Professional Documents
Culture Documents
CARDIOVASCULAR SYSTEM
• Hypertension is defined a systolic blood pressure (SBP) greater
than 140 mmHg or diastolic blood pressure (DBP) greater than
90 mmHg.
▪ venous tone
• CO = HR x SV
• Hypertension could be
– Primary or essential
– Secondary
Management of hypertension
– Any one of the following classes of drugs could be used as first step agents:
• Diuretics
• Beta blockers
• Calcium antagonists
– Alternative Agents
• Alpha blockers
Spirolactone (Aldactone)
• Therapeutic use:-
• Secondary hyperaldasteronism
Adverse effect:
• Hyperkalemia
Drugs
– Guanabenz, Guanfacine
Side effects:
Two subclasses
– Dihydropyridines
– Non-dihydropyridines
➢Nicardipine, Nifedipine
➢Nisoldipine
(Cardioselective CCBs)
➢Verapamil
➢Deltiazem
have direct negative effect on
…
the heart while the dihydropyridines don’t
Clinical uses:
Drug-drug interactions
• MOA:- inhibit
– Aldosterone release
Side Effects
– Hyperkalemia
– Hypotension
– Decrease in GFR
Direct acting vasodilators
Include:
a)Arterial vasodilators eg. hydralazine, minoxidil,diazoxide
b)Arterial and venous dilators eg. Nitroprusside
Vasodilators:
• Produce relaxation of the vascular smooth muscle-decrease
peripheral resistance- decrease BP.
• But, they cause reflex tachycardia and rennin secretion which
increases water and salt retention.
• Therefore, the vasodilators are given with β-blockers and/or
diuretics
• Used for treatment of emergency hypertension.
a) Hydralazine
• Side effects
• Hypertrichosis: refers to
Sodium Nitroprusside
46
Angina is caused by an imbalance
between O2 supply and demand
O2 supply O2 demand
No anginal symptoms
A
B Angina
47
• There are three types of angina
➢Stable angina(angina of effort)
– Also called angina of effort, typical angina
– Is the most common type
– Usually triggered by physical activity
– Also emotional excitement, large meal, cold exposure
can precipitate this type of angina
– Caused by atherosclerosis blockade of blood vessels
➢Variant angina
– Also called Prinzmetal’s or vasospastic angina
– Occurs due to spasm of coronary arteries
– Associated with pain at rest
– May occur with stable angina 48
➢ Unstable angina
– Also c/d crescendo or preinfarction angina
– It is a medical emergency
– Associated with pain at rest
– Occurs as result of high degree of atherosclerosis in the
coronary arteries
– It is the worst of all types of angina
– It has high risk for Myocardial infarction and Death
– Caused by severe stenosis with probable plaque rupture
leading to platelet aggregation, thrombosis and/or
vasoconstriction
Therapeutic Objectives of angina treatment
– Increase blood flow to ischemic heart muscle and/or
decrease myocardial oxygen demand
49
The causes of angina includes:
• atheriosclerotic heart disease, and almost
invariably associated with a significant
obstruction of coronary artery.
• Vasospasm of the coronary artery due to the
effect of sympathetic neurotransmitters
• An increase in workload on the heart due to an
increase in heart rate , contractility and of
ventricular blood volume
• Emboli, etc
▪ Goals of angina treatment
✓ Terminate acute angina pain
✓ Reduce the frequency (recurrence) of angina
attacks
• Reducing myocardial oxygen demand
• Increasing oxygen supply to the myocardium
✓ Prevention of myocardial infarction & death
• This can be achieved by:
– Slowing heart-rate
– Reducing the preload by dilating veins
– Causing heart to contract with less force
– Lowering blood pressure – less resistance in heart
to pushing blood from chambers (reduce after-load)
– Preventing (reducing) lipid & platelet accumulation
in the blood vessels 52
• Classes of Drugs available for angina
treatment
Nitrates
Calcium channel blockers
Beta blockers
Antiplatelet agents
53
– Includes: nitroglycerin, isosorbide mononitrate, isosorbide
dinitrate, pentaerythritol tetranitrate
– Except nitroglycerin which volatile liquid, these drugs are
solid at room temperature
– MOA: nitrates are thought to work by interacting with nitrate
receptors found on vascular smooth muscles
• Nitrate receptors contain sulfohydryl (SH) groups which
reduces nitrates to nitric oxide (NO)
• NO stimulates guanylyl cyclase which synthesizes cGMP
• cGMP causes smooth muscle relaxation which leads to
vasodilation
– Nitrates produce more pronounced dilation on the veins than
the arteries
• Nitrates relieve the symptoms of angina by
restoring the balance b/n myocardial O2 demand &
supply
• O2 demand is lowered as result of:
– Reduction in cardiac preload (as result of venous pooling
of blood)
– Reduction in cardiac afterload (as result of arteriolar
dilation)
• O2 supply is increased as result of:
– Increased blood flow to ischemic areas as result of direct
vasodilatory effects of nitrates on coronary arteries
– Nitrates were also found to prevent platelet aggregation
• Preparations: based on their duration of
action nitrates can be divided into three
groups:
– Short acting (several minutes)
• Amyl nitrate: inhalant, very rapid absorption
• Sublingual: Nitroglycerin, isosorbide dinitrate
• Avoid hepatic first pass metabolism, very short
duration of action
– Intermediate-acting (several hours)
• Oral Erythrityl tetranitrate and pentaerythritol
tetranitrate
• Oral Isosorbide dinitrate, Buccal nitroglycerin slow-
release
• Oral isosorbide mononitrate
– Long-acting
• Transdermal, nitroglycerin slow–release (8-10 hours)
56
• Tolerance & dependence
– Repeated & frequent exposure to organic
nitrates is accompanied by dev’t of tissue
tolerance to the drugs vasodilatory effects
– The mechanism for tolerance to nitrates is not
well understood but could be due to:
• Depletion of SH group
• Decrease in sensitivity of guanylyl cyclase to NO
• Activation of RAAS
– To reduce/prevent nitrate tolerance, clinicians
should employ the smallest effective dose &
administer the drugs infrequently
– A daily nitrate free period is also recommended
• Side effects
– Headache
– Postural hypotension
– Flushing
– Reflex tachycardia are common side effects
• Since an increase in SNS activity is a common
feature of anginal attacks, the use of β-
antagonists is rational
• β-antagonists approved for secondary angina in
USA includes:
– Propranolol & nadolol(non selective β1 &2
antagonists)
– Metoprolol & atenolol (β1 selective antagonists)
• MOA:
– Antagonize the actions of catecholamines on the
heart & reduce HR, FC
• Mechanism not well known but expected to be due
to:
– Reduced HR & FC produces reduced cardiac output
– Reduce plasma renin activity
– An action on the central nervous system
• So, β-antagonists reduce myocardial O2 demand by
reducing 3 of the major determinants of myocardial O2
demand
– HR, FC,
– Generally, β-antagonists produce their antianginal effects
by:
– Decreasing O2 demand (by decreasing HR, FC)
• β-antagonists are particularly indicated in the management of
patients whose anginal attack are frequent & unpredictable
• Side effects
• Reappearance of angina
• Death
– The dose should gradually be tapered off
• They are contraindicated to
– bronchospastic conditions
– Bradycardia
– diabetic cases
– Dihydropyridines:
• Nimodipine-: T1/2 1-2 hours
65
Side effects
• Serious side effects
• Cardiac depression (non-DHPs)
– Cardiac arrest
– Bradycardia
– Atrio-ventricular block
– Heart failure
• Minor side effects
– Headache, flushing, dizziness, nausea,
constipation, coughing, wheezing
– Peripheral edema due to greater arteriolar than
venous dilation
66
• Congestive heart failure is a condition in which
Mechanism of action
i) Vasodilators:
mechanism