Diuretics and CVS.pptx

DIURETICS
DR. MANJOOR AHAMAD SYED,
M.Pharm, Ph.D
Associate. Professor
Department of Medicinal Chemistry,
College of Public Health and Medical Sciences,
Mettu University, Mettu
Post Box No-318
Ethiopia.

Diuretics
Diuretics ("water pills") increase the kidneys' excretion of salt (sodium) and water, decreasing
the volume of fluid in the bloodstream and the pressure in the arteries. Diuretics are the oldest
and most studied antihypertensive agents.
Diuretics (“water pills”) are the drugs which increase the urine output (or) urine volume.
2

Therapeutic approaches
Diuretics are very effective in the treatment of conditions like: -
 chronic heart failure
 nephrotic syndrome
 chronic hepatic diseases
 hypertension
 Pregnancy associated oedema
 Cirrhosis of the liver.
The primary action of most diuretics is the direct inhibition of Na+ reabsorption (increased
excretion) at one or more of the four major sites along the nephron.

CLASSIFICATION OF DIURETICS
I. SITE 1 DIURETICS: CARBONIC ANHYDRASE INHIBITORS
Eg. Acetazolamide, Methazolamide, Dichlorphenamide, Chloraminophenamide.
II. SITE 2 DIURETICS: LOOP DIURETICS (HIGH CEILING DIURETICS)
Eg. Furosemide, Bumetanide and Ethacrynic acid
III. SITE 3 DIURETICS : THIAZIDES AND THIAZIDE LIKE DIURETICS
Eg. Chlorothiazide, Hydrochlorothiazide, Benzthiazide, Hydroflumethiazide, Bendroflumethiazide.
IV. SITE 4 DIURETICS: POTASSIUM SPARING DIURETICS
a. Na+ Channel Inhibitors: Triamterene, Amiloride,
b. Aldosterone Antagonists: Spironolactone
V. MISCELLANEOUS:
Eg. Mannitol (Osmotic diuretics)

SITE 1 DIURETICS: CARBONIC ANHYDRASE INHIBITORS

MECHANISM OF CARBONIC ANHYDRASE INHIBITORS
Wherever carbonic anhydrase enzyme is involved, it produces HCO3
– and H+ ions by
showing its effect on H2CO3.
Carbonic anhydrase
Carbonic anhydrase inhibitors
X
H2CO3
H2O + CO2
H
+
+ HCO 3
-
Resposible for the exchange
of Na+
ions
The H+ move out to replace with Na+ ions (NA+ reabsorption occur) to produce Oedema and
Hypertension.
The above process is prevented by Carbonic anhydrase Enzyme Inhibitors and it prevent
reabsorption of Na+ to act as Diuretics.

ACETAZOLAMIDE
SAR OF ACETAZOLAMIDE
•Presence of sulphonamide moiety necessary for diuretic
activity
•NH2 group of sulphonamide remain unsubstituted for its
activity
•If methyl group on N position attachment to retain its
activity Eg.Methazolamide
USES:
1. Used in the treatment of Drug-induced edema which is caused by CHF and petitmal
epilepsy.
2. is a "water pill" (diuretic) used to prevent and reduce the symptoms of altitude sickness.
N N
S NH
S
H3C
O
N
H2
O
O
N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide
ADR:
Drowsiness, Paraesthesia,
atoxia, dizziness and
thirst

Synthesis:
NH2NH2 H2O
+ NH4SCN
NH NH
S N
H2
S
N
H2
N
N
S
N
H2
SH
N
N
S
NH
O SH
N
N
S
NH
O S
O
O
Cl
N
N
S
NH
O S
O
O
NH2
Hydrazine
hydrate
Ammonium
thiocynate
hydrazine-1,2-dicarbothioamide
Phosgene
Cyclization
Acylation
5-amino-1,3,4-thiadiazole-2-thiol
aq. Cl 2
Oxidation
Acetazolamide

METHAZOLAMIDE
N
N
S
N
O S
O
O
NH2
N-[(2Z)-3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2(3H)-ylidene]acetamide
USES:
1. Methazolamide belongs to a class of drugs known as carbonic anhydrase inhibitors.
2. This medication is used to treat high pressure inside the eye due to certain types of
glaucoma. Lowering high pressure inside the eye helps to prevent blindness, vision loss,
and nerve damage.

SITE 2 DIURETICS: LOOP DIURETICS (HIGH CEILING DIURETICS)
Loop diuretics selectively inhibit NaCl reabsorption in the thick ascending limb of the loop
of Henle.
They are very potent diuretics and induced a dramatic and copious flow of urine rich in NaCl
hence they are called as High ceiling diuretics. The two prototypical drugs of this group are
furosemide and ethacrynic acid

COOH
NH
Cl
H2NO2S
O
4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acid
or
4-chloro-N-furfuryl-5-sulfamoyl anthranilic acid
FURASAMIDE Adverse effects:
hypokalemia,
hypomagnesemia,
hypocalcemia
USES: Furosemide is a type of medicine called a diuretic. It's used to treat high blood
pressure, heart failure and oedema (a build up of fluid in the body). It's also sometimes used
to help you pee when your kidneys aren't working properly. Diuretics are sometimes called
"water pills/tablets" because they make you pee more.
COOH
Cl
Cl
(i) ClSO 2OH
(ii) NH 3
COOH
Cl
Cl
H2NO2S
N
H2
O
Furfulrylamine
(i)
(ii) NaHCO 3
- HCl
COOH
NH
Cl
H2NO2S
O
Furasamide
2,4-dichlorobenzoic acid 2,4-dichloro-5-sulfamoylbenzoic acid

Structural Activity Relationship
1. The substituents at the 1 position must be acidic. The carboxylic group provides optimal
diuretic activity, but other groups such as tetrazole impart good activity.
2. A sulfamoyl group at the position 5 is essential for optimal diuretic activity.
3. The ‘activating’ group at the 4 position can be Cl- or CF3- as in thiazide diuretics. Better
activity was observed when these groups have been replaced by phenoxy, alkoxy, aniline and
benzyl moieties.
4. The substitutions possible on the 2-amino group in 5-sulfamoyl-2- aminobenzoic acid
derivatives is limited in the order furfuryl > benzyl > thienyl methyl only
5. In case of 5-sulfamoyl-3-aminobenzoic acid the 3-amino group can be widely substituted
without much change in the activity.
Cl
H2NO2S COOH
NH CH2
O
1
2
3
4
5
6

ETHACRYNIC ACID
CH2COOH
Cl
Cl
C
H3
O
CH2
[2,3-dichloro-4-(2-methylidenebutanoyl)phenyl]acetic acid
USES:
1. Ethacrynic acid is a "water pill" (diuretic) that works in your kidneys to increase
the amount of urine you make.
2. This helps your body get rid of extra water. This medication is used to decrease
swelling (edema) caused by conditions such as cancer, congestive heart failure,
liver disease, and kidney disease.

CH2COOH
Cl
Cl
CH2
C
H3
O
C
H2
1
2
3
4
STRUCTURE ACTIVITY RELATIONSHIP
1. Activating group (Cl- or CH3-) occupy either the 3 position
or the 2 and 3 positions.
2. An Acryloyl moiety which reacts with sulfhydryl containing
receptor present in renal tissues should be at the para to the
oxyacetic acid group.
3. Reduction or epoxidation of the carbon-carbon double bond
in the acryloyl moiety yielded compounds with little or no
diuretic activity.

SITE 3 DIURETICS: THIAZIDES AND THIAZIDE LIKE DIURETICS
These agents are 1,2,4-benzothiadiazine-1,1-dioxide derivatives and are known as thiazides and hydrothiazides
(lacking double bond at position 3-4).
N
S
NH
R
R
1
H2NO2S
O O
1
2
3
4
5
6
7
8
STRUCTURE ACTIVITY RELATIONSHIP
1. Substitutions at position 2 with small alkyl groups such as methyl (- CH3) does not change the activity
2. Substituents at position 3 determine the potency and duration of action of the thiazide diuretics.
3. Loss of the carbon-carbon double bond between the 3 and 4 positions of the thiazide nucleus increases the potency
approximately 3 to 10 folds.
4. Direct substitution at 4, 5 or 8 positions with an alkyl group usually diminishes diuretic activity.
5. Substitution at the 6 position with an ‘electron withdrawing’ group is essential for diuretic activity. The best
substituents include Cl-, Br-, CF3- and NO2- groups. For example replacement of 6-Cl- by 6- CF3 does not change
potency, whereas replacement with CH3 reduces diuretic activity.
6. The sulphonamide group at the position 7 is essential for diuretic activity. Removal of this group yields compounds
with little or no diuretic activity.
N
H
S
NH
R
R
1
H2NO2S
O O
1
2
3
4
5
6
7
8

MECHANISM OF ACTION OF THIAZIDE and THIAZIDE LIKE DIURETICS
These block the reabsorption of Na+ (and thereby, the reabsorption of Cl-) in the distal
convoluted tubules by inhibiting the luminal membrane-bound Na+ /Cl- cotransport system.
Adverse Effects
Hypersensitivity reactions, Hypokalaemia, slight reduction in the cardiac output
USES
Extremely useful in the treatment of Edema associated with mild to moderate congestive
heart failure. Other uses include hypertension, diabetes insipidus etc.

ADR:
Volume depletion, Electrolyte imbalance, dry mouth, and thirst.
USES:
1. Hydrochlorothiazide is used to treat high blood pressure (hypertension).
2. Hydrochlorothiazide is also used to treat fluid retention (edema) in people with congestive
heart failure, cirrhosis of the liver, or kidney disorders, or edema caused by taking steroids or
estrogen.
HYDROCHLORTHIAZIDE S
NH
N
H
H2NO2S
Cl
O O
6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
Synthesis:
Cl NH2
+ 2 ClSO 2OH
- H2O
Cl NH2
ClO 2S SO2Cl
NH3
Cl NH2
H2NO2S SO2NH2
HCHO
S
NH
N
H
H2NO2S
Cl
O O
3-chloroaniline Chlorosulfonic acid
4-amino-6-chlorobenzene-1,3-disulfonyl dichloride
Hydrochlor thiazide

CHLORTHIAZIDE
S
NH
N
H2NO2S
Cl
O O
6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
USES:
1. Chlorothiazide is a "water pill" (diuretic) that causes you to make more urine.
2. This helps your body get rid of extra salt and water.
3. This medication is also used to decrease swelling (edema) caused by conditions such as
cancer, congestive heart failure, liver disease, and kidney disease.

SITE 4 DIURETICS: POTASSIUM SPARING DIURETICS
Three chemically distinct diuretics have emerged that increase Na+ and Cl- excretion
without a concomitant increase in the urinary excretion rate of K+. These agents are
known as Potassium-sparing diuretics.
A negative feature of all of the above discussed classes of diuretics is that they increase the
renal excretion rate of K+ and can induce hypokalaemia.
The potassium sparing diuretics are divided into two groups on the basis of mechanism of
action.
a) Na+ channel inhibitors: Triamterene and amiloride
b) Aldosterone antagonists: Spironolactone

A) NA+ CHANNEL INHIBITORS
Mechanism of action
Amiloride and triamterene inhibit the sodium channel in the luminal membrane of collecting
tubule and collecting duct.
Inhibition of the sodium channel thus not only inhibits Na+ reabsorption but also inhibits
secretion of K+ and H+, resulting in conservation of K+ and H+.
Triamterene is an aminopteridine derivative and has a structural resemblance to folic acid
whereas Amiloride is a pyrazino guanidine derivative
TRIAMTERENE
USES:
1. Triamterene is a "water pill" (diuretic) that works in your
kidneys to increase the amount of urine you make.
2. This helps your body get rid of extra water. This medication
is used to decrease swelling (edema) caused by conditions
such as cancer, congestive heart failure, liver disease, and
kidney disease.
N
N
N
N
NH2
N
H2
NH2
6-phenylpteridine-2,4,7-triamine

AMILORIDE
USES:
1. Amiloride is used with other "water pills"/diuretics (such as furosemide, thiazide diuretics
like hydrochlorothiazide) to treat high blood pressure (hypertension), heart failure, or extra
fluid in the body (edema).
2. Amiloride also helps to treat or prevent low blood potassium levels caused by the other
diuretics.
3,5-diamino-N-carbamimidoyl-6-chloropyrazine-2-carboxamide
N
N NH2
Cl
N
H2
NH NH2
O NH

B) ALDOSTERONE ANTAGONISTS
Spironolactone is the only available aldosterone antagonist. A metabolite of spironolactone,
“canrenone”, is also active.
Spironolactone is steroidal derivative, structurally related to progesterone
Mechanism of action
Aldosterone, by binding to its receptor increases the Na+ reabsorption and Excretion of K+
Spironolactone competitively inhibits binding of aldosterone to its receptor to prevent Na+
reabsorption and abolishes its biological effects.
SPIRONOLACTONE USES:
1. Spironolactone is used to treat heart failure, high blood pressure
(hypertension), or hypokalemia (low potassium levels in the
blood).
2. Spironolactone also treats fluid retention (edema) in people with
congestive heart failure, cirrhosis of the liver, or a kidney disorder
called nephrotic syndrome.

MANNITOL (OSMOTIC DIURETICS)
MOA:
It exerts its effect by increasing the urine flow without markedly increasing the excretion of Na+
and Cl-
ADR:
Headache, polydypsia, nausea, chest pain
USES:
1. Mannitol is a diuretic that is used to reduce swelling and pressure inside the eye or around
the brain.
2. Mannitol is also used to help your body produce more urine.
3. This medicine is used in people with kidney failure, to remove excess water and toxins from
the body.
CH2OH
O
H H
O
H H
H OH
H OH
CH2OH
hexane-1,2,3,4,5,6-hexol

CARDIOVASCULAR AGENTS
These are the drugs or agents which are used in the treatment of various cardiac disorders are
known as cardiovascular agents.
Based on types of cardiac disorder they are classified
in to different types.
 Cardiac agents or cardiac glycosides
 Antihypertensive agents
 Antianginal agents
 Antiarrhythmic drugs
 Antihyperlipidemic agents
 Coagulants and anticoagulants

CARDIAC GLYCOSIDES
M.Pharm,Ph.D
Department of Pharmacy,
Post Box No-318
Ethiopia.

CARDIOVASCULAR AGENTS
• These are the drugs or agents which are used in the treatment of various cardiac disorders are
known as cardiovascular agents.
• Based on types of cardiac disorder they are classified in to different types.
• Cardiac agents or cardiac glycosides
• Antihypertensive agents
• Antianginal agents
• Antiarrhythmic drugs
• Antihyperlipidemic agents
• Coagulants and anticoagulants

• Enhance the tone of the heart
• Excitability
• Contractibility of the cardiac muscle
• Also the improved circulation tends to improve renal secretion
• This relieves oedema often associated with heart failure
CARDIAC GLYCOSIDES
Definition: Cardiac glycosides are a class of organic compounds that increase the output
force of the heart and decrease its rate of contractions by acting on the cellular sodium-
potassium ATPase pump.
Cardiac glycosides can

According to the type of lactone ring:
cardiac glycosides are classified in to two types
1. Cardenolide (one double bond, lactone ring) :
Has five member lactone ring (unsaturated) attached at C17 β position of steroidal nucleus.
Examples:
Digitalis glycosides: Digoxin, Digitoxin, Gitoxin
Strophanthus gratus glycoside : Oubain
Strophanthus Kombe glycoside : K- strophanthin
2. Bufadienolide: (contain two double bonds, lactone ring):
Has six member ( unsaturated ) lactone ring attached at C-17 alpha– position
Example:
Squill glycosides (scillarins),
Toad poison (Bufotoxin)
8

• The definite mechanism of action is not known.
Some hypotheses have been postulated – Cardiac
glycosides inhibit Na+/K+ - ATPase, the “sodium
pump” which causes more Na to remain inside
myocardial cells Increased intracellular Na
stimulates Na/Ca exchange that brings more Ca
inside heart cells.
• Increased intracellular concentration may promotes
activation of contractile proteins to increase force of
contraction.
• Cardiac glycosides also stimulate the vagus nerve
which decrease heart rate.
Mechanism of Action of Cardia glycosides

Nomenclature :
The cardiac glycosides occur mainly in plants from which the names have been derived.
Digitalis purpurea,
Digitalis lanata,
Strophanthus Kombe
are the major sources of the cardiac glycosides.
Glycosides:
Glycosides are compounds which upon hydrolysis yield a glycone (sugar) part (such as
glucose, rhamnose, digitoxose, ribose, cymarose) and an aglycone (also called genin, the non-
sugar part) part.
1
0

cyclopentanoperhydrophenanthrene
10
AGLYCONE MOIETY(NON SUGAR):
The term 'genin' at the end refers to only the aglycone portion (without the sugar).
The aglycone portion of cardiac glycosides is more important than the glycone portion.
Aglycone part has steroidal nucleus

SUGAR MOIETY(GLYCONE) :
The glycosides usually contain 3 to 4 sugars attached at C-3 OH.
The sugars most commonly used include L-rhamnose, D- glucose, D- digitoxose, D-
digitalose, D-digginose.
Beside Glucose and Rhamnose they usually contain deoxysugars.
These sugars predominantly exist in the cardiac glycosides in the β-conformation.
Digitoxose Digitose
11

• Most sugars that are found in cardiac glycosides are uncommon deoxy-sugars
E.g Digitoxose, Cymarose, Thevetose

STRUCTURE:
These are composed of two structural features :
the sugar (glycone) moiety and
the non-sugar (aglycone - steroid) moieties.
12

The R group at the 17-position defines the class of cardiac glycoside.
Two classes have been observed in Nature:
CARDENOLIDES and
BUFADIENOLIDES .
The cardenolides have an unsaturated butyrolactone ring While the bufadienolides have
an a-pyrone ring.
13

Structural actiity and relationship :-
2) The presence of Alpha & Beta unsaturated lactone ring increases the activity of Cardiac
Glycosides, but if we make it saturated the Cardiac glycosides will lose its activity.
3) The ring junctions Cis, Trans, Cis make the nucleus very stable so more active.
4)The sugar part increases absorption and distribution of Cardiac glycoside in the
body.
Sugar part : Glucose, Rhamnose, Cymarose, Digitoxose16
1)The presence of OH group in C-14 position makes the glycoside
very active and gives rapid action in the body, but if we change it
to (H+) group the drug will be inactive or less active.

Cardenolides
O
R
OH
OH
O O
Sugar
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Digitalis glycosides R= CH 3
Strophanthus glycosides R= CHO or CH 2OH
Cardenolide is a type of steroid. Many plants
contain derivatives, collectively known
as cardenolides, including many in the form
of cardenolide glycosides (cardenolides that
contain structural groups derived from
sugars). Cardenolide glycosides are often toxic;
specifically, they are heart-arresting.

DIGOXIN
Source: It is obtained from the dried leaves of the foxglove plant, Digitalis lanata.
USES:
Digoxin is used to treat heart failure and abnormal heart rhythms (arrhythmias). It helps
the heart work better and it helps control your heart rate.

DIGITOXIN
Source:
USES:
Digoxin is used to treat heart failure, usually along with other medications. It is also used
to treat certain types of irregular heartbeat (such as chronic atrial fibrillation).
It is also may helpful for treating most of the supraventricular tachyarrhythmias.
Treating heart failure may help maintain your ability to walk and exercise and may improve
the strength of your heart.
It is also used in the treatment of atrial fibrillation, atrial flutter, cardiac output, low, shock,
cardiogenic, tachycardia, supraventricular conditions.
It is obtained from the dried leaves of Digitalis Purpurea
and Digitalis lanata (Scrophulariaceae)

Bufadienolides
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Squill glycosides R
1
= OH, R
2
= H
Bufotoxin R
1
& R
2
= Ester group
O
OH
R
1
Sugar
R
2
O
O
• Derives name from the generic name for the toad
(Bufo)
• Possesses doubly unsaturated 6- membered
lactone ring in position C-17
• Bufadienolides are C24 steroid
Bufadienolide is a chemical compound with steroid structure. Its
derivatives are collectively known as bufadienolides, including
many in the form of bufadienolide glycosides
(bufadienolides that contain structural groups derived from
sugars).

Bufadienolides from Squill
Uses
• A potent cardiotonic
• As expectorant specially in chronic bronchitis
• As stimulant
• It is used as a very effective expectotant both in asthma and chronic bronchitis
• It may possess anticancer
• Produces diuresis
• It causes emesis in relatively higher doses
These glycosides include the following:
Scillarin A
Scillarin B

MEDICINAL IMPORTANCE OF CARDIAC GLYCOSIDES
Cardiotonics
Congestive heart failure
Rheumatic heart disease
Atherosclerosis
Diuretics

MEDICINAL IMPORTANCE OF CARDIAC GLYCOSIDES
Cardiotonics
Congestive heart failure
Rheumatic heart disease
Atherosclerosis
Diuretics

ANTIHYPERTENSIVE AGENTS
M.Pharm,Ph.D
Post Box No-318
Ethiopia.

Def:
These are the drugs are agents that reduce high blood pressure are known as Antihypertensive
agents.
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.
A specific cause of hypertension established in only 10–15% of patients.
Patients in whom no specific cause of hypertension are said to have essential or primary
hypertension.
Patients with a specific etiology are said to have secondary hypertension.
Genetic factors, psychological stress, and environmental and dietary factors as contributing to
the development of hypertension. The heritability of essential hypertension is estimated to be
about 30%.

Classification of hypertension on the basis of blood pressure

Hypotension may be defined as a physiologic state where there is a
Hypertension is devided in to 2 types:
1.Primary hypertension or essential hypertension
2.Secondary hypertension or malignant hypertension.

In PRIMARY OR ESSENTIAL HYPERTENSION
In majority of casses where etiology Is unknown cause and is known as primary hypertension.
The following factors may contribute to elevate of B.P
• Dietary intake of more sodium and less potassium.
• In some cases primary hypertension may be herediatary.
• Advancement of age.
• Decreased vascular synthesis of Nitric oxide (NO)( is useful in vasodialatation)

In SECONDARY HYPERTENSION
where etiology can be identified. Secondary hypertension is due to
 Renal disease (kidney disorders ( Chronic glomerular nephritis.)
 Adrenal disease (endocrine disorders)
 Pheochromocytoma (tumour on adrenal medulla) which secretes excessive catechol amines like
adrenaline and nor adrenaline) Hyper aldosteronism.
 Muscular disorders:
Contraction (narrowing)of aorta.
Renal artery stenosis(narrowing of artery )
Toxemia of pregnancy (presence of toxins in the blood stream)
Encephalitis(inflammation of the briain)
Increased intra cranial pressure.
Thyrotoxicosis(toxic condition caused by over activity of thyroid gland) oral contraceptives.

CLASSIFICATION
I. DIURETICS
Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide
High ceiling: Furosemide, Torsemide, ethacrynic acid.
K+ Sparing: Spironolactone, Amiloride
II. ACE INHIBITORS: Captopril, Enalapril, Lisinopril, Perindopril, Ramipril, Fosinopril, etc.
III. ANGIOTENSIN (AT1 RECEPTOR) BLOCKERS:
– Losartan, Candesartan, Irbesartan, Valsartan, Telmisartan
IV. DIRECT RENIN INHIBITOR: Aliskiren
V. β ADRENERGIC BLOCKERS: Propranolol, Metoprolol, Atenolol, etc.
VI. CALCIUM CHANNEL BLOCKERS: Verapamil, Diltiazem, Nifedipine, Felodipine, Amlodipine, Nitrendipine,
Lacidipine, etc.

VII. β + α - ADRENERGIC BLOCKERS: Labetalol, Carvedilol
VIII. α - ADRENERGIC BLOCKERS:
Prazosin, Terazosin, Doxazosin, Phentolamine, Phenoxy benzamine
IX. CENTRAL SYMPATHOLYTICS:
Clonidine, Methyldopa
X. VASODILATORS
Arteriolar: Hydralazine, Minoxidil, Diazoxide Arteriolar + venous: Sodium nitroprusside
XI. OTHERS:
Adrenergic neurone blockers (Reserpine, Guanethidine, etc.), Ganglion blockers (Pentolinium, etc.)

Depending on chemical classification
ACE inhibitors
Sulphydryl
E.g:Captopril
Dicarboxylate
E.g:Enalapril,
Lisinopril
Phosphate
E.g:Fosinopril

ACE INHIBITORS
NOTE: Reduce blood pressure (hypoxia to kidney or less oxygen supply) and lowered Na2+ excretion induces the
release of Renin

ADR:
Dizziness, headache, Fatigue
USES:
1. Enalapril is an ACE inhibitor.
2. Enalapril is used to treat high blood
pressure (hypertension) in adults and
children who are at least 1 month old.
Enalapril is also used to treat
congestive heart failure (CHF)
ENALAPRIL
NH
N COOH
O
H5C2OOC
1-[(N-1-carboxy-3-phenyl propyl)-L-alanyl] proline-1-ethyl ester
N
COOH
S
H
O
1-(2-methyl-3-sulfanylpropanoyl)pyrrolidine-2-carboxylic acid
CAPTOPRIL:
ADR:
Hypotension. Tachy cardia, chest pain, palpitation
USES:
1. Captopril is an ACE inhibitor. ACE stands for
angiotensin converting enzyme.
2. Captopril is used to treat high blood pressure
(hypertension), congestive heart failure,
kidney problems caused by diabetes, and to
improve survival after a heart attack.

RAMIPRIL:
It is a prodrug converted in to active metabolite
Ramiprilate by hepatic biotransformation.
USES:
1. Ramipril (Altace) is an ACE inhibitor.
2. Ramipril is used to treat high blood
pressure (hypertension) or congestive
heart failure, and to improve survival
after a heart attack. Ramipril may
also be used for purposes not listed
in this medication guide.
BENAZEPRIL
USES:
1. Benazepril is used to treat high blood
pressure (hypertension).
2. Lowering high blood pressure helps
prevent strokes, heart attacks, and
kidney problems. Benazepril is an ACE
inhibitor and works by relaxing blood
vessels so that blood can flow more
easily.
ADR:
Nausea, vomiting,
diarrhoea, dizziness

SAR of ACE INHIBITORS
(CH2)n
R
NH
X
O
Ring
 N- ring must contain carboxylic acid group to mimic the ‘C’ terminal carboxylic acid of ACE
enzyme substrate to act as ACE inhibitor.
 The larger hydrophilic heterocyclic in the ‘N’ ring increases the potency and alter
pharmacokinetic property.
 X- is usually methyl group (-CH2), mimic the side chain Alanine of ACE enzyme substrate
to act as ACE inhibitor.
 The R group of ACE inhibitor binds to the cationic site (I.e. Zn++) of the angiotensin
converting enzyme to act as ACE inhibitor with optimum potency.

ANGIOTENCIN RECEPTOR ANTAGONISTS
Angiotensin II receptor antagonists overcome some disadvantages of ACE inhibitors
that is degradation of Bradykinin (contraction of smooth muscle and dilation of
blood vessels)and cough.
LOSARTAN:
N
N
NH
N
CH2 N N
(CH2)3CH3
Cl
HOH 2C
(2-butyl-4-chloro-1-{[2'-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol
USES:
1. Losartan (Cozaar) belongs to a group of
drugs called angiotensin II receptor
antagonists. It keeps blood vessels from
narrowing, which lowers blood pressure
and improves blood flow.
2. Losartan is used to treat high blood
ADR:
Dizziness, upper respiratory infections,
back pain, diarrhoea, fatigue, low
blood sugar, Chest pain.

CANDESARTAN
N
N
COOH
O
N
N
N
H
N
C2H5
ADR:
Cold or flu-like symptoms such as fever, cough, sneezing and
running nose, severe throat pain, dizziness and back pain.
USES:
1. Candesartan is used to treat high blood pressure
(hypertension).
2. Lowering high blood pressure helps prevent strokes, heart
attacks, and kidney problems.
3. Candesartan belongs to a class of drugs called angiotensin
receptor blockers (ARBs).
4. It works by relaxing blood vessels so blood can flow more
easily

DIRECT RENIN INHIBITOR
NH
N
H2
O O
OH
N
H2
O
O
O
ADR:
Dizziness, light headache, cough, diarrhoea,
tiredness, kidney problems.
USES:
1. This medication is used to treat high blood
2. Lowering high blood pressure helps prevent
strokes, heart attacks, and kidney problems.
3. Aliskiren works by relaxing blood vessels so
blood can flow more easily. It belongs to a class
of drugs known as direct renin inhibitors.
ALISKIREN

β - ADRENERGIC BLOCKERS
SAR:
1. The basic structure and side necessary for β- blocking activity because β- lockers
are structurally similar to β-agonists.
2. N, N- di substitution decreases the activity.
3. In the side chain minimum two carbons of chain is necessary for β-blocking
activity.
4. Introduction of -OCH2 group in between aromatic ring and ethylamine side chain
provides β-blocking activity.
5. Nitrogen atom should be 20 amine form to produce optimum β-blocking activity.

PROPRANOLOL O CH2 CH CH2
OH
NH HC
CH3
CH3
1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol
USES:
1. Propranolol is used to treat tremors, angina (chest pain), hypertension (high blood
pressure), heart rhythm disorders, and other heart or circulatory conditions.
2. It is also used to treat or prevent heart attack, and to reduce the severity and
frequency of migraine headaches.
OH
+ Cl CH2 HC CH2
O
-HCl
Epichlor hydrin
Naphthol
O CH2 HC CH2
O
Naphthol
N
H2 HC
CH3
CH3
Isopropylamine
O CH2 CH CH2
OH
NH HC
CH3
CH3
Propranolol
ADR:
Cold extremities, insomnia, fatigue and dizziness.

1. Dihydropyridine - Nifedipine, Nicardipine
2. Phenylalkylamines - Verapamil
3. Benzothiazepines - Diltiazem
4. Diaminopropanol ether – Bepridil
All the above groups are proved to be effective in the management of hypertension by
blocking the movement of Calcium in to the muscle cells through specific ion
channels (i.e. L-type of channel) and their by block impulse formation to reduce
myocardial contractility and peripheral vascular resistance which results in
inhibition of hypertension, arrhythmias and angina pectoris.
CALCIUM CHANNEL BLOCKERS

Dihydropyridine & SAR
N
H
COOR
3
R
2
OOC
R
1
CH3
X
1
2
3
4
5
6
Name of the
compound
R1 R2 R3 X
Amlodipine -CH2O(CH2)2NH2 -C2H5 -CH3 2-Cl
Felodipine -CH3 -C2H5 -CH3 2,3-Cl
Nifedipine -CH3 -CH3 -CH3 2-NO2
1. Phenyl ring substitution at 4th position optimises the activity.
2. Substitution at para position to phenyl ring decreases the activity.
3. 1,4-dihydro pyridine ring is essential for activity.
4. Substitution at ‘N’ or oxidation or reduction of the decreases the activity or abolish
the activity.
5. The 3rd and 5th of ester group optimises the activity, any othe electron withdrawing
substitution decreases the activity.
6. All 1,4-dihydropyridines except Amlodipine have methyl group at C2 & C6 position
enhance the activity.

AMLODIPINE
N
H
O
O
O
O
O
N
H2
Cl
USES:
1. Amlodipine is a calcium channel
blocker that dilates (widens) blood
vessels and improves blood flow.
2. Amlodipine is used to treat chest
pain (angina) and other conditions
caused by coronary artery disease.
3. Amlodipine is also used to treat
high blood pressure
(hypertension).
NIFEDIPINE
N
H
O
O
O
O
NO2
dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
ADR:
Hypotension, peripheral oedema, fatigue, palpitation and
tachycardia etc
USES:
1. Nifedipine is in a group of drugs called
calcium channel blockers. It works by
relaxing the muscles of your heart and blood
vessels.
2. Nifedipine is used to treat hypertension (high
blood pressure) and angina (chest pain).
Nifedipine may also be used for purposes
not listed in this medication guide.
ADR:
Headache, peripheral oedema, fatigue etc

PHENYL ALKYL DERIVATIVES
VERAPAMIL
H3CO
H3CO
CN
N
OCH 3
OCH 3
ADR:
Bradycardia, CHF, Myocardial infraction, and atrio-ventricular block.
USES:
1. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney
problems.
2. Verapamil belongs to a class of drugs known as calcium channel blockers. It works
by relaxing blood vessels so blood can flow more easily.
3. Verapamil is also used to prevent chest pain (angina).

β + α - ADRENERGIC BLOCKERS
LABETOLOL
2-Hydroxy-5-[1-hydroxy-2-[(4-
phenylbutan-2-
yl)amino]ethyl]benzamide
It is a competitive inhibitor of β1, β2, and α1 adrenergic receptor.
ADR:
Orthostatic hypotension, dizziness, and fatigue.
USES:
1. Uses. Labetalol is used with or without other medications to treat high blood
problems. This medication is both an alpha blocker and beta blocker.

α - ADRENERGIC BLOCKERS
PRAZOSIN
N
N
H3CO
H3CO
NH2
N
N
O
O
2-[4-(furan-2-ylcarbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
ADR:
Postural hypotension, syncope, palpitation and lack of energy.
USES:
1. Prazosin is used with or without other medications to treat high blood pressure.
problems.
3. Prazosin belongs to a class of medications called alpha blockers. It works by
relaxing and widening blood vessels so blood can flow more easily

Centrally acting sympatholytics
Mechanism of action
Methyldopa is an α2 adrenergic receptor agonist
acts centrally by decreasing the sympathetic
outflow which inturn lowers B.P.
O
H
O
H
CH2 C
NH2
H3C
COOH
2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid
or
Methyl-3,4-dihydroxy phenyl alanine
METHYL DOPA
USES:
1. This medication is used alone or with other medications to treat high blood pressure
(hypertension).
problems. Methyldopa works by relaxing blood vessels so blood can flow more
easily.
ADR: Peripheral Edema, mental depression,
anxiety and nightmares.

ANTIANGINAL DRUGS
M.Pharm,Ph.D
Post Box No-318
Ethiopia.

ANTIANGINAL DRUGS
Definition: Antianginal drugs are those that prevent, abort or terminate attacks of angina pectoris.
Antianginal drugs may relieve attacks of acute myocardial ischemia by increasing myocardial oxygen
supply or by decreasing myocardial oxygen demand.
CLASSIFICATION
Based on mechanism of action and chemical structure they are classified as follows
I. NITRATES
1. Short acting: Glyceryl trinitrate (GTN, Nitroglycerine)
2. Long acting: Isosorbide dinitrate (short acting by sublingual route), Isosorbide,
mononitrate, Erythrityl tetranitrate, Pentaerythritol tetranitrate
II. β BLOCKERS: Propranolol, Metoprolol, Atenolol and others.
III. CALCIUM CHANNEL BLOCKERS
1. Phenyl alkylamine: Verapamil
2. Benzothiazepine: Diltiazem
3. Dihydropyridines: Nifedipine, Felodipine, Amlodipine, Nitrendipine, Nimodipine,
Lacidipine, Benidipine
4. Diamino propanol ether: Bepridil
IV. POTASSIUM CHANNEL OPENER: Nicorandil
V. OTHERS: Dipyridamole, Trimetazidine, Ranolazine, Ivabradine, Oxyphedrine

NITRATES/ ORGANIC NITRATES
These are the organic nitrates of alcohols.
MECHANISM OF ACTION:
The organic nitrates produce their action either of the following ways.
• Preload reduction: The vasodilating effect of organic nitrates on the veins leads to
Peripheral pooling of blood → decreased venous return (preload reduction).
• Afterload reduction: Nitrates also produce some arteriolar dilatation → slightly
decrease total peripheral resistance or afterload on heart.
• Redistribution of coronary flow: In the arterial tree, nitrates preferentially relax
bigger conducting (angiographically visible) coronary arteries than arterioles or
resistance vessels.
Finally, the organic nitrates restore the balance between O2 supply by venous dilation
and oxygen demand by decreasing the myocardial work load.

H2C
HC
H2C
ONO 2
ONO 2
ONO 2
1,2,3-propane triol trinitrate
NITROGLYCERIN or GLYCERYL TRINITRATE
ADR:
Facial flushing, dizziness, tachycardia (heart rate over 100 beats per minute),
headache etc.
USES:
1. Anti-anginal drug.
2. Nitroglycerin extended-release capsules are used to prevent chest pain (angina)
in people with a certain heart condition (coronary artery disease).
3. This medication belongs to a class of drugs known as nitrates. Angina occurs
when the heart muscle is not getting enough blood.
H2C
HC
H2C
ONO 2
ONO 2
ONO 2
1,2,3-propane triol trinitrate
H2C
HC
H2C
OH
OH
OH
HNO 3/H2SO4
Nitration
Glycerol
Synthesis:

ISOSORBIDE MONONITRATE
O
O
OH
O2NO
USES:
1. Isosorbide mononitrate is used to
prevent chest pain (angina) in patients
with a certain heart condition
(coronary artery disease).
2. This medication belongs to a class of
drugs known as nitrates. It works by
relaxing and widening blood vessels
so blood can flow more easily to the
heart.
ISOSORBIDE DINITRATE
O
O
ONO 2
O2NO
USES:
1. Isosorbide dinitrate is a nitrate that
dilates (widens) blood vessels, making it
easier for blood to flow through them and
easier for the heart to pump.
2. Isosorbide dinitrate is used to treat or
prevent attacks of chest pain (angina).
ADR:
Hypotension, Facial
flushing, dizziness,
tachycardia,
headache etc.
ADR:
Hypotension, Facial
flushing, dizziness,
tachycardia,
headache etc.

ERYTHRITYL TETRANITRATE
H2C
H2C
ONO 2
ONO 2
H ONO 2
H ONO 2
USES:
1. t is a vasodilator with properties similar
to nitroglycerin.
2. It is usually used diluted with lactose or
other suitable inert excipients, in order
to minimise the risk of explosion;
undiluted erythrityl tetranitrate can be
exploded by percussion or excessive
heat.
3. It has a role as a vasodilator agent and
an explosive.
PENTAERYTHRITOL TETRANITRATE
Or
O2NOH 2C
CH2ONO 2
CH2ONO 2
CH2ONO 2
O2NO
ONO 2
ONO 2
O2NO
USES:
1. Pentaerythritol tetranitrate (PETN) is
an explosive used as the primary
ingredient in detonating fuses and as a
component in some plastic explosives.
2. As a nitrate ester, PETN is structurally
similar to Nitroglycerin in its
pharmacological (vasodilatory) and
explosive properties.

POTASSIUM CHANNEL OPENER
These are the drugs that activates ATP-sensitive potassium channels in vascular
smooth muscles. Opening of these channels hyperpolarizes the smooth muscles
which closes voltage sensitive Ca+2 channels and decreases intracellular Ca+2
level this leads to relaxation and vasodilation.
NICORANDIL
USES:
1. It is used to prevent or reduce painful signs (“angina pectoris”) of your heart
disease.
2. It is used in adults who cannot take heart medicines called “beta-blockers” or
“calcium antagonists”.
3. Nicorandil Tablets work by increasing the blood flow through the blood vessels of
the heart
2-[(pyridin-3-ylcarbonyl)amino]ethyl nitrate
ADR:
Facial flushing, dizziness, nausea, headache, mouth ulcers, vomiting etc.

DIPYRIDAMOLE
It is phosphodiesterase-3-inhibitor causes long acting and coronary vasodilator by
increasing coronary blood flow via selective dilation of the coronary arteries.
USES:
1. Dipyridamole helps to prevent platelets in your blood from sticking together and
forming a blood clot on or around an artificial heart valve.
2. Dipyridamole is used to prevent blood clots after heart valve replacement surgery.
3. Dipyridamole may also be used for other purposes not listed in this medication
guide
2,2',2'',2'''-(4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-
diyl)bis(azanetriyl)tetraethanol
ADR:
GI disturbance, dizziness, facial flushing, headache etc.

ANTIARRHYTHMIC DRUGS
M.Pharm,Ph.D
Post Box No-318
Ethiopia.

ANTIARRHYTHMIC DRUGS
These are the drugs or agents which are used to prevent or correct irregularities
of cardiac rhythm are known as Antiarrhythmic drugs.
Arrhythmias is the disturbances in the heart rate, rhythm, impulse generation or
conduction of electrical impulses responsible for membrane depolarization. These
disturbances can lead to alterations in overall cardiac function that can be life
threatening.

Classification:
Based on their mechanism of action they are classified in to different types.
1. Class I: Sodium Channel Blockers (Membrane Stabilizing Agents) - Procainamide,
lidocaine, Quinidine, tocainide, lorcainide, phenytoin, propafenone, mexiletine,
Disopyramide etc.
2. Class II: β-Adrenergic blockers - – Propranolol, acebutolol, esmolol, sotalol
3. Class III: Potassium channel blockers (Repolarization prolongators)- Amiodarone,
Defitilide, Ibutilide, bretylium.
4. Class IV: calcium channel blockers - – Verapamil, diltiazem
5. Miscellaneous
– PSVT: Adenosine, Digoxin
– AV block: Atropine

• Bind to and block Na+ channels (and K+ also)
• Act on initial rapid depolarisation (slowing effect)
• Local Anaesthetic (higher concentration): block nerve conduction
• Do not alter resting membrane potential (Membrane Stabilisers)
• At times, post repolarization refractoriness.
• Bind preferentially to the open channel state
• USE DEPENDENCE: The more the channel is in use, the more drug is bound
Na+ channel blocker

The cardiac action potential. Phase 0—
depolarization because of the opening of fast
sodium channels. Potassium flux also decreases.
Phase 1—partial repolarization because of a rapid
decrease in sodium ion passage as fast sodium
channels close.
Phase 2—plateau phase in which the movement of
calcium ions out of the cell, maintains
depolarization.
Phase 3—repolarization, sodium, and calcium
channels all close and membrane potential returns
to baseline.
Phase 4—resting membrane potential (−90 mV),
resulting from the activity of the Na+/K+ ATPase
pump which creates a negative intracellular
potential because of the exchange of three sodium
ions for only two potassium ions.

QUINIDINE
It is an alkaloid isolated from Cinchona bark. In this quinidine is compound of quinoline
ring and bicyclic quinidine ring system are connected by hydroxy methylene bridge.
ADR:
Muscle weakness, nausea, vomiting, diarrhoea, cinchonism symptoms include
impaired hearing, headache, blurred vision, dizziness, utricaria and skin reactions.
USES:
1. This medication is used to treat or prevent many types of irregular heartbeats
(heart arrhythmias such as atrial fibrillation).
2. Quinidine can greatly improve your ability to perform normal activities by
decreasing the number of irregular heartbeats you have.
6-methoxy cinchonan-9-ol

PROCAINAMIDE
USES:
1. Used as antiarrhythmic drug.
2. Procainamide is used to help keep the heart beating normally in people with
certain heart rhythm disorders of the ventricles (the lower chambers of the heart
that allow blood to flow out of the heart). Procainamide may also be used for
purposes not listed in this medication guide.
N
H2
NH
N
C2H5
O C2H5
4-amino-N-[2-(diethylamino)ethyl]benzamide
ADR:
Severe hypotension, ventricular fibrillation,
heart failure, agranulocytosis and psychosis.

LIDOCAINE or XYLOCAINE or LIGNOCAINE
USES:
1. Lidocaine, also known as lignocaine,
is a medication used to numb tissue
in a specific area (local anesthetic).
2. It is also used to treat ventricular
tachycardia and to perform nerve
blocks.
TOCAINIDE
USES:
 Tocainide affects the way that your
heart beats. Tocainide is used to treat
serious irregularity in heartbeat
patterns.
 Tocainide may also be used for
purposes other than those listed in
this medication guide.
CH3
CH3
NH C CH2
O
N
C2H5
C2H5
2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide
ADR:
Dizziness, drowsiness, confusion,
respiratory depression, andconvulsion.
It is a class I-b Antiarrhythmic drugs.
N-(2,6-dimethylphenyl)alaninamide

Potassium channel blockers (Repolarization prolongators)
Phase -III drugs are increasing the repolarization without
altering the phase ‘0’ which increases the effective
refractory period.
USES:
1. This medication is used to treat certain types of serious (possibly fatal) irregular
heartbeat (such as persistent ventricular fibrillation/tachycardia).
2. It is used to restore normal heart rhythm and maintain a regular, steady heartbeat.
Amiodarone is known as an anti-arrhythmic drug.
AMIODARONE
It has a broad spectrum of activity and effective blockers
of both Na+ & K+ channels.
ADR:
Blue-grey colour discoloration
of skin, photosensitivity,
peripheral neuropathy,
myopathy, ataxia, metallic
taste.
(2-{4-[(2-butyl-1-benzofuran-3-yl)carbonyl]-
2,6-diiodophenoxy}ethyl)diethylamine

BRETYLIUM
USES:
1. Bretylium blocks the release of noradrenaline from the peripheral sympathetic
nervous system, and is used in emergency medicine, cardiology, and other
specialties for the acute management of ventricular tachycardia and ventricular
fibrillation.
It is a class III antiarrhythmic drug.

ANTI-HYPERLIPIDAEMIC DRUGS
M.Pharm,Ph.D
Post Box No-318
Ethiopia.

ANTI-HYPERLIPIDAEMIC DRUGS
Definition -: anti-hyperlipidaemic drugs are those which lower the level of lipids &
lipoproteins in blood. They act either by reduce production of lipoprotein or by
increasing their removal from blood. Main aim is to decrease plasma cholesterol
Hyperlipidaemia is the term used to describe elevated plasma levels of lipids usually
in the form of lipoprotein
Lipoprotein consist of a central core of hydrophobic lipid (triglycerides or cholesteryl
esters) enclosed in amore hydrophilic coat of polar substance

Classification Composition Primary function
Chylomicrons Triglyceride TGs 99%,
1% protein
Transport dietary TGs to
adipose tissue & muscle
VLDL newly synthesized TGs
Lipid 90%, 10% protein
Transport endogenous TGs
to adipose tissue & muscle
IDL intermediate between
VLDL and LDL
They are not usually
detectable in the blood.
LDL Lipid 80%, 20% protein Transport endogenous
cholesterol from liver to
tissues
HDL Lipid 60%, 40% protein Collect cholesterol from the
body's tissues, and take it
back to the liver

S.No Class Examples
1 HMG CoA Reductase
inhibitors
Lovastatin, Simvastatin, Metastatin,
Pravastatin, Fluvastatin, Atorvastatin,
Pitavastatin, Rosuvastatin
2 Fibric acid derivatives Clofibrate, Fenofibrate, Gemfibrozil,
Ciprofibrate, benzaffibrate, Fluvestatin.
3 Bile acid sequestrants Cholestyramine, Colestipol
4 LDL oxidation inhibitor Probucol
5 Pyridine derivatives Nicotinic acid, Nicotinamide
6 Cholesterol absorption inhibitors Ezetimibe
7 Miscellaneous agents β-Sitosterol, Dextrothyroxine
CLASSIFICATION

SIMVASTATIN
CH3
H2C
CH2
O
O
C
H3
O
C
O
C
CH3
CH3
H3CH2C
O
H
USES:
1. Antihyper lipoprotenemic agent to treat cardiovascular diseases.
2. Simvastatin is used along with a proper diet to help lower
"bad" cholesterol and fats (such as LDL, triglycerides) and raise
"good" cholesterol (HDL) in the blood. It belongs to a group of drugs known as
"statins."
3. It works by reducing the amount of cholesterol made by the liver.
ADR:
Headache, nausea, heart burn, and abdominal pain.

SAR for ALL HMGRIS
Confirmation similarity between statin and HMG-CoA reductase enzyme
O
O
O
H
COONa
OH
O
H
COOH
SCoA
O
H
O
HMG - CoA substrate
Parvastatin
Mevastatin
Lovastatin
 All statins consist of two specific structural components a dihydroxy heptanoic acid
and ring system with lipophilic substituents. The dihydroxy heptanoic acid essential
to binds at active site of the enzyme.
 3,5 dihydro carboxylate is essential for activity
 Lactone containing prodrugs require in vivo hydrolysis Eg. Lovastatin, Simvastatin
 Bicyclic ring could be replaced with other lipophilic rings, size and shape of it are
important for activity.

FIBRIC ACID DERIVATIVES
SAR:
MOA:
It works in a variety way
1. Decrease plasma TGs levels more than C levels
2. Fibrates lower blood triglyceride levels by reducing the liver's production of VLDL
(the triglyceride-carrying particle that circulates in the blood) by activation of
lipoprotein lipase and speeding up the removal of TGs from the blood. It is
supported by PPAR-α.
3. Fibrates also are modestly effective in increasing blood HDL cholesterol; however,
fibrates are not much effective in lowering LDL cholesterol.
1. Basic structure necessary for activity.
2. Presence of Isobutyric acid essential for activity.
3. Substitution at R1 chloro group or chlorine containing
isopropyl ring produces an compound with significant activity.
4. The R2 is mostly propyl group for producing active
derivatives.
R
1
O R
2
C COOH
CH3
CH3

CLOFIBRATE
USES:
 It is a drug of choice for the treatment of Type-III hyperlipoproteinemia.
 Clofibrate is used to lower high levels of cholesterol (a type of fat) in the blood.
 Clofibrate is especially good at lowering triglycerides and very-low-density
lipoprotein (VLDL) (a form of cholesterol).
 Clofibrate may also be used for purposes other than those listed in
this medication guide.
Cl O C COOCH 2CH3
CH3
CH3
ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
Cl OH + C CH3
O
H3C + CHCl 3
NaOH / H+
Reflux
Cl O C COOH
CH3
CH3
- H2O
Esterification /
CH3CH2OH
Cl O C COOCH 2CH3
CH3
CH3
Clofibrate
Clofibric acid
4-chlorophenol
Acetone Chloroform
Synthesis:

CHOLESTYRAMINE
USES:
1. Cholestyramine is used to lower high levels of cholesterol in the blood, especially
low-density lipoprotein (LDL) ("bad" cholesterol).
2. Cholestyramine powder is also used to treat itching caused by a blockage in the
bile ducts of the gallbladder.
BILE ACID SEQUESTRANTS
It is a styrene co-polymer with divinylbenzene and
quaternary ammonium functional group.
MOA:
The cation exchange resin simply binds with anionic
bile acids, this form an insoluble complex which
results in increase in the loss of faecal bile acid and
prevent reabsorption in to liver.
ADR:
Constipation, skin rashes haemorrhoids.

LDL OXIDATION INHIBITOR
USES:
1. Probucol is a powerful antioxidant drug normally used to prevent vascular
disease caused by the free radicals in the body.
2. Probucol lowers serum cholesterol by increasing the fractional rate of low-
density lipoprotein (LDL) catabolism in the final metabolic pathway
for cholesterol elimination from the body
PROBUCOL
S
S
CH3
H3C
O
H OH
CH3
H3C CH3
CH3
H3C CH3
H3C
H3C
CH3 H3C
CH3
CH3
It is a most potent cholesterol lowering agent of
a series of alkylidene dithiobisphenols.

PYRIDINE DERIVATIVES
N
COOH
pyridine-3-carboxylic acid
It is the only drug used to increase the HDL-C in higher proportion than any other
drugs available in market.
ADR:
Vomiting, diarrhoea, peptic ulceration and jaundice.
USES:
1. Used to lower triglycerides, cholesterol and to enhance the HDL-C
2. Nicotinic acid (also known as niacin) is vitamin B3, which occurs naturally in food.
Used as a medicine, it can improve levels of blood fats (lipids) such as cholesterol
and triglycerides.
3. Nicotinic acid works by reducing the amount of 'bad' cholesterol and triglycerides
made by the liver.
NICOTINIC ACID

CHOLESTEROL ABSORPTION INHIBITORS
MOA:
It inhibits the absorption of cholesterol from the small intestine and decreases the
amount of cholesterol normally available in the liver cells.
ADR:
Headache, diarrhoea, myalgia, hypersensitivity reactions, myopathy (disease of muscle
fibres)
USES:
1. Ezetimibe is used along with a low cholesterol/low fat diet and exercise to help
lower cholesterol in the blood.
2. Ezetimibe may be used alone or with other drugs (such as "statins" or fibrates).
Ezetimibe works by reducing the amount of cholesterol your body absorbs from
your diet.
EZTIMIBE
1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-
hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one

β-SITOSTEROL
USES:
 It is used to make medicine. Beta-sitosterol is most commonly used for lowering
cholesterol levels and improving symptoms of an enlarged prostate (benign
prostatic hyperplasia or BPH).
 It is also used for other conditions, but there is no good scientific evidence to
support its other uses.
It is structurally similar to cholesterol except ethyl group on c-
24 of its side chain.
MOA:
It inhibits the absorption of dietary cholesterol from the GIT.
ADR:
Diarrhoea, constipation, GI disturbance.

COAGULANTS &
ANTICOAGULANTS
M.Pharm,Ph.D
Post Box No-318
Ethiopia.

COAGULANTS & ANTICOAGULANTS
COAGULANTS:
These are the drugs which are used to stop bleeding or promotes coagulation are
known as coagulants.
Fresh whole blood or plasma provide all the factors needed for coagulation and are
the best therapy for deficiency of any clotting factor; also, they act immediately.
Other drugs used to restore haemostasis.
Haemostasis: The process of arrest of blood loss and blood coagulation, it is
occurred by
(1) vascular constriction
(2) formation of a platelet plug
(3) formation of a blood clot

There are thirteen coagulation
factors

CLASSIFICATION:
I. VITAMIN K
1. Vitamin K1 – Phytonadione (Phylloquinone)
2. Vitamin K3 (Synthetic)
a. Fat soluble – Menadione, Acetomenaphthone
b. Water soluble – Menadione sodium bisulfate, Menadione sodium diphosphate
II. MISCELLANEOUS – Fibrinogen, Antihemophilic Factor, Desmopressin, Andrenochrome
monosemicarbazone, Rutin, Ethamsylate

PHYTONADIONE
Phytomenadione, also known as vitamin K1 or
phylloquinone, is a vitamin found in food and used as a
dietary supplement. As a supplement it is used to treat
certain bleeding disorders. This includes in warfarin
overdose, vitamin K deficiency, and obstructive jaundice.
It is also recommended to prevent and treat vitamin K
deficiency bleeding in infants.
USES:
1. Phytonadione is used to treat vitamin K deficiency,
and to treat certain bleeding or blood-clotting
problems caused by other medicines or medical
conditions.
2. Phytonadione may also be used for purposes not listed
in this medication guide.
MENADIONE
USES:
1. It is used as a nutritional supplement
and for the treatment of
hypoprothrombinemia.
2. It has a role as a nutraceutical.
3. Vitamin K is an essential fat-soluble
vitamin that is important in maintaining
normal coagulation, serving as a
cofactor in the activation of several
clotting factors and
OCOCH 3
OCOCH 3
Aceto Menadione
O
O

ANTICOAGULANTS
Anticoagulants, commonly known as blood thinners, are chemical substances that
prevent or reduce coagulation of blood, prolonging the clotting time.
Anticoagulants and antiplatelet drugs eliminate or reduce the risk of blood clots.
They're often called blood thinners, but these medications don't really thin your
blood. Instead, they help prevent and break up the dangerous blood clots that form
in your blood vessels or heart.
They are usually administered to patient with acute myocardial infraction and the
one undergoing treatment for pulmonary and venous thrombosis.

I. Vitamin K anticoagulants:
1. Coumadins: Warfarin, Acenocoumarol, Dicoumarol
2. 1,3-inadanediones: Phenindione, Anisinedione
II. Heparins and heparinoids:
1. Heparinoids: Heparin, danaparoid
2. Oligosaccharides: Fondaparinux, Idraparinux
3. LMWH (low molecular weight heparin): Dalteparin, Enoxaparin, Nadroparin,
Tinzaparin.
III. Direct thrombin inhibitors
1. Bivalents: Bivalirudin, Desirudin, Lepirudin
2. Univalent: Agratroban, Dabigatran, Melagatran, Ximelagatran
IV. Direct factor Xa inhibitors:
Apixaban, Betrixaban, Edoxaban, Otamixaban, Rivaroxaban.

Adverse effects:
bruising more easily, bleeding that takes longer to stop, irritation, pain, redness, or sores at
the injection site, allergic reactions, such as hives, chills, and fever, increased liver enzymes
on liver function test results.
USES:
Heparin is an anticoagulant (blood thinner) that prevents the formation of blood
clots. Heparin is used to treat and prevent blood clots caused by certain medical conditions or
medical procedures. It is also used before surgery to reduce the risk of blood clots.
HEPARIN Mechanism of action:
Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a
conformational change that results in its activation through an
increase in the flexibility of its reactive site loop. The activated AT then
inactivates thrombin, factor Xa and other proteases.

USES:
1. It is a synthetic anticoagulant
2. Warfarin is an anticoagulant (blood thinner). Warfarin reduces the formation of
blood clots.
3. Warfarin is used to treat or prevent blood clots in veins or arteries, which can
reduce the risk of stroke, heart attack, or other serious conditions.
4. It is also used as rodenticide.
O O
O
OH
3-(acetonyl benzyl)-4-hydroxy coumarin.
WARFARIN
ADR:
Hypersensitivity reaction,
rash, alopecia and
diarrhoea.

DICOUMAROL
O O
OH
O
O
OH
Dicumarol
MOA:
It is appeared to be act by interfering the function of Vit.K in the liver cell, which is a
site for the synthesis of clotting factor including prothrombin.
ADR:
Haemolysis, haematochezia (passage of fresh blood through anus), menorrhagia
and clotting factor disfunctions.
USES:
1. Often used along with heparin for treatment of deep vein thrombosis.
2. Dicumarol is an coumarin-like compound found in sweet clover.
3. It is used as an oral anticoagulant and acts by inhibiting the hepatic synthesis of
vitamin K-dependent coagulation factors (prothrombin and factors VII, IX, and X).

1,3-INADANEDIONES
PHENINDIONE
O
O
2-phenyl-1H-indene-1,3(2H)-dione
O
O
O
+
CHO
C2H5ONa
O
O
Phenindione
benzaldehyde
Phthalic anhydride
Condensation
Synthesis:
These are Oral anticoagulants and their mechanism of action is similar to that of
Coumarin

M.Pharm,Ph.D
Post Box No-318
Ethiopia.

Diuretics and CVS.pptx

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Diuretics and CVS.pptx

Similar to Diuretics and CVS.pptx (20)

More from Dr. Manjoor Ahamad Syed

More from Dr. Manjoor Ahamad Syed (13)

Recently uploaded

Recently uploaded (20)

Diuretics and CVS.pptx