module 2 tuts p7

Pharmacognosy

Study drugs from natural sources: plants, animals, microbes

Crude drugs

drugs of plant, animal and microbial origin that contain natural substances that have undergone only the processes of collection and drying

Quality

Intrinsic value of a drug

Purity

Absence of adulterants

EVALUATION OF CRUDE DRUGS

1. Organoleptic Evaluation

2. Physical Evaluation

3. Microscopic Evaluation

4. Pharmacologic Evaluation (Bioassay)

5. Chemical Evaluation

Organoleptic Evaluation

Use of sense organs – the macroscopic appearance of the drug, its odor and taste, the sound or “snap” of the fracture, and the feel of the drug to the touch.

Physical Evaluation

Applies physical constants (e.g., optical rotation, solubility, melting point) to the active constituents of drugs.

• Ex. Cinnamomum camphora - bark

  • Natural camphor - +41 to +43 Dextrorotatory

  • Synthetic camphor - 0; a Racemic Mixture

Microscopic Evaluation

• Employed for powdered drug samples.

• Use of microscope.

Pharmacologic Evaluation (Bioassay)

Employs animals or excised organs to evaluate the physiological activity/effect of drugs

• Ex. Rabbits for head drop assay (tubocurarine), pyrogen test, assay of insulin

• Cats for mydriatic effects of atropine; and for assay of glucagon

Chemical Evaluation

• Use of reagents or chemical

• Preferred method of determining official potency.

• Ex. Titration (% purity)

C. Organoleptic method (MACROSCOPIC)

This method of evaluating crude drugs involves the use of the organs of senses. The analyst evaluates the macroscopic appearance of the drug, its odor and taste, the sound or “snap” of the fracture, and the feel of the drug to the touch.

A. Microscopic method

B. Biological method

C. Organoleptic method

D. Chemical method

A. Physical method

This method of evaluating crude drugs makes use of physical constants, such as optical rotation, to the active constituents of drugs.

A. Physical method

B. Chemical method

C. Biological method

D. Organoleptic method

anticancer

Taxol (Paclitaxel) is an ___ agent.

Taxus

Taxanes were originally identified from plants of the genus __

Paclitaxel (taxol)

• Prototype of taxane

• From bark of Taxus brevifolia / Pacific Yew

inhibit

Taxanes ____ the depolymerization of microtubules

True

The taxanes, paclitaxel and docetaxel, and cabazitaxel inhibit the depolymerization of microtubules

• Rationale: This stabilizing effect prevents cell division.

True

• Paclitaxel, docetaxel, cabazitaxel are TAXANES

• Sinigrin is an Isothiocyanate Glycoside

• Prunasin is a Cyanogenic Glycoside

True

Taxanes are diterpenes

PRUNASIN

• A cyanogenic glycoside that occurs in the bark of Prunus serotina

  • CYANIDE FORMING GLYCOSIDES = TOXIC

  • Used as anticancer agent

• Aglycone is MANDELONITRILE.

• Yields hydrogen cyanide on hydrolysis

Hydrocyanic acid (HCN)

• Cyanogenic Glycosides when hydrolyzed yield cyanide also known as ___

Cyanogenic Glycosides

Aglycone: MANDELONITRILE

• Prunasin

• Amygdalin

• Laetrile (Vitamin B17)

Cyanogenic Glycosides

Sources:

• Kernels of Apricot (Prunus armeniaca)

• Kernels of Bitter Almond (Prunus amygdalus var. amara)

• Stems and barks of Wild Cherry (Prunus serotina)

GLYCOSIDES

• They are acetals in which the hydroxyl of the sugar (glycone) is condensed with the hydroxyl group of the non-sugar component (aglycone)

GLYCOSIDES

• Both alpha- and beta-glycosides exist, but ONLY the beta form occurs in nature

• Natural enzymes like emulsin hydrolyze only the beta forms

Emulsin

Collective term for Amygdalase and Prunase

• AMYGDALASE catalyzes the hydrolysis of AMYGDALIN → PRUNASIN

• PRUNASE catalyzes the hydrolysis of PRUNASIN → MANDELONITRILE → HYDROCYANIC ACID

• They are beta glucosidases

True

• The non-sugar component of glycosides is aglycone or genin, and the sugar component is glycone.

Naringin

• Flavonol Glycoside

• Aglycone: Flavonoid

FLAVONOIDS

• POLYPHENOLIC molecules containing 15 CARBON atoms and are SOLUBLE in water.

• Examples are naringin, rutin, quercitrin, and hesperidin

Vitamin P (Permeability Factors)

Rutin & Hesperidin are ____ (Permeability Factors); they are Flavonol Glycosides

• Treatment of capillary fragility

• Treat symptoms of common colds

phenolic

Arbutin is a ___ Glycoside

Vitamin P (Permeability Factors)

Rutin and hesperidin are called

• are used in the treatment of conditions characterized by capillary bleeding and increased fragility

FLAVONOIDS

These are aglycones of flavonol glycosides

Hydrolyzable Tannins

• Hydrolysis: + HCl

  • Converted to PHENOLIC ACIDS and SUGARS

  • Gallic acid & Ellagic acid (Gallotannins)

• Ferric Chloride Test

  • Bluish black ppt

• Bromine Water Test

  • No precipitate

• Less resistant to microbial degradation

• Leather: BLOOM LEATHER

Non-hydrolyzable Tannins (Condensed Tannins)

• Hydrolysis: + HCl

  • Not hydrolyzed

  • Polymerize forming red insoluble compounds called as PHLOBAPHENES

• Product of condensation of Flavan-3-ols or Flavan-3,4-diols

• Ferric Chloride Test

  • Greenish black test

• Bromine Water Test

  • Has precipitate

• More resistant to microbial degradation compared to hydrolyzable tannins

• Leather: TANNER'S RED LEATHER

Hydrolyzable Tannins

Gallotannin is a ____

Gallic Acid

Hydrolyzable Tannins consist of ___ or related polyhydric compounds esterified with glucose

PHENOLIC ACIDS & SUGARS

Hydrolyzable Tannins readily hydrolyze to form ____ and ____

Non-hydrolyzable Tannins (Condensed Tannins)

result from the CONDENSATION of 2 or more flavan-3-ols such as catechin or flavan-3,4-diols such as leucocyanidin

PHLOBAPHENES

Non-hydrolyzable Tannins (Condensed Tannins)

• When treated with hydrolytic agents, they tend to polymerize, yielding insoluble, red-colored products called ____

Non-hydrolyzable Tannins (Condensed Tannins)

are SOLUBLE in water, alcohols, and acetone and can coagulate proteins

Non-hydrolyzable Tannins (Condensed Tannins)

are more resistant to microbial attack than hydrolysable tannins

RESINATE

The metallic salts of resins are called

True

Metallic salts of resin acids are called RESINATES

Balsams

Are resinous mixtures that contain cinnamic acid, benzoic acid, or both, or esters of these acids

True

Resins are INSOLUBLE IN WATER; Resins are SOLUBLE in ALCOHOL + ORGANIC SOLVENTS

RESINS

Chemically, ___ are complex mixtures of resin acids, resin alcohols, resinotannols, esters, and resenes

Cinchona Alkaloids

• Used as antimalarial agents

• QUINIDINE - antimalarial and antiarrhythmic agent

• CHEMICALLY, they are QUINOLINE ALKALOIDS

• Parent alkaloid is CINCHONINE

• CINCHONINE is the DEXTRO ISOMER of CINCHONIDINE

• QUINIDINE is the DEXTRO ISOMER of QUININE

Cinchona Alkaloids

Source

• Bark of Cinchona succirubra (Red)

• Bark of Cinchona calisaya (Yellow)

Cinchonine

the parent alkaloid of the quinine series

6-methoxycinchonine

Quinine and Quinidine chemically _____

QUINOLINE ALKALOIDS

Cinchonine, Cinchonidine, Quinine, and Quinidine are

True

• CINCHONINE is the DEXTRO ISOMER of CINCHONIDINE

• QUINIDINE is the DEXTRO ISOMER of QUININE

ANTIMALARIAL

Cinchona alkaloids are ___ agents

GUMS AND MUCILAGES

• POLYSACCHARIDES

• HETEROGLYCAN

• Upon hydrolysis, they yield different types of sugar units

  • Ex. Carrageenan (marine gum) → Glucose, Arabinose, Galactose, Fructose

Shrub or Plant Exudates

Aki & Travis Stayed in India

• Aki - Acacia

• Travis - Tragacanth

• Stayed - Sterculia (Karaya gum)

• India - Indian Gum (Ghatti)

Alcohol, USP

Acacia gum is incompatible with ___ (turbid soln)

Tragacanth

MOST RESISTANT TO ACID HYDROLYSIS

Sterculia (Karaya Gum)

MOST FETID GUM (amoy tae)

Ghatti

Substitute for acacia

Marine Gums

Dan and Al went to Japan using a Car

• Dan - Danish Agar

• Al - Algin

• Japan - Japanese Isinglas (Agar)

• Car - Carrageenan

Algin

Isolated from brown seaweeds (Macrocystis pyrifera)

Seed Gums

The Queen & St. John must be Guarded from Psychotics

• The Queen - Quince or Cydonium

• St. John - St. John’s Bread (Locust Bean Gum)

• Guarded - Guar gum

• Psychotics - Psyllium

Microbial Gums

• Xanthan - Xanthomonas campestris

• Dextran

Cellulose Derivatives Gum

• Carboxymethylcellulose

• Alternative to gums n mucilages

Pectin

Plant Extract; Extracted from the inner rind of citrus fruits and apple pomace

True

1. Locust Bean Gum → Seed Gums

2. Pectin → Plant Extract

3. Xanthan → Microbial Gum

4. Carboxymethylcellulose → Cellulose Derivatives

5. Tragacanth → Shrub or Tree Exudate

VOLATILE OILS

also known as essential oils, are aromatic oily liquids found in many plants. They are highly volatile and evaporate easily at room temperature.

VOLATILE OILS

• Isoprenoids or Terpenoids (via mevalonic acid pathway)

• Phenylpropanoids (via shikimic acid pathway)

METHODS OF EXTRACTING VOLATILE OILS

1. Water Distillation

2. Direct Steam Distillation

3. Water and Steam Distillation

4. Destructive Distillation

5. Expression

6. Ecuelle

7. Enfleurage

8. Enzymatic Action

Water Distillation

• Dired parts

• Example: Turpentine oil - from dried parts of Pinus palustris

Direct Steam Distillation

• Fresh parts

• Example: Spearmint oil from Mentha spicata; Peppermint oil from Mentha piperita

Water and Steam Distillation

• Dried or Fresh

• Example: Clove oil; Cinnamon oil

Destructive Distillation

• Aka pyrolysis (subjected to high temperature without the presence of air)

• Empyreumatic oils

• Example: Tar oil from Pinus palustris

True

• Distillation is the most common but it employs heat so it cannot be used in heat sensitive volatile oils

• For heat labile volatile oils, expression is used (ecuelle & enfleurage & sponge method)

Ecuelle

• Citrus volatile oils

• Example: Lemon oil from Citrus limon

Enfleurage

• Flower petals

• Example: Rose oil

Enzymatic Action

• Glycosidic volatile oils

• Example: Mustard oils

  • Black mustard - Sinigrin → Allyl Isothiocyanate

  • White mustard - Sinalbin → Acrinyl Isothiocyanate

  • They are converted by MYROSIN to Allyl and Acrinyl Isothiocyanate = glycosidic volatile oils

True

Volatile oils contain

• Terpenoids - H, C, and another element (isoprenoids) via MVA

• Terpenes - H, C (isoprene) via MVA

  ---

• Phenylpropanoids - aromatic via shikimic acid pathway

TERPENES

• Made up of isoprene units

ISOPRENE

5-carbon compound: CH₂=C(CH₃)-CH=CH₂

• Iso = branch/substituent on the 2nd carbon

• Ene = double bonds

• C5H8

Monoterpenes

• 2 isoprene units - C₁₀H₁₆

• Examples:

  • Carvone (Caraway oil) - ketone

  • Linalyl acetate (Lavender oil) - ester

  • Diosphenol (Buchu oil) - ketone

  • Methylsalicylate (Wintergreen oil) - ester

Sesquiterpenes

• 3 isoprene units - C₁₅H₂₄

• Examples:

  • Artemisinin ⭐

  • Bisabolol

  • Farnesol

  • Eudesmol

Artemisinin

Novel antimalarial agent (new); isolated from a plant Sweet Wormwood (Artemisia annua

• Ester derivative:

  • Artesunate - prone to hydrolysis

• Ether derivative

  • Artemether - most potent

  • Combined with Lumefantrine

  • For chloroquine resistant malaria

• Metabolite of Artesunate, Artemether, Artemisinin

  • Dihydroartemisinin

Artesunate

• Ester derivative of artemisinin; prone to hydrolysis

Artemether

• Ether derivative of artemisinin - most potent

• Combined with Lumefantrine for chloroquine resistant malaria

Dihydroartemisinin

• Metabolite of Artesunate, Artemether, Artemisinin - not a prodrug

Diterpenes

• 4 isoprene units - C₂₀H₃₂

• Examples:

  • Phytol

  • Retinal/Retinol/Vitamin A

  • Paclitaxel

  • Gingkolides

  • Bilobalides

Triterpenes

• 6 isoprene units - C₃₀H₄₈

• Examples:

  • Lanosterol

  • Squalene

Tetraterpene

• 8 isoprene units - C₄₀H₆₄

• Examples:

  • Beta carotene (precursor of retinol)

  • Lycopene

  • Lutein

True

Volatile oils act as insect attractants and insect repellants

Glandular Hairs

Sa labia maraming hair

• Lamiaceae / Labiatae (MINT family)

  • Mentha piperita - peppermint

  • Mentha spicata - spearmint

  • Thymus vulgaris - thyme

  • Lavandula angustifolia - lavender

  • Origanum vulgare - oregano

Modified Parenchymal Cells

Si pare na mahilig sa pipe

• Piperaceae

  • Piper nigrum - black pepper

  • Peperomia pellucida - pansit pansitan or ulasimang bato for gout

Vittae (oil tubes)

Sa belli may tae

• Apiaceae / Umbelliferae (carrot family)

  • Foeniculum vulgare - fennel

  • Coriandrum sativum - coriander

  • Carum carvi - caraway

  • Conium maculatum - poison hemlock

Schizogenous and Lysigenous Passages

• Pinaceae (pine) & Rutaceae (citrus)

  • Pinus palustris

  • Pinus strobus

  • Citrus spp

  • Artemisia absinthium

D. Steam Distillation

Peppermint oil is isolated from the fresh leaves of Mentha piperita. Determine the best method to isolate the oil.

A. Enfleurage

B. Extraction with a volatile solvent

C. Expression

D. Steam Distillation

B. Diterpenes

What type of terpenes are retinol and phytol?

A. Monoterpenes

B. Diterpenes

C. Triterpenes

D. Sesquiterpenes

B. Diterpenes

This group of terpenes are composed of 20 carbon atoms.

A. Sesquiterpenes - C15

B. Diterpenes

C. Triterpenes - C30

D. Tetraterpenes - C40

B. Schizogenous intercellular spaces

What special secretory structures are found in Pinus palustris?

A. Modified parenchyma cells

B. Schizogenous intercellular spaces

C. Vittae

D. Glandular hairs

CH2=C(CH3)-CH=CH2

Isoprene is a

A. 5-carbon compound with the formula: CH3-CH(CH3)-CH2CH3

B. 3-carbon compound with the formula: CH2=C=CH2

C. 4-carbon compound with the formula: CH2=CH-CH=CH2

D. 5-carbon compound with the formula: CH2=C(CH3)-CH=CH2