General pharmacology

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Zaporizhzhia State Medical University
Pharmacology Department
Lecture №1
General Pharmacology
Lecturer: Assoc. Prof. Irene Borisovna Samura

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«All is a poison, all is a medicine;
either depends on the dose»
Paracelsus
(1493-1541)
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4. PHARMACOKINETICS PROCESSES:

► Absorption
►Distribution
►Binding /Localization /Storage
►Biotransformation
►Elimination
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For most majority of drugs
BIOAVAILABILITY is equal to
40-70% - Average level
If Bioavailability
< 40% - Low level
< 70% - High level
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13. VOLUME of DESTRIBUTION (Vd) – a hypothetical volume of fluid into which the drug is disseminated

Water compartments in the body:
1). EXTRACELLULAR Volume - 14 L
a). PLASMA Volume - 4 L
b). INTERSTITIAL Volume - 10 L
2). INTRACELLULAR Volume - 28 L
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Volume of destruburion (Vd) –
is a hypothetical volume of fluid into which
the drug is dissemineted
Water compartments in the body:
1. Extracellular Volume - 14
● plasma Volume - 4
L
L
●interstitial Volume - 10
2. Intracellular Volume - 28
L
L
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Vd is the ratio of
the total amount of drug in the body to
the concentration of drug in plasma:
Vd = D/C or C = D/Vd
D – total amount of drug in the body
C – plasma concentration of drug
Vd = 100 mg / 25 mg/L = 4 L
Vd = 100 mg / 7 mg/L = 14 L
Vd = 100 mg/0.25 mg/L = 400 L
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Phase I – Metabilic Biotransformation
Lipophilic molecules => Polar Molecules by
introducing or unmasking a polar functional group,
such as –OH or –NH2
a) Utilizing the Cytochrome P-450
b) Not involving the Cytochrome P-450
►Oxidation
►Reduction
► Hydrolysis

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Phase II – Conjugation Reactions with
an Endogenous substrate:
● Glucuronic acid
● Sulfuric acid
● Acetic acid
● Amino acid
=> Polar Water-Soluble compounds that are
most often therapeutically inactive
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Enzyme Induction - the ability of some drugs
to induce CYP-450 by:
the rate of its synthesis or
its rate of degradation:
Phenobarbital
Isoniazid
Glucocorticoides
Anticonvulsants
Macrolid antibiotics
Chronic ethanol administration
Steroids
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Enzyme Inhibition - the ability of drugs
to inhibit CYP-450 by:
the rate of its synthesis or
its rate of degradation.
Cimetidine and Ketoconazol bind to
the heme iron of CYP-450 and
Metabolism of Endogenous Substrates and
other coadministered drugs.
Ethinylestradiol
Spironolacton
Allobarbital
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Clearance of a Drug
Cl = Rate of Elimination / C
10 µg / mL
———
DRUG IN
ORGANS OF
DRUG
ELIMINATION
(kidney, liver etc)
500 µg
per min
< 10 µg / mL
———
PLASMA
500 µg / min
CL = ————— = 50 mL/ min
10 µg /ml
First-order (exponential ) kinetics
Rate of Elimination = Cl x C
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Steady State Plasma Concentration (Css)
Dose
Css = ———— or Dose = Css x Cl
Cl
!! Doubling the Dose rate would Double the Css
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For drugs with Michaelis-Menten kinetics, elimination
changes from 1st Order to Zero Order kinetics
over the therapeutic range
Vmax x C
Rate of Elimination = ——————
KM + C
Vmax - the maximum rate of drug elimination
Km - the drug concentration at which
the rate of elimination is 50% of Vmax
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For drugs with 1st order kinetics:
Vmax x C
Rate of Elimination = —————
KM + C
For drugs with Zero Order kinetics over
the therapeutic range:
Vmax x C
Rate of Elimination = ————
C
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= Vmax

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50 % of the drug is lost after one T1/2
75% - after 2 T1/2
> 90% - after 4 T1/2
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Placebo is an inert substance which
is given in the garb of a medicine.
Placebo causes some effects up to 20-40% of cases.
It can be:
1) Positive - 84%
2) Negative 5-7%
3) Mix placebo effect - 9-12%
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Thank You for Attention!
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