Cardiovascular system

Question 1

Digoxin

Answer 1

Cardiac Glycoside
Inhibits Na+/K+ ATPase, reverses activity of Na+/Ca2+ exchange leading to positive inotropy
Enhances vagal activity, reduces conductivity in AV node - antiarrythmic
Heart failure and supraventricular arrythmias
Can’t use in heart failure that is bradycardic or has normal heart rate.
Side effects: Bradycardia, nausea, vomiting, diarrhoea, arrthymias

Question 2

Bendroflumethiazide & Indapamide

Answer 2

Thiazide & thiazide like diuretic
Act on NaCl cotransporter in DCT
Used in hypertension, first line if CCB not appropriate or as an add on
ADRS: hypokalaemia and hyponatraemia, hyperglycaemia, dyslipidaemia, postural hypotension
DDIS: less effective when given with NSAIDS as GFR reduced. Can’t use in renal failure for the same reason.

Question 3

Furosemide and Bumetanide

Answer 3

Loop Diuretics
Act on NaKCC2 channels in thick ascending limb
Use in fluid overload - pulmonary oedema, heart failure, ascites
ADRS: hypovolaemia and dehydration, hypokalaemia and hyponatraemia, ototoxicity
DDI: aminoglycosides - ototoxicity and nephrotoxicity, reduced excretion of drugs excreted by the kidneys

Question 4

Amiloride

Answer 4

Potassium sparing diuretic
Inhibit ENaC in late DCT and CDs
Weak on their own, used alongside thiazide or loops to avoid hypokalaemia
ADRs: GI upset, hypotension, urinary frequency. Don’t use in hyperkalaemia or renal impairment.
DDIS: don’t use with potassium or spironolactone. May alter renal clearance of drugs like digoxin

Question 5

Spironolactone

Answer 5

Aldosterone antagonist - potassium sparing diuretic
Inhibiting aldosterone reduces activity of ENaC in late DCT and collecting ducts.
Used in ascites and oedema in liver disease, primary hyperaldosteronism (Conns disease)
ADRs: hyperkalaemia, gynaecomastia, liver impairment and jaundice
DDIs: Potassium elevating drugs. Don’t give in renal impairment or Addisons Disease

Question 6

Adenosine

Answer 6

Antiarrthymic
Binds adenosine receptors, decreases automaticity, increases refractoriness. Slows rate. Breaks re-entry circuit if involves AVN
Indications: supraventricular tachycardia (AF). Very short half life - give bolus,
ADRS: bradycardia and asystole, unpleasant sensation (short lived)
Contraindication: Hypotension, ischaemia, decompensated heart failure (if patient cant tolerate bradycardia), Asthma and COPD (Bronchospasm)
DDI: Dipyridamole - blocks cellular uptake of adenosine and prolongs its affect.

Question 7

Amiodarone

Answer 7

Class III antiarrthymic - K+ channel blocker. Blocks Na+ and Ca+, as well as Alpha and Beta adrenoceptor antagonist (so can be all the classes)
Used in tachyarrthymias - AF, Atrial Flutter, VF, VT
ADRS: hypotension, pneumonitis, hepatitis, photosensitivity, thyroid disease.
DDIs: digoxin, CCBs

Question 8

Flecainide

Answer 8

Class IC antiarrthymic (Na+ channel blocker)
Uses: Wolff-Parkinson-White, used in supraventricular arrthymias and ventricular tachycardias
Take care in AF, heart block and atrial flutter
ADRs: Arrthymia and sudden death post MI, increased ventricular response to atrial rhythm in atrial flutter (give with AV node conductance block) CNS and GI effects
DDI - Amiodarone increases plasma concentration. Take care with beta blockers.

Question 9

Lidocaine

Answer 9

Class 1B antiarrthymic - Na+ channel blocker. Use dependent blockade - binds opened or inactivated channels - more effective in diseased tissue. Reduces action potential direction, slows conduction velocity, increases refractory period.
Uses: VT and VF
ADRs: hypotension and arrthymias, drowsiness, tremor and fits.

Question 10

Atenolol, Bisoprolol & Propranolol

Answer 10

Beta Blockers - Antagonise beta-adrenoceptors. Propranolol is non-selective, Bisoprolol and Atenolol are selective for Beta-1 receptors.
Reduce automaticity, slow heart rate, reduce force of contraction - reduce oxygen demand of myocardium, inhibit renin release.
Uses: Left ventricular systolic dysfunction (stable heart failure), angina, sinus tachyarrthymias, protecting ventricles from high atrial rates
ADRs: Lethargy, reduced exercise tolerance, bradycardia, Raynauds, impaired glucose tolerance. Bronchoconstriction - dont give in asthma, hypotension, don’t use in partial AV block

Question 11

Sotalol

Answer 11

Class III antiarrthymic - Potassium channel blocker, also acts as beta blocker.
Caution: prolongs QT interval
Uses: supraventricular and ventricular tachycardia
ADRs: proarrthymic, fatigue, insomnia (centrally available)

Question 12

Doxazosin

Answer 12

Alpha Adrenoceptor antagonist - selective for post-synaptic alpha-1 adrenoceptors. Antagonise contraction of vascular smooth muscle, reduce TPR.
ADRs: Postural hypotension, dizziness, headache and fatigue, oedema
DDIs: Dihydropyiridines - worsen oedema

Question 13

Lisinopril & Ramipril

Answer 13

Angiotensin Converting Enzyme Inhibitors - Inhibit production of angiotensin II and potentiates the effect of bradykinin. Lead to arteriolar vasodilation and venodilation, reduced circulating aldosterone.
First line agent for hypertension in people under 55 who aren’t black.
ADRs: dry cough, angio-oedema, renal failure, hyperkalaemia

Question 14

Candesartan, Losartan

Answer 14

Angiotensin Receptor Blockers.
Bind AT1 receptor, inhibit vasoconstriction and aldosterone stimulation - no effect on bradykinin.
Well tolerated. Side effects - renal failure and hyperkalaemia.
DDIs = diuretics that lead to hyperkalaemia.

Question 15

GTN spray, Isosorbide Mononitrate

Answer 15

Nitrates - used as sublingual spray for angina.
Cause vasodilation -
Contraindications - hypotension and hypovolaemia, RICP, cardiomyopathy, aortic stenosis
ADRs: postural hypotension, throbbing headaches, dizziness, nausea and vomiting

Question 16

Amlodipine

Answer 16

Calcium Channel Blocker - Dihydropyridine
Vasodilation - lowers blood pressure
Metabolised by Liver
ADRs: SNS activation - tachycardia, palpitations. Flushing, sweating, headache, oedema, gingival hyperplasia

Question 17

Verapamil

Answer 17

Calcium Channel Blocker - Phenylalkaline
Prolongs action potential and effective refractory period (Class IV antiarrthymic)
Use in supraventricular tachycardia
Causes vasodilation - reduction in preload and contractility, antihypertensive.
ADRs: Constipation, Bradycardia, Negative inotropy can worsen heart failure.

Question 18

Diltiazem

Answer 18

Calcium Channel Blocker - Benzothiazepine
Prolongs action potential and effective refractory period (Class IV antiarrthymic)
Vasodilation - lowers blood pressure.
Use in supraventricular tachycardia to control the ventricles or convert to sinus rhythm.
ADRs: Bradycardia, negative ionotropy (worsening of heart failure)

Question 19

Warfarin

Answer 19

Coumarin - inhibits production of vitamin K dependent clotting factors (2, 7, 9 & 10) by inhibiting recycling of vitamin K. Slow onset and offset.
Metabolised by CYP450
Indications: DVT, PE, AF, Prosthetic valves, inherited thrombophilia, CVA, cardiomyopathy, MI.
ADRs: Teratogenic, bleeding (GI, epistaxis, intracranial)
DDIs: CYP inhibitors potentiate effect (Amiodarone, Quinolone, Metronidazole, Cimetidine, Alcohol). Platelet inhibitors potentiate - aspirin. Reduced vitamin K production from gut bacteria potentiates (Cephalosporins).
Inhibition of warfarin by CYP inducers - antiepileptics except valproate, Rifampicin and St Johns Wort

Question 20

Heparin

Answer 20

Anticoagulant - activates Anti-Thrombin III, deactivates Xa, IIa, IXa
Can get unfractionated (IV) or LMWH (SC).
Uses: prophylactic perioperatively - used instead of warfarin when bleeding may need to be quickly stopped eg surgery, or as a loading dose whilst warfarin kicks in - DVT, PE, AF, ACS. Can be used in pregnancy.
ADRs: Bleeding - Intracranial, injection site, GI, epistaxis. Thrombocytopenia (Autoimmune, depletion of platelets as they are activated by immune complexes). Oseoporosis.

Question 21

Protamine Sulphate

Answer 21

Used to reverse Heparin therapy, if actively bleeding.
Dissociates Heparin from ATIII, binds irreversibly
ADRS: Anaphylaxis

Question 22

Aspirin

Answer 22

Anti-platelet Drug - Inhibits COX-1. This prevents formation of thromboxane A2 and inhibits platelet aggregation.
Indications: Secondary prevention in AF, claudication, angina and ACS
ADRs: Bleeding, Bronchospasm, hypersensitivity

Question 23

Dipyridamole

Answer 23

Anti-platelet drug - inhibits phosphodiesterase, increasing intracellular levels of cAMP and inhibiting aggregation.
Indications: Secondary prevention of stroke
ADRS: positive inotropy, vasodilation (flushes and headaches)

Question 24

Clopidogrel

Answer 24

Anti-platelet drug - ADP antagonist - prevents ADP binding P2Y12 receptor. Receptor is usually Gi so decreases cAMP levels, blocking it increases cAMP levels which inhibits aggregation.
Indications: Acute coronary syndrome, PCI.
ADRS: Bleeding, don’t use long term.

Question 25

Alteplase, Reteplase

Answer 25

Fibrinolytics - recombinant tissue plasminogen activator. Activates plasminogen which cleaves fibrin, as well as factors 2, 5 & 8.
Indications: Acute myocardial infarction. Alteplase is also used for stroke, DVT and PE.
ADRS: Nausea, Vomiting, Bleeding, reperfusion arrthymias, hypotension

Question 26

Simvastatin, Atorvastatin

Answer 26

Statins - inhibit HMG-CoA reductase, inhibit cholesterol synthesis in hepatocytes, increased synthesis of LDL receptor. Increased clearance of IDL and LDL
Indications: Primary and Secondary Prevention of Cardiovascular Disease
ADRs: Increased transaminase levels (rapidly reversible, no evidence of chronic liver disease), myopathy (muscle pain) - especially high dose combined with cyclosporine, gemfibrozil. GI Complaints, arthralgias and headaches.

Question 27

Bezafibrate

Answer 27

Fibrate - PPAR (Peroxisome Proliferator-Activated Receptor) agonist - increases lipoprotein lipase production. Reduces triglyceride production and some reduction in LDL. Increases fatty acid uptake and oxidation.
Indications: Adjunctive therapy to diet, hypertriglyceridemia, hyperlipidaemia with low HDL
ADRs: GI Upset, cholethiasis, myositis, abnormal LFTs
Contraindications: Hepatic or Renal dysfunction, gallbladder disease.

Question 28

Ezetimibe

Answer 28

Selective inhibition of intestinal cholesterol reabsorption - reduced delivery of cholesterol to the liver, increased expression of LDL receptors. Undergoes enterohepatic circulation which reduces systemic exposure
Indication: Hypercholesterolaemia
ADRs: Headache, abdominal pain and diarrhoea

Question 29

Nicotinic Acid

Answer 29

Inhibits lipoprotein a synthesis. Effect = reduces VLDL, increases HDL, reduces coronary events
ADRs: flushing, itching, headache , hepatotoxicity, GI upset (if sustained release), activation of peptic ulcers, hyperglycaemia and reduced insulin sensitivity
Contraindications: active liver disease or LFT elevations, peptic ulcer disease