This slide content Basic information which are useful for studying pharmacolgy.

1. BASIC PHARMACOLOGY
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2. Pharmacology: Introduction and Routes of Administration
 Pharmacology Is the science of drug which is derived from the Greek
which means pharmacon = drug; logos =to study .
 Rudolf Buchhiem founded the very first Institute of pharmacology in1847
in Germany.
 Oswald Schmiedeberg regarded as father of pharmacology as he have
proposed some fundamental concepts of pharmacology.
 Pharmacology has two main divisions and they are
i. Pharmacodynamics
ii. Pharmacokinetics
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3. i. Pharmacodynamics
It is derived from greek word which means power. It includes
physiological and biochemical effects which are produced at organ system /
subcellular/ macromolecular levels . By a Drug and its mechanism .
ii. Pharmacokinetics
It Means movement in greek.
So as movement of drug in body. It mainly
includes absorption, distribution, metabolism
and excretion(ADME).
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4.  All these processes involves transport of drug across biological membrane.
 Biological membrane
i. This is bilayer about 100 A thick and made up of phospholipid and
cholesterol Molecule.
ii. Protein is also Present on membrane.
iii. Drugs are transported across the membrane by two ways
1. Passive diffusion:
i. The drug diffuses across The membrane by concentration gradient
which means from higher to lower concentration.
ii. So greater the concentration difference faster the diffusion.
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5. 2. Specialized Transport
i. Carrier transport
ii. Active transport
iii. Facilitated diffusion
iv. Pinocytosis
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6. 1. ABSORPTION
Absorption is the process by which a drug moves from its site of application
into the blood stream .
 Factors Affecting Absorption
i. Aqueous solubility of preparation,
ii. Concentration/Amount,
iii. Area of absorbing surface,
iv. Tissue vascularity
 Route of Administration
1. Oral route:
i. Non-ionize and lipid solubility → increase absorption from stomach as
well as intestine.
ii. Acidic drugs E.g., Salicylates, barbiturates etc., are unionized at acidic
pH → absorb from stomach mucous membrane but this has small
surface area so affect the absorption.
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7. iii. Basic drugs, morphine, atropine, quinine etc. are unionize at alkaline pH
and absorb in the intestine. Drugs can degrade by the gastric juice, E.g.,
Penicillin G, Levodopa and insulin so these drugs ineffective orally.
 Presence of food
Decrease the salicylate absorption. Ca+2 ion of food forms complex
with tetracycline decrease in absorption. Concurrently administered drugs
form insoluble complexes, e.g., Tetracyclines with iron preparation and
antacids, Phenytoin with sucralfate etc. → Decrease in absorption.
2. Subcutaneous and intramuscular
Vasoconstrictor action reduces the absorption E.g., Adrenaline
(vasoconstrictor) with anaesthetic agents. Hyluronidase increases
tissue permeability → increase absorption.
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8.  Bioavailability
i. The proportion of an administered dose that is absorbed chemically
unchanged into the systemic blood circulation.
ii. Its denoted by F ,as it measure of fractions .
iii. Bioavailability of IV is 100 %,
but oral is lowered because of
i. Incomplete absorption
ii. first pass metabolism
i. it is calculated by drug
delivered = D
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9.  Bioequivalence:
i. Oral formulations of a drug from different Brands or different batches
from the same manufacturer may have the same amount of the drug
(chemically equivalent) but may not yield the same blood levels-
biologically in equivalent.
ii. Two preparations of a drug are considered bioequivalent when the rate
and extent of bioavailability of the active drug doesn't have much
difference is less.
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10. 2. DISTRIBUTION
This refers to the movement of drug backwards and forwards
between blood and the various tissues of the body.
 Extent of drug distribution depends on its
i. Lipid solubility
ii. Ionization
iii. Protein binding
iv. Blood flow
 Highly lipid soluble drugs get first entered in organ with high blood flow
such as heart And kidney etc. and later on less vascular but bulky tissues
such as fat and muscle take the Drug, this is called as redistribution.
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11.  Plasma protein binding:
i. Many drugs have physicochemical affinity for plasma proteins and they
get attached reversibly to plasma. This makes Drug long acting.
ii. Acidic drug binds with the albumin protein E.g., Barbiturates,
Benzodiazapines, NSAIDs, Penicillin, Phenytoin, Sulfonamides,
Warfarin, Tolbutamide etc.
iii. Basic drug binds with α1–glycoprotein E.g., β–blockers, lignocaine,
Disopyrmide, Imipramine, Methadone, Prazosin, Quinidine, Verapamil
etc.
iv. One drug can bind many sites on the plasma protein and conversely more
than one drug can bind with same site.
v. This can give rise to displacement interactions among drugs bind to the
same site. ex. Aspirin displaces sulfonylueas, Indomethacin displaces
warfarin.
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12.  Blood brain barrier :
i. The capillaries of brain are very tightly arranged and does not have
spaces.
ii. This are lipoidal so only lipid soluble drugs can get entered .
 Placental barrier :
i. Placental membrane is highly made up of proteins and only lipophilic
drugs get entered .
ii. Placenta is also a site of metabolism so minimal amount of drug get
entered.
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13. 3. METABOLISM (BIOTRANSFORMATION)
Chemical alteration of the drug in the biological system”.
 In this process, in metabolic sites like liver, kidney lungs, plasma etc.
various chemical alteration of drug molecule i.e., inactivation, active
metabolite form an active drug, activation of inactive drug (prodrug) and
finally non-polar compound converts into polar compounds → which are
excreted in urine.
 Example :
i. Active Metabolite from Active Drug:
ii. E.g., Digitoxin → Digoxin, Spironolactone → Canrenone,
Codeine → Morphine, Phenacetin → Paracetamol
i. Activation of Inactive Drug: .g., Levadopa → Dopamine,
Dipivefrine → Adrenaline, Cyclophosphamide → Aldophosphamide
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14.  Metabolism can be divided into 2 Processes :
i. Nonsynthetic /phase 1/ functionization reaction
ii. Synthetic /conjugational/phase two reaction
 Non-synthetic reactions
Oxidation, reduction, hydrolysis, cyclization and decyclization etc.
 Synthetic Reactions
i. Glucuronide conjugation
Hydroxyl or carboxylic acid group are easily conjugated with
glucuronic acid. E.g., Chloramphenicol, Aspirin, Morphine,
Metronidazole, Steroids, and throxine hormone.
ii. Acetylation
Compounds which have amino or hydrazine group are conjugated
with acetyl coenzyme-A. E.g., Sulfonamides, Isoniazid, PAS etc.
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15.  Sulfate conjugation
Sulfate is added E.g., phenolic group compounds E.g., Steroids,
Chloramphenicol, Catecholamines etc.
 Glutathione conjugation
Forming a mercaptopurate E.g., Paracetamol.
 Hofmann elimination
Inactivation of drugs in body fluid by spontaneous rearrangement
without any arrangement. E.g., Atracurium.
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16.  Inhibition of enzymes Drugs may competitively inhibit the enzymes used
in other drug metabolism → decreases metabolism of that drug.
i. Enzyme inhibitor drugs Ketoconazole, Cimetidine, Isoniazid,
Phenylbutazone, Chloramphenicol, Disulfiram etc.
ii. Microsomal enzyme induction drugs may induce the microsomal
enzymes and induce the metabolism of other drugs. E.g., Phenytoin,
Barbiturates, Rifampin, Glucocorticoids etc.
 First pass Metabolism :
i. This is referred as metabolism of oral drug during absorption from site
to the systemic circulation.
ii. They get metabolized In liver or intestinal wall by enzyme where they
reach by Portal vein which are present in gut .
iii. This can be minimized by giving drug through parentral route.
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17. 4. EXCRETION
Excretion means “passage out of systemic absorbed drug”.
They can get out of body by means of urine, faeces, sweat, exhaled
air, milk etc. Renal excretion is most widely system of elimination
 Renal excretion
1. Glomerular filteration
Glomerular capillaries have pores. Non-protein bound drug filtered
in the filterate.
2. Tubular reabsorption:
Lipid soluble unionized drug reabsorbed from Proximal Convoluted
Tubule but non lipid soluble drug (ionized) excretes in unchanged form as
parallel to Glomerular Filtration Rate (GFR) E.g. Aminoglycosides.
i. weak bases ionize more and less reabsorb in acidic urine.
ii. weak acidic drug ionize more and less reabsorb in alkaline urine.
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18. 3. Tubular secretion
i. Drugs utilize same active transport, and compete with each other.
E.g., Salicylates block the uricosuric action of probenecid and
sulfinpyrazone and decrease tubular secretion of methotrexate
ii. Rate of elimination = Mass x K ,
iii. where k = the elimination rate constant - expresses rate of drug
elimination as the proportion of body load being eliminated per unit
time.
iv. Zero order (linear) kinetics = rate of elimination remains constant
and not dependent on concentration.
v. First order (exponential) kinetics = rate of elimination
α[proportional]to drug concentration
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19. 5. ROUTES OF ADMINISTRATION
 Drugs usually enter the body at sites from the target tissue or organ and
thus require transport by the circulation to the intended site of action.
 Common routes of administration and some of their features include the
following:
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20.  Local routes Action on particular local area and systemic absorption of
drug is minimal.
i. Topical: The topical route includes application to the skin or to the
mucous membrane of the eye, nose, throat, airway, or vagina for
local effect.
ii. Deeper tissue: Injection in the deep capsulated areas of body and
systemic absorption is slow. Example Intra–articular injection
(hydrocortisone), intrathecal injection (amphotericin B for
meningitis), retrobulbar injection (hydrocortisone acetate).
iii. Arterial supply: Intra arterial injection of contrast media in the
angiography.
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21.  Systemic routes drug is absorbed into the blood circulation and distributed
all over including site of action.
Routes Features
Oral The oral route offers maximum convenience, and
slower absorption compared to parentral. But
associated with some limitation: gastric
irritancy,nausea, vomiting.
Some drugs are affected or degraded by Gastric
juice. Ex. Penicillin G and In liver E.g. Nitroglycer-
ine, Testosterone Lignocaine.
Buccal and
Sublingual
Between the pouch of gums and cheek and
permits direct absorption into the systemic venous
circulation, bypassing the hepatic portal circuit and
firstpass metabolism. E.g., Nitroglycerine,
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22. Rectal
[Suppository]
The rectal route offers partial avoidance from the
firstpass effect. Larger amounts of drug and drugs
with unpleasant taste are better administered rectally.
But this method is inconvenient and embrassing.
E.g., Enema, aminophylline, paraldehyde, diazepam.
TransdermaL The transdermal route involves application to the skin
for systemic effect. Absorption usually occurs very
slowly, but the first-pass effect is avoided. E.g., Patches
of Nitroglycerine, Fentanyl, Nicotine etc.
Inhalational Volatile liquid and gases are given by inhalation for
systemic action E.g., General anaesthetics, broncho-
dilator spray used in asthma. This route provides rapid
absorption because of the large alveolar surface area
available.
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