Antagonists and modulators
An antagonist at a receptor displays affinity for that receptor but it has
no efficacy; i.e. it does not produce a functional effect after it binds.
Antagonists compete with agonists for binding to the same
specific sites on rec
Alcohol & evolution?
Alcohol use dates back to prehistoric times & distillation was
invented by the Arabs, from whom it spread to Europe in the
g of alcohol:
bA s(4-5% EtOH)drink glass of wineabout 13.61.5 oz (43 ml
Tolerance to drugs
There are two forms of
tolerance to drugs:
1. Metabolic (pharmacokinetic)
2. Functional (pharmacodynamic)
After the chronic administration of many drugs, tolerance
can be seen to develop.
This means that higher doses of the drugs may ne
Behavioural pharmacology is the study of changes in
behaviour produced by a drug, and the mechanisms by
which the drug produces these changes.
Ultimately we are concerned by the behavioural effects of
drugs in humans, but we perfo
Action potentials travel
down the axon leading to
This is chemical
Neurotransmitters are small molecules released by
neurons which bind receptors and elicit functional
Drug abuse and dependence
No agreement has been reached on the exact definition of
the word addiction. The pattern of behaviour leading to
the excessive use of psychoactive substances is generally
referred to as drug dependence.
Drug dependence can be def
Behavioural Pharmacology III
Behavioural models of mental disorders
Animal models of human disorders are useful in the
development of new drugs for those disorders.
A. Models for Anxiety
1. Elevated plus maze
An elevated plus maze is a cross-shaped (t-sha
History and miscellaneous facts
Teratology is the study of congenital (birth) defects. Even 7000 years
ago the Babylonians were aware of at least 62 abnormalities that could
be recognized at birth.
As mentioned in an earli
Pharmacological principles of chemical teratogenesis
Placental transfer. The placenta is not a barrier completely
protecting the fetus from external chemicals; instead it acts
as a type of sieve, allowing small chemicals (<600 Da) and
excluding only those
Behavioural Pharmacology II
Effects of drugs on learning and memory
Learning can be defined as a semi-permanent change in behaviour
resulting from the occurrence of a previous event. Memory is the
storage of learned information in a manner that permits it
Principles of cancer chemotherapy
1. A clonogenic cell has the potential to produce progeny to such an
extent that results in the death of the host. The goal of
chemotherapy is to kill all clonogenic cells.
2. A constant fraction of cancer cells is killed
of cancer is a
Initiation of carcinogenesis
The covalent binding of the ultimate carcinogen to DNA
alters the coding of the DNA at that site, and if not
detected and corrected before cell division, may lead
Toxicology is the study of the adverse effects of chemical agents on
A number of classifications can be used to subdivide the general field of
Toxic agents themselves
may be classified
according to: (1) the
What are your chances of developing some sort of cancer
in your lifetime?
1 in 1000?
1 in 100?
1 in 20?
1 in 10?
1 in 3?
Incidence and mortality from cancers rises with age.
Most (60-90%) of cancers are primarily due to
Predictive toxicology: assesses risks associated with a
situation in which the toxic agent, the subject and exposure
conditions are defined.
LOEL: Lowest observed effect level.
NOEL: No observed effect level.
Increasing technological sophist
The simultaneous usage of several therapeutic agents concurrently is
commonplace, with most patients in general hospitals receiving at least 5
drugs concurrently at some point in their stays.
The median number of drugs administered to pa
Sources of variation in drug responses
Dosing amounts and schedules are determined empirically, based on
extensive clinical observations. These doses are those that have
therapeutic efficacy in most patients on most occasions, and produce the
An agonist is a ligand or drug that binds to specific receptors and
exerts some sort of functional effect after binding; i.e., it has efficacy
as well as affinity. It may mimic the effect of an endogenous
compound. A partial agonist only
Adverse Drug Reactions
All drugs have the potential to produce deleterious consequences. Even
Hippocrates (400 BC) was aware of this: Above all, do no harm. Voltaire
didnt have a very high opinion of physicians stating They poured drugs
of which they knew
Specificity of drug action
No drug is entirely specific in the sense that it acts exclusively only on
one type of cell or tissue, having just the desired effect and no other.
Drugs vary in their specificities and the usefulness of a drug clinically
Pharmacogenetics is the study of the influence of heredity
on the responses to drugs, or their fates in the body.
When administering a drug, a physician would like to be
able to predict, explain and control variability in the
The second major type of neurotransmitter receptor
Principles of Drug Action (BIO 365) Test #2
March 22, 2013
Each of the 12 multiple choice questions is worth 1 mark out of 30.
1. W hich one of the following statements is TRUE?
The acetylcholine molecule can convert between the cis and trans fo
More drug unbound
More drug bound
You wish to prescribe drug X to Mr. Smith, a 70 kg man who has a
body water percentage of 60%. Assuming that drug X partitions
completely into body water, how much X must you administer to
obtain a lev
Dependence of drug absorption on pH and drug protonation
Almost all drugs can be classified as: (1)
uncharged molecules; (2) organic acids;
or (3) organic amines.
For example, an amine type of drug can
take two forms as shown to the right;
Many drugs produce their actions by binding
to specific receptors on target cells in the
Paul Ehrlich more than a century ago coined
the term magic bullet to describe the
specificity of drug action.
The direct identification of recept
Time to steady state concentration
Once again assume a drug follows first-order kinetics and is administered
by continuous iv administration.
The Css depends on the rates of administration and elimination of the drug.
However, the rate of approach to
Effect of dosing on duration of drug
action can be dramatic if
absorption is not fast in comparison
At low doses the drug effect
appears quite late and lasts only a
short time. Larger doses bring
about an earlier appearance of the
A central question of drug therapy is: What is the proper dose of a drug
that will produce the desired therapeutic effect without harmful side
doses and responses are
discussed in terms of log
A review of fate of drugs in the body.
The quantitative description of the rates of the various steps of drug
1. absorption of drugs
2. distribution to organs and tissues
3. elimination by biotransformation and exc