Cardiovascular Flashcards
What are organic nitrates used to treat? How do they work?
Treat angina
Mimic NO-> vasodilation by activating guanylyl cyclase ->cGMP->reduces intracellular Ca2+
Effect of dilating venous capacitance vessels
Peripheral poling of blood -> reduced venous return -> reduced preload -> reduced myocardial O2 demand
Effect of dilating arterial resistance vessels
Reduced resistance to L ventricular emptying (afterload) so lowers blood pressure -> decreased cardiac work
Effect of dilating coronary arteries
Blood supply to ischaemic areas of myocardium and relieves coronary vasospasm
2 examples of organic nitrate and details
GTN = Glyceryl Trinitrate (sublingually, 100% 1st pass metabolism, 1/2 life 2 mins) Isosorbide Mononitrate (orally, longer 1/2 life)
Sinus node inhibitors treat what? How?
Treat angina by lowering heart rate -> less stress on myocardium
Inhibits If channels in cardiac pacemaker cells to reduce diastolic depolarisation of SA node
Example of sinus node inhibitor?
Ivabradine
What is Ivabradine?
A sinus node inhibitor used to treat angina by slowing dow heart rate
What is GTN?
Glyceryl Trinitrate is an organic nitrate used to treat angina by causing vasodilation
What is Isosorbide Mononitrate?
An organic nitrate used to treat angina by causing vasodilation
What do B-adrenoreceptor antagonists treat and how?
Treat angina and hypertension by slowing heart rate.
Block NA at B-receptors, blocking Ca2+ entering cell and blocking adenylyl cyclase forming cAMP (so less Ca2+ in SR-> cardiac contractility force and velocity decreased)
Also treat hypertension through secretion of renin from JGA
Side effects of B-adrenoreceptor antagonists
Tiredness, bradycardia, bronchospasm (B2 effects), congestive heart failure, cold hands (B1), nightmares and impotence (CNS effects)
3 examples of B-adrenoreceptor antagonists that are selective for B1
Metoprolol, Atenolol, Bisoprolol
What is Metoprolol?
B1-adrenoreceptor antagonist
What is propranolol?
B-adrenoreceptor antagonist (not selective for B1)
Name 6 B-blockers
Propranolol, Metoprolol, Atenolol, Bisoprolol, Labetalol, Carvedilol
How do calcium channel blockers work? What do they treat?
Treat angina and high bp
Blocks Ca2+ channels in membrane (discourages release from SR too) so no excitation/contraction coupling ->relaxation &dilation
Side effects of calcium channel blockers?
Vasodilator effects-headache
Reduced contractility- heart failure and peripheral oedema
Gut disturbance
Name the two classes of calcium channel blockers
Dihydropyridines and Non dihydropyridines
Name 4 calcium channel blockers of 2 classes
Dihydropyridines- Amlodipine, Nifedipine
Non-dihydropyridines- Diltiazem, Veapamil
What is Nifedipine?
A calcium channel blocker used to treat angina or high blood pressure
What do potassium channel openers treat and how?
Angina by causing hyperpolarisation of smooth muscle cells so Ca2+ channels resist opening
Also generates NO for venous dilation
Name a potassium channel opener and the type of channel it works on
Nicorandil- ATP-sensitive K+ channel
What is Nicorandil?
A K+ channel opener used to treat angina
Name 5 things that activate platelets
vWF, collagen, thrombin, ADP and thromboxane (TXA2)
Name 3 things that inhibit platelet aggregation
NO, ADPase, Prostacyclin (PGI2)
What are platelets?
Non nucleated fragments of megakaryocytes in bone marrow
What drug works by irreversibly inhibiting COX-1? How does this cause the effect?
Low dose aspirin (75mg/day), acetylation of COX-1 means reduced thomboxane (TXA2) synthesis so reduced platelet aggregation
What is low dose aspirin used for?
Frontline anti-platelet drug, used to prevent MI in patients with previous MI/angina
For thrombolysis after MI what drugs are used?
Medium dose aspirin (150-300mg) + Clopidogrel
What is Clopidogrel?
An anti platelet drug-
Non competitive antagonist, irreversibly blocks platelet ADP receptors (P2Y12) and reduced expression of gpIIb/gpIIIa and production of TXA2
Problems with Clopidogrel?
Inter-individual variability (14% poor converters from prodrug by P450)
Side effects- GI bleeds and severe neutropenia
Glycoprotein IIb/IIIa antagonists work by-
Blocking the GP IIb/IIIa receptors for fibrinogen, fibrin, collagen and vWF so disabling binding of platelets to subendothelium and thrombus formation
Give 2 examples of GPIIb/IIIa antagonists and how they are administered
Abciximab- IV
Tirofiban- IV
What is Tirofiban and when is it used?
Non peptide anti platelet drug (antagonist of gpIIb/IIIa)
Used in angioplasty procedures (eg stents) with Heparin and Aspirin
Name 2 other anti platelet drugs
Dipyridamole
Epoprostenol
How does Dipyridamole work?
Inhibits platelet phophodiesterase, increases cAMP, reduces aggregation and promotes vasodilation
How does Epoprostenol work?
By mimicking anti-aggregatory effects of prostacyclin (PGI2) and increases cAMP to reduce platelet adhesion
Name 3 thrombolytic drugs and how they work
Activate plasminogen to plasmin to degrade fibrin
Streptokinase (from streptococcus),
Anistreplase (acylated strep-plasmingogen complex), Urokinase (from human urine)
Name 3 rt-PA drugs and why they are better than others
Alteplase, Reteplase, Tenecteplase
Recombinant tissue plasminogen activators so no allergies
In acute MI what are the 4 stages of treatment?
Reduce anginal pain, initiate reperfusion, protect myocardium and secondary prevention
What drugs are used to reduce anginal pain in acute MI?
Oxygen, GTN, Opiate and an anti-emetic (Metoclopramide)
Anti emetic= against vomiting and nausea
What drugs are used to initiate reperfusion in acute MI?
Anti platelet (Clopidogrel, Aspirin)
Thrombolytic (rt-PA)
Primary angioplasty
Anticoagulant (Heparin)
What drugs are used to protect the myocardium in acute MI?
ß-blocker and ACE inhibitor
What does secondary prevention in acute MI involve?
Aspirin (low dose), lipid lowering drug (statin) and lifestyle changes
Give 4 other approaches to deal with acute MI
Delivery of thrombolytic drugs with arterial catheter
PTCA (precutaneous transluminal coronary angioplasty)
Coronary stents
Artery/vein grafts to aorta
Give 2 examples of ACE inhibitors
Captopril
Ramipril
What is Captopril?
An ACE inhibitor used in heart failure and hypertension
How do ACE inhibitors work?
By blocking conversion of AngI -> AngII
Inhibits breakdown of bradykinin- vasodilation, lowers bp & dry cough
Reduces preload, afterload and is antifibrotic
Name 2 AT1 receptor antagonists
Losartan
Candesartan
(SARTAN)
How do AT1 receptor antagonists work?
By inhibiting AngII actions
So antifibrotic, vasodilative (less NA release)
Name 4 classes of anti-coagulant drugs
Warfarin, Heparins, Oligosaccharides, Direct thrombin inhibitors, Direct factor Xa inhibitors
How does Warfarin work?
Inhibits decarboxylation of clotting factors by competing with Vit K (so clotting factors can’t be activated)
What is the antidote for warfarin?
Vit K or plasma donation
How is warfarin administered and what are its side effects?
Administered orally (slow onset and offset) Side effects= haemorrhage, crosses placenta, narrow therapeutic index and metabolised by P450
What affects the metabolism of warfarin?
Alcohol& Cimetidine increase activity of warfarin
Phenobrabitone& Pheytoin decrease activity of warfarin
Antibiotics increase activity of warfarin (gut flora produce vit K which competes with warfarin)
How do Heparins work?
By enhancing the activity of Anti-thrombin III 1000fold! which suppresses activity of thrombin and factor X
Heparin+ATIII+active clotting factor -> Inactive clotting factor+ATIII+Heparin
Side effects of unfractionated Heparin and antidote
Haemorrhage (esp in elderly&heavy drinkers)
Osteoporosis (over several weeks)
Thrombocytopenia (not enough platelets in blood)
Name 2 low MW heparins
Dalteparin and Enoxaparin
Why are low MW better than unfractionated heparin?
Double the duration, 2xdaily SC injection, predictible effects and less risk of osteoporosis and thrombocytopenia
How do Oligosaccharides work?
Anticoagulant,
Pentasaccharide unit binds to ATIII
Longer 1/2 life, parenteral
Name an oligosaccharide and its purpose
Fondparinux, anti coagulant
What is Fondparinux?
An oligosaccharide anti coagulant
Name 2 direct thrombin inhibitors
Lepirudin
Dabigatran
How do thrombin inhibitors work? How do you administer them?
Rapidly inhibit thrombin (so no fibrin activation) independently of ATIII
Lepirudin- parenteral as protein from leeches
Dabigatran- orally
What is Lepirudin?
An anti coagulant
Direct thrombin inhibitor
Name a direct factor Xa inhibitor
Rivaroxaban (XABAN)
How do direct factor Xa inhibs work and how are they administered?
Inhibit activated factor X so prevent conversion of prothrombin->thrombin
Orally administered
What is the main use for direct thrombin inhibitors?
For DVT prophylaxis
What drugs are used in hypertension (in order of prescription)
ACE inhibitors (or AngII receptor blocker) Calcium channel blockers Diuretic (thiazide-like)
What is the problem with dihydropyridine CCBs?
Reflex tachycardia when reduces peripheral resistance. Can cause peripheral oedema as only dilated arterial side so nowhere for fluid to go.
Explain how non-dihydropyridines work
Block calcium channels with a negative chronotropic effect (slow SA firing) and negative inotropic effect (reduced contractility)
Name 4 other types of anti-hypertensive drugs
Alpha-antagonists, K+ channel openers, nitrovasodilators and centrally acting SNS.
What drug might be used to treat hypertension in pregnancy?
Alpha-antagonists eg Methyldopa.
Treats pre-eclampsia
What are the centrally acting anti-hypertensives?
Imidazoline receptor agonists (eg Moxonidine)
Decreased SNS activity
What factors need to be considered when treating hypertensive patients
White coat syndrome, age, ethnicity, pregnancy stage