Pharmacology

Lecture (1) Pharmacology Dr. Dalia A. Muhsin
Pharmacology:
The science that studies the changes produced in the living organism by drug. Pharmacology is concerned with the knowledge of the history, sources, physical and chemical properties, compounding, biochemical and physiological effects, mechanisms of action, absorption, distribution, biotransformation , excretion, and therapeutic and other uses of drugs.
Drug:
Substance that brings about a change in the biological function of a cell, tissue, organ or organism.
It may be synthesized within the body like hormones or may be a chemical not synthesized in the body (xenobiotic).
Pharmacotherapeutics:
Relate to the use of drugs in the prevention , diagnosis and treatment of disease ( clinical indications of the drugs).
The two main area of pharmacology are:
1-pharmacodynamic :
The study of the effect of the drug on biological system.
2- pharmacokinetic :
The study of the effect of biological system on the drug.


Pharmacokinetic
In practical therapeutics, a drug should be able to reach its intended site of action after administration by some convenient route. In many cases, the active drug molecule is sufficiently lipid soluble and stable to be given as such. In some cases, however, an inactive precursor chemical that is readily absorbed and distributed must be administered and then converted to the active drug by biologic processes—inside the body, Such a precursor chemical is called a prodrug.

In only a few situations is it possible to apply a drug directly to its target tissue, eg, by topical application of an anti-inflammatory agent to inflamed skin or mucous membrane. Most often, a drug is administered into one body compartment, eg, the gut, and must move to its site of action in another compartment, eg, the brain in the case of an antiseizure medication. This requires that the drug be absorbed into the blood from its site of administration and distributed to its site of action, permeating through the various barriers that separate these compartments. For a drug given orally to produce an effect in the central nervous system, these barriers include the tissues that make up the wall of the intestine, the walls of the capillaries that perfuse the gut, and the blood-brain barrier, the walls of the capillaries that perfuse the brain. Finally, after bringing about its effect, a drug should be eliminated at a reasonable rate by metabolic inactivation, by excretion from the body, or by a combination of these processes.
Four pharmacokinetic properties determine the speed of onset of drug action, the intensity of the drug’s effect, and the duration of drug action:
• First Absorption: drug absorption from the site of administration permits entry of the therapeutic agent (either directly or indirectly) into plasma.
• Second, Distribution, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.
• Third , Metabolism: the drug may be biotransformed by metabolism by the liver, or other tissues.
• Finally, Elimination: the drug and its metabolites are eliminated from the body in urine, bile, or feces ( Fig. {1.1}).
These four pharmacokinetic parameters allow the clinician to design and optimize treatment regimens, including decisions as to the route of administration for a specific drug, the amount and frequency of each dose, and the duration of treatment.


ROUTES OF DRUG ADMINISTRATION
The route of administration is determined primarily by the properties of the drug (for example, water or lipid solubility, ionization) and by the therapeutic objectives (for example, the desirability of a rapid onset of action, the need for long-term treatment, or restriction of delivery to a local site).

Routes of administration can be classified as follows:
1. Enteral (GIT): oral, sublingual, and rectal.
2. Parenteral: IM, IV, ID, SC, inhalation, topical, and others
ABSORPTION OF DRUGS
Absorption is the transfer of a drug from its site of administration to the bloodstream via one of several mechanisms. The rate and efficiency of absorption depend on both factors in the environment where the drug is absorbed and the drug’s chemical characteristics and route of administration (which influence its bioavailability).
For IV delivery, absorption is complete. That is, the total dose of drug administered reaches the systemic circulation (100% bioavailability).
Drug delivery by other routes may result in only partial absorption and, thus, lower bioavailability.
Mechanisms of absorption of drugs from the GI tract
Depending on their chemical properties, drugs may be absorbed from the GI tract by passive diffusion, facilitated diffusion, active transport, or endocytosis.
1. Passive diffusion:
• The driving force for passive absorption of a drug is the concentration gradient across a membrane separating two body compartments. In other words, the drug moves from a region of high concentration to one of lower concentration.
• Passive diffusion does not involve a carrier,
• is not saturable, and
• shows a low structural specificity.
The vast majority of drugs gain access to the body by this mechanism. Water-soluble drugs penetrate the cell membrane through aqueous channels or pores, whereas lipid-soluble drugs readily move across most biologic membranes due to their solubility in the membrane lipid bilayers (Figure 1.6A).
2. Facilitated diffusion:
Other agents can enter the cell through specialized transmembrane carrier proteins that facilitate the passage of large molecules. These carrier proteins undergo conformational changes, allowing the passage of drugs or endogenous molecules into the interior of cells and moving them from an area of high concentration to an area of low concentration. This process is known as facilitated diffusion.
• It does not require energy,
• can be saturated,
• and may be inhibited by compounds that compete for the carrier (Figure 1.6B).
3- Active transport: This mode of drug entry also involves specific carrier proteins that span the membrane. A few drugs that closely resemble the structure of naturally occurring metabolites are actively transported across cell membranes using these specific carrier proteins. Energy-dependent active transport is driven by the hydrolysis of adenosine triphosphate (Figure 1.6C).
• It is capable of moving drugs against a concentration gradient, from a region of low drug concentration to one of higher drug concentration.
• The process shows saturation kinetics for the carrier
• Active transport systems are selective and may be competitively inhibited by other cotransported substances.


4- Endocytosis and exocytosis:
These types of drug delivery systems transport drugs of exceptionally large size across the cell membrane. Endocytosis involves engulfment of a drug molecule by the cell membrane and transport into the cell by pinching off the drug filled vesicle(Figure1.6D).

Exocytosis is the reverse of endocytosis and is used by cells to secrete many substances by a similar vesicle formation process. Vitamin B is transported across the gut wall by endocytosis, whereas certain neurotransmitters (for example, norepinephrine) are stored in intracellular membrane-bound vesicles in the nerve terminal and are released by exocytosis.