3 - Cardiovascular and renal pharmacology Flashcards
Lidocaine
Local anaesthetic acting on VGNa channels
Stabilise inactivated state and make it harder to reactivate
Acts on intracellular surface
Shows use dependence
Nifedipine
Dihydropyridine
2 binding sites
- S6 segment and association loop of domain 4
- Close to phenylalkylamine binding site
Verapamil
Phenylalkylamine
Binding site at S6 and part of S5-6 loop
Diltiazem
Benzothiazepines
Block from outside
Modulate DHP binding
Propanolol
Non-specific B-antagonist
Blocks the effect of catecholamines
Atenolol
B1-antagonist
Blocks the effect of catecholamines
Coupled to Gs GProtein, so coupled to a rise in cAMP
Quinidine
Anti-dysrhythmic drug
Class 1A
Block VGNa channels
Increased AP duration, intermediate rate of association/dissociation
Procainamide
Anti-dysrhythmic drug
Class 1A
Block VGNa channels
Increased AP duration, intermediate rate of association/dissociation
Lidocaine (Class)
Anti-dysrhythmic drug
Class 1B
Block VGNa channels
Decreased AP duration, fast rate of association/dissociation
Flecainide
Anti-dysrhythmic drug
Class 1C
Block VGNa channels
No effect on AP duration, slow rate of association/dissociation
Propanolol/Atenolol
Antidysrhythmic agent
Class2
Sympathetic antagonists (B blockers)
Digoxin / Digitoxin
Cardiac glycosides Antidysrhythmic Alleviate oedema Inhibit NaKATPase pump Increase intracellular Na, reduce driving force for Ca exit, Ca builds up in cell
Oubain
Cardiac glycosides
Inhibit NaKATPase pump
Used experimentally - too powerful to be used clinically
Dobutamine
B1 selective analogue of dopamine
Intravenous
+ve ionotropic effect greater than chronotropic
Shock, increase CO after heart surgery, heart failure with no hypertension
However - increase oxygen demand, increase heart rate and blood pressure
Bisoprolol / Carvedilol
3rd generation B1 antagonist
Used in stable heart failure
Limit damaging effects of chronic stimulation by catecholamines and improve cardiac function
(reverse desensitization and downregulation of B adrenoceptors)
Inodilators
Phosphodiesterase inhibitors Raise intracellular cAMP Mimic B stimulation Can lead to dysrhythmias Vasodilation in smooth muscle, decreases afterload on heart
Milrinone
Inodilator Phosphodiesterase type 3 inhibitor Raide intracellular cAMP cGMP inhibited Dysrhythmias - short term treatment of severe heart failure
Dipyridamole
Inodilator
Phosphodiesterase type 5 inhibitor
Raise intracellular cAMP
cGMP specific
Sildenafil
Inodilator
Phosphodiesterase type 5 inhibitor
Raise intracellular cAMP
cGMP specific
Caffeine
Methylxanthine (caffeine/theophylline)
Non selective phosphodiesterase inhibitors
Also adenosine A1 A2 antagonists –> release of Ca from intracellular stores
Positive ionotropic and chronotropic effects
Pimobendan
Inodilator Calcium sensitizer Increase cardiac Ca binding efficiency to troponin without more energy requirement Peripheral vasodilation (PDE3 inhibitor) -canine dilated cardiomyopathy -canine mitral valve regurgitation
Levosimendan
Inositol/Ca sensitizer
Licensed for human use in heart failure in the UK
Bosentan
Non specific Endothelin 1 antagonist
Treat pulmonary arterial hypertension
Streptokinase
Clot lysis
Binds plasminogen activator and generates plasmin
Degradation of fibrin in clots and breakdown of clotting factors 2, 5, 7
Anistreplase
Combination of plasminogen and anisoylated streptokinase
Inactive until anisoyl group removed in blood
More prolonged activity
Alteplase
Recombinant human tissue plasminogen activator
Single chain
Greater activity on plasminogen bound to fibrin in clots - localising action
Duteplase
Recombinant human tissue plasminogen activator
Double chain
Greater activity on plasminogen bound to fibrin in clots - localising action
Aspirin
Alongside clot lysis therapies
Prevent further thrombosis
Can cause GI bleeding by influencing gastric acid secretion
Clopidogrel
With aspirin, alongside clot lysis therapies
Inhibits platelet aggregation by inhibiting ADP binding to receptor on platelets
Improves morbidity and mortality in heart disease patients
Eptifibatide
Inhibitor of glycoprotein 2b/3a receptor
(receptor needed for fibrinogen bridging between platelets)
Cyclic heptapeptide inhibitor
Prevention of myocardial infarction in patients with unstable angina
Tirofiban
Inhibitor of glycoprotein 2b/3a receptor
(receptor needed for fibrinogen bridging between platelets)
Non-peptide inhibitor
Prevention of myocardial infarction in patients with unstable angina
Abciximab
Monoclonal antibody against glycoprotein 2b/3a receptor (prevents fibrinogen bridging between platelets)
Also binds vitronectin receptor on platelets, endothelial cells and vascular smooth muscle cells - for coronary artery thrombosis
Heparin
Natural anticoagulant produced by basophils and mast cells
Binds to enzyme inhibitor anti-thrombin 3 (AT3) exposing active site
Activated AT3 inactivates thrombin and factor Xa
Used for unstable angina, treat deep vein thrombosis and as a prophylactic drug to prevent clots
Warfarin
Inhibits clotting, given orally
Inhibits synthesis of clotting factors 2, 7, 9 and 10 and regulatory factors protein C, S and Z
Prevent clotting on prosthetic heart valves
Interacts with many other chemicals
Rodenticide
Dabigatran
Thrombin inhibitor
In patients with atrial fibrillation and one additional risk factor for stroke.
Aminocaproic acid
Similar to lysine, competitively inhibits plasminogen activation
Inhibits severe bleeding caused by excessive clot lysis
Tranexamic acid
aminocaproic acid analogue
Similar to lysine, competitively inhibits plasminogen activation
Inhibits severe bleeding caused by excessive clot lysis
Renin
Production of angiotensin2
Furosemide
Loop diuretic
‘High ceiling’ - high rate of diuresis
Sulphonamide
Blocks NaK2Cl co transport in apical membrane thick ascending limb
Weak inhibition of carbonic anhydrase
Venodilation, reduce atrial filling pressure
Increase renal blood flow without a change in GFR
Ca Mg and K loss
Metabolic alkalosis
Uric acid excretion decreased –> gout
Bumetanide
Loop diuretic
‘High ceiling’ - high rate of diuresis
Sulphonamide
Eptifibatide
Inhibitor of glycoprotein 2b/3a receptor
(receptor needed for fibrinogen bridging between platelets)
Cyclic heptapeptide inhibitor
Prevention of myocardial infarction in patients with unstable angina
Tirofiban
Inhibitor of glycoprotein 2b/3a receptor
(receptor needed for fibrinogen bridging between platelets)
Non-peptide inhibitor
Prevention of myocardial infarction in patients with unstable angina
Abciximab
Monoclonal antibody against glycoprotein 2b/3a receptor (prevents fibrinogen bridging between platelets)
Also binds vitronectin receptor on platelets, endothelial cells and vascular smooth muscle cells - for coronary artery thrombosis
Heparin
Natural anticoagulant produced by basophils and mast cells
Binds to enzyme inhibitor anti-thrombin 3 (AT3) exposing active site
Activated AT3 inactivates thrombin and factor Xa
Used for unstable angina, treat deep vein thrombosis and as a prophylactic drug to prevent clots
Warfarin
Inhibits clotting, given orally
Inhibits synthesis of clotting factors 2, 7, 9 and 10 and regulatory factors protein C, S and Z
Prevent clotting on prosthetic heart valves
Interacts with many other chemicals
Rodenticide
Dabigatran
Thrombin inhibitor
In patients with atrial fibrillation and one additional risk factor for stroke.
Aminocaproic acid
Similar to lysine, competitively inhibits plasminogen activation
Inhibits severe bleeding caused by excessive clot lysis
Tranexamic acid
aminocaproic acid analogue
Similar to lysine, competitively inhibits plasminogen activation
Inhibits severe bleeding caused by excessive clot lysis
Renin
Production of angiotensin2
Furosemide
Loop diuretic
‘High ceiling’ - high rate of diuresis
Sulphonamide
Bumetanide
Loop diuretic
‘High ceiling’ - high rate of diuresis
Sulphonamide
Hydrochlorothiazide
Thiazide diuretic
Some inhibition of carbonic anhydrase
Cortical segment of thick ascending limb
Distal tubule - block NaCl co transport
Vasodilator effects by diuretic action and directly acting on vessels
Metabolic alkalosis
Hypokalaemia - cant use with cardiac glycosides, as potentiate action
Increase Mg excretion but not Ca
Uric acid excretion decreased –> gout
Bendroflumethiazide
Thiazide diuretic
Some inhibition of carbonic anhydrase
Cortical segment of thick ascending limb
Distal tubule - block NaCl co transport
Vasodilator effects by diuretic action and directly acting on vessels
Metabolic alkalosis
Hypokalaemia - cant use with cardiac glycosides, as potentiate action
Increase Mg excretion but not Ca
Uric acid excretion decreased –> gout
Amiloride
Potassium sparing diuretic
Prevent Na reabsorption by blocking apical Na channels
K is not drawn into lumen as no gradient created
Weak diuretic effect
Triamterene
Potassium sparing diuretic
Prevent Na reabsorption by blocking apical Na channels
K is not drawn into lumen as no gradient created
Weak diuretic effect
Spironolactone
Potassium sparing diuretic
Antagonist to the action of aldosterone
Aldosterone binds steroid receptor and translocates to nucleus, where synthesis of Na channels and NaKATPase
Spironolactone metabolised to Canreone
Potassium Canreonate acts as K sparing diuretic
Compete for steroid receptor binding site
Only effective when distal tubule cells under effect of aldosterone
Acetazolamide
Carbonic anhydrase inhibitor
Inhibit NaHCO3 reabsorption in proximal and distal tubules
NaHCO3 reabsorption is driven by the NaKATPase pump
CAinhibitors decrease the availability of H, K loss is increased
Therapeutic use in glaucoma
Suppress HCO3 secretion, which forms aqueous humour in eye
Excessive loss leads to metabolic acidosis
Mannitol
Osmotic diuretic
Filtered at glomerulus but not reabsorbed
Retain their osmotic equivalent of water so increase urine volume
Used when urine flow reduced because low GFR causes excessive reabsorption of salt and water
Maintain urine flow
Rapidly reduces intracranial and intraocular pressure - does not cross BBB
Captopril
ACE inhibitor - antagonism of renin-angiotensin system
Antihypertensive
Enalapril
ACE inhibitor - antagonism of renin-angiotensin system
Antihypertensive
Converted in liver to active metabolite - enalaprilat
Saralasin
Angiotensin 2 partial agonist
Peptide - not suitable for oral administration
Losartan
Angiotensin 2 antagonist
Angiotensin receptor blocker (ARB)
Act on AT1 receptor
Verapamil (Class)
Class 4 antidysrhythmic agent
Ca channel blocker - reduce Ca entry
Amiodarone
Class 3 antidysrhythmic agent
Prolong action potential and refractory period
Isobutylmethylxanthine (IBMX) ?
Methylxanthine
Non selective phosphodiesterase inhibitors
Also adenosine A1 A2 antagonists –> release of Ca from intracellular stores
Positive ionotropic and chronotropic effects
Reserpine
Antihypertensive drug
a2-adrenoceptor agonist
Dope racehorses
