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INTRODUCTION
General Pharmacology
Pharmacology is the science dealing with biochemical and physiologic
aspects of drug effects, including absorption, distribution, metabolism, elimination,
toxicity doses, and specific mechanisms of drug action. Pharmacology includes three
major divisions: theoretical (general), experimental, and clinical. Theoretical
pharmacology touches upon common regularities of interactions of drugs with an
organism. Experimental pharmacology investigates drugs influence on the organism
of animals. Clinical pharmacology examines drugs influence on the organism of
patient. Pharmacotherapy studies the use of medicaments for cure of a concrete
illness. Some branches of pharmacology are different sciences: phytotherapy,
toxicology, vitaminology, endocrinology, and chemotherapy. Pharmacology is
closely connected with pharmacy. Pharmacology is based on the advances of physics,
chemistry, biology, biochemistry, physiology for the explanation of drugs mechanism
of action. Pharmacology is the basis for therapy and other clinical disciplines. The
pharmacological effect is the changes of metabolism and function of cells.
Mechanism of action is the way by means of which the initial reaction is realized.
The initial pharmacological reaction is characterized by biochemical,
physiological, physical and chemical changes of metabolism and function of systems
and organs. The two main areas of pharmacology include pharmacokinetics and
pharmacodynamics. Pharmacokinetics refers to the way the body handles drug
absorption, distribution, biotransformation, and excretion. Pharmacodynamics is the
study of biochemical and physiological effects of drugs and their mechanisms of
action.
PHARMACOKINETICS
Drug transport. The movement of drug molecules in the body is subject to
absorption, distribution, and excretion. Drugs can cross cellular membranes by
various mechanisms. The mechanisms of absorption are similar to the mechanisms of
membrane transport: passive diffusion, carrier-mediated diffusion, filtration, active
transport, or pinocytosis. Being a bimolecular lipid layer, the cell membrane can also
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act as a barrier to some drugs.
Passive diffusion. Most compounds penetrate into cells by diffusing as the un-
ionized moiety through the lipid membrane. Factors affecting the passage of a
molecule through a membrane are the molecule's size and charge, the lipid-water
partition coefficient, and the concentration gradient. The two types of passive drug
transport are simple diffusion and filtration.
Simple diffusion. Simple diffusion is characteristic of organic acids and
alkaline. The greater the concentration gradient, the greater the rate of absorption.
The larger the absorbing surface, the greater the drug flux. The diffusion constant is
directly proportional to the temperature and is inversely related to the molecular size.
The greater the lipid-water partition coefficient, the greater the drug flux. In simple
diffusion, molecules cross the lipid membrane in an uncharged form. The pH of the
medium affects the absorption and excretion of a passively diffused drug. Acidum
acetylsalicylicum and other weak acids are best absorbed in the stomach because of
its acidic environment. Alkalinic drugs are best absorbed in the small intestine, which
has a higher pH.
Filtration is a character of urea pure. Water, ions, and some polar and no polar
molecules of low molecular weight can diffuse through membranes, suggesting that
pores or channels may exist. The capillaries of some vascular beds (e.g. in the
kidney) have large pores, which permit the passage of molecules as large as proteins.
Carrier-mediated facilitated diffusion is character of amino acids, vitamins
and other drugs. In this type of transport, movement across the membrane is
facilitated by a macromolecule. It is a saturable process; that is, external
concentrations can be achieved in which increasing the external/internal
concentration gradient will not increase the rate of influx. It is selective for the
chemical structure of a drug; that is, the carrier mechanism transports only those
drugs having a specific molecular configuration. It requires no energy. It cannot
move against a concentration gradient and, therefore, is still diffusion.
Active transport is a character of cardiac glycosides and others. Active
transport is similar to carrier-mediated diffusion in several ways: movement across
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the membrane is mediated by macromolecules. It is a saturable process, selective for
chemical structure. Several important features distinguish active transport from
diffusion processes. Active transport requires metabolic energy; this is often
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generated by the enzyme known as Na -K -ATPase. It transports molecules against a
concentration gradient.
Pinocytosis is typical of lipid soluble vitamin drugs. A vacuolar apparatus in
some cells is responsible for this process. There exist both fluid-phase pinocytosis
for substances such as sucrose and adsorptive-phase pinocytosis for substances such
as insulin.
Bioavailability is the relative rate and extent by means of which a drug
reaches the general circulation; this is especially important when a drug is
administered orally. Factors that influence bioavailability are: solubility of the drug in
the contents of the stomach, dietary patterns, tablet size, quality control in
manufacturing and formulation.
Absorption is the rate at which a drug leaves the site of administration and the
extent to which this occurs. The absorption of a drug through the mucosal lining of
the gastrointestinal tract or through capillary walls depends on the physical and
chemical properties of the drug.
Route of administration is an important determinant of the rate and efficiency
of absorption.
Enteral routes are the most common routes of administration. Examples of
enteral routes are peroral, rectal, sublingual, subbuccal, and duodenal. Advantages
of peroral administration. An alimentary route is physiological, generally the
safest route of administration. The delivery of the drug into the circulation is slow
after oral administration, so that rapid, high blood levels are avoided and adverse
effects are less likely. The dosage forms available for alimentary administration are
convenient and do not require sterile technique.
Disadvantages of alimentary administration. It is not convenient for the first
aid. The main disadvantage is that the rate of absorption varies. It becomes a problem
if a small range in blood levels separates a drug desired therapeutic effect from its
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toxic ones. Irritation of mucosal surfaces can occur. A patient compliance is not
ensured. With peroral administration of some drugs extensive hepatic metabolism
may occur before a drug reaches its site of action. This is known as a first-pass effect.
Passage through the liver and the resulting initial hepatic metabolism are avoided by
administering the drug sublingually. But only some drugs may penetrate through
mucose surfaces.
Parenteral routes. The main merit is that the medicine bypasses the
alimentary tract. Examples of parenteral routes: intravenous, intramuscular,
subcutaneous, intraperitoneal, intra-arterial, intrathecal, transdermal, intranasal, and
inhalational etc.
Advantages of parenteral administration. A drug gets to the site of action
faster, providing a rapid response, which may be required in an emergency. The dose
can often be more accurately delivered. Parenteral administration can be used when
the alimentary route is not feasible (e.g. when a patient is unconscious). Large
volumes can be delivered intravenously.
Disadvantages of parenteral administration. More rapid absorption can lead
to increased adverse effects. A sterile formulation and an aseptic technique are
required. Local irritation may occur at the site of injection. Parenteral administration
is not suitable for insoluble substances. Parenteral administration may lead to HIV
infection and phlebitis.
Topical administration is useful in the treatment of patients with local
conditions; with topical administration there is usually little systemic absorption.
Drugs can be applied to various mucouse membranes and skin. Inhalation provides a
rapid access to circulation; it is the common route of administration for gaseous and
volatile drugs. It is managed well. In the case of inhalation there may occur allergic
reaction and any disease may be aggravated.
Factors affecting drug absorption. Solubility of a drug in water and lipid
affects absorption. Dosage affects the drug concentration at its site of action and,
thus, greatly influences a biologic response to a drug. The larger the dose, the greater
the effect, until a maximum effect is achieved. This is called a dose-response
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