Vous êtes sur la page 1sur 5

GENERAL PRINCIPLES OF PHARMACOLOGY Drug Receptor Bonds

Chemical forces or bonds thru which


Pharmacology
the drug interacts with the receptors
- Body of knowledge with the action of
Weaker bonds are more selective bonds
chemicals on biologic systems,
Covalent Bonds
especially by binding to regulatory
Strongest
molecules (receptors) and activating or
Irreversible
inhibiting normal body processes.
Electrostatic Bonds
Medical Pharmacology More common
- Area of pharmacology concerned with Weaker
the use of chemicals in the prevention, Hydrophobic Bonds
diagnosis, and treatment of the disease, Weakest
esp in humans Highly lipid soluble drugs

Toxicology The movement of drugs in the body


- Are of pharmacology concerned with To reach the receptors and bring about
the undesirable effects of chemicals on biologic effect
biologic systems A drug molecule (e.g. sedative) must
travel from the site of administration
Molecular Biology (e.g. GIT)to the site of action (e.g. brain)
Drug any substance that brings about
a change in biologic function thru A. Permeation
chemical actions 1. Aqueous Diffusion
Receptor specific molecule in the Movement of molecules thru the
biologic system that plays a regulatory watery extracellular and
role intracellular spaces
Membranes of capillaries with
The Nature Of Drugs small water-filled pores
Inorganic ions, non-peptide organic Passive process
molecule, small peptides and proteins, Governed by Ficks Law
nucleic acids, lipids, and carbohydrates 2. Lipid Diffusion
Found in plants or animals, many are Movement of molecules thru
partially or completely synthetic membranes and other lipid
structures
Physical Nature Of Drugs
Most important factor for drug
Solid
permeation
Liquid
- Large lipid barriers that
Gas
separate the compartments of
**Drugs are given at a site distant from the
the body
intended site of action.
Passive process
Drug Size And Molecular Weight (Mw) Governed by Ficks Law
Vary in size 3. Transport by Special Carriers
MW 7 (Lithium) Drugs transported across barriers
MW 50,000 (Thrombolytic agents)_ by mechanisms that carry similar
Majority have MW between 100 and endogenous substances
1000 - Amino acid carriers, weak acid
100 MW carriers
For selective binding Capacity limited
1000 MW Not governed by Ficks Law
For traversing to different barriers of Active Transport
the body
- Needs energy
>1000 MW
- Against a concentration
Cannot move w/in the body
gradient
Given directly at the site of action

PHARMACOLOGY LEC (CHAPTER 1) 1 | AEOC


Facilitated diffusion 2. LIPID DIFFUSION
- No energy required Many drugs are weak bases or
- downhill weak acids
4. Endocytosis pH of the medium determines the
Binding to specialized fraction of molecules charged
components (receptors)on cell (ionized) versus uncharged (non-
membranes ionized)
Internalization by enfolding of the fraction of molecules in the
area membrane and contents of ionized state can be predicted by
the vesicle are subsequently means of the H-H equation
released into the cytoplasm
Permits very large or very lipid- THE HENDERSON-HASSELBACH EQUATION
insoluble chemicals to enter the
cell ( )
E.g. B12 with intrinsic factor and ( )
iron with transferrin
Protonated means associated with a protein (a
5. Exocytosis
hydrogen ion)
Reveres process
Encapsulated material from the
3. IONIZATION OF WEAK ACIDS AND
cell
WEAK BASES
B. Ficks Law of Diffusion WEAK BASES
Predicts the movement of molecules - Neutral molecule that can
across a barrier form a cation (+ charged_
Drug absorption is faster in organs by combining with a proton
with larger surface areas (e.g. small (hydrogen ion)
intestine) than from organs with
smaller absorbing areas (e.g. RNH3+ RNH2 + H+
stomach) Protonated weak unprotonated weak proton
base (charged, base (uncharged,
more water-soluble) more lipid-soluble)
( )
RCOOH RCOO- + H+
C1 higher conc. C2 lower conc. Protonated weak unprotonated weak proton
acid (uncharged, acid (uncharged,
more lipid-soluble) more lipid-soluble)
Permeability coefficient measure of
the mobility of the drug in - Ionized, more polar, molar
medium of the diffusion path. water-soluble
Thickness length of the diffusion path WEAK ACID
- Neutral molecule that can
C. Water and Lipid Solubility of Drugs reversibly dissociate into an
1. AQUEOUS DIFFUSION anion (- charged) and a
Aqueous solubility of a drug is a proton ( Hydrogen ion)
function of the electrostatic - Not ionized, less polar, less
charge (degree of ionization, water soluble when they
polarity) of the molecule are protonated
Water molecules are attracted to
charged drug molecules forming The Henderson-Hasselbach Equation
an aqueous shell around them Clinically important when it is necessary
Lipid solubility of a molecule is to estimate or alter the partition of drugs
inversely proportional to its charge between compartments of different pH

PHARMACOLOGY LEC (CHAPTER 1) 2 | AEOC


When a patient takes an overdose of a 3. INTRAMUSCULAR (IM)
weak acid drug, excretion maybe Absorption is often faster and
accelerated by alkalinizing the urine. more complete (higher
Weak acids dissociate to its charged, bioavailability) than oral
polar form in alkaline urine and cannot Large volumes (>5 mL into each
readily diffuse back from the renal buttock) if the drug is not irritating
tubule back to the blood First pass effect is avoided
Large number of drugs are weak bases Heparin cannot be given by this
with amine containing molecules route, causes bleeding in the
Nitrogen of a neutral amine has 3 atoms muscle
associated with it plus a pair of 4. SUBCUTANEOUS
unshared electrons Slower absorption than IM route
First pass effect is avoided
PRIMARY SECONDARY TERTIARY QUATERNARY Heparin can be given by this
route, does not cause
H R R R
R N R N R N R N R hematoma
H H R R 5. BUCCAL AND SUBLINGUAL
Buccal route (in the pouch
ABSORPTION OF DRUGS between gums and cheeks)
A. ROUTES OF ADMINISTRATION Permits absorption direct into the
Drugs usually enter the body remote systemic circulation, bypassing
from the target tissue or organ and hepatic portal circuit and first-
require transport by the circulation to pass metabolism
the intended site of action Slow or fast depending on
BIOAVAILABILITY is equal to the formulation of the product
amount absorbed into the systemic Sublingual route (under the
circulation over the amount of drug tongue) offers the same features
administered 6. RECTAL (suppository)
Partial avoidance of first-pass
1. ORAL (swallowed) effect (not completely as the
Maximum convenience sublingual route)
Absorption maybe slower, and Suppositories tend to migrate
less complete upward in the rectum where
Same drugs have low absorption is partially into the
bioavailability when given orally portal circulation
Subject to first pass effect Larger amounts of unpleasant
(significant amount of the agent drugs are better administered
is metabolized in the gut wall, rectally
portal circulation, and liver May cause significant irritation
before it reaches the systemic 7. INHALATION
circulation) For respiratory disease
2. INTRAVENOUS (IV)/ PARENTERAL Delivery closest to the target
Instantaneous and complete tissue
absorption Results into rapid absorption
Bioavailability by definition is because of the rapid and thin
100% alveolar surface area
Potentially more dangerous, high Drugs that are gases at room
blood levels reached if temperature (eg. nitrous oxide),
administration is too rapid or easily volatilized (anesthetics)

PHARMACOLOGY LEC (CHAPTER 1) 3 | AEOC


8. TOPICAL Binding of drugs to
Application to the skin or mucous macromolecules in the blood
membrane of the eye, nose, or tissue compartment will
throat, airway, or vagina for local tend to increase the drugs
effect concentration in that
Rate of absorption is slower compartment
compared to other routes
B. APPARENT VOLUME OF DISTRIBUTION
9. TRANSDERMAL 1. Vd
Application to the skin for Amount of drug in the body
systemic effect to concentration in the
Rate of absorption occurs very plasma
slowly
First-pass effect is avoided METABOLISM OF DRUGS
A. AS MECHANISM OF TERMINATION OF
B. BLOOD FLOW DRUG ACTION
Influences absorption from IM, Action of many drugs is
subcutaneous, and in shock terminated before they are
High blood flow maintains a high excreted
drug depot-to-blood Metabolized to biologically
concentration gradient inactive derivatives
- Maximizes absorption Conversion to a metabolite is
a form of elimination
C. CONCENTRATION
Concentration gradient B. AS MECHANISM OF DRUG ACTIVATION
Major determinant of the rate of PRODRUGS
absorption (Ficks Law) Inactive as administered and
must be metabolized in the body
DISTRIBUITION OF DRUGS to become active
A. DETRMINANTS OF DISTRIBUTION - Eg. levodopa, minoxidil
1. SIZE OF THE ORGAN Many drugs are active as
Size of the organ determines administered and have active
the concentration gradient metabolites as well
between blood and the - Some benzodiazepines
organ
Eg. skeletal muscle and brain C. DRUG ELIMINATION WITHOUT
2. BLOOD FLOW METABOLISM
Important determinant of the Drugs not modified by the body
rate of uptake Continue to act until they are
Well-perfused organs excreted
- Brain Eg. lithium
- Heart, kidneys
- Splanchnic organs ELIMINATION OF DRUGS
3. SOLUBILITY Determinants of the duration of action for most
If the drug is very soluble in drugs
cells, the concentration in the Dosage
perivascular space will be Rate of elimination following the last
lowered and diffusion from dose
the vessel into the - Disappearance of the active
extravascular tissue will be molecules from the bloodstream
facilitated Drug elimination is not the same as drug
4. BINDING excretion

PHARMACOLOGY LEC (CHAPTER 1) 4 | AEOC


A drug may be eliminated by B. ZERO ORDER ELIMINATION
metabolism long before the modified Rate of elimination is constant
molecules are excreted from the body regardless of concentration
For most drugs, excretion is by way of Occurs with drugs that saturate
the kidneys (except anesthetic gases their elimination of mechanism at
lungs) concentrations of clinical interest
For drugs with active metabolites (eg. Concentration of such drugs in
diazepam), elimination of the parent plasma decrease in linear fashion
molecule by metabolism is not over time
synonymous with termination of action With higher doses, there will be
For drugs that are not metabolized, bigger chances of toxic effect
excretion is the mode of elimination because the patient may not be
A small number of drugs combine able to eliminate it
irreversibly with their receptors, Eg. alcohol, phenytoin, aspirin
disappearance from the bloodstream is
not equivalent to cessation of drug ZERO ORDER KINETICS
action 2.5 units/h
Very prolonged action
Eg. phenoxybenzamine, irreversible Plasma
inhibitor of alpha receptors is eliminated Conc. (Cp) 2.5 units/h
from the bloodstream in 1 hour or less
after administration, drugs action lasts
for 48 hours 2.5 units/h
A. FIRST ORDER ELIMINATION
Rate of elimination is
Time (h)
proportionate to the
concentration (ie., the higher the
conc, the greater the amount
eliminated per unit time)
Drugs conc in plasma decreases
exponentially with time
Half-life elimination is constant
regardless of amount of drug in
the body
Concentration of such drug in
the blood will decrease by 50%
for every half-life
Most common process
Followed by most drugs
FIRST ORDERKINETICS

5 units/h

Plasma
Conc. (Cp) 2.5 units/h

1.25 units/h

Time (h)

PHARMACOLOGY LEC (CHAPTER 1) 5 | AEOC