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principles of pharmacology

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Grado
Pharmacology

Institución
Universidad Rey Juan Carlos (URJC)

Book
Rang & Dale\'s Pharmacology

Complete course of principles of pharmacology for engineering students, specially biomedical engineers. This course introduces the basis of pharmacology, along with some engineered applications. The contents are the following: 1. Pharmacokinetics and pharmacodynamics 2. Pharmaceutical formulations ...

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Subido en 20 de enero de 2020
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pharmacology

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PHARMACOLOGY
Biomedical Engineering
H.S.Yaben

,I. Pharmacokinetics and pharmacodynamics

When a drug enters the body, the body begins immediately to work on the drug: absorption, distribution, metabolism
(biotransformation), and elimination. These are the processes of pharmacokinetics. We can define pharmacokinetics
(from Ancient Greek pharmakon "drug" and kinetikos "moving, putting in motion"), sometimes abbreviated as PK,
as the branch of pharmacology dedicated to determine the fate of substances administered to a living organism. It
analyzes chemical metabolism, this is, it studies the processes that affects the drug from the moment that it is
administered up to the point at which is completely eliminated from the body.

The drug also acts on the body, an interaction to which the concept of a drug receptor is key, since the receptor is
responsible for the selectivity of drug action and for the quantitative relationship between drug and effect. The
mechanisms and effects of drug action are the processes of pharmacodynamics (PD). The time course of therapeutic
drug action in the body can be understood in terms of pharmacokinetics and pharmacodynamics.

I.I Pharmacokinetics: How organism affects drugs

I.I.I Drug transport across biological membranes

For drugs to cause an effect, they must interact with our body. The human body is meant to combat the invasion of
external (potentially toxic) substance. For that, we have a
system to face anything that comes into our body, the immune
system. The bad point is that it limits the ability of a drug to act
in the organism. (i.e: Skin, layers of cells, cell membranes,
immune system, pH, enzymes). The ability of a drug to pass
these barriers depends on its biological properties.

Most of the biological barriers in our bodies are membranes.
The absorption, distribution, metabolism, and excretion of a
drug all involve its passage across cell membranes. Mechanisms
by which drugs cross membranes and the physicochemical
properties of molecules and membranes that influence this
transfer are critical to understanding the disposition of drugs in
the human body.

The characteristics of a drug that predict its movement and availability at sites of action are:

 Molecular size and shape.

 Degree of ionization (charge): Drugs can be non-polar (all charges cancel out), polar (with charge) or dipolar
(with both positive and negative charges). If it’s neutral and small enough it can cross the membrane. If it has a
charge it will take a lot of time. Neutral charges will move depending on concentration gradient and polar charges
move depending on electrochemical gradient.

, Lipid solubility of its ionized and nonionized forms: Water and lipid solubility of drugs is crucial for its
absorption or distribution, but also in how they are eliminated from the body.

 Electrochemical gradient: gradient that consists of two parts, the chemical gradient, or difference in solute
concentration across a membrane, and the electrical gradient, or difference in charge across the membrane.

 Binding to serum and tissue proteins.

They can easily pass:

 Small lipophilic (non-polar) and uncharged.

 Small hydrophilic (polar) and uncharged molecules.

The transport of substances through cell membranes is carried out through various types of mechanisms. The
substances can be transported in favor of an electrochemical gradient (descendant) or against an electrochemical
gradient (ascending). Descendant transport is produced by simple or facilitated diffusion and does not require any type
of metabolic energy. The ascending transport is produced by active transport, which can be primary or secondary. The
primary and secondary active transports are differentiated by the type of energy they use. The first uses a direct
contribution of energy while the second uses an indirect energy contribution.

Other differences between transport mechanisms are based on whether the process includes a transport protein.
Simple diffusion is the only form of transport that is not mediated by a carrier protein. In the facilitated diffusion, in the
primary and secondary active transport, numerous integral membrane proteins are involved and are called transport
mediated transport.

I.I.I.I Passive transport

Passive transport is a kind of transport that does not require energy.

1. Simple diffusion

The simple diffusion allows the transport of small non-polar and hydrophobic (lipophilic) molecules such as oxygen,
carbon dioxide, N2 and benzene and uncharged hydrophilic polar molecules such as water, glycerol, urea and ethanol
through the lipid bilayer or pores.

It does not require membrane proteins or external energy source. Although it does require a concentration gradient
(from one compartment with higher concentration to another with lower concentration). The water will spread through
the osmosis process, which is slow since the hydrophobic tails will limit this process. In the kidney, aquaporins will
allow water to be absorbed more quickly. Example: oxygen diffusing in or carbon dioxide diffusing out.

This process is non-saturable, unspecific and non-inhibitable (it cannot be inhibited).

, 2. Facilitated diffusion

Facilitated diffusion is a type of passive transport that consists of
transporting molecules facilitated by proteins (SLC: solute carriers,
superfamily transporter proteins). It transports large uncharged
molecules such as amino acids, glucose or nucleosides and charged
molecules such as sodium, potassium, chlorine, hydrogen,
regardless of their size. Example: glucose or amino acids moving
from blood into a cell. This process needs a concentration
gradient, there is no energy expense and it is a saturable, specific and inhibitable process (it can be inhibited).

Water filled proteins (channels): the channel proteins do not undergo changes in their conformation while the
carrier proteins ligands bind to the receptors of these proteins causing conformational changes that allow their passage
into the cell interior.

→ Aquaporins: allow passage of water.

→ Ion channels: the passive transport mediated by protein channel involves the transport of small molecules with
charge. The net force that drives the transport of charged molecules depends on two forces, which must go in the
same direction for passive transport and do not require energy:

→ Concentration gradient.

→ Membrane voltage potential.

Water filled channels may be open or gated channels:

1. Open channels are open most of the time and have no gates.

2. Gated channels spend most of the time in the closed configuration and are:

→ Chemically gated.

→ Voltage gated.

→ Mechanically gated.

→ Light gated.

Carrier proteins: they do not form channels that are open to both the ECF and ICF. They move larger molecules
across the membrane and they operate as:

→ Uniport carrier proteins: transport one type of molecule and only in one direction. Example: glucose and
amino acids.

→ Cotransport carrier proteins: transport more than one type in.

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