This Presentation provides a knowledge about Antihypertensives, types of blood pressure, hypertension types, normal blood pressure regulation, baro receptors, classes of antihypertensive drugs,recent discovery on hypertension. This is an assignment for the subject, Advanced Pharmacology-I, 1st year M.Pharm, 1st semester.

1. ADVANCED PHARMACOLOGY - I
“Hypertensives”
By
Chetan A., M.Pharm 1st Year (Pharmacology)
K.K. College of Pharmacy
Chennai, TamilNadu

2. Learning Objective
• Definition
• Types of Blood Pressure
• Types of Hypertension
• Antihypertensives Definition
• Normal Blood Pressure Regulation
• Baro Receptors
• Classes of Antihypertensives
• Recent Discovery
• Facts
• Reference

3. Hypertension
• It is defined as a physiologic condition where there is an increase in the arterial blood
pressure above normal.
• It is a multifactorial disease.
• Normal B.P is 120/80 mm Hg. An individual is hypertensive when B.P is >140/90
mm Hg.
• It is one of the leading causes of mortality & Morbidity due to stroke, heart attack &
kidney failure.

4. Types of Blood pressure
• Normal blood Pressure
120mmhg _80mmHg
• Pre Hypertension B.P
• Stage 1: 150_160mmHg to 100_110mmHg
• Stage 2 : 180_200mmHg to 120_140mmHg
• Post/Chronic B.P
More than 200mmHg to more than 150mmHg

5. Types of hypertension
Essential or primary Hypertension - a disorder of unknown
origin
• Contributors include: salt sensitivity, insulin resistance,
genetics, environmental factors,others
Secondary Hypertension - Caused by other disorders
• Renal, adrenal, coarctation of the aorta, steroids, pregnancy

6. Antihypertensives
• These are the class of drugs that are used to treat hypertension
(high blood pressure).
• Antihypertensive therapy seeks to prevent the complications of
high blood pressure, such as stroke and myocardial infarction.

7. Normal Blood Pressure Regulation
• Blood Pressure = Cardiac output (CO) X Resistance to passage of blood
through precapillary arterioles (PVR)
• Physiologically CO and PVR -is maintained by – Arterioles,
postcapillary venules heart and kidney
• Baroreflex, humoral mechanism and renin- angiotensin- aldosterone
system regulates the above 4 sites
• Local agents like Nitric oxide
• In hypertensives – Baroreflex and renal blood - volume control system –
set at higher level
• All antihypertensives act via interfering with normal mechanisms

8. Baro Receptor
• Baro reflexes are responsible for minute to
minute regulation of blood pressure.
Central sympathetic neurons in vasomotor
area are tonically active.
• When there is stretch in vessel wall, baro
receptor stimulation occurs & inhibits
sympathetic activity
• Reduction in stretch increases baro
receptor activity.

9. Classes of Antihypertensives
•Diuretics
•Adrenergic receptor antagonists
•Benzodiazepines
•Calcium channel blockers
•Renin Inhibitors
•ACE inhibitors
•Angiotensin II receptor antagonists
•Aldosterone receptor antagonists
•Vasodilators
•α2 agonists
•Endothelin receptor blockers

11. • Hydrochlorothiazide, a popular
thiazide diuretic
• Loop diuretics:
–Furosemide
• Thiazide diuretics:
• Thiazide-like diuretics:
• Potassium-sparing diuretics:
–spironolactone
Diuretics

12. Action
Act on kidney
Remove more
sodium and water
from water
Relax blood vessel
walls
Lower blood
pressure

13. • Thiazide diuretics are recommended as the first line of
treatment for high blood pressure. They are usually
recommended as one of at least two medicines to control high
blood pressure.
• Loop diuretics are prescribed for people who also have heart
failure, kidney problems, or swelling in their legs (edema)
Diuretics

14. • Furosemide, like other loop
diuretics, acts by inhibiting
NKCC2, the luminal Na-K-
2Cl symporter in the thick
ascending limb of
the loop of Henle.
• By inhibiting the transporter,
the loop diuretics reduce the
reabsorption of NaCl and also
diminish the lumen- positive
potential that derives from K+
recycling
Diuretics

15. • Spironolactone is used primarily to treat heart failure,
edematous conditions such as nephrotic syndrome or ascites
in patients with liver disease, essential hypertension,
hypokalemia.
• spironolactone is only a weak diuretic because it primarily targets the
distal nephron (collecting tubule), where only small amounts of
sodium are reabsorbed, but it can be combined with other diuretics to
increase efficacy.
• The antihypertensive effect of spironolactone may exceed that of
complex combined regimens of other antihypertensives since it targets
the primary cause of the elevated blood pressure.
Diuretics

16. Adrenergic receptor antagonists
• Beta blockers
– atenolol
– Metoprolol
• Alpha blockers
• Mixed Alpha + Beta
blockers:
– labetalol

17. Beta
Blockers
Inhibits the
effect of nor
epinephrineand
epinephrine
And lessens the
feedback
mechanism
G protein receptor
kinase inhibits
receptor activity
Increase in cyclic
Adenosine
monophosphate
Improves
contractions
Decrease heart
rate, Calcium
entry intofailing
myocytes

18. Labetalol combines both
selective, competitive, alpha-1-adrenergic blocking and nonselective,
competitive, beta-adrenergic blocking activity in a single substance.
Stimulation of
beta receptors
within
myocardium
Stimulation of
alpha receptors
within vascular
smooth muscles
Decrease in
systemic arterial
blood pressure
and systemic
vascular resistance
Without a reduction in
heart rate, cardiac
output or stroke
volume.

19. Benzodiazepines
• They work as an agonist of the GABA-a receptors in the brain, thus slowing
down neurotransmission and dilating blood vessels.
• benzodiazepines inhibit the re-uptake of a nucleoside chemical called Adenosine,
which serves as an inhibitory chemical mentioned above. It also serves as a
coronary
vasodilator, allowing the cardiac muscle to relax and dilating cardiac arteries.

20. Calcium channel
blockers
Peripheral arterial
dilatation
Stimulation of
renin and
formation of
angiotensin
Decrease systemic
vascular resistance
Decrease in
blood pressure
Amlodipine,
Nifedipine &
Diltiazem block the
entry of calcium into
muscle cells in artery
walls.

21. Diltiazem
• Diltiazem is a potent vasodilator, increasing blood flow and variably
decreasing the heart rate via strong depression of A-V node conduction.
• Because of its negative inotropic effect, diltiazem causes a modest
decrease in heart muscle contractility and reduces myocardium oxygen
consumption.
• Its negative chronotropic effect results in a modest lowering of heart
rate, due to slowing of the sinoatrial node. It results in reduced myocardium
oxygen consumption.
• Because of its negative dromotropic effect, conduction through the
AV (atrioventricular) node is slowed, which increases the time needed for
each beat. This results in reduced myocardium oxygen consumption

22. Renin Inhibitors
Renin inhibitors bind to
the active site of renin and
inhibit the binding of renin to
angiotensinogen.
renin inhibitors prevent
the formation of Ang I and
Ang II A reduction in Ang II
levels or blockade of
angiotensin receptors
suppress the feedback
loop
increased plasma renin
concentrations (PRC)
and plasma renin
activity(PRA)

23. ACE
Inhibitors
Blocks the conversion of
angiotensin I to angiotensin II
Lower arteriolar
resistance
Increase venous
capacity
Normally Angiotensin II
causes vasoconstriction and
hence hypertension.
Decrease
cardiac output
Stimulates adrenal gland to
release aldosterone which
causes sodium retention and
hence increase in blood
pressure.
Stimulates post. Pituitary to
release vasopressin which
also increases water
retention
With ACE inhibitors, the
production of angiotensin II
is decreased, leading to
decreased blood pressure.
Captopril
Enalapril
Ramipril
Increase excretion of
sodium in the urine

24. Angiotensin
II receptor
antagonists
These substances are AT1-receptor
antagonists; that is, they block the
activation of angiotensin II AT1 receptors.
vasodilatation.
reduces secretion of
vasopressin.
reduces production
and secretion
of aldosterone.
The combined effect
reduces blood
pressure.
olmesartan
telmisartan

25. Vasodilators
• Vasodilators act directly on the smooth muscle of
arteries to relax their walls so blood can move
more easily through them; only used in
hypertensive emergencies.
Vasodilatation works to decrease
TPR and blood pressure through
relaxation of smooth musclecells
in the tunica media layer of
large arteries and smaller
arterioles.
TPR: total peripheral resistance

26. α2 agonists
Stimulate alpha
receptors in the brain
Open peripheral
arteries
For treating
hypertension, these
drugs are usually
administered in
combination with a
diuretic.
Adverse effects of this class
of drugs include
sedation, drying of the nasal
mucosa and rebound
hypertension.

27. Endothelin receptor blockers
By blocking this
interaction, bosentan
decreases pulmonary
vascular resistance.
Under normal
conditions, endothelin-1
binding of ET-A or ET-B
receptors
causes constriction of the
pulmonary blood vessels.
Bosentan is a competitive
antagonist of endothelin-1 at
the endothelin-A (ET-A) and
endothelin-B (ET-B)
receptors.

28. Side
Effects
of Diuretics
Potassium-sparing diuretics retain the potassium that other
diuretics cause the body to excrete. Common side effects of
these diuretics include nausea, headache and stomach upset.
The most
common side
effect of loop
diuretics, such
as Lasix, is
hypokalemia, or
low potassium.
Other side effects
include dry
mouth, weakness
, diarrhea and
headache.
difficulty
urinating, gout, a
nd hives are
severe side
effects and
should be
addressed
immediately.
Thiazide diuretics
can cause
orthostatic
hypotension.

29. Side
Effects of
ACE
Inhibitors
Common side effects of ACE
inhibitors are
diarrhea, headache and
joint pain.
Fever and chills, trouble
breathing or jaundice
requires immediate
attention.

30. May include
fatigue, dizziness
and weakness.
Side
Effects of
Beta
Blockers

31. Regular check-Up

32. Recent Discovery
Central Corneal Thickness in the Ocular Hypertension Treatment Study (OHTS) (James D.
Brandt MD 2001)
• Central corneal thickness influences intraocular pressure (IOP) measurement.
Results:
• Mean central corneal thickness was 573.0 ± 39.0 μm. Twenty-four percent of the OHTS
subjects had central corneal thickness > 600 μm. Mean central corneal thickness for African
American subjects (555.7 ± 40.0 μm; n = 318) was 23 μm thinner than for white subjects
(579.0 ± 37.0 μm; P < 0.0001). Other factors associated with greater mean central corneal
thickness were younger age, female gender, and diabetes.
Conclusions
• OHTS subjects have thicker corneas than the general population. African American subjects
have thinner corneas than white subjects in the study. The effect of central corneal thickness
may influence the accuracy of applanation tonometry in the diagnosis, screening, and
management of patients with glaucoma and ocular hypertension.

33. Facts
• More than 10 million cases per year in India.
• Hypertension can last for years or be lifelong.
• High blood pressure may be linked to dementia.
• High B.P causes thickening of a part of heart (Left Ventricle).
• Blood pressure is normally lower at night while you're sleeping. Our blood pressure
starts to rise a few hours before you wake up, peaking in the middle of the afternoon
and drop in the evening.
• Anxiety can rise and lower blood pressure.
• Losartan Potassium Tablets, USP and Losartan Potassium/Hydrochlorothiazide
Tablets if stopped immediately may harm the patient.
• Sweaty workouts can lower B.P in Hypertension.

34. Reference
• Google Search
• Shareslide
• Wikipedia
• Elsevier Inc.

35. Quote
~ “An idiot with a plan can beat a Genius without an plan”