GENERAL PHARMACOLOGY.

Statement.
The general pharmacology is involves the aspects of
sources of drugs, route of administration of drugs,
absorption of drugs and factors affecting them,
distribution, bio-transformation and excretion
Pharmacokinetics.
The word Pharmacokinetics is derived from two words,
Pharmacon meaning drug and kinetics meaning putting
in motion. It can be defined as:
“The branch of pharmacology that deals with the
absorption, distribution, metabolism and excretion of
drugs and their relationship with the onset, duration and
intensity of the drug effect.”
What the body does to the drug is pharmacokinetics. For
example, the absorption, distribution, metabolism and
excretion of Paracetamol is included in
Pharmacokinetics.
Routes of drug administration.
 Classification
 Enteral route
 Parenteral route
 Inhalation
 Topical
 Enteral Route:
 Enteral route is through the alimentary canal. It might be:
 Oral
 Sublingual
 Per rectum
Oral Route.
Oral route is the most common route of drug
administration. It is mostly used for the neutral drugs. It
may be in the form of tablets, capsules, syrup, emulsions
or powders.
Advantages:
It is convenient
It is the cheapest available route
It is easy to use.
Disadvantages:
Less amount of drug reaches the target tissue.
Absorption has to take place which is slow, so is not
preferred during emergency.
 Sublingual Route:
 Sublingual route involves tablets placed under the tongue or
between cheeks . The drug should be lipid soluble and small.
 Advantages:
 Rapid absorption takes place.
 Drug is dissolved easily
 Drug enters the blood directly
 Disadvantages:
 This method is inconvenient.
 Might be unpleasant in taste.
 Rectal Route:
 Drugs in solid forms such as suppositories or in liquid forms
such as enema are given by this route. This route is mostly
used in old patients
 Advantages:
 This route is preferred in unconscious or uncooperative
patients.
 This route avoids nausea or vomiting
 Disadvantages:
 This route is generally not acceptable by the patients.
 Locally acting drugs include glycerin and Bisacodyl
suppository
Parenteral Route.
Parenteral route includes:
Injections:
Intra muscular
Intra venous
Intra-arterial
Intraperitoneal
Intra-articular
Intradermal (Intracutaneous)
Subcutaneous route (Hypodermic)
 Intramuscular route:
 Intramuscular route might be applied to the thigh, deltoid.
 Advantages:
 Absorption is rapid than subcutaneous route.
 Oily preparations can be used.
 Disadvantages
 Using this route might cause nerve or vein damage.
 Intravenous injections:
 Intravenous injections might be applied to the cubital, basilic and
cephalic veins.
 Advantages:
 Immediate action takes place
 This route is preferred in emergency situations
 This route is preferred for unconscious patients.
 Disadvantages:
 There is no retreat
 This method is more risky
 Intraarterial route:
 This method is used for chemotherapy in cases of malignant
tumors and in angiography.
 Intradermal route:
 This route is mostly used for diagnostic purposes and is
involved in:
 Dick test for Scarlet fever
 Vaccines include polio
 Intra-articular route:
 Intra-articular route involves injection into the joint cavity.
Corticosteroids may be injected by this route in acute arthritis.
 Intraperitoneal route:
 Intraperitoneal route may be used for peritoneal dialysis.
 Subcutaneous:
 Subcutaneous route might be used for the arm, forearm, thigh
and subscapular space.
 Advantages:
 Absorption is slow and constant
 It is hygienic
 Disadvantages:
 It might lead to abscess formation
 Absorption is limited by blood flow
 Inhalation:
 Inhalation may be the route of choice to avoid the systemic
effects. In this way drugs can pass directly to the lungs. Drugs
used involve volatile drugs and gases. Examples include
aerosols like salbutamol.
 Advantages:
 Rapid absorption takes place.
 Rapid onset of action takes place.
 Disadvantages:
 Special apparatus is required.
 Irritation of the respiratory tract may take place.
 Topical route:
 Drugs may be applied to the external surfaces, the skin and the
mucous membranes. Topical route includes:
 Epidermic route:
 When the drug is rubbed into the skin, it is known as epidermic
route. Examples include different oils.
.
Absorption of drugs.
 Absorption is the process by which drug molecules cross
biological membranes. It is usually associated with oral drugs
and their absorption through the GIT.
 Processes Determining Absorption:
 These processes include:
 Passive transport
 Simple Diffusion:
 Most of the drugs are absorbed by simple diffusion, which is the
movement of molecules down the concentration gradient i.e.
from higher concentration to lower concentration. This type of
transport occurs mostly for the lipid soluble drugs.
Filtration:
Filtration involves the aqueous channels or pores
through which hydrophilic drugs can pass.
Bulk flow is the phenomenon mostly seen with the
intra muscular and subcutaneous injections. Drug
is injected in bulk form into the muscle. Drug
molecules along with the aqueous medium pass
through the pores of endothelium, and diffuse into
the blood.
Active transport
 Active membrane transport is for the drugs which cannot
cross the lipid membrane and require transport proteins.
like amino acids, neurotransmitters, which have the
transport proteins. Active transport is the carrier mediated
transport.
 The drug moves against the concentration gradient. Energy
in the form of ATP is required for the process to occur.
 Primary Active Transport:
 When the substance moves against the concentration
gradient by the expenditure of energy, the process is called
primary active transport.
 Secondary Active Transport:
 When the substance moves against the concentration gradient
by the energy stored by a substance moving down the
concentration gradient, the process is called secondary active
transport.
 Phagocytosis:
 Phagocytosis is also known as cell eating. This type of
transport is utilized by large molecular weight drugs.
 Pinocytosis:
 Pinocytosis, or cell drinking, requires expenditure of energy.
Fat soluble vitamins, protein molecules and folic acid enter the
cells by this process.
 Facilitated transport involves the drug moving down the
concentration gradient by the help of transport proteins. No
energy expenditure is required. This type of transport is
also specific and saturable.
Simple Diffusion Facilitated Diffusion Active Transport

Down concentration gradient Down concentration gradient Against concentration

gradient

No energy required No energy required Energy required

No carrier protein involved Carrier proteins involved Carrier proteins involved

Non-specific Specific Specific

Non-saturable Saturable Saturable

Lipid soluble drugs Non-diffusible drugs Lipid insoluble drugs

Distribution of Drugs
 Drugs enters the body by absorption. Inside the body, drugs
move in the blood to different parts of the body. Distribution
of drugs can be defined as:
 “The process by which a drug reversibly leaves the blood
stream and enters the interstitium (extracellular fluid) and/or
the cells or tissues.”
 Compartment models of Distribution.
 Compartment models simulate drug
absorption distribution and elimination.
 A single compartment model is the least accurate, as it
assumes a homogeneous distribution of the drug in the body.
 Futher types of one compartment model.
 One compartment open model IV bolus
 OCOM IV infusion
 OCOM Extravascular zero order kinetics. ( when dose
increase ,not effect on kinetics them drug accummulate,
toxicity produce
 OCOM Extravascular first order kinetics. ( if dose increase or
decrease then effect on kinetics).
 One Compartment model

Behold, a bucket.
 This bucket is your patient. Into this bucket, a drug has
been added. The drug is instantly and completely dispersed
to every corner of the bucket and is thereafter
homogeneously distributed throughout the volume.
 Unidirectional
 Rate of absorption is equal to rate of elimination.
Second compartment model
 Again, the same dose of drug is administered into the same
compartment. Let us call it the "central" compartment.
There is now also a "peripheral"compartment in the
system. Though the drug is still distributed instantly and
homogeneously into all of the central compartment, it now
also diffuses gradually into (and out of) the peripheral
compartment.
 The drug travel in two compartments. The drug move
central to peripheral compartment then reverse back to
central compartment then elimination occur.
 Rate of absorption is not equal to rate of elimination.
 Not unicellular
 In central kidney,heart,liver.
 In peripheral tissues,muscles.
Metabolism:
Biotransformation means chemical alternation of drug in
body.
It needs to render nonpolar (lipid soluble) compounds
and polar (lipid insoluble) so they are not reabsorbed in
renal tubules and are excreted.
In absence of metabolism body will not able to get rid of
lipophilic substance and they become very long acting.
The primary site of drug metabolism is liver other are
kidney lungs and plasma.
Biotransformation of drugs:
Inactivation:
Most drugs and their active metabolite are render inactive or less active
like ibuprofen,paracetamol. Biotransformation provide alternateve method
of terminating drug action to excretion.
Active metabolite from an active drug:
Drug found to partially converted to one and more active metabolite
Like digitoxin (Active drug)_(active metabolite)digoxin
Codine( Active drug)_(active metabolite) morphine.
Activation of inactive drug:
Some drugs are inactivate and need conversion in body to one or more
active metabolite. Such drug called Prodrug like
Prodrug(Levodopa)-active form(dopamine)
Pathways of drug biotransformation:
Biotransformation reaction can be divided in two
Nonsynthetic/phase1/functionalization reaction
Synthetic/conjugation/phase 2 reactions.
Phase l
Phase I reactions of drug metabolism involve
oxidation, reduction, or hydrolysis of the parent
drug, resulting in its conversion to a more polar
molecule.
These reactions serve to convert lipophilic
drugs into more polar molecules by adding a
polar functional group such as –OH.
This reaction can be achieved by direct
introduction of functional group or by modify
existing functionalites e.g reduction of ketones
and aldehyde to alcohol.
Oxidation of alcohol to acids .
Phase ll
Phase II reactions consist of adding hydrophilic
groups to the original molecule, a toxic
intermediate or a nontoxic metabolite formed
in phase I, that requires further transformation
to increase its polarity. These reactions include
conjugation reactions, glucuronidation,
acetylation, and methylation.
Goal of phase II reactions is to form water-
soluble products that can be excreted by the
body.
Conjugated metabolites are readily excreted in
urine are generally devoid of pharmacological
activity and toxicity in humans.
Other phase II pathways such as methylation,
acetylation terminate biologyical activity.
Excretion:
It is defined as a process whereby drug’s or metabolites are
irreversibly transferred from internal or external environment
through renal or non renal route
Excretion along with metabolism and tissue redistribution is
important in determining both the duration of drug action and rate
of drug elimination.
Organs that are involved in excretion:
Kidneys (renal excretion)
Bile ( biliary excretion)
Milk (mammary excretion)
Sweat ( skin excretion)
Renal excretion:
Drugs are eliminated from the body by kidney’s
Renal mechanism involves in excretion of drug are as
Glomerular filtration
Active tubular secretion
Active tubular reabsorption
Glomerular filtration:
The structure of glomerular capillary wall is such that
it allow a high degree of fluid filtration while
restricting the passage of compounds having relatively
lagre molecular weight.
 This selective filtration is important as it prevents the
filtration of plasma proteins like albumin that are
important for maintaining the plasma volume.
Several factors include molecular size , charge and
shape, increase the glomerular filtration of large
molecule’s.
GFR normally is 120ml/min.
Active tubular secretion:
Many drugs which do not enter in GF but do so by
tubule secretion which mainly occur in proximal
tubules.
It is a carrier mediated process which require energy
for transportation of compounds against concentration
gradient.
It rapidly and efficiently remove many protein bound
drugs from blood and transport them. Into tubular
fluid.
Active tubular reabsorption.
Some substances filtered at glomerulus are reabsorbed
by passive diffusion and depends on lipid solublity and
ionization of drug at the existing urinary pH.
Lipid soluble drug’s filtered from GF but 99% of drug
is reabsorbed but non lipid soluble are highly ionized
drugs are unable to do so.
Biliary excretion:
Bile juice is excreted by hepatic cell of liver and
important for digestion and absorption of fats.
Large molecular (MW>300) are eliminated by bile.
Drug in bile enter GIT after storage in gall bladder. It
then excreted from body by the stools
Skin excretion
Drugs excreted though skin by sweating. Excretion of
drugs though skin may lead to urticaria and dermatitis.
Heavy metals like lead, mercury are excreted in sweat.
Pulmonary excretion:
Gasses and other volatile substance such as general
anesthesia that enter body primarily through respiratory
tract can be expected to be excreted by pulmonary route.
The rate of loss of gases is not constant it depends on
rate of respiration and pulmonary blood flow.
Mammary excretion:
Milk is consist of lactic secretions which is rich in fats
and proteins.
Excretion of drug in milk is important as it gains entry in
breast feeding infants.
High plasma bound drugs like diazepam less secreted in
milk.
Amoumt of drug excreted in milk is less than 1 % and
fraction consumed by infant is too less to produce
toxic effects.