What is Ivabradine?
Selective blocker of HCN channels
What is the effect of ivabradine?
Reduces slope of pacemaker potentialSlow HR reduces oxygen consumption
What are the side effects of ivabradine?
Arrythmias
Hypotnesion
What are examples of beta-adrenoceptor agonists?
Dobutamine (beta-1 selective)
Adrenaline
Noradrenaline
What is the mechanism of a beta-adrenoceptor agonist?
Results in stimulation of adenylyl cyclase and production of cAMP which generates protein kinase A
Phosphorylation increases Ca-influx & CICR
Increased contractility, force and rate
Decrease cardiac efficiency
What are side effects of beta-adrenoceptor agonists?
Arrhythmias
Acute MI
What is an example of a non-selective beta-blocker?
Propranolol
What is an example of a selective for beta-1 beta blocker?
Metprolol
Atenolol
What is the effect of a beta blocker?
Decrease HR, contractility and MAP
Decrease O2 consumption
What are the side effects of beta-blockers?
Asthma Fatigue Cold peripheries Heart failure Bradycardia (heart block) Hypoglycaemia
What is an example of a non-selective muscarinic antagonist?
Atropine
What is the effect of atropine?
Increase heart rate
What are the side effects of atropine?
Arrythmias
Hallucinations
Confusion
What type of drug is digoxin?
Cardiac glycoside
What is the mechanism of of digoxin`
Competes with K+ at the alpha subunit and blocks the Na/K/ATPase pump
Increase contractility by backing the sarcolemma ATPase
What are the indirect effects of digoxin?
Increased vagal activity, slows SA node discharge
What re the direct effects of digoxin?
Shortens action potential and refractory period
What are the overall effects of digoxin?
Increase force, contraction and CO
The effects of digoxin are dangerously enhanced with?
Hypokalaemia
What are the side effects of digoxin?
Heart block
Dysrhythmias
Myocarditis
What is Levosimendan?
Calcium sensitizer
What is the mechanism of Levosimendan?
Binds to troponin C in myocytes sensitising them to Ca
What are calcium sensitisers used for?
Acutely decompensated congestive heart failure
Increased contractility
What are the side effects of calcium sensitisers?
Headaches
Arrhythmias
Hypokalaemia
Class I AADs act on?
Voltage activated Na+ channels
Example of Class I AAD?
Flecainide
What is the effect of Flecainide?
Reduce Na channel current
What are the side effects of flecainide?
Negative inotropic effects
What is Flecainide used for?
Rhythm control
What is an example of a Class II AAD?
Propanolol (beta-adrenoceptor)
What is propranolol used for?
Rate control
What is an example of a Class III AAD?
Amiodarone
Sotalol
What do Class III AADs act on?
Activated K channels
What is the effect of Class III AADs?
Action potential prolongation
What are Class III AADs used for?
Rhythm control
What is an example of a Class IV AAD?
Verapamil
Verapamil is an example of a?
Ca channel antagonist
Class IV AADs are used to control`
rate
What are examples of nitrates?
Isosobride mononitrate
GTN spray
What is the mechanism of nitrates?
Mimic effect of endothelium
Produce nitric oxide which is formedthorugh influx of calcium, activation of eNOS and L-arginine
NO caused efflux of calcium producing hyper polarisation and relaxation
cGMP is also produced which regulates protein kinase G activity causing relaxation
Endothelin is also produced
What is the effect of nitrates?
Venorelaxation (decreased preload and after load, CO maintained as HR increase)
Arteriolar dilation, increased coronary blood flow
What are side effects of nitrates?
Headache
Hypotension
Tolerance is common
What are examples of ACEI?
Lisinopril
What is the mechanism of ACEI?
Block conversion of angiotensin I - II
Aldosterone and ADH not stimulation
What is the effect of an ACEI?
Vasodilation and arterial dilation
What are side effects of ACEI?
Dry cough
Renal dysfunction (bas with renal artery stenosis / god for diabetic nephropathy)
Angioneurotic oedema
Fetal abnormalities
What is an example of an ARB?
Losartan
What are side effects of ARBs`
Renal dysfunction
Oedema
Contraindicated in pregnancy
What are examples of calcium antagonists?
Amlodipine
Verapamil
Diltiazem
What is the mechanism of calcium antagonsits?
Decrease conduction at SA and AV node
Decrease heart rate
What are side effects of calcium antagonists?
Ankle oedema
Bradycardia
What are examples of alpha Blockers?
Doxazosin
What is the mechanism of alpha blockers`
Block alpha-adrenoceptors to cause vasodilation
What are side effects of alpha blockers?
Postural hypotension
What are examples of potassium channel openers?
Minoxidil
Nicorandil
What is the mechanism of K-channel openers?
Causes hyperpolarisation whcih striches of calcium channels
Mediated by ATP
Relaxation of vascular smooth muscle
What are side effects of K-channel blockers?
Tachycardia
Salt and water retention
What is the mechanism of a thiazide diuretic?
Inhibit NaCl reabsorption in distal tubules by blocking NaCl co-transporter
Increase excretion of Na, Cl, water – decrease blood volume
What is the mechanism of a loop diuretic?
inhibit NaCl reabsorption in the thick ascending limb of the loop of Henle
Increase excretion of Na, Cl, water – decrease blood volume
What are side effects of diuretics?
Hypokalaemia Arrythmias Fatigue Hyperglycaemia Increase uric acid = gout (arthritis due to uric acid deposits)
What are examples of statins?
Sim/Atorvastatin
What is the mechanism of statins?
Block HMG CoA reductase which inhibits the formation of cholesterol
Decrease LDL and total cholesterol
Stabilise atherosclerotic plaque and decrease thrombosis
What are side effects of statins?
Myalgia, myopathy, myositis (rarely rhabdomyolosis)
What are examples of fibres?
Bezafibrate
Gemfibrozil
What is the mechanism of fibres?
Agonsit of nuclear receptors which enhances transcription of lipoprotein lipase (LPL) which hydrolyses triglycerides to fatty acids and glycerol
What are side effects of fibres?
Myositis
What are examples of bile acid binding resins?
Colestyramine, colestipol, colsevelam
What is the effect of bile acid binding resins?
Inhibit cholesterol absorption
What is the mechanism of bile acid resins?
Causes the excretion of bile salts resulting in more cholesterol to be converted to bile salts
Bile resins bind bile in th intestine so it is not absorbed in the duodenum
Liver uses metabolised cholesterol to compensate for loss
What are the side effects of bile acid resins?
GI tract irritation
What is the mechanism of ezetimibe?
Decrease in LDL
What are side effects of Ezetimibe?
Diarrhoea
Abdominal pain
Headache
Contraindicated in breast feeding
What is the mechanism of warfarin?
Blocks clotting factors 2, 7, 9, and 10 (serine proteases - glycoprotein precursors of active thrombin factors)
G-carboxylase enzyme is stimulated by vitamin K and modifies the serine proteases
Anticoagulants act as vitamin K antagonists which prevents production of mature coagulation factors
What are side effects of warfarin?
Haemorrhage anywhere
Reversed by vitamin K
What is the mechanism of heparin?
Binds to antithrombin II, increasing its affinity for serine proteases to greatly increase their rate of activation
What is the mechanism of LMWH (enoxaparin and date-aron)?
Inhibit factor Xa (activates thrombin IIa - fibrin - blood clot)
Dabigatran and etexilate directly inhibit?
Thrombin
Ravaroxaban directly inhibits?
Factor Xa
What are side effects of anticoagulants (heparin, LMWH, Dbigatran, rivaroxaban)?
haemorrhage
Osteoporosis
hypoaldosteronism
Hypersensitivity reactions
What is the mechanism of aspirin?
Blocks COX inhibiting formation of TXA2 which causes cross linking of platelets
What is the mechanism of clopidgrel?
Blocks ADP from binding to P2Y12 receptor and formation of fibrin
What are the side effects of anti platelets (aspirin/clopidogrel)?
Haemorrhage anywhere
Peptic ulcer
Aspirin sensitivity –> asthma
What are examples of fibrinolytic drugs?
Streptokinase
Tissue plasminogen activator
Alteplase, duteplase
The fibrinolytic cascade opposes the?
Coagulation cascade
Fibrinolytic drugs activate formation of plasmid from plasminogen which …
lyses fibrin into fibrin fragments causing lysis of the clot
What are side effects of fibrinolytic drugs?
Haemorrhage risk (controlled by tranexamic acid which inhibits plasminogen activation)