Cardiovascular system substances Flashcards
Cardiac muscle contraction mechanism
Increase in the myofibril membrane permeability for Na ions, the flow of sodium ions across the membrane into the cell and depolarisation of the membrane.
Entry of the Ca ions into the cell and/or the release from sarcoplasmic reticulum.
The increase in the concentration of calcium in the cell will lead to a reaction between ATP, myosin and actin, as a result of which ATP energy will be released, the myosin-actin complex is formed and contraction occurs.
Expulsion of K from the cell with the participation of Na, K-ATPase and the repolarization of the membrane terminates the access of Ca into the cell.
The potential of the cardiac cell membrane depends upon the difference in concentrations
of Na and K ions inside the cell and on the external surface of the cell.
The cardiac cell membrane is selectively more permeable for
K ions during diastole compared to Na.
This results in different charges occurring between the internal and external surface and the action of the sodium-potassium pump becomes possible.
Positive inotropic effect
the systolic contraction of the heart becomes faster and improves, the tone of the myocardium improves and the dimensions of a dilated myocardium are reduced, minute and beat rate increase.
Blood circulation becomes more efficient, the venous blood pressure drops.
Negative chronotropic effect =
decreases in heart rate
Negative dromotropic effect
an inhibition or decrease in velocity of the impulse formation and impulse transmission system.
Positive bathmotropic effect
cardiac excitability
increase the response of muscle to stimulation / the heart’s reaction to catecholamines (norepinephrine, epinephrine, dopamine).
Cardiotonics are substances that
restore the energy resources of the heart, used primarily for the treatment of chronic heart failure.
“drugs used to increase the efficiency and improve the contraction of the heart muscle, which leads to improved blood flow to all tissues of the body. Cardiotonic drugs increase the force of the contraction of the muscle (myocardium) of the heart.”
Cardiotonics i.e. cardiac glycosides i.e. digitalis (digoxin) glycosides
Cardiac stimulants are substances that
acts as a stimulant of the heart – e.g., via positive chronotropic or inotropic action. Examples of cardiac stimulant drugs are cocaine, methamphetamine, epinephrine.
ACE inhibitors stands for
Angiotensin-converting-enzyme inhibitors
Mechanism of action of ACE inhibitors
They inhibit the conversion of the inactive angiotensin I to the active angiotensin II, thereby reducing arteriolar resistance and glomerular filtration rate in the glomerular capillaries.
However, each ACE inhibitor has its own pharmacologic characteristics.
Angiotensin is a polypeptide that (2-3)
constricts blood vessels,
increases the secretion of aldosterone
(indirectly increases blood pressure)
Main effects of ACE inhibitors (4)
ACE inhibitors increase the concentration of bradykinin, the vasodilator effect of bradykinin is maintained.
the activity of noradrenaline is reduced and the activity of renin is increased in the plasma
the vasoconstrictor effect of angiotensin II is reduced
excretion of sodium and water is increased
(angiotensin II-mediated release of aldosterone is decreased: aldosterone – mineralocorticoid, responsible for reabsorption of water and ions in the kidney)
Representatives of ACE inhibitors: (6)
Benazepril
Captopril
Enalapril
Fosinopril
Quinapril
Ramipril
ACE inhibitor use for heart failure (3)
ACE inhibitors increase cardiac output and performance of the heart.
Improve hemodynamics, improve quality of life, delay mortality (in dogs and cats).
Ace inhibitors are also classified as vasodilators.
ACE inhibitor use for renal failure (3)
Simultaneous administration of ACE inhibitors and diuretics (e.g furosemide) lead to the same effect as in the case of simultaneous administration of diuretics and cardiac glycosides, however the risk of occurrence of hypokalemia or ventricular arrhythmia is higher when glycosides are administered.
A combination of for example captopril - digoxin.
Drug interactions to note regarding ACE inhibitors. (2)
ACE inhibitors potentiate the effect of diuretics, but renal flow decreases (angiotensin II maintains glomerular filtration rate, while ACE inhibitors decrease GFR), thus it can lead to azotemia (plasma urea concentration increases).
NSAIDs may diminish the effect of ACE inhibitors.
Side effects of ACE inhibitors. (min. 3)
They are relatively safe for dogs.
Vomiting, diarrhea and anorexia may be experienced.
Sometimes, an excessively sharp and powerful drop in blood pressure may be experienced.
Hypokalemia may be experienced.
Captopril
ACE inhibitor
bioavailability in dogs after administration through the oral route is approximately 75%.
in case of a full gastrointestinal tract it is 30%.
Maximum effect is reached 1 to 2 hours after administration.
Primary effect in dogs: vasodilation.
Enalapril
ACE inhibitor
bioavailability of 65%, maximum effect is reached after 2 hours.
Duration of effect 12-14 hours.
Effects: clinical improvement in dogs with heart failure due to dilated cardiomyopathy or mitral regurgitation.
Lisinopril
ACE inhibitor
bioavailability of 25-50%, fullness of the gastrointestinal tract does not impact the bioavailability.
Maximum effect is reached 6 to 8 hours after administration.
Benazepril
ACE inhibitor
bioavailability increases with repeated dosing, slight accumulation of a drug.
For treatment of congestive heart failure in dogs.
Effects of cardiac glycosides (a type of cardiotonic): (4)
strengthen the systolic contraction,
increases heart rate per minute,
reduces the myocardial oxygen demand,
increases the energy resources of the heart (the glycogen and creatine content of the myocardium)
These type of effects can also be achieved using beta - adrenomimetics (temporarily).
Representatives of cardiotonics (6)
Digitoxin, digoxin and gitoxin - glycosides obtained from the leaves of the common foxglove (Digitalis purpurea).
k-Strophanthidin - a glycoside obtained from the seeds of Strophantus hispidus.
g-Strophanthidin - glycoside of Strophantus gratus.
Convallatoxin - a glycoside extracted from the lily-of-the-valley (Convallaria majalis).
Cymarin (cardiac glycoside)
Scillaren – glycoside extracted from the squill (a flowering plant).
Pharmacokinetics of cardiotonics
Digitoxin is absorbed best from the GI tract, next best is celanide. Strophanthidin is not absorbed from the GI tract at all, it is only injectable.
Primarily absorbed in the small intestine subsequent to p.o. administration. Digoxin and digitoxin are absorbed in dogs and cats p.o. 75-90%, Strophanthidin 5-10%.
Water soluble DG are injected into the vein, onset of action is within minutes.
Administration SC and IM not done, because
of tissue irritation (necrosis).
Absorbed DG are partially bound to blood proteins.
The half-life depends on the preparation and animal species.
Biotransformation in the liver, excreted through kidneys. Accumulated in the heart, liver, kidneys, GIT.
Digitoxin is excreted at the slowest rate and Strophanthidin is excreted at the fastest rate.
Absorption of cardiotonics from the GI tract depends on what?
Depends on the lipid solubility and number of OH groups in the structure of the drug molecule, plus the breakdown induced by gastric acid.
Digitoxin only has one OH group, it is absorbed very well from GIT. Strophanthidin has 5 OH groups, is not absorbed at all so is thus only IV injectable.
Absorbed DG are partially bound to blood proteins.
