Introduction to the Clinical

Pharmacology

Dr. Haroon Habib

Associate Professor Alatoo International University
 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
 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
 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
 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 .
 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
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
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.
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.
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).
 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
Terminologies In Pharmacokinetics
• 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).
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
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
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.
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.
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
Tolerance and 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.