Introduction to pharmacology

05/27/1505/27/15 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006
INTRODUCTION TOINTRODUCTION TO
PHARMACOLOGYPHARMACOLOGY
Pharmacology :Pharmacology :
- Is the branch of science that deal with- Is the branch of science that deal with
drugs . It is a detailed study of drugs ,drugs . It is a detailed study of drugs ,
particularly their action on living tissues -particularly their action on living tissues -
these actions may be beneficial orthese actions may be beneficial or
harmful – and their fate in the body . Thisharmful – and their fate in the body . This
science provides the basis ofscience provides the basis of
therapeutics .therapeutics .

Pharmacology vs other medical sciencesPharmacology vs other medical sciences

Drugs :Drugs :
 A drug is defined as any substance usedA drug is defined as any substance used
for the purpose of diagnosis ,for the purpose of diagnosis ,
prevention , relief or cure of a disease .prevention , relief or cure of a disease .
WHO defines the word drug as aWHO defines the word drug as a
substance or product that is used orsubstance or product that is used or
intended to be used to modify or exploreintended to be used to modify or explore
physiological systems or pathologicalphysiological systems or pathological
status for the recipient .status for the recipient .

Pharmacognosy :Pharmacognosy :
 It is the science that deals with naturalIt is the science that deals with natural
drugs from plant origin and theirdrugs from plant origin and their
constituents .constituents .

Pharmacy :Pharmacy :
 It is the science of identification ,It is the science of identification ,
selection , prevention , standardization ,selection , prevention , standardization ,
compounding , proper utilization andcompounding , proper utilization and
dispensing of medicinal substances .dispensing of medicinal substances .

Pharmacokinetics :Pharmacokinetics :
 It is what the body does to the drug . It isIt is what the body does to the drug . It is
the study of absorption , distribution ,the study of absorption , distribution ,
biotransformation and excretion of drugsbiotransformation and excretion of drugs
and their relationship to pharmacologicaland their relationship to pharmacological
response . It is the fate of drugs in theresponse . It is the fate of drugs in the
body .body .

Pharmacodynamics :Pharmacodynamics :
 It is what the drug does to the body . It isIt is what the drug does to the body . It is
the study of biochemical andthe study of biochemical and
physiological effects of drugs and theirphysiological effects of drugs and their
mechanism of action .mechanism of action .

Therapeutics :Therapeutics :
 It is the application of knowledge ofIt is the application of knowledge of
pharmacology in the prevention andpharmacology in the prevention and
treatment of diseases .treatment of diseases .

Toxicology :Toxicology :
 It is the science that deals with theIt is the science that deals with the
adverse effects of drugs given in largeadverse effects of drugs given in large
doses , measurement and detection ofdoses , measurement and detection of
poisons ( substances that producepoisons ( substances that produce
harmful , dangerous or fatal symptoms .)harmful , dangerous or fatal symptoms .)
as well as treatment of poisoningas well as treatment of poisoning
(=anitdote )are all included in this(=anitdote )are all included in this
science .science .

Chemotherapy :Chemotherapy :
 It deals with the effects of drugs onIt deals with the effects of drugs on
microorganisms and parasites , livingmicroorganisms and parasites , living
and multiplying in another livingand multiplying in another living
organism . It also includes the treatmentorganism . It also includes the treatment
of malignancy .of malignancy .

ClinicalClinical
pharmacology :pharmacology :
 It is the scientific study of drugs inIt is the scientific study of drugs in
humans . It includes pharmacodynamicshumans . It includes pharmacodynamics
and pharmacokinetics investigations inand pharmacokinetics investigations in
healthy volunteers and in patients ;healthy volunteers and in patients ;
evaluations of efficacy and safety ofevaluations of efficacy and safety of
drugs and comparative trials with otherdrugs and comparative trials with other
forms of treatment ; surveillance offorms of treatment ; surveillance of
patterns of drug use , adverse effectspatterns of drug use , adverse effects
..etc ...etc .

Pharmacopoeia :Pharmacopoeia :
 This field of study defines the standardsThis field of study defines the standards
that the drugs and medicinalthat the drugs and medicinal
preparations must meat and theirpreparations must meat and their
average adult dose e.g. Britishaverage adult dose e.g. British
Pharmacopeia (B.P.).Pharmacopeia (B.P.).

Various sources ofVarious sources of
drugs :drugs :
 Animal sources e.g. insulin and thyroid hormones .Animal sources e.g. insulin and thyroid hormones .
 Plant sources e.g. morphine , reserpine and digoxin .Plant sources e.g. morphine , reserpine and digoxin .
 Microorganism e.g. antibiotics like penicillin andMicroorganism e.g. antibiotics like penicillin and
streptomycin.streptomycin.
 Synthetic e.g. aspirin and sulphonamide .Synthetic e.g. aspirin and sulphonamide .
 Minerals e.g. liquid paraffin and kaolin .Minerals e.g. liquid paraffin and kaolin .
 Drugs produced by genetic engineering (DNADrugs produced by genetic engineering (DNA
recombinant- tehnology )e.g. human insulin andrecombinant- tehnology )e.g. human insulin and
human growth hormones .human growth hormones .

Orphan Drugs :Orphan Drugs :
 These are drugs ment for diagnosis ,These are drugs ment for diagnosis ,
prevention or treatment of rare diseasesprevention or treatment of rare diseases
e.g. certain anticancer drugs , antivirale.g. certain anticancer drugs , antiviral
drugs , pentamidine ..etc.drugs , pentamidine ..etc.

Drug developmentDrug development
is the process of bringing a newis the process of bringing a new
pharmaceutical drugpharmaceutical drug to the market once ato the market once a
lead compound has been identifiedlead compound has been identified
through the process ofthrough the process of drug discoverydrug discovery. It. It
includes pre-clinical researchincludes pre-clinical research
(microorganisms/animals) and clinical(microorganisms/animals) and clinical
trials (on humans) and may include thetrials (on humans) and may include the
step of obtaining regulatory approval tostep of obtaining regulatory approval to
market the drug.market the drug.

Pre-clinicalPre-clinical
New chemical entitiesNew chemical entities (NCEs, also known as new molecular(NCEs, also known as new molecular
entities or NMEs) are compounds which emerge from theentities or NMEs) are compounds which emerge from the
process ofprocess of drug discoverydrug discovery. These will have promising. These will have promising
activity against a particular biological target thought to beactivity against a particular biological target thought to be
important in disease; however, little will be known about theimportant in disease; however, little will be known about the
safety,safety, toxicitytoxicity,, pharmacokineticspharmacokinetics andand metabolismmetabolism of thisof this
NCE in humans. It is the function of drug development toNCE in humans. It is the function of drug development to
assess all of these parameters prior to human clinical trials.assess all of these parameters prior to human clinical trials.
A further major objective of drug development is to make aA further major objective of drug development is to make a
recommendation of the dose and schedule to be used therecommendation of the dose and schedule to be used the
first time an NCE is used in a human clinical trial ("first time an NCE is used in a human clinical trial ("
first-in-manfirst-in-man" [FIM] or First Human Dose [FHD])." [FIM] or First Human Dose [FHD]).

In addition, drug development is required to establish theIn addition, drug development is required to establish the
physicochemical properties of the NCE: its chemicalphysicochemical properties of the NCE: its chemical
makeup, stability, solubility. The process by which themakeup, stability, solubility. The process by which the
chemical is made will be optimized so that from beingchemical is made will be optimized so that from being
made at the bench on a milligram scale by amade at the bench on a milligram scale by a
medicinal chemistmedicinal chemist, it can be manufactured on the, it can be manufactured on the
kilogram and then on thekilogram and then on the tonton scale. It will be furtherscale. It will be further
examined for its suitability to be made intoexamined for its suitability to be made into capsulescapsules
, tablets, aerosol, intramuscular injectable, subcutaneous, tablets, aerosol, intramuscular injectable, subcutaneous
injectable, or intravenous formulations. Together theseinjectable, or intravenous formulations. Together these
processes are known in preclinical development asprocesses are known in preclinical development as
Chemistry, Manufacturing and Control (CMC).Chemistry, Manufacturing and Control (CMC).

Many aspects of drug development are focused on satisfyingMany aspects of drug development are focused on satisfying
the regulatory requirements of drug licensing authorities. Thesethe regulatory requirements of drug licensing authorities. These
generally constitute a number of tests designed to determine thegenerally constitute a number of tests designed to determine the
major toxicities of a novel compound prior to first use in man. Itmajor toxicities of a novel compound prior to first use in man. It
is a legal requirement that an assessment of major organ toxicityis a legal requirement that an assessment of major organ toxicity
be performed (effects on the heart and lungs, brain, kidney, liverbe performed (effects on the heart and lungs, brain, kidney, liver
and digestive system), as well as effects on other parts of theand digestive system), as well as effects on other parts of the
body that might be affected by the drug (e.g. the skin if the newbody that might be affected by the drug (e.g. the skin if the new
drug is to be delivered through the skin). While, increasingly,drug is to be delivered through the skin). While, increasingly,
these tests can be made usingthese tests can be made using in vitroin vitro methods (e.g. with isolatedmethods (e.g. with isolated
cells), many tests can only be made by using experimentalcells), many tests can only be made by using experimental
animals, since it is only in an intact organism that the complexanimals, since it is only in an intact organism that the complex
interplay of metabolism and drug exposure on toxicity can beinterplay of metabolism and drug exposure on toxicity can be
examined.examined.

Clinical phaseClinical phase
Clinical trials involves three or four steps:Clinical trials involves three or four steps:
Phase I trials, usually in healthy volunteers, determine safetyPhase I trials, usually in healthy volunteers, determine safety
and dosing.and dosing.
Phase II trials are used to get an initial reading of efficacy andPhase II trials are used to get an initial reading of efficacy and
further explore safety in small numbers of sick patients.further explore safety in small numbers of sick patients.
Phase III trials are large, pivotal trials to determine safety andPhase III trials are large, pivotal trials to determine safety and
efficacy in sufficiently large numbers of patients.efficacy in sufficiently large numbers of patients.
Phase IV trials are post-approval trials that are sometimes aPhase IV trials are post-approval trials that are sometimes a
condition attached by the FDA, also called post-marketcondition attached by the FDA, also called post-market
surveillance studies.surveillance studies.

The process of drug development doesn't stopThe process of drug development doesn't stop
once an NCE begins human clinical trials. Inonce an NCE begins human clinical trials. In
addition to the tests required to move a noveladdition to the tests required to move a novel
drug into the clinic for the first time it is alsodrug into the clinic for the first time it is also
important to ensure that long-term or chronicimportant to ensure that long-term or chronic
toxicities are determined, as well as effects ontoxicities are determined, as well as effects on
systems not previously monitored (fertility,systems not previously monitored (fertility,
reproduction, immune system, etc.). Thereproduction, immune system, etc.). The
compound will also be tested for its capability tocompound will also be tested for its capability to
cause cancer (carcinogenicity testing).cause cancer (carcinogenicity testing).

If a compound emerges from these tests withIf a compound emerges from these tests with
an acceptable toxicity and safety profile, and itan acceptable toxicity and safety profile, and it
can further be demonstrated to have the desiredcan further be demonstrated to have the desired
effect in clinical trials, then it can be submittedeffect in clinical trials, then it can be submitted
for marketing approval in the various countriesfor marketing approval in the various countries
where it will be sold. In the US, this process iswhere it will be sold. In the US, this process is
called a New Drug Application or NDA. Mostcalled a New Drug Application or NDA. Most
NCEs, however, fail during drug development,NCEs, however, fail during drug development,
either because they have some unacceptableeither because they have some unacceptable
toxicity, or because they simply do not work intoxicity, or because they simply do not work in
clinical trials.clinical trials.

Drug Discovery :Drug Discovery :
History :History :
Medicines were obtained from botanical or zoological originsMedicines were obtained from botanical or zoological origins
up to 1950s when synthetic organic chemicals increased toup to 1950s when synthetic organic chemicals increased to
reach the discovery of DNA-recombinant technology .reach the discovery of DNA-recombinant technology .
Antimicrobial chemotherapy revolutionized the chances forAntimicrobial chemotherapy revolutionized the chances for
patients surviving severe infections .patients surviving severe infections .
A major advance was the safe use of naturally derived agentsA major advance was the safe use of naturally derived agents
by isolation , purification and characterization of the activeby isolation , purification and characterization of the active
component leading to :component leading to :
 A controlled amount of the active agent .A controlled amount of the active agent .
 Only the active component can be given (no cocktails ) .Only the active component can be given (no cocktails ) .
 A defined mode of action of each drug was known .A defined mode of action of each drug was known .

Drug Nomenclature :Drug Nomenclature :
The use of recommended InternationalThe use of recommended International
Non-proprietary Name ( rINN) forNon-proprietary Name ( rINN) for
medicinal substances was directive .medicinal substances was directive .
rINN was identical in most cases to therINN was identical in most cases to the
British Approved Name (BAN) .British Approved Name (BAN) .
If they are not identical , one should useIf they are not identical , one should use
the rINN .the rINN .

Drug Approval :Drug Approval :
-All drugs and formulations licensed for-All drugs and formulations licensed for
sale must pass three principal aspects :-sale must pass three principal aspects :-
** SafetySafety ::
A drug is put under regulatory systemsA drug is put under regulatory systems
as to protect patients from toxicities andas to protect patients from toxicities and
ensure benefits.ensure benefits.

** Quality :Quality :
Drugs have to comply with definedDrugs have to comply with defined
criteria for purity i.e. no potentially toxiccriteria for purity i.e. no potentially toxic
impurities .impurities .
Drugs have to be stable and sterile .Drugs have to be stable and sterile .
Drugs must contain a defined amount ofDrugs must contain a defined amount of
the active ingredient that is released at athe active ingredient that is released at a
specific rate .specific rate .

** Efficacy :Efficacy :

- All medicines must be tried for efficacy for their - All medicines must be tried for efficacy for their
licensed indications .licensed indications .
- Efficacy and safety are established through:-- Efficacy and safety are established through:-
                1-Preclinical studies for basic pharmacology 1-Preclinical studies for basic pharmacology
using animals and in vitro testing .using animals and in vitro testing .
                2-Phase І clinical studies for human 2-Phase І clinical studies for human
pharmacology and safety profile .pharmacology and safety profile .

 3- Phase studies for the dose responseǁ3- Phase studies for the dose responseǁ
and dosage protocol and extensiveand dosage protocol and extensive
safety data .safety data .

 4- Phase for efficacy and safetyǀǁ4- Phase for efficacy and safetyǀǁ
profile in patients with indications .profile in patients with indications .

 5- Pharmacovigillance to monitor5- Pharmacovigillance to monitor
adverse events after approval andadverse events after approval and
spread of the disease .spread of the disease .

Measuement of toxicity :Measuement of toxicity :
Lethal doses :Lethal doses :
LDLD5050 is the dose of the drug that can kill 50% of a group of is the dose of the drug that can kill 50% of a group of
the undertest – animals . It varies at a range of 0 – 100 % the undertest – animals . It varies at a range of 0 – 100 %
lethality . Mortality rate per a fixed time is then determined lethality . Mortality rate per a fixed time is then determined
and can fraction a mortality / dose curve .and can fraction a mortality / dose curve .
This is unsatisfactory because :This is unsatisfactory because :
It varies widely with species and hence can not always be It varies widely with species and hence can not always be
applied in man .applied in man .
It does not report about sublethal doses .It does not report about sublethal doses .
It does not report about long-term toxicities .It does not report about long-term toxicities .
It does not report about idiosyncratic reactions .It does not report about idiosyncratic reactions .

Therapeutic Index :Therapeutic Index :
  T I = Max. non-toxic dose / Min. effective dose . =T I = Max. non-toxic dose / Min. effective dose . =
LDLD5050 / ED/ ED50 .50 .
It is defined as the margin of safety in the use of a drug It is defined as the margin of safety in the use of a drug
with special review to relationship between the with special review to relationship between the
effective and toxic doses .Its limitations in clinical use effective and toxic doses .Its limitations in clinical use
are :are :

 LDLD50 50  is based only on mortality . is based only on mortality .
 EDED50 50 is often  undefined .is often  undefined .
 Idiosyncratic reacstions are not considered .Idiosyncratic reacstions are not considered .

Introduction to pharmacology

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Introduction to pharmacology