Introduction to Pharmacology Flashcards
What is Pharmacology
it is the study of how substances interact with living systems and processes. occurs by binding or activating or Inhibiting body processes
Medical Pharmacology
- It is the science of substances used to prevent,
diagnose and treat diseases. - Aimed at understanding the action of drugs or
chemicals on individual organisms which includes
both therapeutic and toxic effects
Toxicology
- Branch of Pharmacology that deals with the undesirable effects of chemicals on living
systems, from individual cells to humans to a complex ecosystem.
Environmental Toxicology
- It refers to the effects of chemicals on all organism and their survival in groups and as a species.
Pharmacogenetics
- This refers to the study of genetic influences in response to a drug.
- Not all drugs will have the same effect on an individual.
- It focuses on the Familial-induced hepatic drug reaction where affected individuals show an abnormal adverse response to a class of drug.
- It now covers a broader variation in drug response where the genetic basis is more complex.
Pharmacogenomics
- It refers to the relation of an individual’s genetic
make up to his/her response to specific drugs. - The recent term overlaps with pharmacogenetics.
This is greater in the use of genetic information to
guide the choice of drug on individual basis. - It also refers to the difference of individuals with
their response to therapeutic drugs that can be
predicted from their genetic make-up.
how does rapid or slow acetylators affected by isozanoid acetylation?
Rapid acetylators will
have a lesser level of the drug and lesser
risk for toxicity than those who are slow
acetylators. Most Asians are considered
rapid acetylators of isoniazid.
Pharmacoepidemiology
- Is the study of drug effects at population level.
- It is concerned with the variability of drug effects
between individuals and at a population level. - It also takes into account the patient’s compliance
and other factors that apply when drugs are used
under real life situations
Pharmacoeconomics
- Is the branch of economics that aims to quantify in economic terms the cost and benefit of drugs that are used therapeutically.
- One objective of basic pharmacology is to identify a drug based on its safety, adverse effect, necessity, and efficacy.
Drug –
defined as any substance that brings about a
change in biological function through its chemical actions.
- Many drugs found in nature are alkaloids.
- A drug should bind to a receptor for it to develop
its effect.
Physical nature of the drugs
o Often determine as the best route of administration. Solid form at room temperature (e.g. Aspirin, Atropine) – oral The liquid form (e.g. Nicotine, Ethanol) – parenteral or oral Gaseous form (e.g. Nitrous Oxide) – Inhalation
Drug size
o Affects clearance and distribution.
molecular weight between 100 MW – 1000 MW.
(Lithium ion = MW 7) and MW (Alteplase [t-PA] = MW
59,050).
o A molecule should in most cases be at
least 100 MW units in size because if that
the drug is very small it can bind to different
receptors thereby reducing its selectivity.
o This also determines the ability of the
drugs to pass the blood-brain barrier as
well as the placental barrier.
o Drugs much larger than MW 1000 do not
diffuse readily between compartments of
the body.
Drug reactivity and drug-receptor bonds
o Drugs interact with receptors by means
of chemical forces or bonds
Covalent
strongest and irreversible; most antagonists form covalent bonds, specially irreversible antagonists (e.g. Binding of Proton pump inhibitors (PPIs) to Hydrogen-Potassium ATPase forms a covalent bond thereby inactivating that proton pump which can last for 18-24 hours.)
Electrostatic bond
more common but
weaker than covalent
bond.
Hydrophobic
weakest and important in the interactions of highly lipid-soluble drugs with lipids of cell membranes
Drug shape
o Complementary to the receptor site in the same way that the key is complementary to that of the receptor site. o Involves chirality and stereoisomerism e.g. Carvedilol has 2 isomers wherein one isomer [S(-)- carvedilol] is a potent beta receptor blocker while the [R(+)0carvedilol] is 100-fold weaker at the beta-blocker.
DRUG-BODY INTERACTIONS
Pharmacodynamics Action (or effect) of the drug to the body Pertains to the Mechanism of Action o Pharmacokinetics It describes the effect of the body to the drugs Absorption, Distribution, Metabolism and Excretion
agonist receptor
o A drug that would activate the receptor
o Ach, when released to the synaptic cleft,
it would bind to the receptor activate
the receptor
antagonist receptor
competes with the binding of molecule, atropine ach bound
allosteric agonist
different site other than the agonist. inhibit agonist
allosteric antagonist
Different receptor than antagonist
inhibits antagonist
To function as a receptor:
o An endogenous molecule must first be
selective in choosing a ligand to bind.
o It must also change its function upon
binding.
Drugs that mimic agonists inhibit metabolically enzymes
o Acetylcholinesterase inhibitor
Receptors
o Selective (to avoid constant activation)
and changes its function upon binding
that the function of the biologic system is
altered
o Diphenhydramine is highly selective to
H1 receptor and Ranitidine highly
selective to H2 receptor.
inert binding sites
o Binding of the drug to a non-regulatory
molecule such as albumin that would
result in no detectable change in the
function of the biologic system.
o Affects the distribution of drug within the body and determines the amount of free drug in circulation.
AGONISTS THAT INHIBIT THEIR BINDING MOLECULES
Some drugs mimic agonist drugs by inhibiting
molecules responsible for terminating the action
of an endogenous agonist.
They do not bind to the receptor however they
can prolong the effect of the agonist.
Ach as Agonist inhibitor
Acetylcholine. Once it is released in
the synaptic cleft, it binds to the receptor
and some of the Ach would be then
metabolized by your
Acetylcholinesterase. If you will inhibit
the action of the Acetylcholinesterase by
Acetylcholinesterase inhibitor, it can
prolong the effect of your Ach in the
synapse.
agonist mimics are safer, because?
they amplify the effects of
physiologically released agonist ligands, their
effects are sometimes more selective and less
toxic than those of exogenous agonist
Full agonist –
activate receptor systems to the
maximum event of which the system is capable.
Partial agonist –
bind to the same receptors and
activate them in the same way but do not evoke a response, no matter how high the
concentration.
Inverse agonist –
the drug will reduce constitutive
activity, resulting in effects that are opposite of the effects produced by the conventional agonist at the receptor
DURATION OF DRUG ACTION
n some cases, the effect lasts only as long as the
drug occupies the receptor, and dissociation of
drug from the receptor automatically terminates
the effect. In many cases, however, the action
may persist after the drug has dissociated
because, for example, some coupling molecules
are still present in activated form.
- In the case of drugs that bind covalently to the
receptor site, the effect may persist until the drugreceptor complex is destroyed and new receptors
or enzymes are synthesized, for example Aspirin.
what is the desensitization mechanism?
Many receptor-effector systems incorporate
desensitization mechanisms for preventing
excessive activation when agonist molecules
continue to be present for long periods.
PHARMACOKINETIC priniple
Make a rational dosing possible by quantifying
processes such as absorption, distribution,
metabolism and elimination.
Absorption
Route of administration Blood flow influences absorption from intramuscular and subcutaneous sites and, in shock, from gastrointestinal tract o Concentration important in determining the concentration gradient relative to the blood. High blood flow maintains high concentration the gradient between the drug depot and the blood and thus facilitates absorption.
Distribution
Determinants of distribution Size of the organ – concentration gradients Blood flow – rate of uptake of the drug Solubility – drug’s concentration in the ECF Binding – warfarin bound to albumin
Apparent volume of distribution and
physical volumes
Relates the amount of drug in the
body to the concentration in the
plasma
Metabolism
Drug metabolism as a Mechanism of Activation or Termination of Drug Action termination of drugs before excretion as they are metabolized to biologically inactive metabolites (eg. Sympathomimetics, phenothiazines)
lithium is a drug that is eliminated without?
Metabolism
most of the drug metabolism in liver occurs by?
Cyt P450 enzyme
Elimination
o Is not the same as drug excretion o A drug may be eliminated by metabolism long before the modified molecules are excreted from the body o For most drugs and their metabolites, excretion is kidney o Volatile anesthetic gases, a major exception is excreted primarily by the lungs.
First Order Elimination –
rate of elimination is
proportional to the concentration.
o Have a characteristic constant half-life.
Zero Order Elimination –
rate of elimination is constant regardless of concentration.
o Concentration of drugs in plasma
decreases in linear fashion over time.
o They do not have a constant half-life.
