P22: Cardiovascular System & Anti-Coagulants

What are the types of drugs used to treat heart and blood vessel disorders?

positive inotropes, antihypertensives and vasodilators, anti anaemic agents, agents influencing blood coagulation

What are the types of positive inotropes?

cardiac glycosides, phosphodiesterase inhibitors, catecholamines

What are the types of antihypertensives and vasodilators?

acetylcholinesterase (ACE) inhibitors, calcium channel blockers, alpha-blockers, beta-blockers, diuretics, other hypotensives

What are the types of agents influencing the blood coagulation?

anticoagulants, drugs used to treat bleeding

What do positive inotropes do?

increase the strength of cardiac muscle contraction by increasing the quantity of intracellular calcium available for binding by muscle proteins

What is an example of cardiac glycosides?

digoxin

What is an example of phosphodiesterase inhibitors?

pimobendan

What is pimobendan used for?

treatment of congestive heart failure due to dilated cardiomyopathy and chronic degenerative mitral valvular disease in dogs

What is another term for catecholamines?

β-adrenergic agonists

What are examples of catecholamines?

dopamine, dobutamine, epinephrine, isoproterenol

Why are catecholamines used?

cause positive inotropic effect by activating β-receptors with subsequent stimulation of adenylate cyclase and increased cAMP

What are examples of angiotensin-converting enzyme inhibitors?

enalapril, benazapril, captopril, lisinopril, ramipril

What are ACE inhibitors used for?

treat chronic congestive heart failure in dogs and cats stemming from a wide variety of diseases; manage systemic hypertension in dogs and cats

What are examples of calcium channel blockers?

amlodipine, diltiazem

What are calcium channel blockers used for?

vasodilators (individual agents have different relative potencies and additional effects)

What are examples of β-blockers?

propranolol, metoprolol, esmolol

What are β-blockers used for?

slow heart rate and reduce myocardial oxygen consumption

What are examples of α-blockers?

prazosin

What is the use of prazosin?

α1-adrenergic receptor blocker and mixed vasodilator; rarely used clinically in small animals to treat primary cardiac disease

What are diuretics used for?

therapy in animals with congestive heart failure characterised by cardiogenic pulmonary oedema, pleural effusion, ascites, or a combination

What are the classes of diuretics used to treat congestive heart failure in dogs and cats?

loop diuretics, thiazide diuretics, potassium-sparing diuretics, other hypotensives

What is an example of loop diuretics?

furosemide

What is an example of thiazide diuretics?

chlorothiazide

What is an example of potassium-sparing diuretics?

spironolactone

What is an example of other hypotensives (vasodilators) used as diuretics?

nitroglycerine

What are examples of anti anaemic agents?

vitamin B12, folic acid, iron (ferrum)

Why are anti anaemic agents used?

provide components needed for red blood cell production, including haemoglobin synthesis, and by stimulating bone marrow formation of red blood cells

What are anticoagulants?

substances that effect blood clotting by interfering with the reaction of the clotting cascade

How do anticoagulants work?

block either synthesis of clotting factor VII (prothrombin) or the formation of fibrinogen

What are the phases of the coagulation process?

activation of prothrombin; clotting phase; retraction phase

What happens in the activation of prothrombin?

release of thrombokinase from platelets and damaged vascular endothelium, with calcium ions catalysing conversion of prothrombin into thrombin

What happens in the clotting phase?

thrombin rapidly converts soluble fibrinogen into insoluble meshwork of fibrin, forming clot

What happens in the retraction phase?

fibrin chains initially are loosely bound; process stabilises and strengthens meshwork of the clot; final clot retraction and serum extrusion

What are the ways in which anticoagulants are used?

in vivo; in vitro

Where do in vivo anticoagulants work?

administered directly into the body or on the body surface to prevent the formation of blood clots

Where do in vitro anticoagulants work?

added to the blood in the laboratory to facilitate experimental and diagnostic investigations

Where is serum extracted from?

coagulated blood

What is blood serum used for?

serological surveys for diagnostic identification of antibodies that are formed as a response to disease

Where is plasma extracted from?

uncoagulated blood

What is blood plasma used for?

laboratory examinations and determination

What is required for the extraction of blood plasma?

anticoagulants

What are the non cellular components of blood used for?

determination of concentration of catecholamines, hormones, vitamins, mineral substances, enzymes

What is measured in cellular blood components?

blood cell counts, agglutination, haemagglutination, various tests

What is measured in plasma components?

enzyme activities, coenzymes, mineral substances, metabolites and proteins

What are the groups of anticoagulants?

inhibitors of clotting factors;
vitamin K antagonists;
calcium chelators;
enzymes

What are examples of inhibitors of clotting factors?

heparin, dalteparin, enoxaparin, nadroparin, parnaparin, reviparin, sulodexide

What effect does heparin have?

stimulates antithrombin III, which inhibits proteolytic action of clotting factors IX, X, XI, XII, and thrombin;
binds to endothelial cell walls and interferes with platelet aggregation and adhesion;
prevents thrombosis and embolism

Describe location, formation, and structure of heparins

obtained from bovine liver and lung tissue, or porcine intestinal mucosa;
naturally formed in mast cells, basophils, and vascular epithelium;
heterogenous mixture of sulphated mucopolysaccharides

What may happen after the administration of heparins?

haematoma

How do vitamin K antagonists work?

interfere with vitamin K dependent clotting factors (II, VII, IX, X) in hepatic synthesis of vitamin K

Which type of anticoagulant can only work in vivo?

vitamin K antagonists

Which type of anticoagulants can only work in vitro?

calcium chelators

What are the types of vitamin K antagonists?

coumarin anticoagulants, indandione anticoagulants

What are examples of coumarin anticoagulants?

warfarin, dicumarol, biscoumacetate

Describe sodium warfarin

most commonly used vitamin K antagonist;
indicated for blood thinning as prevention of venous thrombosis and thromboembolism of aorta;
higher doses are toxic and cause haemorrhagic diathesis

Describe ethyl biscoumacetate

used for prophylaxis and treatment of thrombosis and embolism

How do calcium chelators work?

chelate calcium that catalyses conversion of prothrombin to thrombin (with coagulation factors)

What are examples of calcium chelators?

sodium citrate, sodium oxalate, EDTA (ethylene diamine tetraacetic acid)

How do enzymes work as anticoagulants?

dissolve blood clots;
inactivate fibrinogen and fibrin

What are examples of enzymes used as anticoagulants?

streptokinase, alteplase, urokinase, fibrinolysine

Describe streptokinase

product of some strains of haemolytic streptococci of group C;
catalyses conversion of plasminogen to plasmin, which prevents the formation of blood clots or dissolves already formed clots

What are the types of drugs used to treat bleeding?

haemostatics, lyophilised concentrates, astringents

What do haemostatics do?

help to clot blood

How are lyophilised concentrates used?

applied to the skin (or a particular area) to help control capillary bleeding; normally absorbed by the body

How are astringents used?

directly at the site of bleeding to control bleeding by constricting blood vessels and tissue to help slow and stop blood flow

What are examples of astringents

epinephrine, norepinephrine