PHARMACOKINETICS AND DRUG RECEPTORS.

1. PHARMACOKINETICS
AND DRUG RECEPTORS
LECTURE # 5

2. PHARMACOKINETICS
 Pharmacokinetics is defined as quantitative, time dependent changes of both the
plasma drug concentration and the total amount of drug in the body.
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3. BIOAVAILABILITY
 The proportion of a drug or other substance which enters the
circulation when introduced into the body and so is able to have an
active effect.
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BIOAVAILABILITY
Equation 1: F = total amount of drug in the body ÷ plasma drug concentration.
Equation 2: F = mass of the drug delivered to the plasma ÷ total mass of the
drug administered.
Equation 3: F = AUC for X route of administration ÷ AUC for IV administration.

5. Types of bioavailability
 Absolute Bioavailability: When the drug is administered through the intravenous
route, the bioavailability of the drug achieved will be 100 percent.
 Relative Bioavailability: It is the bioavailability of the drug when obtained and it is
compared with a reference standard.
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6. Bioavailability of oral drugs
The fraction of the drug dosage that
finally reaches the therapeutic site of
action.
In many cases, most of the orally
administered drug is metabolized and
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7. Oral bioavailability
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8. Half Life (t 1/2)
 Plasma Half Life is the time taken for the drug concentration to fall to half
its original value
 t1/2 = 0.693 Vd/ CL total
 Half life is directly proportional to volume of distribution and
Inversely proportional to total body clearance
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9. FACTORS EFFECTING HALF LIFE
 COMPROMISED KIDNEY
 REDUCE METABOLISM IN HEPATIC INSUFFICIENCY
 ADDITION OF SECOND DRUG THAT DISPLACES FIRST
FROM ALBUMIN
 DIMINISHED RENAL PLASMA FLOW CARDIAC SHOCK,
HEART FAILURE OR HEMORRHAGE
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10. 1. KINETICS OF IV INFUSION
 STEADY STATE CONCENTRATION
1. Plasma concentration rises until the rate of drug elimination balance the input
rate
2. In steady state plasma drug concentration remains constant.
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11. Steady State
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13. Influence of infusion rate on steady state
plasma concentration
STEADY STATE PLASMA CONCENTRATION (Css)
1. DIRECTLY PROPORTIONAL TO RATE OF INFUSION (Ro).
2. INVERSELY PROPORTIONAL TO CLEARANCE OF DRUG (CLt)
Css = Ro/CLt
Factors decreasing clearance increase steady state plasma concentration like liver
or kidney diseases.
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15. Loading Dose
 a loading dose is an initial higher dose of a drug that may be given at
the beginning of a course of treatment
 To achieve quickly desired blood plasma levels of steady state followed
by maintenance dose.
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16. Bolus Dose
 A single dose of a drug or other substance given
over a short period of time.
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17. Advantage Of Loading Doses in IV
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18. 2. Kinetics Of Fixed Doses, Fixed Time
Intervals
 MORE CONVENIENT
 TIME DEPENDANT FLUCTUATIONS IN CIRCULATING LEVELS OF DRUGS
1. Single IV Injections
2. Multiple IV injections
3. Oral Medicines
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19. Single IV Injection
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20. Iv infusion
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21. Multiple IV Dosing
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24. Drug Receptors
 Many drugs interact with specific cellular proteins known
as receptors.
 As a result of this interaction, activation or inhibition of a
sequence of biochemical events is usually initiated.
 Receptors may be located on the cell membrane, in
the cytosol or in the nucleus.
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25. Type according to location
1. intracellular receptors, which are found inside of the cell (in the cytoplasm
or nucleus), and
2. cell surface receptors, which are found in the plasma membrane.
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26. Drug receptors lock and key model
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28. Agonist vs Antagonists Drugs
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29. Reversible antagonist
Definition: An antagonist that binds to the receptor in a reversible
manner.
The interaction between the antagonist and the receptor is not covalent and
therefore the antagonism is surmountable at a certain concentration of the
agonist.
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30. Irreversible Antagonists
An irreversible antagonist is a type of antagonist that binds permanently to a
receptor, by
1. forming a covalent bond to the active site
2. binding so tightly that the rate of dissociation is effectively zero
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31. Partial Agonist
A partial agonist is an agonist which is unable to induce
maximal activation of a receptor population, regardless of
the amount of drug applied.
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32. Therapeutic Index
 RATIO OF DOSE PRODUCING TOXICITY TO THE DOSE PRODUCING
CLINICALLY DESIRED OR EFFECTIVE RESPONSE.
 THERAPEUTIC INDEX = TOXIC DOSE/ EFFECTIVE DOSE
 MEASURES DRUG SAFETY
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Therapeutic Index

34. DRUG ELIMINATION
1. RENAL ELIMINATION
2. HEPATIC ELIMINATION
3. PULMONARY
4. OTHERS
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35. ELIMINATION OF DRUG
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37. RENAL CLEARANCE
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38. TOTAL BODY CLEARANCE
 TOTAL BODY CLEARANCE = CL total
1. CL hepatic + CL renal + CL pulmonary + CL others
2. CL total = Ro / Css (Rate of infusion divide by steady state
concentration)
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39. EFFICACY VS POTENCY OF DRUG
 Potency denotes the amount of drug needed to produce a given effect.
 Efficacy: Refers to the relative ability of a drug-receptor complex to produce
a maximum functional response.
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40. Potency vs Efficacy
 Potency is less significant than efficacy. While efficacy is more
significant than drug potency.
 Certainly, a drug with greater efficacy than greater potency is more
therapeutically beneficial. Efficacy may be beneficial in the determination
of clinical effectiveness of a drug.
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THANK YOU!