introduction in clinical pharmacology. Main principles of clinical pharmacology pharmacokinetics and pharmacodynamics.

1. Department Of Clinical Pharmacology
Group : 4th
course : 5th
Name : Abdelrahman Talaat Ezzat
Topic : introduction in clinical pharmacology. Main
principles of clinical pharmacology: pharmacokinetics
and pharmacodynamics.

2. Introduction to clinical
pharmacology
 Clinical pharmacology - the science that studies the
characteristics, effects, properties, reactions and uses of
drugs—especially their therapeutic effect in humans—
including toxicology, safety, pharmacodynamics and
pharmacokinetics.
 Tasks of clinical pharmacology • The study of clinical
pharmacokinetics • The study of clinical pharmacodynamics
• The study of drug interactions • The study of adverse and
toxic effects of drugs • Monitoring of efficacy and safety of
drug treatment • Formulating of good recommendations to
drug therapy for rational drug use.

3.  General principles of drug therapy • Safety – providing the
benefit exceeding than risk • Rationality – optimal ratio of
benefit/risk • Minimizing – use of minimal numbers of drugs
and minimally effective duration of drug therapy, excluding
of polypharmacy • Monitoring of efficacy and safety of drug
therapy • Individualizing – accounting of pharmacologic
properties of drugs depending on patients individual
peculiarities and clinical characteristics of disease.
 Rational use of drugs The rational use of drugs requires that:
–patients receive medications appropriate to their clinical
needs, –in doses that meet their own individual requirements
–for an adequate period of time, and –at the lowest cost to
them and their community.

4.  Rational use of drugs should ensure:
• correct drug
• appropriate indication
• appropriate drug considering efficacy, safety, suitability for
the patient, and cost
• appropriate dosage, administration, duration
• no contraindications
• correct dispensing, including appropriate information for
patients
• patient adherence to treatment.
 IMPACT OF IRRATIONAL PRESCRIBING • Delay in cure •
More adverse effects • Prolonged hospitalization • Emergence
of antimicrobial resistance • Loss of patient’s confidence in
the doctor • Loss to the patient/community • Lowering of
health standards.

5.  Prescription: Types of Irrational Drug Use • Under-
prescribing • Incorrect prescribing • Extravagant prescribing •
Over-prescribing • Multiple prescribing.
 HOW TO CHOOSE A DRUG ? • Ask the following sequence
of questions before writing the prescription • Is the drug
therapy Indicated ?!! • Which drug? • Which class---which
group----which particular drug • Which route? • Which
formulation? • What dosage regimen?
 Good prescribing (rational drug use) is to give: • Right drug
in the right dose • In the right formulation • At the right
frequency • For the right duration .

6. Pharmacokinetics
 Pharmacokinetics is the study of Movement of drugs in
the body and it describes the drug absorption,
distribution within body, and drug elimination over time.
It involves Four Processes
1. Absorption
2. Drug distribution
3. Metabolism
4. Drug elimination

7.  1.Absorption It is the process of entry of drug from site of
administration into systemic circulation. The bioavailability
of the drug depends on the extent of the absorption.
Bioavailability is the percentage of drug that reaches the
systemic circulation in an unchanged form and becomes
available for biological effect following administration by any
route.
Bioequivalence occurs when two formulations of the same
compound have the same bioavailability and the same rate of
absorption.

8.  Distribution of Drugs: Distribution is the movement of
drug from the central compartment (blood) to peripheral
compartments.
Here the concentration gradient is being the driving force for
the movement from plasma to tissues. It depends on,
Ionization, Molecular size, Binding to plasma proteins,
Differences in regional blood flow Presence of tissue-specific
transporters.

9. Metabolism (Biotransformation )
 Biotransformation means chemical alteration of the drug in
the body.
 It is needed to render nonpolar (lipid-soluble) compounds
polar (lipid insoluble) so that they are not reabsorbed in the
renal tubules and are excreted.
 The primary site for drug metabolism is liver; others are-
kidney, intestine, lungs and plasma. Phases of
biotransformation: Phase I (Non-synthetic) reactions - A
functional group is generated or exposed-metabolite may be
active or inactive. Phase II (Synthetic) reactions – Mostly a
conjugation reaction - Metabolite is mostly inactive (except
few drugs).

10.  Elimination Or Excretion Elimination-Termination of
Drug Action by which a drug or metabolite is eliminated
from the body. Drugs and their metabolites are excreted in
Urine, Faeces, Exhaled air, Saliva and sweat.
 Two-stage kidney process (filter, absorption) Metabolites
that are poorly reabsorbed by kidney are excreted in urine.
Some drugs have active (lipid soluble) metabolites that are
reabsorbed into circulation (e.g., pro-drugs) Other routes of
elimination: lungs, bile, skin

11. Terminologies In Pharmacokinetics
1. Elimination Half-Life - time required for drug blood levels
to be reduced by 50% Dose
2. Plasma Concentration
3. Clearance = Volume of blood cleared of drug per unit time
Volume of Distribution = (theoretical volume that would
have to be available for drug to disperse).

12. Pharmacodynamics
 Pharmacodynamics refers to the relationship between drug
concentration at the site of action and the resulting effect,
including the time course and intensity of therapeutic and
adverse effects.
 The effect of a drug present at the site of action is determined
by that drug’s binding with a receptor.
 The concentration at the site of the receptor determines the
intensity of a drug’s effect.
 Drug Action Four major types of bio- macromolecular targets
of drug action is there, (A) Enzyme (B) Transmembrane ion
channel (C) Membrane bound transporter (D) Receptor

13. Factors Affect Drug Response
 Density of receptors on the cell surface
 the mechanism by which a signal is transmitted into the cell
by second messengers.
 Regulatory factors that control gene translation and protein
production may influence drug effect

14. Dose-response Curves
 Individual responses to varying doses
 Threshold: Dose that produces a
 just-noticeable effect.
 ED50: Dose that produces a 50% of
 maximum response.
 Ceiling: Lowest dose that produces
 a maximal effect.

15. Maximum Effect(Emax) & EC50
 When the logarithm of concentration is plotted versus effect,
one can see that there is a concentration below which no
effect is observed and a concentration above which no greater
effect is achieved.
 50% effective concentration Or EC50 the concentration at
which 50% of the maximum effect is achieved.
 The EC50 does not, however, indicate other important
determinants of drug response, such as the duration of effect.

16. Duration of effect
 Duration of effect is determined by a complex set of
factors, including
 The time that a drug is engaged on the receptor
 Intracellular signaling
 Gene regulation.
 Time Course Studies important for Predicting
dosages/dosing intervals
 Maintaining therapeutic levels
 Determining time to elimination

17. Tolerance
 The effectiveness can decrease with continued use is
referred to as tolerance.
Tolerance may be caused by
 The pharmacokinetic factors, such as increased drug
metabolism, that decrease the concentrations achieved
with a given dose.
 The pharmacodynamic factors like when the same
concentration at the receptor site results in a reduced effect
with repeated exposure.

18. Thank you