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Pharmacology
Body of knowledge concerned with the action of chemicals on biologic systems, especially by binding to regulatory molecules (receptors) and activating or inhibiting normal body processes.
Pharmacology
study of substances that interact with living systems through chemical processes.
beneficial therapeutic effect
These substances may be chemicals administered to achieve a ___ on some process within the patient or for their toxic effects on regulatory processes in parasites infecting the patient.
chemical
drug or any chemical which can affect our biological system
binding site or a receptor
chemicals have a ___, if not, it will not affect any biological change
receptors
___ are able to regulate (regulatory) function of our body, the drug can either activate or inhibit that function by binding to that receptor.
Medical pharmacology and toxicology
understanding the actions of drugs as chemicals on individual organisms
first domain (left)
both beneficial & toxic effects
Pharmacokinetics
absorption, distribution, and elimination of drugs
how the drug will be handled by the patient
movement of the drug into, within, and out of our body
Pharmacodynamics
actions of the chemical on the organism.
denotes the actions of the drug on the body, such as mechanism of action and therapeutic and toxic effects
how the drug would affect our body
Environmental toxicology
effects of chemicals on all organisms and their survival in groups and as species
second domain (right)
increasing resistance
discovery of new target processes
recognition of new diseases
why are new drugs added every year?
pharmacology
represents an area where anatomy, biochemistry, genetics, physiology, pathology, clinical medicine, and the environment meet
pharmacologic tools
many problems that the health practitioner confronts can now be corrected or mitigated using ___
Pharmacogenomics
field of research that studies how a person's genes affect how he or she responds to medications
relation of the individual’s genetic makeup to his or her response to specific drugs
Decoding of the genomes of many species
___ led to the recognition of unsuspected relationships between receptor families and the ways that receptor proteins have evolved.
discovery of regulatory functions
___ has opened a new area of possible manipulation of the genes—epigenetics—that control pharmacologic responses.
neighbors of chromosomes and the noncoding regions of DNA on the expression of exons
discovery of regulatory functions are exerted by ___
small interfering RNAs (siRNAs) and micro-RNAs (miRNAs
discovery that small segments of RNA can interfere with protein synthesis with extreme selectivity has led to investigation of ___ as therapeutic agents.
antisense oligonucleotides (ANOs)
___, synthesized to be complementary to natural RNA or DNA, can interfere with the readout of genes and the transcription of RNA
toxic
General principles that the student should remember are:
that all substances can under certain circumstances be ___
the much greater proportion of impurities
General principles that the student should remember are:
chemicals in botanicals are no different from chemicals in manufactured drugs except for ___
artificial separation
General principles that the student should remember are:
all dietary supplements and all therapies promoted as health-enhancing should meet the same standards of efficacy and safety as conventional drugs and medical therapies. there should be no ___ between scientific medicine and “alternative” or “complementary” medicine
Pharmacogenomics
Finds the exact mechanism of action of drugs
Identifies the receptors
brought about by the exploration of the human gene
Drug
Any substance that brings about a change in biologic function through chemical actions
Any substance that can bring about a biological functional change through its chemical actions
Receptor
Specific molecule in the biologic system that plays a regulatory role
what is present in our body which plays a regulatory role that can be altered by the drug.
an agonist (activator) or antagonist (inhibitor)
nature of drugs:
the drug molecule interacts as ___ with a specific target molecule that plays a regulatory role in the biologic system.
chemical antagonists
nature of drugs:
may interact directly with other drugs
osmotic agents
nature of drugs:
interact almost exclusively with water molecules.
Poisons
drugs that have almost exclusively harmful effects
Paracelsus (1493–1541)
“the dose makes the poison,” meaning that any substance can be harmful if taken in the wrong dosage.
Toxins
defined as poisons of biologic origin synthesized by plants or animals
alkaloids
Many drugs found in nature are ___, which are molecules that have a basic (alkaline) pH in solution, usually as a result of amine groups in their structure.
enantiomers
Many biologically important endogenous molecules and exogenous drugs are optically active; that is, they contain one or more asymmetric centers and can exist as ___.
the appropriate size, electrical charge, shape, and atomic composition
physical nature of drugs:
drug molecule must have ___
Solid
physical nature of drugs:
includes tablets, granules or powder contained inside the capsules.
Liquid
physical nature of drugs:
syrup or suspension.
Syrup
physical nature of drugs (liquid):
homogeneous
Suspension
physical nature of drugs (liquid):
there would be undissolved particles, it tends to settle down. When you dispense and do not properly shake, the concentration would vary and the effect would also vary because of the varying dose of the drug
Gas
physical nature of drugs:
mostly like anesthetics, aerosolized anesthetics, for those who are nebulizing that is vaporized
site distant
Drugs are given at a ___ from the intended site of action
necessary properties
a useful drug must have the ___ to be transported from its site of administration to its site of action
delayed
The onset of action would be ___ if you give it at a far distant site
pH differences
alters the degree of ionization of weak acids and bases
MW 7
drug size & molecular weight:
Lithium can be used as chemotherapeutic drug
MW 50,000
drug size & molecular weight:
thrombolytic agents
Heparin
100 MW
drug size & molecular weight:
For selective binding
It could easily be eliminated
Disadvantage of being a small drug
easily be distributed because they can pass through smaller pores or gaps in between blood vessels
can diffuse easily
Advantage of being a small drug
1000 MW
drug size & molecular weight:
For traversing to different barriers of the body
1000 MW
drug size & molecular weight:
Cannot move within the body
Given directly at the site of action
poorly absorbed and poorly distributed in the body
lower limit
drug size & molecular weight:
set by the requirements for specificity of action.
prevent its binding to other receptors
at least 100 MW units in size
upper limit
drug size & molecular weight:
drugs must be able to move within the body
do not diffuse readily between compartments
complementary
drug shape:
drug’s shape is ___ to that of the receptor site
Stereoisomerism
drug shape:
Can affect the potency of the drug
enantiomeric
drug shape:
they exist as ___ pairs
Carvedilol
drug shape:
(S)(-) isomer, potent beta receptor blocker
(R)(+) isomer, weak beta receptor blocker
Ketamine
drug shape:
(+) more potent anesthetic and less toxic than the (-)
Racemic mixer
Rational design of drugs
ability to predict the appropriate molecular structure of a drug on the basis of information about its biologic receptor.
Drug Receptor bonds
Chemical forces or bonds through which the drugs interacts with the receptors
more selective bonds
Drug Receptor bonds:
Weaker bonds are ___
Strongest
Drug Receptor bonds: Covalent Bonds
cannot be easily dislodged or separated from each other
Irreversible
Drug Receptor bonds: Covalent Bonds
The backside is it is quite ___
Aspirin with its receptor, cyclooxygenase
Electrostatic Bonds
Drug Receptor bonds:
More common
Weaker than covalent
bonds vary from relatively strong linkages between permanently charged ionic molecules to weaker hydrogen bonds and very weak induced dipole interactions
Hydrophobic Bonds
Drug Receptor bonds:
weakest
Utilized by highly lipid soluble drugs
uncharged areas
pockets
Hydrophobic Bonds are important in the interactions of highly lipid-soluble drugs with the lipids of cell membranes and perhaps in the interaction of drugs with the internal walls of receptor “___.”
Pharmacodynamics
Drug-Body Interactions:
actions of the drug on the body
determine the group in which the drug is classified, deciding whether that group is appropriate therapy
Pharmacokinetics
Drug-Body Interactions:
actions of the body on the drug
govern the absorption, distribution, and elimination of drugs
great practical importance in the choice and administration of a particular drug
drug ligand molecules
Pharmacodynamic Principles:
Drug actions are mediated through the effects of ___ on drug receptors in the body.
Drug (D) + receptor-effector (R) → drug-receptor-effector complex → effect
Pharmacodynamic Principles:
A cholinergic drug reaches the acetylcholine. If for example the cholinergic drug is in the muscle, you will experience muscle contraction or muscle twitch. This happens because the cholinergic receptor is an effector.
D + R → drug-receptor complex → effector molecule → effect
Pharmacodynamic Principles:
When the drug reaches and binds to its receptor, the drug-receptor complex produces an intracellular effector. This intracellular effector mediates the action of the drug. The effect would greatly depend on the available effectors inside.
The receptor is normally in the cell membrane. When a drug binds to it, it produces or activates the intracellular effector.
D + R → D-R complex → activation of coupling molecule → effector molecule → effect
Pharmacodynamic Principles:
The drug binds to its receptor extracellular and the drug-receptor complex activates a coupling molecule or enzyme inside. The activated coupling molecule or enzyme inside will be the one to produce the effector molecule. And the effector molecule will be the one who will produce the effect.
Inhibition of metabolism of endogenous activator → increased activator action on an effector molecule → increased effect
Pharmacodynamic Principles:
The drug actually doesn't need to bind to the receptor
drug will target the endogenous activator or metabolism.
constitutive or basal activity
Pharmacodynamics:
Some of the receptor pool must exist in Ra form
May produce same physiological effect as agonist-induced activity
Occurs in the absence of the agonis
higher affinity
Pharmacodynamics:
Agonists have a much ___ for the Ra configuration and stabilize it, so that a large percentage of the total pool resides in the Ra–D fraction and a large effect is produced
receptor
Pharmacodynamics:
Agonist binds to and activate the ___
Full agonist
Pharmacodynamics:
Activates receptor-effector system to the maximum extent (Ra-D pool)
Partial agonist
Pharmacodynamics:
Bind to the same receptors and activate them in the same way but do not evoke as great a response, no matter how high the concentration.
Such drugs are said to have low intrinsic efficacy
pindolol, a β-adrenoceptor partial agonist
Pharmacodynamics: Partial agonist:
may act either as an agonist or as an antagonist
Allosteric modulators
Pharmacodynamics:
Binds to a site on the receptor molecule separate from the agonist binding site
Modifies receptor activity without blocking agonist activity
May increase or decrease response to agonist
noncompetitive
allosteric activator
Pharmacodynamics: Allosteric modulators
when they increase, they are ___
allosteric inhibitor
Pharmacodynamics: Allosteric modulators
when they decrease, they are ___
Inverse agonist
Pharmacodynamics:
Drug has a stronger affinity for the Ri pool
Reduces constitutive activity
Results in effects that are opposite of the effects produced by conventional agonist
Ri
Pharmacodynamics: Inverse agonist
the inactive receptor or the nonfunctional form of the receptor
Antagonist
Pharmacodynamics:
Binds to a receptor, compete with and prevent binding by other molecule
neutral antagonism
Pharmacodynamics: Antagonist
the presence of the antagonist at the receptor site will block access of agonists to the receptor and prevent the usual agonist effect
lock & key mechanism
drug shape:
Prodrug
Pharmacokinetics:
Inactive precursor
Must be administered and converted to the active drug by biologic process inside the body
Biodisposition
term sometimes used to describe the processes of metabolism and excretion
Permeation
Movement of Drugs in the Body:
Movement of drug molecules into and within the biologic environment
Aqueous Diffusion
Movement of Drugs in the Body: Permeation
Movement of molecules through the watery extracellular and intracellular spaces
Membranes of capillaries have small water-filled pores
Passive process
Governed by Fick’s law
Fick’s law of Diffusion
area
Movement of Drugs in the Body: Aqueous Diffusion: Fick’s law of Diffusion
the cross-sectional area of the diffusion
permeability coefficient
Movement of Drugs in the Body: Aqueous Diffusion: Fick’s law of Diffusion
measure of the mobility of the drug molecules in the medium of the diffusion path
thickness
Movement of Drugs in the Body: Aqueous Diffusion: Fick’s law of Diffusion
the length of the diffusion
the lipid:aqueous partition coefficient
Movement of Drugs in the Body: Aqueous Diffusion: Fick’s law of Diffusion
is a major determinant of mobility of the drug because it determines how readily the drug enters the lipid membrane
Lipid Diffusion
Movement of Drugs in the Body: Permeation
Followed by lipid soluble drugs
Movement of molecules through membranes and other lipid structures
Most important limiting factor for drug permeation
Passive process
Governed by Fick’s law
Henderson-Hasselbalch equation
Movement of Drugs in the Body: Lipid Diffusion
the ratio of lipid-soluble form to water-soluble form for a weak acid or weak base is expressed by ___
Transport by Special Carriers
Movement of Drugs in the Body: Permeation
transported across barriers by mechanisms that carry similar endogenous substances
Capacity limited
Not governed by Fick’s law
Active Transport
Movement of Drugs in the Body: Permeation: Transport by Special Carriers
Needs energy
Against a concentration gradient
Facilitated Diffusion
Movement of Drugs in the Body: Permeation: Transport by Special Carriers
no energy
downhill
Note 
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