Pharmacy Pharmacology - Chapter I - Part 2.pdf

It discuss about unit general pharmacology of health and medicine students used to supporive

1. Cont…
•Drug Formulations (Dosage Forms)
-Dosage forms of a drug are the forms of
preparations designed for administration to the body
-are different preparations of a drug which help to
facilitate drug administration & delivery
-After development of a specific chemical entity for its
pharmacological effects, it is formulated in a form
that is suitable for administration and even efficacy
and for the stability of the drug itself
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2. Cont…
-An ideal dosage form should:
Deliver the right amount of the drug to the right site
Minimize drug exposure to unwanted sites
Associated with minimal discomfort or inconvenience
Be economical & need lesser expertise knowledge
But there is no such ideal dosage form

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3. Cont…
-There are different dosage form designs intended for
the various routes of administration

-Four types of dosage forms exist
Solid dosage forms
Semisolid dosage forms
Liquid dosage forms
Gaseous dosage forms


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4. Cont…
(A)Solid dosage forms
-Are those drug preparations which exist as solids
-exist in different forms/preparations
(i)Tablets – Written as tab or tabs
-Are most common forms of solid dosage forms and
generally administered orally
-containing the active ingredient with or without
suitable diluent, binder, disintegrant, lubricant,
coloring agent, sweetening agent, flavoring agent,
etc.

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5. Cont…
-Most tablets are uncoated but a few are coated
tablets:
Film coated tablets: covered with thin layer of
polymeric substance that protects the drug from
atmospheric conditions and masks unpleasant taste
and odor of the drug
Sugar coated tablets: covered with sugar to make
the drug more palatable and mask unpleasant taste

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6. Cont…
Enteric coated tablets: used to protect the drug
from destruction by acidity of the gastric juice and
to prevent gastric irritation by the drug
Modified release tablets: coated or uncoated,
prepared by special procedures that modify the
rate of release of the drug at a predetermined rate
Prolongs the duration of action
Reduces the frequency of administration
More patient compliance
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7. Cont…
(ii)Lozenges
-Are sweet tablets containing sugar, water & flavoring
agents
-are to be chewed/held in the mouth not swallowed
(iii)Pellets/beads
-Prepared as sheets or beads for sustained release
of drugs, E.g. Norplant
(iv)Powders (internal use)
-Are solid preparations which need to be
reconstituted before use,
E.g. penicillin injection (PPF)
-For external use ?????
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8. Cont…
(v)Capsules – Written as cap or caps
-Are solid dfs which the solid or liquid drug is
enclosed in a hard or soft soluble gelatin shell to
mask its bad taste and odor
-Overcome problem of taste of drugs and to some
extent stability
-They are intended for internal use (orally
administered)
-More expensive than tablets

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9. Cont…
-Capsules are prepared in two forms:
(a)Soft capsules – are made of soft gelatin
Contain liquid inside & are sealed
E.g. Vitamin A & E capsules
(b)Hard capsules – are made of hard gelatin
Contain two separable pieces or cup and body
Contain powder or granules inside
E.g. Amoxicillin, tetracycline capsules

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10. Cont…
-Spansules (sustained release capsules): contain
the drug in the form of granules having different
coatings that dissolve at different time intervals
and provide uniform release of drug over a
prolonged period

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11. Cont…
(vi)Suppositories & Pessaries
-Are solid dosage forms with various sizes and shape
for administration into body cavities (rectum, vagina,
and urethra)
-Rectal suppositories are conical or bullet shaped,
vaginal suppositories spherical (oval), and urethral
suppositories pencil shaped
-Used for local effects, or for children, vomiting &
unconscious patients
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12. Cont…
-Advantages of solid dosage forms:
Easy for administration
Accuracy and reproducibility of dosing
Increased stability of drug
Ease for mass production
-Disadvantages of solid dosage forms:
Slow absorption
Slower onset of action
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13. Cont…
(B)Semi-solid dosage forms
-Are dosage forms that are too soft to be solid and
too hard to be liquid
-are mainly used for topical administration
(i)Ointments
-Are semi-solid preparations containing the medicinal
agent intended for use for application on skin or
mucous membranes, E.g. tetracycline ointment
(ii)Creams
-Creams are emulsions of oil & water for external use
as protective or emollients to soften and sooth the
skin, E.g. hydrocortisone cream
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14. Cont…
(C)Liquid dosage forms
-Are found in liquid states
-Can be either clear solutions, suspensions or
emulsions
(i)Solutions
-Are clear mixtures/fluids
-Are prepared by dissolving active medicinal
substance in a solvent
-They don’t need to be shaken/mixed even after long
period of storage
-are of different forms - can be for internal or external
use
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15. Cont…
(a)Elixirs
–are clear solutions which contain alcohol & water as
solvent and they also contain flavoring agents
–are mainly used for pediatric use
(b)Syrups
–are also clear solutions which contain water, sugar &
flavoring agent
–don’t contain alcohol, E.g. multivitamin syrup
(c)Tinctures
–are clear solutions which contain both water & alcohol
as solvent
–But, unlike elixirs, they are used for external use and
don’t contain flavoring agent
E.g. iodine tincture


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16. Cont…
(d)Injectables – are sterile preparations for
parenteral route (IV, IM, SC, etc.)
-They may be labeled as:-
“for injection”: a sterile powder pre-packed in a
vial which on the addition of a suitable vehicle
forms a clear solution
“injection”: a ready made sterile liquid preparation
in an ampoule or vial
“sterile suspension”: a ready made suspension
for parenteral uses, but not for intravenous injection
“sterile for suspension”: a sterile powder
prepacked in a vial which on addition of a sterile
vehicle is made into a suspension for parenteral
uses, but not for intravenous injection

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17. Cont…
(ii)Suspensions
-Are liquid preparations containing drugs, uniformly
dispersed with the help of a dispersing agent
-are not clear liquids
Contain fine, undissolved drug particles suspended in
a liquid
-Shaking is necessary before use since the solid
particles sediment upon storage
Every suspension should have a label “shake well
before use”
E.g. antacid suspensions

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18. Cont…
-Suspensions include:
Emulsions: preparations consisting of two non-
miscible liquids, with an emulsifying agent
may be used for both internal and external use
Mixtures: preparation of any solid material suspended
in a liquid, and intended for internal use
Lotion: an aqueous suspension to be applied without
friction, for soothing, cleansing or antiseptic action on
the skin
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19. Cont…
Solutions for external use:
Drops: are aqueous preparations intended for topical
administration to the nose, throat, eye or ear
Eye drops should be clear and sterile aqueous
solutions, adjusted to a suitable pH and osmotic
pressure
Gargles: are aqueous solution used to treat disease
of the pharynx or nasopharynx and as deodorant or
antiseptic
Enemas: are aqueous solutions to be placed in the
rectum to evacuate the bowel or to bring about local or
systemic therapeutic action
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20. Cont…
•Advantages of liquid preparations
–Rapid absorption
–Prompt onset of action
•Disadvantage of liquid preparations
–Dosage form is relatively bulky
–Greater chance of chemical incompatibility
–Disagreeable odor and taste can not be masked
completely
–Less stable

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21. Cont…
(D)Gaseous dosage forms
-Contain medical gases & aerosols
(i)Medical gases:
-Are preparations for intrapulmonary administration
-Are inhaled through breathing apparatus
-The active ingredient is found as gas or volatile
liquid
-Gas : like oxygen, nitrous oxide and carbon dioxide
-Volatile liquids: e.g. halothane, ether

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22. Cont…
(ii)Aerosols:
-Are another gaseous dosage forms
-Contain an active drug suspended or dissolved in a
gaseous vehicle (propellant)
-are dispersions of solid particles or liquid droplets in
a gaseous vehicle
-packed in a pressurized dispenser


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23. Cont…
(2)Drug Distribution
•is the process by which a drug reversibly leaves the
bloodstream and enters the interstitial space
(extracellular fluid) and from there into the cells
(tissues)
•Once a drug has gained access to the blood stream,
it gets distributed to other tissues that initially had no
drug, concentration gradient being in the direction of
plasma to tissues
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24. Cont…
•Phases (steps) of drug distribution
(i)Drug delivery to tissues
-In the first phase of distribution, drugs are carried by
the blood to the tissues and organs of the body
-The rate at which drugs are delivered to a particular
tissue is determined by cardiac output and blood flow
to that tissue
-Blood flow to the “vessel-rich organs” (brain, liver,
and kidney) is greater than that to the skeletal
muscles, adipose tissue, skin, and viscera
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25. Cont…
(ii)Exiting the vascular system
-After a drug has been delivered to an organ or tissue
via the blood, the next step is to exit the vasculature
-Because most drugs do not produce their effects
within the blood, the ability to leave the vascular
system is an important determinant of drug actions
-Exiting the vascular system is also necessary for
drugs to undergo metabolism and excretion
-Drugs in the vascular system leave the blood at
capillary beds
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26. Cont…
Drug movement at typical capillary beds
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27. Cont…
-Most capillary beds offer no resistance to the
departure of drugs. Why?
-Because, in most tissues, drugs can leave the
vasculature and move into the interstitial space
simply by passing through pores in the capillary wall
Pass between capillary cells rather than through them
•Diffusion of drug into the interstitial fluid occurs
rapidly because of the highly permeable nature of
the capillary endothelium
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28. Cont…
(iii)Entering cells
-Some drugs must enter cells to reach their sites of
action, and
-All drugs must enter cells to undergo metabolism
and excretion
-Drugs must be able to cross the cell membrane
-Drugs producing their effects by binding with
receptors located on the external surface of the cell
membrane do not need to cross the cell membrane
to act
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29. Cont…
•Factors affecting drug distribution
-Concentration of drugs in different tissues differ due
to different factors:-
(i)Plasma protein binding
(ii)Tissue uptake (affinity of drugs to tissue)
(iii)Physiological barriers
(iv)Tissue perfusion
(v)Lipid solubility of the drug
(vi)Pka of the drug
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30. Cont…
(i)Plasma Protein Binding (PPB)
-Many drugs which circulate in the bloodstream
bound to plasma proteins – In reversible fashion and
in dynamic equilibrium
D+P→[DP] →D+P
-Drugs in systemic circulation exist as bound and free
form
-As free drug leaves the systemic circulation the
bound drug dissociates


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31. Cont…
Protein binding of drugs
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32. Cont…
-Factors affecting plasma protein binding:
Drug affinity for binding sites
Number of binding sites
Drug concentration

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33. Cont…
-The extent of this binding will influence the drug’s
distribution and rate of elimination b/c only the
unbound drug can:
Diffuse through capillary and cell membrane
Produce pharmacological effect
Produce toxic effect
Be metabolized
Be secreted
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34. Cont…
-The major binding macromolecules are:
(a)Albumin
–Most drug binding glycoprotein
–Mainly binds acidic and hydrophobic drug
–Some factors affect the binding of drugs with albumin:
•Age
•Pregnancy
•Disease state
–hyperalbuminemia
–Hypoalbuminemia
–Uremia
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-Hyperbilirubinemia
-Liver disease

35. Cont…
(b)α1-acid glycoprotein:
–Binds mainly basic drugs
–Level differs in situations such as:
•Stress, injury, trauma
•Rheumatoid arthritis
•Surgery
(c)Others: include
–Lipoprotein
–Globulin
–Hormone binding factor
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36. Cont…
-The clinically significant implications of PPB are:
Highly plasma protein bound drugs are largely
restricted to the vascular compartment
The bound fraction is not available for action
High degree of protein binding generally makes the
drug long acting
PPB can be a source of drug interactions
In hypoalbuminemia, binding may be reduced and
high concentrations of free drug may be attained
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37. Cont…
(ii)Tissue Uptake
-Is determined by the partitioning of drug between
blood and the specific tissue, which in turn depends
on:
Lipid solubility of drugs
pH gradient between plasma and the tissue (ion
trapping)
The relative binding of drug to plasma proteins and
tissue macromolecules
-Some tissues act as storage sites by accumulating
the drug and releasing it slowly over a period of time 37

38. Cont…
The effect of ion trapping on drug distribution
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39. Cont…
-Drug distribution is not always uniform, due to
different tissue affinity
-Adipose tissue: drugs with extreme lipid solubility
–May result:-
•Decrease therapeutic activity (thiopental)
•Prolonged activity (fat depot preparation)
•Toxicity (DDT)
-Kidney: contain proteins, metallothionein, that has
high affinity for metals
Cadmium, lead, mercury accumulation---toxicity

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40. Cont…
-Bone: e.g. TTC, lead
TTC accumulation may cause dysplasia, poor bone
development
Lead accumulation result bone brittleness
Slow release of toxic effect may occur from lead
accumulation
-Teeth: e.g. TTC-yellow-brown discoloration of teeth
-Liver: e.g. Chloroquine
Generally tissue accumulation of drug may have:
Adv: target tissue therapy e.g. Chloroquine, iodine
Disadv: mainly toxicity
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41. Cont…
(iii)Physiological Barriers
(a)Blood Brain Barrier (BBB)
-BBB regulates transfer of drug to CNS (brain)
-ionized drug, Lipid insoluble drugs, Bound drug
donot cross BBB
-Inflammation such as due to meningitis or
encephalitis increase the permeability of BBB so
permeating the passage of ionized , lipid soluble
drugs; E.g.:- penicillin G and ampicillin
-Pgp transport system: ↓ the concentration of some
drugs in CNS
Pump back to systemic circulation

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42. Cont…
(b)Placenta Barrier (PB)
-Blood vessels of mother and fetus separated by PB
-Do not allow passage of ionized (highly polar) and
lipid insoluble drugs
-Lipid soluble drugs are contraindicated during
pregnancy
Have undesirable effects, teratogenic and
carcinogenic effect
E.g. TTC, chloramphenicol, thalidomide


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43. Cont…
(iv)Tissue perfusion/ blood flow
-Different tissue have d/t rate and amount of blood
flow
-As blood flow increases, the drug distribution to the
tissue increases
Highly perfused tissue:- heart, lung, brain, liver, kidney
Intermediate perfused tissue:- skeletal muscle
Poorly perfused tissue:- skin, bone, nail, fat tissue


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44. Cont…
(v)Lipid solubility of the drug
-Lipid soluble drugs have ability of the drug to cross
cell membranes
(vi)pH differences across membrane barriers
-A drug will pass through the membrane better if it is
unionised
-pH is important regarding whether the drug is an
acid or a base
An acid drug will be unionised in an acid environment,
a basic drug will be unionised in a basic environment
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45. Cont…
•Re-distribution
-Is mobilization of the drug from its site of action into
other tissues or sites
•Results into termination of drug effect
Termination of drug effect can also occur due to
metabolism and excretion
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46. Cont…
-Example: Thiopental
Is highly lipid soluble general anesthetic
Because it is lipid soluble.....able to pass BBB
rapidly due to the high brain perfusion
Administered intravenously because to act quickly
and produce anesthetic effect.
has a short duration of action because it redistributes
quickly to muscle.....muscle is reservior...↓
conc.at the site of action
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47. Cont…

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