1.4.

NATURE,SOURCES AND DOSAGE FORMS PHARMACOLOGY

Dr. Glenn D. Guevarra | JUNE 19, 2013 1ST 2013-2014

OUTLINE 4. Narrow therapeutic window

I. History
II.Drug development
o There is a limited space between efficacy and toxicity,
II. Various sources of drugs increasing risk for adverse reactions.
A. From nature o Theophylline – extracted from inorganic source; Xanthine
B. Synthetic
III. Description different dosage forms oxidase inhibitor; antiasthma (3rd line treatment) that
produces produces complications
References:
o Salbutamol – Beta-2 agonist (sympathomimetic);
Katzung,2015B Trans,Pharma Manual and Dr Guevarra’s lecture 2013
bronchodilator; no adverse reactions
I. HISTORY 5. New disease / new strain
A. 3800 B.C. o New drugs are being explored because of Multiple Drug
 Ancient medicine involves the practice of Chinese and Ayurvedic Resistant TB.
medicine. o Many drugs are tested for HIV.
 Most drugs were from nature and administered orally. 6. Drug resistance
 Drugs were called “magic potions.” o Before they only use amoxicillin as antibiotic but they develop
 Cure during this time was by mere gut feel. resistance against amoxicillin which leads to development of
 Drugs were sold in “apothecary shops.” Apothecaries were the new drugs such as co-amoxiclav
medical specialists.
o Augmentin (Co-Amoxiclav) – amoxicillin and clavulanic acid
 Chinese herbs were also popular. In China, specialization in this
kind of medication is still being offered.
 In the Philippines, the Mambabarang was popular in provinces to B. Future Drugs
seek for cure of diseases.  Candins – anti-fungal (from Candida species)
 Natives also refer to Hilot as form of medical treatment (Mang  Epothilones – anti CA (from marine sponges)
Kepweng)
 Ketolides – from Erythromycin; more powerful Macrolide-resistant
bacterial infections
B. 1800 A.D.
 Glycylcyclines –from Tetracyclines; address resistance to
 Discovery of chemical science
Tetracyclines
 Studies in chemistry, pharmaceuticals and other specialized field of
studies paved way for more scientific approach in the use of drugs  Teicoplanin – an old drug being reused today as it is deemed more
from natural products. effective and safe from resistance
 One of the earliest pain reliever and antibiotics are Aspirin and  Pristinamycin – treatment for Vancomycin-resistant infections
Penicillin.
III. SOURCES
C. At present
 60% of pre-approved drugs
 There is an increase in the number of drugs that are produced  15% of biological
synthetically which have higher bioavailability and less toxicity (eg. vaccines & antibodies) from natural sources
 80% of antibiotics
II. DRUG DEVELOPMENT  Various sources are:
A. Factors that Trigger Drug Development o Plants, Microbes, Animals, Minerals
1. Adverse reactions
o Thalidomide (sedative) – anaesthetic that causes Phocomelia A.Plant Drugs
(birth defect involving the limbs)
2. Lower efficacy (ZANTAC VS. OMEPRAZOLE)  500,000 natural products - from plants
o Zantac (Ranitidine): H2 blocker that decreases secretion of  160,000 - used worldwide
gastric acids which causes gastroduodenal bleeding  100,000 new secondary metabolites - being studied (half from
o Omeprazole: proton-pump inhibitor; more effective than plants & half from microbes)
Zantac - decreases the chances of having ulcer for those with I. Alkaloids
gastritis o Basic organic substances containing mainly nitrogen atoms
o Omeprazole has higher efficacy than Ranitidine including carbon, hydrogen, oxygen
3. Narrow spectrum (CLOXACILLIN VS. AMOXICILLIN) o Amino acid derived
o Cloxacillin – narrow-spectrum drug exclusively for Gram- o Occur in almost all parts of plants but are most often found in
positive cocci in wounds seeds, roots & leaves
o Amoxicillin – broad-spectrum antibiotic for Gram-positive, o Are also produced by microbes, bacteria, fungi & animals
Gram-negative bacteria and anaerobes o Keep plants protected from injury
o Have high potency leading to increased risks of adverse
reactions

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GroupNumber #10: Candeloza,Canlas,Canta,Cara,Carandang,Carpio,Casas
 PHARMA 1.3
o 3 types:  Found in the plant Digitalis purpurea
 True alkaloids  Used in treating heart diseases (cardiac glycoside)
 Protoalkaloids b.) OUABAIN
 Pseudoalkaloids  Aglycone part is a steroidal nucleus
o Alkaloids from ORNITHINE:  Found in the ripe seeds of African plant Strophantus gratus
a.) ATROPINE  Used in treating heart diseases
 Anti-cholinergic drug
 Tropane alkaloid extracted from Atropa belladonna III. OILS
 Does not cross blood brain barrier o FIXED OILS
 Used to reverse organophosphate poisoning but not  Substances that are in a viscous liquid state that are not
always used due to its adverse effects volatile; thus they do not evaporate
 Used to dilate pupils (children exhibit strongest  Used as base oil, extracted from vegetables or seeds of
accommodation or the ability to shift vision to near flowers & plants
objects)  Includes olive, coconut, linseed & castor oils (laxative),
 Causes paralysis of the ciliary ms.  flaxseed oil (source of omega 3 and lactic acid)
 Narrow therapeutic window  Leaves a stain
b.) SCOPOLAMINE o VOLATILE OILS
 Anti-cholinergic drug  Concentrated, hydrophobic liquid containing volatile
 Similar to atropine but crosses blood brain barrier aromatic compounds from plants
 Used to treat severe motion sickness (eg. Bonamine)  Evaporates readily w/o leaving a stain e.g. Peppermint,
 Available in patches spearmint, oil of Wintergreen, oil of Thyme
 Have high adverse reactions
c.) COLCHICINE IV. RESIN
 Anti-inflammatory o Rosin-like substance usually formed by the oxidation of volatile
 Used to treat gout oils
 Cox-2 inhibitors can also be used for treating gout but o Most are used as cathartics
poses high risk of hyperacidity o A viscous fluid composed mainly of volatile fluid terpenes , with
d.) COCAINE less components of dissolved nonvolatile solids like frankincense
 Highly addictive substance o Produced by most plants eg. Pine rosin, frankincense
 For sympathetic (vasoconstrictor) activity
 Has higher risk of cardiovascular toxicity V. GUM
 Used to treat sympathetic nerve compression o Secretory products from plants
o Carbohydrates that absorb water & swell to form thick
o Alkaloids from TYROSINE: mucilaginous colloid solutions
a.) DOPAMINE o A polysaccharide that can cause a large viscosity increase in
 Sympathomimetic, Alpha-1 adrenergic agonist, solution, even at small concentrations like gum tragacanth (eg.
Dopaminergic agent Gum acacia, gum tragacanth)
b.) MORPHINE
 Highly potent analgesic drug (opioid) VI. TANNIN
 Principal active agent in Opium (comes from the poppy o Complex principle found widely distributed in plants
seed of opium) o Has an astringent action & is used in treating inflammation,
 Highly addictive; acts directly in the CNS burns, diarrhea & haemorrhoids
 Stimulates opioid receptors o Any large polyphenolic compound containing sufficient
 Other derivatives: Codeine, Heroin, Fentanyl & Demerol hydroxyls & other suitable groups

o Alkaloids from TRYPTOPHAN: VII. ANTIBIOTIC

a.) QUININE o Any substance produced by a microorganism that has a lethal or
 Used to treat malarial infections but can cause adverse inhibitory action on other microorganisms in high dilution
effects & resistance o Capsaicin - extracted from pepper
b.) VINCRISTINE o Artemicin - anti-malaria
 Used for chemotherapy (anti-cancer agent), but has o Tawa-tawa - not an antibiotic, but it increases the platelet; for
limited effects due to high adverse reactions dengue
o Β-Lactams like penicillin derivatives that came from Penicillium
II.GLYCOSIDES species, Cephalosporins, Monobactams & Carbapenems
o Ether-like combinations of sugar with some other organic
substances B. Animal Drugs
o To qualify as a glysoside, the sugar must be bonded with a non-
 Insulin – extracted from humans and administered to patients
sugar
o Sugar group = glycone  Thyroid hormone – naturally dessicated from pigs
o Non-sugar group = aglycone or genin  Vaccines – few are from animals (i.e chicken, sheep)
o Examples:
C. Mineral Drugs
a.) DIGOXIN
 Aglycone part is a steroidal nucleus  Iron – needed in RBC synthesis, for anemic & pregnant women

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 PHARMA 1.3
 Iodine – needed in the synthesis of thyroid hormone; treatment of Table 1. Routes of administration, bioavailability and general
goiter characteristics
 Aluminum & Magnesium Hydroxide – used as antacids Route Bioavailability Characteristics
(%)
D. Synthetic Drugs Intravenous (IV) 100 Most rapid
 Purely chemical substances produced in a laboratory onset
 Made by emulating or imitating substances found in nature (i.e Intramuscular 75 to 100 Large volumes
barbiturates, sulfonamide, aspirin, procaine) (IM) often feasible;
may be painful

IV. ROUTES OF ADMINISTRATION Subcutaneous 75 to 100 Smaller volumes

A.Oral (SC) than IM; may be
painful
 Can be liquid, solid or gas
 Tablets, capsules, pills Oral (PO) 5 to 100 Most
 Convenient; increases compliance convenient; first
Disadvantage: goes through first pass effect (less amount utilized) pass-effect may
be significant
B.Parenteral Rectal (PR) 30 to 100 Less first pass-
 Vials, ampules effect than oral
 Intravenous – fastest route, direct to the vein, and no first pass
effect Inhalation 5 to 100 Often very rapid
 Intramuscular – 2nd fastest route, some issues in absorption onset
 Subcutaneous or subdermal – insulin Transdermal 80 to 100 Usually very
 Subdermal – vaccines; e.g. BCG sow absorption;
used for lack of
first-pass effect;
C. Sublingual, Buccal, Transdermal and Rectal prolonged
 Sublingual – form of tablet absorbed directly to the circulation duration of
without use of syringe. Klonidine and nifedipine are examples of action
sublingual used for hypertension
 Buccal (same characteristics as sublingual but sublingual is the
faster route)
 Rectal – if unable to swallow oral drugs; usually for children V.DOSAGE FORMS
(Paracetamol); fast absorption due to rich blood supply in the A.LIQUID PREPARATIONS
rectum I. AQUAEOUS SOLUTIONS
 Transdermal – drug patches for sustained release of active a. Solution
ingredient e.g. Nitroglycerin for angina or M.I.  Homogenous system prepared by dissolving a
solid, liquid or gas in water.
D. Topical E.g. Strong Iodine Solution, Saturated Solution of
 Examples of drugs are ointments, creams, nasal sprays Potassium Iodide
b. Aromatic Water
 Skin, eye, ears and nose
 Saturated solutions of volatile substances, usually
 Drugs that are used, mostly to preserve moisture and to absorb
volatile oils, dissolved in water.
active ingredient
E.g. Peppermint Water, Spearmint Water
 To obtain a more localized effect
c. Syrup – concentrated solution of sugar in water or other
aqueous liquid.
E. Intrathecal, Intracranial, Intracardiac, Intraoccular,  Flavored Syrup – employed to mask the taste of unpleasant-
Intrasynovial tasting drugs and to add stability to
the preparation.
 Given directly to the site
E.g. Raspberry Syrup, Cherry Syrup
 Intrathecal – directly in the brain and spinal cord across the
arachnoid space  Medicinal Syrup
E.g. Paracetamol Syrup, Multivitamins Syrup
 Intraoccular – drug route for patients with diabetic retinopathy
d. Douche
 Some Examples of Drugs
 Aqueous solution directed against a part or into a
o Co-amoxiclav (Augmentin)– tablet (for adults), suspension (for
cavity of the body for purposes of cleansing.
children), parenteral route (if there is a progression of the
 Usual excipients are buffers because certain pH needs to be
disease and if the drug has significant first pass effect e.g.
maintained.
gentamycin)
E.g. Vaginal douche, eye douche
o Ofloxacin – intravenous and tablet have the same
bioavailability, but IV is for the unconscious patients e. Enemas
o Chloramphenicol – oral & intravenous; but oral has greater  Rectal injections employed to evacuate the bowel,
bioavailability than IV to influence the general system by absorption or
to affect locally the seat of disease.
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 PHARMA 1.3
 usually for surgery preparation and to prevent post operative c. Lotion – aqueous suspension of insoluble substances
infection. applied to the skin.
 can also be used for giving of barium for visualization of the E.g. Phenolated Calamine Lotion,
intestine. Betamethasone Valerate Lotion
f. Gargles
 Aqueous solutions used for treating the pharynx V. EXTRACTIVES
And nasopharynx by forcing in from the lungs a. Tincture
Through the gargle which is held in the throat.  Alcoholic or hydroalcoholic solution prepared from
 Stinging sensation is due to alcohol Vegetable materials or from chemical substances
 Some gargles do not have the stinging sensation because  Very saturated solution, ususally a few drops is enough to
chlorine replaces alcohol as the anti-septic. achieve therapeutic effect
g. Nasal Solution Note: alcohol content 15-80%
 Aqueous solution for administration to nasal e.g. Belladonna Tincture
passages in nasal drops or sprays Opium Tincture
h. Mucilage Iodine Tincture
 Aqueous solution of gummy substance used as b. Extract
vehicle and demulcent  Concentrated, solid or semisolid preparation made by
i. Decoction Percolation and evaporation of the percolate; adjusted
 Obtained by boiling medicinal herbs in water To a specific strength and generally 2 to 6 times as
(“nagpapakulo ng gamot”) Strong as the crude drug from which it is prepared
j. Infusion Note: can be made into three forms:
 Obtained by extracting the active principle of a substance by o Semiliquid – syrupy consistency
using either hot or cold water E.g. Tea bag o Pilular
j. Percolation o Powdered
 The process of a liquid slowly passing through a filter. It's how e.g. Thyroid Extract
coffee is usually made. c. Fluid Extract
 Hydroalcoholic extract of vegetable drugs made by
percolation so that 1 ml of the fluid extract represents
II.ALCOHOLIC PREPARATIONS
the active principles in 1 gm of the crude drug.
a. Elixir
 Highly concentrated form of vegetable drugs is ten
 sweetened, pleasantly-flavored hydroalcoholic
times stronger than the tinctures.
solution intended for oral use. They are used as
e.g. Aromatic Cascara Sagrada Fluid Extract
flavors and vehicles.
 Aromatic Elixir and Isoalcoholic Elixir – used mainly as diluting
VI. MISCELLANEOUS LIQUID PREPARATION
vehicle
a. Glycerite – solution or mixture of medicinal
 Medicated Elixir
substances in not less than 50% by weight of
E.g. Codeine Elixir, Diphenhydramine Hydrochloride
glycerine.
Elixir
b. Liniment (aka embrocations)
b. Spirit or Essence
 Solutions or mixtures of substances in oil,
 Alcoholic or hydroalcoholic solutions of
alcoholic solutions or emulsions which are
Volatile substances
intended for external application usually by
Eg. Peppermint spirit, spirit of ammonia
rubbing
C. Tincture
Note: used as rubefacient, counterirritant (pain alleviation)
 Prepared from vegetable materials or from
E.g. Camphor Liniment
Chemical substances
c. Ophthalmic Preparations
 Sterile products intended for instillation into
III. EMULSION the eye
 A preparation composed of two immiscible liquids in  Can be in the form of solutions, suspensions
which one liquid is dispersed in the form of small or ointment
droplets throughout another liquid. An emulsifying E.g. Silver Nitrate Opthalmic Solution, Terramycin
agent is used to prevent the separation of the two Ointment , Pilocarpine HCl Solution,
liquids. Naphazoline HCl
d. Otic Preparations
IV. SUSPENSIONS  Aqueous solutions or suspensions and
 Preparations of finely divided drugs suspended ointments for topical application to the ear.
In water by means of suspending or dispersing E.g. Cerumenex Ear Drops, PediOtic Suspension
Agent. Includes:
a. Mixture/Oral suspension – suspension of a solid
B. PARENTERAL PREPARATIONS
material in a liquid
b. Magmas and milk – bulky suspension of poorly I.Solutions
soluble substances in water which resemble milk or  Aqueous solution
cream. They differ from gels in that the suspended o Usually prepared in an ampule
particles are larger. E.g. Ranitidine injection, Atropine Sulfate Injection
E.g. magnesia Magma
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 PHARMA 1.3
o Hypodermic Tablets - soft, readily soluble tablets originally
 Dry solids used for the preparation of solutions to be injected
o Contains no buffers, diluents, or other added substances, o Sustained-Release Tablets – releases effects in a steady,
and which upon the addition of suitable solvents, yield controlled manner or repeat-action manner; can also come
sterile solutions suitable for injection in capsule form
E.g. Crystalline Penicillin G injection
II. CAPSULES
 A solid oral dosage form consisting of a shell and a filling. The
AMPULE vs. VIAL
shell is composed of a single sealed enclosure, or two halves
 Ampule: can be administered directly that fit together and which are sometimes sealed with a band.
 Vial: contains solids; with powder to be mixed with liquid (sterile
water) to form a solution a.Hard Gel Capsule
 There are vials that can turn into suspension, or solution o a.k.a dry-filled capsule
o contains a powdered substance
II.Sterile Suspensions b.Soft Gel Capsule
 Solids suspended in suitable liquid which are to be administered o contains liquids
intramuscularly or subcutaneous o e.g. Vit E capsule, Omega-3 capsules
 They are not to be injected intravenously or intrathecally o Tablets that are considered as capsules (Dr. G)
 E.g. Benzathin Penicillin G injection, Spectinomycin injection c.Spansule
o Coating the active ingredient with substance that allows
gradual release of the drug in the GIT. It contains proteins
III.Sustained-Release Preparations
o Spansules taken at lunch but can have effected delayed until
 Intramuscular injection – may be in the form of aqueous the evening (Dr. G)
suspensions, oil solutions, and oil suspensions
 Subcutaneous implants
III. PILLS
 Small,
C. SOLID PREPARATIONS round,
 Comes in different colors, shapes and sizes  avoids confusion solid
for patients especially those with multiple medications dosage
 A higher dosage can be compacted into a single tablet or forms
capsule instead of taking it multiple times via liquid form (e.g. containing
amoxicillin) medicinal
I. TABLETS agents
 Solid pharmaceutical dosage forms containing drug substances intended
with or without suitable diluents and prepared by either for oral administration
compression or molding methods  Originally referred specifically to a soft mass rolled into a ball
shape, rather than a compressed powder
a. Coated Tablets
o Film-coated tablets – covered with a thin layer of a water- IV. TORCHES/LOZENGES/PASTILLES
soluble material  A discoid-shaped solid containing the medicinal agent in a
o Sugar-coated tablets – covers unwanted taste or odor of the suitably flavored base
drug for better compliance  Placed in the mouth where they slowly dissolve, liberating the
 Poten-cee, Enervon C active ingredients.
o Enteric-coated tablets –able to resist gastric fluid but Ex. Strepsils (Lozenges)
disintegrate in the intestine
 Bisacodyl (Dulcolax) V. SUPPOSITORY
b. Multilayer Tablet  A drug mixed with a firm base such as gelatin and shaped for
o Two or more active ingredients combined into one insertion into the body (e.g., rectum, vagina)
o E.g. Alaxan = Ibuprofen + Paracetamol  The base dissolves gradually at body temperature, releasing the
c. Scored Tablets drug
o Can be cut depending on the dosage you need
o Used by some patients for expensive tablets that need to be
VI. POWDER
taken over a prolonged period of time
 A finely ground drug or drugs; some are used internally, others
o Promotes better compliance
externally
d. Other Types of Tablets
o Tablet Triturate –made from moist material using a triturate  Usually wrapped in paper and mixed with water
mold which gives them the shape of cut sections of a
cylinder
o Effervescent Tablets – liberated carbon dioxide when mixed
with water
o Buccal and Sublingual Tablets - buccal drugs dissolve slowly
while sublingual drugs dissolve faster

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Table 2. Advantages and disadvantages of capsules and tablets
TABLETS
Advantage
 Economy of
preparation
 Notching possible
for dose splitting
 Compactness &
portability
 Custom size, shape
& appearance
Disadvantages:
 Excessive
compaction, poor
dissolution
 Granulation
technique can add
heat/moisture to
viable components
 Coating
sensitivities
PHARMA 1.3
c. Ointment
CAPSULES o Semi-solid greasy preparation intended for skin and
Advantages: mucous membrane
 Easily o Longer lasting than gels, lotions, and creams
administered and o Water in oil form
easier to swallow; e.g. Mupirocin ointment
doesn’t stick to d. Poultice
your throat or o Similar to ointments but applied with cloth
mouth o Used as a counterirritant
 Good oxygen E.g. Numotizine
barriers e. Paste
 ↓ o Ointment-like preparation consisting of an absorptive
gastrointestinal powder dispersed in petrolatum
irritation o Used in the treatment of oozing lesions
 For older children, o Thicker preparation can hydrate surface better, but most
parents can take susceptible to dirt
of the capsule and E.g. Zinc Oxide paste
mix the contents
with something
else for better
administration
(Dr. G)
 Oil and fat-
soluble nutrient
delivery (soft gel)
Disadvantages:
 Can be
susceptible to
moisture
 Ingredients can
interact with
capsule shell
 Capsule or
lubricant
sensitivities
 Softgel contents
restricted to a
tight pH range

D. SEMI-SOLID PREPARATIONS
Factors Affecting Choice of Topical Preparation
 Effect of the vehicle to alter hydration
 Effect of the vehicle to promote or prevent collection of sweat
and dirt
 Partition coefficient of drug in vehicle-water system
 Permeability of the skin to undissolved drug and vehicle
a. Gel
o A semi-solid homogenous preparation in which a
substance is distributed uniformly throughout the liquid.
The liquid may be water, alcohol, or oil
o Majority used for hydration
e.g. Benzoyl peroxide gel
b. Cream
o Liquid or semi-solid emulsions that are applied to the
skin
o water-soluble and non-greasy
o Oil in water form
e.g. Halomethasone monohydrate cream

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