Evaluation of Capsules.

Pharmacopeial tests for Capsules.

A) Content of Active Ingredient

Weight of active ingredients in each capsule	Subtract from the lower limit for samples of			Add to the upper limit for samples of
	15	10	5	15	10	5
0.12 g or less	0.2	0.7	1.5	0.3	0.8	1.8
More than 0.12g And less than 0.3g	0.2	0.5	1.2	0.3	0.6	1.5
0.3g or more	0.1	0.2	0.8	0.2	0.4	1.0

B) Disintegration

Type of capsule		Disintegration time
Hard Capsules		30 minutes
Enteric Capsules	0.1M hydrochloric acid	Should not disintegrate in 2 hours
	mixed phosphate buffer pH 6.8	60 minutes
Soft Capsules	0.1M hydrochloric acid	60 minutes

C)Uniformity of Weight

Average weight of capsule contain	Percentage deviation
Less than 300 mg	10
300mg or more	7.5

D) Uniformity of content:

• The capsules comply with the test if not more than one of the individual values thus obtained is outside the limits 85 to 115% of the average value and none is outside the limits 75 to 125%.
• If two or three individual values are outside the limits 85 to 115% of the average value repeat the determination using another 20 capsules.
• The capsules comply with the test if in the total sample of 30 capsules not more than three individual values are outside the limits 85 to 115% and none is outside the limits 75 to 125% of the average value.

GPAT Test Series: Test No. 5

GPAT Test Series: Test No. 5

Instructions:

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4. Attempt the MCQs.

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Important Drugs and their active Isomers.

Important Drugs and their active Isomers.

• GPAT and other exams always ask at least one question regarding the subject stated above, this is an effort to bring important drugs together for easy study.
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Name of drug	Stereospecific isomer
Ethambutol	Dextro isomer is 16 times more active than meso
Cyclophosphamide	Levo form has twice activity than D form
Chloprothixene	Z isomer is more active
Doxepin HCL	Z isomer is more active
Lysergic acid diethyl amide	Dextro is active
Epinephrine	Levo form is active
Pseudoephedrine	(+) threo isomer
Propranolol	Only levo isomer is a potent beta antagonist
Hyoscyamine	Levo isomer
Atropine	Racemic mixture
Captopril	S isomer is active
Sulindac	Z isomer
Ibuprofen	(s) – (+) isomer
Ephedrine	(-) erythro is active

Drugs Acting on "Renin-Angiotensin-Aldosterone System (RAAS)".

Drugs Acting on "Renin-Angiotensin-Aldosterone System (RAAS)".

• The drugs which alter the functioning of  Renin-Angiotensin-Aldosterone System (RAAS) comes under this category and are employed in the management of hypertension and various cardiovascular disorders.

Classification: 

A) Drugs inhibiting "Renin" release:

1. Propranolol.
2. Clonidine.
3. Methyl DOPA.

B) Drugs that blocks the actions of "Renin":

1. Alaskirin.
2. Remiskirin.

C) Angiotensin Converting Enzyme (ACE) Inhibitors :

1. Captopril.
2. Enalpril.
3. Lisinopril.
4. Ramipril.
5. Quinapril.

D) Angiotensin Receptor Blockers (ARB):

1. Losartan.
2. Valsartan.
3. Telmisartan.

A) Drugs inhibiting "Renin" release:

• Renin is an enzyme secreted by "juxtaglomerular apparatus." (specialized structure formed by the distal convoluted tubule and the glomerular afferent arteriole.)
• 
  
  
• Renin is responsible for conversion of inactive "Angiotensinogen" to "Angiotensin I".
• The drugs under this class release are known to inhibit release of renin from kidneys. e.g.

1. Propranolol.
   
2. Clonidine.
3. Methyl DOPA.

B) Drugs that blocks the actions of "Renin":

• These drugs blocks the action of renin on Angiotensinogen released by the liver.
• e.g.
  

1. Alaskirin.
2. Remiskirin.

C) Angiotensin Converting Enzyme (ACE) Inhibitors :

• Angiotensin Converting Enzyme is an endothelial enzyme present in lungs.
• The enzyme is responsible for the conversion of Angiotensin-I to Angiotensin-II.
• Angiotensin-II is a powerful vasoconstrictor and also has a direct action on adrenal gland causing release of the powerful mineralocorticoid Aldosterone.
• The hypotensive action results from, inhibitory action on RAAS and stimulatory action on kinin-kallikrein system.
• e.g.
  1. Captopril.
  2. Enalpril.
  3. Lisinopril.
  4. Ramipril.
  5. Quinapril.
     

  Uses of ACE inhibitors:

1. Hypertension.
2. Reverse Ventricular Hypertrophy.
3. To decrease preload, afterload or sympathetic activity.
4. Congestive Cardiac Failure: Cardio protective effect.
5. Myocardial infarction: increases survival rate.

        Adverse Effects of ACE inhibitors:

1. Persistent dry cough (due to bradykinin release/accumulation).
2. Hyperkalemia.
3. Neutropenia.
4. Severe hypotension.
5. Allergic manifestations.
6. On prolonged use causes renal inefficiency.

D) Angiotensin Receptor Blockers (ARB):

• Angiotensin II is formed under the effect of two enzymes:

a.      Angiotensin converting enzyme
b.      Kinase

• When ACE inhibitors are given, angiotensin II is still formed under the effects of kinase.
It acts on two types of receptors:

1. Angiotensin I receptor (AT-1)
2. Angiotensin II receptor ( AT-2)

• When angiotensin I receptors are stimulated, they produce effects similar to angiotensin II.
• When angiotensin II receptors are stimulated, they produce effects that of opposite to angiotensin II (hypotensive activity, beneficial in treatment of hypertension).
• Basically they competitive block AT-1 receptors, thus have effects of angiotensin II through angiotensin II receptors.

Renin-Angiotensin-Aldosterone-System (RAAS).

Renin-Angiotensin-Aldosterone-System (RAAS).

• Renin is a proteolytic enzyme that is secreted by the juxtaglomerular apparatus (composed by renin-secreting cells) when certain physiological stimuli such as reduced renal perfusion pressure and reduced NA+ concentration in distal tubular fluid are present. 

• Renin will cut angiotensinogen (released into circulation by the liver) into a shorter peptide called angiotensin I. 

• Angiotensin-conversing enzyme (ACE) then remove 2 amino acids from angiotensin I to form an octapeptide called angiotensin II. 

• Amino peptidase A and N will remove amino acids from angiotensin II to angiotensin III and angiotensin IV respectively. 

• ACE is an enzyme normally found on the surface of endothelial cells and is abundant in the lungs.

• Angiotensin II is  a potent vasoconstrictor that causes arterioles to constrict resulting in increased arterial blood pressure, angiotensin II also stimulates the secretion of aldosterone from adrenal cortex. 

• Angiotensin III stimulates aldosterone secretion and is involved in thirst. 

• Angiotensin IV associated with the release of plasminogen activator inhibitor-1 from the endothelium. 

• Aldosterone acts on the tubular epithelial cells of the kidneys to stimulate reabsorptions of NA+ and water.

Key points:

1. Angiotensinogen is released in the blood circulation by "liver".
2. Renin is released in the blood circulation by "Kidney" in response to fall in blood pressure and fluid volume of the body.
3. Renin acts on "inactive Angiotensinogen" and converts it into "Angiotensin-I".
4. Through blood "Angiotensin-I" reaches Lungs where it get converted to active "Angiotensin-II" by action of the enzyme "Angiotensin Converting Enzyme".
5. "Angiotensin-II" directly acts on "Adrenal Gland" and releases "Aldosterone".
6. "Angiotensin-II" also acts directly on blood vessels causing "vasoconstriction" this results directly in "rise of the blood pressure".
7. "Aldosterone" is a powerful "Mineralocorticoid" acts directly on "Distal Convoluted Tubule of the Kidney" and results in reabsorption and retention of "Na and Water" this results in "increased circulating plasma level and hence rise in Blood Pressure."

"Various drugs are available which act on different stages of "Renin-Angiotensin-Aldosterone-System (RAAS)." and are employed in the management of hypertension and various CVS disorders."

Lecture note on Glycosides

Lecture note on "Glycosides".

• Glycosides are the compounds of plant and animal origin which on hydrolysis yields a sugar compound (glycone) and a nonsugar compound (aglycone), having marked physiological actions.

• Common sugars found in glycosides are glucose, mannose, rhamnose, & digitoxose.

• The common non- sugar part is alcohol/ phenol/ amine.

• The activity of glycoside is due to non-sugar part (aglycone).

• Glycone part plays role in pharmacokinetic properties of the glycoside like, absorption, metabolism, distribution and excretion..

·         Physical Properties:

• Glycosides are crystalline colorless solids.

•  Non- reducing in nature and are generally laevorotatory.

•  They are soluble in alcohol & water.

•  Dilute acids and enzymes cause their hydrolysis.

·         Biological role: -

• They protect the plant from insects & animals.

•  They stimulate growth, reproduction & metabolism of the plant.

•  Glycosides act as a storage of chemicals for many plants.

Classification: - Glycosides can be classified by two methods

• 1.      According to the basis of chemical nature of Aglycone.

• 2.      According to the chemical linkage between Glycone & Aglycone.

 A) Classification according to the chemical nature of Aglycone: -

·         1) Cyanophoric or cyanogenic glycosides: -

• This type of glycoside produces one molecule of Hydrocyanic acid (HCN) & sugar on hydrolysis.

•   e. g. Amygdaline in bitter almond.

·         2) Cardiac Glycoside: -

•  This type of glycoside acts on heart muscle they increase the force of contraction of the heart.

•  Cardiac glycosides are again divided into Cardenolides (C₂₃)  & Bufadienolides (C₂₄)

•  e.g. Purpurea glycosides in digitalis leaf.

·         3) Isothiocyanate glycosides: -

• These glycosides give one molecule of sulfur on hydrolysis.

•  e. g. sinigrin in black mustard

·         4) Saponins: -

• These on hydrolysis gives aglycone known as sapogenin.

• They form soapy, a colloidal solution with water.

•  They cause breakdown of R. B. Cs (hemolysis) in very low concentration.

•  Saponins are good detergents & emulsifying agents.

•  e. g. Digitonin, gitonin in digitalis leaf.

·         5) Phenolic Glycosides: -

• According to chemical nature, these glycosides are divided into following types:

Type	Aglycone	Source
Simple Phenolic glycoside	Salicin	Salix species
Anthraquinone glycosides	Barbaloin, aloe- emodin	Aloe, Rhubarb, Senna
Coumarin glycosides	Umbelliferone	Asafoetida, Tobacco
Flavone & flavonoid	Gentisin, Kaempferol	Senna, Gentian, Liquorice
Anthocyanidine	Cyanidin, Malvidin	Rose, Purple grapes.

B) Classification according to the chemical linkage between glycone & Aglycone:

·         1) O-glycosides: -

·         If the glycoside sugar combines with OH group of the non- sugar part.

·         e.g R – HO + OH C₆ H₁₁ O₅   ------>  -O C₆ H₁₁ O₅  (e. g Cardiac glycosides.)

·         2) C – Glycosides: -

·         In this type, the carbon atom from aglycone combines with sugar.

·         e.g R – CH + OH C₆ H₁₁ 0₆ = -C-C₆ H₁₁  (e. g. Aloin in Aloe)

·         3) S- Glycoside: -

·         In this type, the sulfur atom from aglycone combines with sugar.

·         R – SH + OH + C₆ H₁₁ O₅ = -S – C₆ H₁₁ O₅ (e. g Isothiocyanate glycoside that is sinigrin)

·         4) N – Glycosides: -

·         In this type nitrogen from aglycone combines with sugar.

·         > N – H + OH C₆ H₁₁ O5 = > -N – C₆ H₁₁ O₅ e. g. Nucleosides.

Isolation of Glycosides: -

1.      Extract the powdered drug with water or alcohol.

2.      Due to this, enzymes present in the tissues get destroyed.

3.      Add lead acetate solution to precipitate impurities present in the drug sample.

4.      Filter the solution & pass H₂S gas through filtrate to neutralize excess of lead.

5.      Now concentrate the extract to get crude product.

      Purify the product by using chromatography techniques.

Identification tests for Glycosides:-

1)        Test for Anthraquinone glycoside: Bontrager's Test.

2)       Test for cardiac glycoside Write keller killiani test of digitalis.

3)       Test for saponins.

1.         Test for saponins are –

A)        Shake the powdered drug with water to form soapy solution

B)         If powdered drug is added to the sample of blood it causes breaking of R.B.Cs (hemolysis).

2. Test for Anthraquinone Glycosides:

A) Borntrager's Test:

B) Modified Borntrager's Test:

C) Keller Killani Test for Cardiac Glycosides:

D) Other Chemical tests for glycosides: