoconstrictive effects of angiotensin II (main effect)
- Inhibits aldosterone secretion* caused by angiotensin II leading to reduced Na+ and H2O resorption, and therefore decreased BP
- Increases bradykinin*, resulting in further vasodilation (angiotensin II normally metabolises bradykinin to its inactive form)

*2/4 to pass

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24
Q

What are the adverse effects of ACE inhibitors?

A
  1. Cardiovascular:
    - Hypotension* (first dose, especially if hypovolaemic, diuretics, NaCl restriction, GI loss) and dizziness
  2. Neurological:
    - Headache
    - Weakness
    - Loss of taste
  3. GIT:
    - Nausea
    - Diarrhoea
  4. Renal:
    - AKI
    - Hyperkalaemia (due to decreased aldosterone secretion)
  5. Other:
    - Fever
    - Rash
    - Joint pain
    - Angioedema
    - Cough, wheeze
  6. Reproductive:
    - Teratogenic

*needed to pass + 2 others

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25
Q

What other drugs can interact with ACE inhibitors and how?

A

2 to pass:
- Diuretics: hypotension, fluid loss
- K+-sparing diuretics, K+ supplements: hyperkalaemia
- Other nephrotoxins: AKI
- Lithium: hyperkalaemia, reduced effect of ACEIs, lithium toxicity
- Anaesthetics (any): hypotension
- NSAIDs: hyperkalaemia, makes ACEIs ineffective

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26
Q

What advantages do angiotensin receptor blockers have over ACEIs?

A
  • No effect on bradykinin, so reduced incidence of cough and angioedema
  • More complete inhibition of actions of angiotensin II (as there are enzymes other than ACE capable of generating angiotensin II)
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27
Q

Describe the pharmacodynamics of irbesartan

A
  • Competitive selective antagonist of angiotensin II type 1 (AT1) receptor*
  • Results in vasodilation and inhibition of aldosterone secretion

*needed to pass + 1/2 effects

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28
Q

What are the specific contraindications of angiotensin II receptor blockers?

A

2/5 to pass:
- Non-diabetic renal failure
- Pregnancy
- Allergy / previous adverse reaction
- Hyperkalaemia
- Renal artery stenosis

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29
Q

What is the mechanism of action of prazosin?

A
  • Selective alpha-1 receptor antagonist* in arterioles and venules
  • Reduces arterial pressure by dilating both resistance and capacitance vessels
  • a1-receptor selectivity allows noradrenaline to exert unopposed negative feedback (mediated by presynaptic alpha-2 receptors) on its own release

*needed to pass

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30
Q

List three non-BP effects of prazosin

A
  1. Cardiovascular:
    - Postural hypotension, dizziness, syncope
    - Reflex tachycardia, palpitations
  2. Neurological:
    - Headache
    - Lethargy
  3. Genitourinary:
    - Reduces prostate smooth muscle tone (alleviating prostatic urinary obstruction)
  4. Metabolic:
    - Decreased LDL and triglycerides, increased HDL
  5. Other:
    - Positive serum antinuclear factor
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31
Q

What non-antihypertensive benefits do ACEIs have in diabetes mellitus?

A
  • Diminishes proteinuria and stabilises renal function (even in the absence of lowering of blood pressure)
  • Now recommended in diabetes even in the absence of HTN
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32
Q

How is ramipril eliminated? Why is this important?

A
  • Eliminated primarily by the kidneys*
  • Doses of these drugs should be reduced in patients with renal insufficiency

*needed to pass

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33
Q

What is the mechanism of action for beta blockers in general?

A
  • Bind to beta receptors in the heart, lung and endocrine tissue
  • Beta receptor activation by circulating catecholamines is antagonised by beta blockers*
  • Selective bind beta 1 receptors, non-selective bind beta 1 and 2 receptors*
  • Most are pure antagonists

*needed to pass

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34
Q

Describe the pharmacokinetics of metoprolol

A
  1. Absorption *:
    - Rapid and complete
    - Given orally (onset 1-2hrs) and IV (onset 20mins when infused over 10mins)
    - Oral bioavailability 50% * due to significant first pass effect
  2. Distribution *:
    - Large (3.2-5.6L/kg, >200L)
    - Crosses the BBB
    - 10-12% protein binding to albumin *
  3. Metabolism *:
    - Extensive hepatic metabolism via CYP2D6
    - Elimination half-life 3-4hrs *
  4. Excretion *:
    - Urine 95%
  • 4/7 to pass
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35
Q

What are the side effects of beta blockers?

A
  1. Cardiovascular*:
    - Hypotension
    - Bradycardia
    - Heart block
    - Depressed myocardial contractility
    - Heart failure
    - Dizziness
    - Peripheral vasoconstriction, Raynaud’s, claudication
  2. Neurological:
    - Fatigue
    - Sedation
    - Depression
    - Nightmares
    - Abrupt withdrawal effects
    - Sexual dysfunction
  3. Respiratory:
    - Bronchospasm
  4. Endocrine:
    - Masks signs of hypoglycaemia (e.g. tachycardia, pupil dilatation)
  5. Interactions:
    - Exacerbates Ca2+ channel blocker effects

*cardiac + 2 others to pass

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36
Q

What are the cardiovascular effects of metoprolol?

A
  • Negative inotropic and chronotropic effects*
  • Slows AV node conduction with increased PR interval on ECG
  • Decreases BP by a mechanism not fully understood but probably includes suppression of renin release and CNS effects

*needed to pass

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37
Q

How does metoprolol differ from propranolol in its receptor action?

A
  • Metoprolol is B1 specific and propranolol is not* (equipotent at B1 and B2)
  • B1 equipotent (full agonist)
  • B2 50-100x less potent
  • At higher doses is less specific

*needed to pass

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38
Q

Describe the pharmacodynamics of propranolol

A

Mechanism of action:
- Competitive non-selective B antagonist

Effects:
1. Cardiovascular:
- Negative inotropy and chronotropy
- Increased PR interval
- Decreased BP if high
- Decreased renin release
2. Respiratory:
- Bronchospasm
3. Eye:
- Decreased IOP due to decreased humour production
4. Metabolic:
- Glycogenolysis
- Increased VLDL, decreased HDL

39
Q

Describe the effects of verapamil on the heart and blood vessels

A
  • Reduced contractility / CO*, reduced O2 demand
  • Reduced impulse generation, AV node conduction block*
  • Vascular smooth muscle relaxation* (less than dihydropyridines) or reduced coronary artery spasm

*2/3 to pass

40
Q

What are the indications for verapamil?

A
  • Angina*
  • HTN*
  • Atrial arrhythmias*
  • Migraine

*2/3 to pass

41
Q

What class of drug is frusemide?

A

Loop diuretic

42
Q

What are the pharmacokinetics of frusemide?

A

3 to pass:
1. Absorption:
- Well absorbed with variable oral bioavailability, 10-100%
- Onset post oral 1-3hrs, IV 15-30mins
- Peak effect oral 1hr, IV 30mins
- Duration of action oral 2-6hrs, IV 2hrs
2. Distribution:
- Highly albumin bound (>95%)
3. Metabolism:
- 50% conjugated in kidney and 50% excreted in urine unchanged
- Small amount metabolised by liver
- Elimination half-life 1.5-2hrs
4. Elimination:
- Renal (tubular secretion)

43
Q

What are the adverse effects of frusemide?

A
  1. Cardiovascular*:
    - Orthostatic hypotension
    - Dehydration
  2. Metabolic*:
    - Hyponatraemia
    - Hypokalaemia
    - Hypomagnesaemia
    - Hyperglycaemia
    - Metabolic alkalosis
    - Raised uric acid and gout
    - Increased LDL and triglycerides, decreased HDL
  3. Neurological:
    - Ototoxicity (with high dose IV)
    - Tinnitus
    - Vertigo
  4. GIT:
    - Pancreatitis
    - Jaundice
    - Nausea and vomiting
  5. Renal:
    - Interstitial nephritis
  6. Haematological:
    - Thrombocytopaenia
    - Eosinophilia
  7. Allergic:
    - Hypersensitivity reactions
    - Rash
    *1 of each to pass
44
Q

What are the possible drug interactions of frusemide?

A

1 to pass:
- NSAIDs
- Aminoglycosides
- Anticoagulants
- Digoxin
- Lithium
- Propranolol
- Probenecid
- Thiazides
- Amphotericin B
- Cisplatin

45
Q

How does frusemide exert its action?

A
  • Selectively inhibits Na+/K+/2Cl- transporter in thick ascending limb of loop of Henle to prevent resorption of Na+ and Cl-*
  • Abolishes counter-current concentrating mechanism leading to dilute urine
  • Increases prostaglandin synthesis -> inhibits salt transport in thick ascending limb, increases renal blood flow, decreases pulmonary congestion, decreases LV filling pressures

*needed to pass

46
Q

Why is mannitol used in the management of head injury?

A

Mannitol is used to reduce intracranial pressure post head injury

47
Q

What is the mechanism of action of mannitol?

A
  • Mannitol is an osmotic diuretic*
  • Alters Starling forces as it does not cross the intact BBB and thus draws water out of cells to reduce intracellular volume (hence reducing intracranial volume and intracranial pressure)
48
Q

What are the other clinical effects of mannitol besides its effect on intracranial pressure?

A

2/4 to pass:
- Reduces intraocular pressure
- Diuresis / dehydration / hypovolaemia
- Hypernatraemia
- Hyperkalaemia

49
Q

What is an appropriate dose of mannitol in head injury?

A

1-2g/kg as an IV bolus over 15mins*

  • 0.25-2g/kg acceptable range
50
Q

Describe the mechanism of action of thiazides

A

Inhibition of Na+/Cl- transporter in the distal convoluted tubule*, leading to increased NaCl excretion and diuresis

*needed to pass

51
Q

What are the major clinical indications for thiazide diuretic use?

A
  • Heart failure*
  • HTN*
  • Nephrolithiasis
  • Nephrogenic diabetes insipidus
  • Generalised oedema
  • Nephrotic syndrome
  • Cirrhosis

*needed to pass

52
Q

What are the potential adverse effects of thiazide diuretics?

A
  1. Cardiovascular:
    - Orthostatic hypotension, hypovolaemia*
    - Dehydration*
  2. Metabolic:
    - Hypokalaemia*
    - Hyponatraemia*
    - Hyperuricaemia
    - Hypercalcaemia
    - Metabolic alkalosis
    - Impaired carbohydrate tolerance, hyperglycaemia
  3. GIT:
    - Pancreatitis
  4. Allergy:
    - Cross-reactivity with sulphonamides

*2/4 to pass + 1 other

53
Q

What is the mechanism of action of clopidogrel?

A

Antiplatelet effect by inhibiting ADP pathway*:
- Irreversible blockade of ADP receptor on platelet for life of platelet

*needed to pass

54
Q

Describe the pharmacokinetics of clopidogrel

A
  1. Absorption:
    - Loading dose 300-600mg* or 75mg daily*
  2. Metabolism:
    - Prodrug* metabolised to pharmacologically active metabolite and inactive metabolites
    - Activated in liver by cytochrome P450 enzymes* (including CYP2C19)
    - 80% of platelet activity inhibited within 5hrs of oral dose
    - Elimination half-life 0.5-1hrs*
    - Effects last the life of the platelet*
  3. Elimination:
    - Following an oral dose: 50% excreted in the urine and 46% in the faeces in next 5 days
    * 2/6 needed to pass
55
Q

What are the adverse effects of clopidogrel?

A
  1. Haematological:
    - Bleeding*
    - Pancytopaenia, TTP (rarely)
  2. GIT:
    - Reflux
    - Gastric ulcers
    - Abdominal pain
    - Diarrhoea
  3. Neurological:
    - Paraesthesias
  4. Dermatological:
    - Rash

*needed to pass + 2 others

56
Q

How does heparin act?

A
  • Heparin binds endogenous antithrombin and enhances its activity*
  • Antithrombin inhibits factors IIa, IXa and Xa* by complexing with them and inducing a conformational change

*needed to pass

57
Q

How may heparin be administered?

A
  • Parenteral (IV or subcut)*, nebulised
  • Continuously (following bolus) vs intermittent
  • Therapeutic vs prophylactic

*needed to pass

58
Q

What are the potential adverse effects of heparin?

A
  1. Haematological:
    - Bleeding*
    - Heparin-induced thrombocytopaenia*
  2. Dermatological:
    - Alopecia
  3. Allergy
  4. Endocrine:
    - Osteoporosis
    - Mineralocorticoid deficiency
    *needed to pass + 1 other
59
Q

What are the advantages of low molecular weight heparins compared with unfractionated heparin?

A
  • Have equal efficacy
  • Increased subcut bioavailability
  • Require less frequent dosing
  • Require less monitoring
  • Shorter chain heparin with less effect on thrombin (IIa)
60
Q

Describe the mechanism of action of rivaroxaban

A

Inhibits both free and prothrombinase-bound forms of activated factor X

61
Q

Describe the pharmacokinetics of rivaroxaban

A
  1. Absorption:
    - Oral bioavailability >80%
    - Peak levels 3hrs post-ingestion
  2. Distribution:
    - Small volume of distribution (<50L)
    - Highly protein bound
  3. Metabolism/elimination:
    - Elimination renal (predominant)* and hepatic (CYP3A4) with steady state half-life 5-14hrs
    - Prolonged with renal impairment

*needed to pass + 2 others

62
Q

What clinical advantages does rivaroxaban offer over warfarin?

A

2 to pass:
- More rapid onset/offset of action
- More predictable effect = easier dosing, wider therapeutic index
- INR monitoring not required
- Fewer drug and dietary interactions

63
Q

Do the pharmacokinetics of rivaroxaban present any clinical disadvantages relative to warfarin?

A

Predominant renal excretion means dose must be adjusted in renal failure, and is not suitable for dialysis patients

64
Q

What are the classes of thrombolytic agents?

A
  1. tPA* (tissue plasminogen activator; e.g. alteplase, tenecteplase, reteplase)
  2. Streptokinase* (protein synthesised by streptococci)

*needed to pass

65
Q

What is the mechanism of action of tissue plasminogen activator?

A
  • tPA is an enzyme that directly converts plasminogen to plasmin*
  • Plasmin is the major fibrinolytic enzyme
  • Preferentially activates plasminogen bound to fibrin by several hundred fold, therefore is considered clot-specific
  • Short half-life therefore heparin is an essential adjunct
  • Naturally-occurring

*needed to pass

66
Q

What are the adverse effects of thrombolytic agents?

A
  1. Haematological:
    - Bleeding* (including cerebral haemorrhage, gastrointestinal haemorrhage, and from sites of recent surgery/wounds)
  2. Allergy (especially streptokinase)

*needed to pass

67
Q

What are the clinical uses of tPA?

A
  • AMI*
  • PE*
  • Acute ischaemic stroke*
  • Severe DVT
  • Intra-arterial peripheral limbs

*needed to pass

68
Q

Describe the mechanisms by which drugs interact with warfarin

A

Pharmacokinetic*:
- Enzyme inhibition (majority)
- Enzyme induction
- Altered plasma protein binding
- Altered absorption

Pharmacodynamic*:
- Synergism (impaired haemostasis)
- Competitive antagonism (clotting factor synthesis/concentration)

*1 example of each to pass

69
Q

Give some examples of drugs that increase INR when administered with warfarin

A

1 to pass:
- Aspirin
- Heparin
- Corticosteroids
- Metronidazole
- Fluconazole
- Trimethoprim-sulfamethoxazole
- Third generation cephalosporins
- Macrolides
- Amiodarone
- SSRIs
- Tramadol

70
Q

Give some examples of drugs that decrease INR when administered with warfarin

A

1 to pass:
- Vitamin K
- Diuretics
- Barbiturates
- Phenytoin
- Carbamazepine
- Rifampicin
- Dicloxacillin
- Azathioprine

71
Q

What is flecainide’s mechanism of action?

A
  1. Na+ channel blockade *:
    - Predominant action is to inhibit fast Na+ channel responsible for rapid upstroke of the myocardial action potential in cardiac conducting tissue
    - Class 1C * action with minimal effect on AP duration and slow dissociation from the channel (also no effect on QT interval)
    - Decreases the rate of rise of action potential with little effect on duration
72
Q

Describe flecainide’s pharmacokinetics

A

2 point to pass:
Absorption:
- Well-absorbed orally
- Peak plasma levels at 3hrs
- Usual dose 100-200mg daily
Distribution:
- Vd 5-12.4L/kg
Metabolism and elimination:
- Elimination half-life 20hrs
- 30% excreted unchanged in urine, remainder by hepatic metabolism

73
Q

In which patients is flecainide contraindicated?

A
  • Hypotension
  • LV dysfunction
74
Q

Describe the mechanism of action of lignocaine on the heart

A
  • Class 1B antiarrhythmic *
  • Blocks activated and inactivated Na+ channels *, with greater effect in ischaemic tissue
  • Decreases pacemaker activity
  • No vagal effects
  • May cause hypotension by depressing myocardial contractility in those with heart failure

*needed to pass

75
Q

Describe the adverse effects of lignocaine

A

3 to pass:
1. CNS:
- Ototoxicity
- Tinnitus
- Dizziness
- Tremor
- Visual disturbance
- Paraesthesia
- Slurred speech
- Seizure
2. CVS:
- Bradycardia
- Hypotension
- Cardiovascular collapse
- Proarrhythmia (uncommon; includes SA arrest)
- Worsening of CCF
3. Respiratory:
- Respiratory depression
4. GIT:
- Anorexia
- Nausea and vomiting
5. Allergy

76
Q

What are the clinical uses of lignocaine?

A

2/3 to pass:
- Type 1B antiarrhythmic
- Local anaesthetic
- Post-herpetic neuralgia

77
Q

What features distinguish lignocaine from other class 1 antiarrhythmics?

A
  • Does not prolong duration of AP *
  • Dissociates from channel with rapid kinetics
  • No effect on normal cells (preferentially affects ischaemic tissue)

*needed to pass

78
Q

How are class 1 anti-arrhythmics classified? Give an example of each

A

1A (intermediate dissociation): quinidine, procainamide
1B (rapid dissociation): lignocaine, phenytoin
1C (slow dissociation): flecainide

79
Q

What are the differing effects on the action potential of class 1A, B and C antiarrhythmics?

A

1A: prolongs
1B: nil
1C: minimal

80
Q

List the classes of drugs used for the management of AF in the ED

A

3/5 to pass:
- B blockers
- Ca2+ channel blockers
- Cardiac glycosides
- Class 1c antiarrhythmics
- Class 3 antiarrhythmics

81
Q

Describe the pharmacodynamics of sotalol

A
  • Non-selective B-blocker (class II)
  • Prolongs plateau phase (class III)
82
Q

What are the main side effects of sotalol?

A
  • Proarrhythmic (especially QT prolongation * with risk of TdP)
  • CCF
  • AV blockade
  • Asthma

*needed to pass + 1 other

83
Q

What drug interactions with sotalol prolong the QT?

A

2 to pass:
1. Drugs which prolong QT:
- E.g. phenothiazines, macrolides, quinolones, antidepressants
2. Drugs which cause hypokalaemia and hypomagnesaemia
3. Myocardial depressant drugs
4. Drugs that increase refractory time and contraction
- E.g. CCBs, class 1a antiarrhythmics

84
Q

List some drugs used in hypertensive emergencies

A

3 to pass:
- GTN
- Nifedipine
- Diazoxide
- Hydralazine
- Nitroprusside
- Esmolol
- Labetalol

85
Q

Describe the pharmacokinetics of sodium nitroprusside

A

Absorption:
- IV administration
- Onset within minutes *
- Peak effect within minutes
Metabolism:
- Elimination half-life 2mins *
- Duration of action 1-10mins
- To cyanide in RBCs *
- To thiocyanate in liver *
Excretion:
- Renally excreted

*2/4 to pass

86
Q

What are the potential toxicities of sodium nitroprusside?

A
  1. Cyanide toxicity:
    - Hypotension
    - Metabolic acidosis
    - Pink skin
    - Tachypnoea
    - Hyporeflexia
    - Mydriasis
    - Coma
  2. Thiocyanate:
    - Ataxia
    - Blurred vision
    - Headache
    - Nausea and vomiting
    - Tinnitus
    - SOB
    - Delirium
    - Unconsciousness
87
Q

What are the effects of Ca2+ channel blockers on smooth muscle?

A

Relax smooth muscle, especially vascular:
- Arterioles more sensitive than veins
- Does affect bronchiolar, GIT and uterine

88
Q

Why is verapamil more efficacious than dihydropyridines in the treatment of arrhythmias?

A
  • Blockade of L-type channels is more marked in tissues that fire frequently
  • Therefore more pronounced effects on tissues less polarised at rest and that depend on Ca2+ channels for activation (i.e. SA and AV nodes)
89
Q

By what mechanisms do Ca2+ channel blockers control angina?

A
  • Decrease myocardial contractility *
  • Decrease O2 demand
  • Decrease afterload by relaxing vascular smooth muscle *
  • Verapamil/diltiazem have a non-specific anti-adrenergic effect and decrease HR
  • Relieve and prevent coronary artery spasm

*needed to pass

90
Q

What are the actions of acetazolamide?

A

Carbonic anhydrase inhibitor, acting in:
- Ciliary body
- Choroid plexus
- Proximal renal tubules

91
Q

What are the toxic effects of acetazolamide?

A
  • Hyperchloraemic metabolic acidosis
  • Renal stones (PO43-, Ca2+)
  • Renal K+ wasting
  • Drowsiness, paraesthesia
  • Increased risk of neurological toxicity with renal failure due to reduced elimination
  • Hepatic encephalopathy in patients with cirrhosis due to reduced renal excretion of ammonia
92
Q

How are osmotic diuretics handled by the kidney?

A
  • Freely filtered by glomeruli
  • Not reabsorbed
  • Causes water retention in the freely permeable sections of the nephron (proximal tubule and descending loop of Henle)
93
Q

What are the clinical indications for antiplatelet agents?

A

3/4 to pass:
- IHD
- TIA/CVA
- Pregnancy for prophylaxis of pre-eclampsia
- Post acute coronary intervention

94
Q

Why is there a delay in the onset of action of warfarin?

A
  • 8-12hr delay due to partially inhibit synthesised and unaltered degradation of vitamin K dependent clotting factors (II, VI, IX, X)
  • Depends on degradation half-life in circulation (VII 6hrs, IX 24hrs, X 40hrs, II 60hrs)

ACEM Primary VIVA (45 decks)

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