Lecture 9 - Cardiovascular Pharmacology Flashcards
*List the major effects of angiotensin II in the body.
- increases BP by stimulating the Gq protein in vascular smooth muscle cells (which in turn activates an IP3-dependent mechanism leading to a rise in intracellular calcium levels and ultimately causing contraction).
- acts at the Na/H exchanger in the proximal tubules of the kidney to stimulate Na reabsorption and H excretion which is coupled to bicarbonate reabsorption. This ultimately results in an increase in blood volume, pressure, and pH
*List the classes of vasodilator treatments used for CHF + examples
DIRECT SMOOTH MUSCLE RELAXANTS
=hydralazine, minoxidil, sodium nitroprusside
ACE INHIBITORS
= Captopril, Enalapril,
Fosinopril, Lisinopril, Quinapril, Raminpril, Trandolapril
*Give a detailed account of the compensatory physiological responses to CHF.
Body compensates=>
- Retaining salt and water to increase the amount of blood in the bloodstream.
- Increasing the heart rate.
- Increasing the size of the heart.
*Understand the relationship between blood pressure and cardiac output.
Cardiac output regulated by sympathetic and parasympathetic
influences
- SA node -
para decreases HR; symp increases HR
- Cardiac ventricles -
para decreases CF; symp increases CF
- HR = heart rate; CF = contractile force
Peripheral resistance regulated by sympathetic nerves only
- Arterioles - symp increases VR
- Venules - symp decreases VC
- VR = vascular resistance; VC = venous capacitance
*Give a detailed account of the mechanism by which the
b-adrenergics affect cardiac contractility.
(Inotropic agent)
1. Binding of b-adrenergic agonist (e.g. dobutamine) to receptor, activates adenylyl cyclase which produces cAMP.
- cAMP activates protein kinase, which in turn phosphorylates a Ca channel.
- Phosphorylation of Ca channel increases Ca flow into cell causing increased force of contraction of heart mc.
- Phosphodiesterase inhibitors prevent hydrolysis of cAMP and thus prolong action of protein kinase
*Outline the pathological defects that can reduce the efficiency of the body to pump blood around the body.
- Weakening of the heart’s pumping
CONGESTIVE HEART FAILURE - Irregular heart rate ARRHYTHMIA
- Narrowing and clogging of the blood vessels by fatty deposits ATHEROSCLEROSIS
- Chest pain caused by insufficiency of oxygen at the heart muscle ANGINA
- Abnormally high blood pressure HYPERTENSION
*List with examples the b-adrenergics used as positive inotropic agents
Dobutamine
Dopamine
Isoproterenol
*Give a detailed account of the mechanism by which the cardiac glycosides affect cardiac contractility.
(positive inotropic agent)
Mode of action: The digitalis drugs (digoxin, digitoxin) work by inhibiting the sodium-potassium ATPase pump (Na goes out K goes in), which increases intracellular Na, leading to Ca influx from Ca(in) Na(out) pump. The increased intracellular calcium causes stronger systolic contraction.
*List with examples the cardiac glycosides used as positive inotropic agents
DIGOXIN (most widely used)
& DIGITOXIN
The use of a Digitalis purpurea extract containing cardiac glycosides for the treatment of heart conditions was first described by William Withering. He found
- Increase in force of myocardial contraction
- Improved systemic circulation
- Reduction of signs & symptoms of CHF
*List the treatments used for CHF
TYPES OF DRUGS
INOTROPIC AGENTS
Increase the strength of contraction of cardiac muscle.
VASODILATORS
Reduce the load on the myocardium.
DIURETICS
Decrease extracellular fluid volume
*Give a detailed account of the mechanism of cardiac contractility.
- dependent upon sympathetic and parasympathetic
influences through catecholamines => increase contractile force by the β adrenoceptor-adenylyl cyclase system or by stimulation of α-receptors. - increased Stroke Volume = ^ contractility
- Increase in afterload causes an increase in ventricular contractility (inotropy) due to the activation of
catecholamines
*Give a detailed account of the pathophysiology of congestive heart failure.
= chronic failure of the heart to provide a sufficient cardiac output for the body’s functional needs.
common causes => CARDIOMYOPATHY ( loss of viable myocytes by disease, infarction or drugs) MYOCARDIAL ISCHEMIA & MI HYPERTENSION CORONARY HEART DISEASE CARDIAC VALVE DISEASE
*List the common pharmacological strategies used treat diseases of the cardiovascular system.
- POSITIVE INOTROPIC AGENTS which enhance cardiac muscle contractility and thus increase cardiac output.
- VASODILATORS which dilate (widen) blood vessels reducing cardiac preload and afterload and dropping blood pressure
- DIURETICS which relieve oedema and decrease cardiac workload.
- ION CHANNEL BLOCKERS (Ca2+ , K+ , Na+ ) which affect depolarisation / repolarisation mechanisms in the myocardium and are used to treat arryhthmias
- BETA BLOCKERS are b1-adrenergic receptor antagonists which suppress activation of the heart.
- ANTIHYPERLIPIDAEMIC drugs are compounds which reduce elevated serum lipid levels, a major cause of coronary artery disease.
*define CARDIAC OUTPUT (calculations)
and STROKE VOLUME
CARDIAC OUTPUT = HR x STROKE VOLUME
The amount of blood that is pumped by the heart litres per minute (l/min).
STROKE VOLUME = volume of blood that is pumped out by the left ventricle of the heart in one contraction
Symptoms and Clinical features of CHF
Acute CHF Tachycardia Shortness of breath Oedema (peripheral/pulmonary) Decreased exercise tolerance
Chronic CHF Various arrhythmias Hypertension Cardiomegaly Oedema (peripheral/pulmonary)
CLINICAL FEATURES Reduced force of cardiac contraction Reduced cardiac output Reduced tissue perfusion Increased peripheral vascular resistance Oedema
