Mechanism of Action and Pharmacological Consideration of Drugs Acting on Cardiovascular System and Autonomic Nervous System as well as about Antihistamines and Classification of Various Drugs
3. Content
Drugs act on CVS
Treatment of Hypertension
Treatment of Angina
Treatment of Myocardial Infarction and Stroke
Treatment of Arrhythmia
Treatment of Heart Failure
Autacoids
Antihistamines
Drugs Acting on ANS
4. Drugs Used in the Treatment of Hypertension
Diuretics
Mechanism of Action of Diuretics:
• Diuretics initially work on the kidneys by
increasing diuresis (water loss).
• Deplete sodium and body fluid volume.
• This decrease in body fluids causes a decrease
in cardiac output.
• blood pressure remains low!
5. Thiazide Diuretics and their Pharmacological Consideration
Mechanism of Action
Site of Action: Acts primarily in the ascending
early distal convulated tubule.
Inhibit tubular reabsorption of sodium and
chloride ions.
Target at fluid loss as fluid loss causes lowering of
blood pressure.
Result: Water, sodium and chloride are excreted.
Potassium is also excreted to a lesser extent.
Dilate the arteriols by direct relaxation.
7. Mechanism of Action
Site of Action: Acts in thick ascending loop of Henle.
Inhibits Na, K and Cl ions transport.
Decreased Na and Cl ions absorption.
Increased urine passed.
Changes in systemic and renal blood flow: Resulting in
decreased reabsorption at proximal tubules.
Increase renal prostaglandins, resulting in the dilation of
blood vessels and reduced peripheral vascular resistance.
Loop Diuretics and their Pharmacological Consideration
8. Loop Diuretics and Pharmacological Consideration
Drug
Furosemide
( Furosemide 40)
Bumetanide
( Urinide 5)
9. ACE Inhibitors and their Pharmacological Consideration
Mechanism of Action
Inhibit the functions of angiotensin converting enzyme
Prevent the conversion of Angiotensin II from
Angiotensin I.
When conversion of Angiotensin II is stopped at the
initial step, it helps to decrease blood pressure.
Also prevent the breakdown of vasodilating substance
Bradykinins.
11. Angiotensin II Inhibitors and their Pharmacological
Consideration
Mechanism of Action
Work by competitively antagonizing the angiotensin-
II receptor site.
As a result, Angiotensin cannot bind to the receptor
to show its effect.
Hence, blood pressure is lowered.
It does not accumulate bradykinin.
ARB also functions in reducing ventricular and
arterial hypertrophy.
14. Nitrates and their Pharmacological Consideration
Mechanism of Action
Administered as pro-drug which are converted into
nitric oxide.
Focus on increasing oxygen reaching level to heart.
Target at dilating veins, reducing heart muscle
tension and decreasing oxygen demand.
Reduce the amount of work needed to pump blood
out of heart.
16. β-Adrenergic Blockers and their Pharmacological
Consideration
Mechanism of Action
Mainly applied to reduce the heart’s demand for
oxygen.
Target for decreasing the heart rate and the cardiac
output of heart by decreasing the frequency.
Blocking the activity of sympathetic nervous system
on cardiac muscle
Reduce the workload of heart so that the heart
demands less oxygen.
18. Drugs Used in the Treatment of
Myocardial Infarction and Stroke
19. Anti platelet and their Pharmacological
Consideration
Mechanism of Action
Interfere with the steps in the clot formation process.
mainly works by blocking the final pathway of
platelet aggregation,
interfering with platelet adhesion and aggregation
Aspirin is effective for the treatment of post myocardial
infarction and stroke.
Aspirin blocks the enzyme cyclooxygenase, reduce
plaque formation
Decrease the thickness or viscosity of blood by reducing
the concentration of fibrinogen.
21. Anti-Coagulant and their Pharmacological
Consideration
Mechanism of Action
Increase the activity of anti-thrombin III .
Inhibit activity of clotting factors Xa and IIa.
Results in prevention of clot formation.
Fondaparinux and Tinzaparin also inhibit the
activity of Xa.
Warfarin interferes with the formation of vitamin K
dependent clotting factors.
24. Anti-Arrhythmic Agents and their Pharmacological
Consideration
Class II Antiarrhythmic agents:
Beta blockers antagonize the stimulation of SA
and AV node.
increasing refractory period, decreasing
automaticity, slowing conduction velocity.
Class III Antiarrhythmic agents:
blocking the potassium channel (except
lidocaine).They mainly target at prolonging
depolarization and prolonging refractory period.
Class IV Antiarrhythmic agents:
Class IV antiarrhythmic agents block Ca++ channel.
Mechanism of Action
Class I Antiarrhythmic Agents: show their effects
by acting on sodium channel as well as by slowing the rate
of depolarization.
Depolarization is most prominently important for the
occurrence contraction.
Hence, slowing the rate of depolarization automatically
results in delay conduction, reduced automaticity, prolonged
the refractory period.
▪ Sub Classes:
Class IA Antiarrhythmic Agents -moderate effect on
depolarization and intermediate effect on Na channel.
Class IIA Antiarrhythmic Agents -minimum effect on
depolarization and their effects on Na channel is rapid.
Class IIIA Antiarrhythmic Agents - Effect on Na channel
is slow and produce marked effect depolarization.
25. Anti-Arrhythmic Agents and their Pharmacological
Consideration
Drugs
Procainamide
Lidocaine
Propafenon
27. Cardioglycoside and their Pharmacological
Consideration
Mechanism of Action
Provide positive inotropic effect on the heart.
Decreasing conduction velocity, prolonging the
refractorty period, causing reduction in
depolarization number.
Positive inotropic effect is actually the inhibition of
Na+/Ca++ ATPase pump which leads to increased
myocardial force.
Results in increased cardiac output and reduced
diastolic size.
28. Cardioglycoside and their Pharmacological
Consideration
Precautions
Hypokalemia:
enhances digitalis
toxicity.
Myocardial ischaemia:
severe arrhythmias
are more likely
Myxoedema: these
patients eliminate
digoxin more slowly
Drugs
Digoxin
29. Diuretics and their Pharmacological
Consideration
Mechanism of Action
The diuretics are mainly used to treat over-
loadness of volume as well as low blood
pressure.
Diuretics mainly prevent the heart failure at the
very initiative step by lowering blood pressure as
high blood pressure can intensify the present
heart failure.
30. Diuretics and their Pharmacological
Consideration
Drugs
• Chlorothiazide
• Chlorthalidone
• Indapamide
32. Autacoids : Definition, Classification, Functions
Definitions:
Autacoid: This term is derived from Greek: autos—self,
akos—healing substance or remedy. These are diverse
substances produced by a wide variety of cells in the body,
having intense biological activity, but generally act locally
(e.g. within inflammatory pockets) at the site of synthesis
and release. They have also been called ‘local hormones’.
However, they differ from ‘hormones’ . Hormones are
produced by specific cells, and are transported through
circulation to act on distant target tissues. Autacoids are
involved in a number of physiological and pathological
processes (especially reaction to injury and immunological
insult).
Classification:
Amine autacoids: Histamine, 5-HT
Lipid derived: Prostaglandins,
Leukotrienes: Platelet activating
factor
Peptide autacoids: Bradykinin,
Kallidin, Angiotensin
Functions of Autacoids
1. Inflammation
2. Allergic reactions
3. Anaphylactic reactions (not so much)
4. Neurotransmission
5. Gastric acid secretion
6. Neuroendocrine regulation
33. Classification Example
a) H1 Antagonist or Antihistamine. Eg: Diphenhydramine
b) H2 Antagonist or H2 Blocker. Eg: Cimetidine
c)H3 Antagonist Eg: Mecilizine
Antihistamines
34. H1 and H2 Antagonists and their Pharmacological
Action
Mechanism of Action of H2-
Antagonist:
Gastric acid is secreted from parietal
cells of stomach by H2 receptors of
histamine.
H2 antagonists inhibit acid production
by reversibly competing with histamine
for binding to H2 receptors on the
basolateral membrane of parietal cells.
H2 antagonists bind to H2 receptors on
the membrane of parietal cells and
inhibit acid production.
Mechanism of Action of H1-
Antagonist:
The primary mechanism of
antihistamine action is to be
competitive antagonism of histamine
binding to cellular receptors
Act on nerve endings, smooth
muscles, and glandular cells.
However, H1-receptor antagonism
may not be their sole mechanism of
action in treating allergic rhinitis.
35. H1 and H2 Antagonists and their Pharmacological
Action
Drugs
Doxylamine
Diphenhydramine
Fexofenadine
37. Sympathomimetics and Sympatholytics Drugs
Sympathomimetics Drugs
The Mechanism of Action:
Adrenergic drugs stimulate both alpha1 and beta2
receptor sites.
receptor sites are located in the smooth muscle of blood
vessels, the GIT tract, and genitourinary tract.
Produce vasoconstriction when stimulated by adrenergic
drugs.
When stimulated by adrenergic drugs, they produce
increased contractility (resulting in increased heart rate).
Beta2-adrenergic receptors in the respiratory system,
located in the bronchial muscle, produce bronchodilation
when stimulated by adrenergic agents.
Sympatholytics Drugs
The Mechanism of Action:
Adrenergic blockers reduce delivery of
catecholamines to the adrenergic receptors by
disrupting catecholamine synthesis, storage,
or release.
These drugs are the most commonly
prescribed class of autonomic drugs.
Adrenergic blocker agents are also effective
on all adrenergic alpha- and beta-receptors.
38. Pharmacological Considerations
Adverse Effects
(Sympathomimetics)
•hypertension
•Slow heart rate.
•headache,
•tremors,
•nervousness,
•Palpitation
•nausea, vomiting
Adverse Effects
(sympatholytics)
•orthostatic
• hypotension,
• edema, headache,
dizziness, vertigo,
•Somnolence,
•fatigue,
•nervousness, and anxiety.
Precautions
(Sympathomimetics)
• Not to use in
hypersensitivity.
• Unsafe for elders
• should not use in
people with blurred
vision, chest pain,
seizures.
Precautions
(sympatholytics)
• Hypersensitivity
• Unsafe in Pregnancy.
• Hypotension,
• unsafe for child
• Renal disease
• Not use in heart failure
39. Parasympathomimetics and Paraympatholytics
Drugs ( Cholinergic Agonists and Blockers)
Para-sympathomimetics Drugs:
The Mechanism of Action:
Mimic action of the PNS
Increase concentration of acetylcholine at
cholinergic transmission sites.
Have direct stimulant action on voluntary
muscle fibers
Para-sympatholytic Drugs:
The Mechanism of Action:
Act by selectively blocking all
muscarine responses to
acetylcholine.
blockers depress the CNS.
Antisecretory action includes
suppression of sweating, lacrimation,
salivation.