introduction to pharmacology

04/15/2304/15/23 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006

INTRODUCTION TO INTRODUCTION 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 or these actions may be beneficial or harmful – and their fate in the body . This harmful – and their fate in the body . This science provides the basis of therapeutics science provides the basis of therapeutics ..

Pharmacology vs other medical sciencesPharmacology vs other medical sciences



Drugs :Drugs :

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


Pharmacognosy :Pharmacognosy :

It is the science that deals with natural It is the science that deals with natural drugs from plant origin and their drugs 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 and compounding , proper utilization and dispensing of medicinal substances .dispensing of medicinal substances .


Pharmacokinetics :Pharmacokinetics :

It is what the body does to the drug . It is It is what the body does to the drug . It is the study of absorption , distribution , the study of absorption , distribution , biotransformation and excretion of drugs biotransformation and excretion of drugs and their relationship to pharmacological and their relationship to pharmacological response . It is the fate of drugs in the response . It is the fate of drugs in the body .body .


Pharmacodynamics : Pharmacodynamics :

It is what the drug does to the body . It is It is what the drug does to the body . It is the study of biochemical and the study of biochemical and physiological effects of drugs and their physiological effects of drugs and their mechanism of action .mechanism of action .


Therapeutics :Therapeutics :

It is the application of knowledge of It is the application of knowledge of pharmacology in the prevention and pharmacology in the prevention and treatment of diseases .treatment of diseases .


Toxicology :Toxicology :

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


Chemotherapy :Chemotherapy :

It deals with the effects of drugs on It deals with the effects of drugs on microorganisms and parasites , living microorganisms and parasites , living and multiplying in another living and multiplying in another living organism . It also includes the treatment organism . It also includes the treatment of malignancy .of malignancy .


Clinical pharmacology : Clinical pharmacology :

It is the scientific study of drugs in It is the scientific study of drugs in humans . It includes pharmacodynamics humans . It includes pharmacodynamics and pharmacokinetics investigations in and pharmacokinetics investigations in healthy volunteers and in patients ; healthy volunteers and in patients ; evaluations of efficacy and safety of evaluations of efficacy and safety of drugs and comparative trials with other drugs and comparative trials with other forms of treatment ; surveillance of forms of treatment ; surveillance of patterns of drug use , adverse patterns of drug use , adverse effects ..etc .effects ..etc .


Pharmacopoeia :Pharmacopoeia :

This field of study defines the standards This field of study defines the standards that the drugs and medicinal preparations that the drugs and medicinal preparations must meat and their average adult dose must meat and their average adult dose e.g. British Pharmacopeia (B.P.).e.g. British Pharmacopeia (B.P.).


Various sources of Various 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 and Microorganism 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 (DNA Drugs produced by genetic engineering (DNA

recombinant- tehnology )e.g. human insulin and recombinant- 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 diseases prevention or treatment of rare diseases e.g. certain anticancer drugs , antiviral e.g. certain anticancer drugs , antiviral drugs , pentamidine ..etc.drugs , pentamidine ..etc.

Drug developmentDrug development

is the process of bringing a new is the process of bringing a new pharmaceutical drug to the market once a to the market once a lead compound has been identified lead compound has been identified through the process of through the process of drug discovery. It . It includes pre-clinical research includes pre-clinical research (microorganisms/animals) and clinical (microorganisms/animals) and clinical trials (on humans) and may include the trials (on humans) and may include the step of obtaining regulatory approval to step of obtaining regulatory approval to market the drug.market the drug.


Pre-clinicalPre-clinical

New chemical entities (NCEs, also known as new molecular (NCEs, also known as new molecular entities or NMEs) are compounds which emerge from the entities or NMEs) are compounds which emerge from the process of process of drug discovery. These will have promising . These will have promising activity against a particular biological target thought to be activity against a particular biological target thought to be important in disease; however, little will be known about the important in disease; however, little will be known about the safety, safety, toxicity, , pharmacokinetics and and metabolism of this of this NCE in humans. It is the function of drug development to NCE 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 a A further major objective of drug development is to make a recommendation of the dose and schedule to be used the recommendation 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-man" [FIM] or First Human Dose [FHD])." [FIM] or First Human Dose [FHD]).


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


Many aspects of drug development are focused on satisfying Many aspects of drug development are focused on satisfying the regulatory requirements of drug licensing authorities. These the regulatory requirements of drug licensing authorities. These generally constitute a number of tests designed to determine the generally constitute a number of tests designed to determine the major toxicities of a novel compound prior to first use in man. It major toxicities of a novel compound prior to first use in man. It is a legal requirement that an assessment of major organ toxicity is a legal requirement that an assessment of major organ toxicity be performed (effects on the heart and lungs, brain, kidney, liver be performed (effects on the heart and lungs, brain, kidney, liver and digestive system), as well as effects on other parts of the and 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 new body 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 using these tests can be made using in vitroin vitro methods (e.g. with isolated methods (e.g. with isolated cells), many tests can only be made by using experimental cells), many tests can only be made by using experimental animals, since it is only in an intact organism that the complex animals, since it is only in an intact organism that the complex interplay of metabolism and drug exposure on toxicity can be interplay 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 safety Phase I trials, usually in healthy volunteers, determine safety and dosing.and dosing.

Phase II trials are used to get an initial reading of efficacy and Phase 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 and Phase 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 a Phase IV trials are post-approval trials that are sometimes a condition attached by the FDA, also called post-market condition attached by the FDA, also called post-market surveillance studies.surveillance studies.


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


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


Drug Discovery :Drug Discovery :

History :History :

Medicines were obtained from botanical or zoological origins Medicines were obtained from botanical or zoological origins up to 1950s when synthetic organic chemicals increased to up 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 for Antimicrobial chemotherapy revolutionized the chances for patients surviving severe infections .patients surviving severe infections .

A major advance was the safe use of naturally derived agents A major advance was the safe use of naturally derived agents by isolation , purification and characterization of the active by 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 .04/15/2304/15/23 Dr. Medani A.B. ,2006Dr. Medani A.B. ,2006

Drug Nomenclature : Drug Nomenclature :

The use of recommended International The use of recommended International Non-proprietary Name ( rINN) for Non-proprietary Name ( rINN) for medicinal substances was directive .medicinal substances was directive .

rINN was identical in most cases to the rINN was identical in most cases to the British Approved Name (BAN) .British Approved Name (BAN) .

If they are not identical , one should use If 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 systems A drug is put under regulatory systems as to protect patients from toxicities and as to protect patients from toxicities and ensure benefits.ensure benefits.


* * Quality :Quality :

Drugs have to comply with defined Drugs have to comply with defined criteria for purity i.e. no potentially toxic criteria 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 of Drugs must contain a defined amount of the active ingredient that is released at a the 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 ǁ studies for the dose response 3- Phase ǁ studies for the dose response and dosage protocol and extensive and dosage protocol and extensive safety data .safety data .

4- Phase ǀǁfor efficacy and safety 4- Phase ǀǁfor efficacy and safety

profile in patients with indications .profile in patients with indications . 5- Pharmacovigillance to monitor 5- Pharmacovigillance to monitor

adverse events after approval and adverse 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 . = LDLD50 50 / 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

Education

fate of drugs

detailed study of drugs

natural drugs

word drug

science of identification

branch of science

study of absorption

substance useda drug