Antihypertensive drugs

Antihypertensive drugs and recent advancement

1. ANTIHYPERTENSIVE
DRUGS
Submitted to :
Dr.M.N.Noolvi
H.O.D.
(P’ceutical chemistry)
1
 Submitted by:
Kirti N patel
M.pharm(III
rd
sem.)
(P’ceutical chemistry)

2. Hypertension:
 Hypertension is defined as either a
sustained systolic blood pressure (SBP)of
greater than 140 mm Hg or a sustained
diastolic blood pressure of greater than 90
mm of Hg.
 An agent that reduces high blood
pressure is called as an
ANTIHYPERTENSIVE.
2

3. Prehypertension-systolic between 120 to
139 mm/Hg and diastolic between 80 to 89
mm/Hg.
 Effects of Hypertension
Increases risk of heart disease ,
heartfailure, kidney disease, blindness,
and stroke.
 Primary Hypertension- No known
reason.
Secondary Hypertension-due to some
cause such as kidney disease,
abnormalities of adrenal glands
will try nonpharmacological methods first.3

4. 
#Causes:
It results from:
Increased arterial resistance
Reduced capacitance
Increased peripheral vascular smooth
muscle tone
4

5. Decrease
in blood
pressure
Increased
blood
pressure
Increased
sympathetic
activity
Increased
activation of
β1
adrenoceptor
s on heart
Increased
cardiac
output
Increased activation
of α1 adrenoceptors
on smooth muscle
Increased
peripheral
resistance
Decreased
renal blood
flow
Increased
renin
Increased
angiotensin II
Decreased
GFR
Increased
aldosterone
Increased
Na-H
2
O
Retention
Increased
blood
volume
5

6. Miscellaneous
α2 receptor
agonist
α1 receptor
antagonist
Calcium
Channel
blocker
ACE
Inhibitors
Beta
blockers
Diuretics
ANTI
HYPERTENSIVE
DRUGS
6

7. CLASSIFICATION OF DRUGS
1.ACE INHIBITORS
Captopril,enalapril,lisinopril,perindopril,ramipril.
2.ANGIOTENSIN ANTAGONISTS
Losartan,irbesartan,candesartan
3.CALCIUM CHANNEL BLOCKERS
Verapamil,diltiazam,nifedipine,felodipine,amlodipine,lacidipine,
4.DIURETICS
Thiazide=hydrochlorothiazide,chlorthalidone.indapamide
High ceiling=furosemide
K+ sparing=spironolactone.amiloride,
5.ß - ADRENERGIC BLOCKERS
Propranolol,metaprolol,atenolol.
6.+ß ADRENERGIC BLOCKERS
Labetalol,carvedilol.
7. - ADRENERGIC BLOCKERS
prazosin.,terazosin,phentolamine
8.CENTRAL SYMPATHOLYTIC
Clonidine,methyldopa
9.VASODILATORS
Hydralazine,minoxidil sodium
7

8. Diuretics
Thiazide Type:
Hydrochlorothiazide,Chlorothalidone,Bendroflume-
thiazide,Trichloromethazide
Potassium Sparing:
Spironolactone,Amiloride,Triamterene
Loop Diuretics:
Furosemide,Ethacrynic Acid,Bumetanide,Torasemide
8

9. THIAZIDE
DIURETICS
Sodium,water
retention
Blood
volume
Cardiac
output
Peripheral
resistance
Decrease in blood
pressure
9

10. Potassium Sparing
Diuretics:
Includes:
Spironolactone (a synthetic steroid that
antagonizes aldosterone at intracellular
cytoplasmic receptor site)
Triamterene & Amiloride (blocks Na
transport channels resulting in a decrease in Na/K
exchange)
10

11. Loop Diuretics:
Inhibit the co-transport of Na/K/Cl in the
luminal membrane in the ascending limb of the
loop of Henle
Examples:Furosemide,Bumetanide,Ethacrynic
acid
11

12. Beta Blockers:
Non-selective(β
1/β
2):Propranolol,Timolol
Nadolol,Pindolol
propranolol structure ;
12

13. Selectiveβ
1
:

Atenolol,Acebutalol
Atenolol structure;
13
Selectiveβ
1
:

Atenolol,Acebutalol
Atenolol structure;

14. Beta
adrenoceptor
blocker
Activation of
β1 receptors
on the heart
Renin
Cardiac
output
Peripheral
resistance
Angiotensin II
Aldosterone
Na/Water
retention
Blood
Volume
Decrease in
blood pressure
14

15. Examples of ACE Inhibitors:
Captopril
Enalpril
Lisinopril
Ramipril
15

16. ACE Inhibitors:
ACE Inhibitors blocks the ACE that
cleaves angiotensin-I to form the
potent vasoconstrictor angiotensin-II
by reducing circulating angiotensin-II
levels , ACE inhibitors also decrease
secretion of aldosterone, resulting in
decreased sodium & water retention.
16

17. Angiotensin II receptor
antagonist
E.g.,losartan,irbesartan,candesartan,
valsartan.
Losartan
Irbesartan
17

18. Angiotensin II receptor
antagonist
They produce vasodilation and block
aldosterone secretion, thus lowering
blood pressure and decreasing salt
and water retention.
18

19. Calcium channel
blockers:
Dihydropyridine:Nifedipine,nicardipine
Phenylalkylamines:Verapamil
Benzothiazepines:Diltiazem

19

20. Calcium channel blockers:
It inhibits cellular influx of Ca, which is
responsible for muscle contraction.
Calcium channel blockers protect
tissue by inhibiting entrance of Ca
into cardiac & smooth muscle cells of
coronary & systemic arterial beds.
All Ca channel blockers are
vasodilators that ultimately cause
dilation of coronary & peripheral
arteries,reduce heart rate.
20

21. α-1 adrenergic receptors
antagonist:
Decrease the peripheral vascular resistance
& lower the arterial blood pressure by
causing relaxation of both arterial & venous
smooth muscle
Examples:
Prazosin
Doxazosin
Terazosin
21

22. α-2 adrenergic receptor
agonist:
Clonidine acts centrally to produce
inhibition of sympathetic vasomotor
centers.
22

23. 23
Miscellaneous
α-methyl dopa
Neuronal blockers (bretylium,
guanethidine)
Bretylium

24. #Rauwolfia and derivatives
(reserpine, deserpidine)
reserpine
24

25. #Ganglionic blockers
(guanadrel, mecamylamine)
Guanadrel
25

26. #Non specific vasodilator
(hydralazine, minoxidil)
Hydralazine minoxidil
26

27. Recent anti-hypertensive
drugs
AT
1
ANTAGONIST
Olmesartan minoxidil
Azilsartan minoxidil
27

28. Serotonin receptor
antagonist
Ketanserin: At higher conc. it inhibits
α-1 adrenergic receptors.
28

29. Endothelin receptor
antagonist
E.g.,ambrisentan,sitasenten,bosentan,
darusentan.
Ambrisentan
Darusenten
29

30. ET-1 is a more potent vasoconstrictor than
angiotensin II and has high affinity for the ET
A

receptor subtype which mediates the
vasoconstriction characteristics of the Endothelin.
30

31. Protein Kinase C inhibitors
Staurosporin(antibiotic);it is a natural
product isolated in 1977 from
bacterium “streptomyces
staurosporeus”.
31

32. CALCIUM CHANNEL
BLOCKER
Cilnidipine
Azelnidine
Clevidipine
32

33. BUCINDOLOL
Non-selective β-blocker and weak α-
blocker.
Mild vasodilator.
33

34. CHYMASE INHIBITORS
Chymase inhibitors may be useful for
preventing cardiovascular diseases
and fibrosis via inhibition of
angiotensin II formation and
transforming growth factor-beta
activation.
E.g.,SPF-32629A
34

35. PROSTACYCLINE ANALOGUE
M/C:-Direct vasodilation of pulmonary and
systemic arterial beds;also inhibits platelet
aggregation.
E.g.,Treprostinil
35

36. CONTRAINDICATIONS
Antihypertensive drugs are contraindicated
in patients with known hypersensitivity to
the individual drug
ACEIs: Contraindicated in patients with
impaired renal function, congestive heart
failure, salt or volume depletion, bilateral
stenosis, or angioedema, also during
pregnancy or lactation
Use of the ACEIs and the angiotensin II
receptor blockers during the second and
third trimester of pregnancy is
contraindicated because use may cause
fetal and neonatal injury or death
36

37. SYNTHESIS OF NIFEDIPINE
Claisen schmidt condensation
37

38. 38

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