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

1. “Mechanism of
Action and
Pharmacological
Considerations of
Drugs Act on CVS,
Antihistamines as
Well as ANS”
Pharmacology II

2. Prepared By:
Tasfi Anwar Mitul
ID: 999-26-15
Sem: Spring, 2020
Dept: Pharmacy
Southern University Bangladesh

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.

6. Thiazide Diuretics and Pharmacological Consideration
Drugs
• Chlorothiazide
( Abetis plus)
• Chlorthalidone
( Thalidone 50)
Interactions
Lithium, NSAIDs,
Corticoids

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.

10. ACE Inhibitors and their Pharmacological Consideration

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.

12. Angiotensin II Inhibitors and their Pharmacological
Consideration

13. Drugs Used in the Treatment of Angina

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.

15. Nitrates and their Pharmacological Consideration

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.

17. β-Adrenergic Blockers and their Pharmacological
Consideration

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.

20. Anti platelet and their Pharmacological
Consideration

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.

22. Anti-Coagulant and their Pharmacological
Consideration
Drugs
 Warfarin
 Heparin

23. Drugs Used in the Treatment of Arrhythmia

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

26. Drugs Used in the Treatment of Heart Failure

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

31. Autacoids

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

36. Drugs Acting on ANS System

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.

40. Pharmacological Considerations
Adverse Effects
(Parasympathomimetics)
• Headache
•Epigastric distress
•Nausea
•Vomiting
• Colic
• asthma
• excessive salaivary
Adverse Effects
(Parasympatholytics)
• Hallucinations
• headache
• ataxia
• dizziness
• convulsion,
• weakness
• Mental depression
• irritability
Precautions
(Parasympathomimetics)
•hypertension
• coronary insufficiency
• pheochromocytoma
• hyperthyroidism
• asthma
Precautions
(Parasympatholytics)
•patients with hypersensitivity
to belladonna alkaloids,
•angle-closure glaucoma,
•parotitis,
•obstructive uropathy,
•obstructive GI tract diseases
• myasthenia gravis.