Learn about General Pharmacology and the terms used in it.

1. 11
GENERALGENERAL
PHARMACOLOGYPHARMACOLOGY

2. 22
««All is a poison, all is a medicine;All is a poison, all is a medicine;
either depends on the doseeither depends on the dose»»
ParacelsusParacelsus
(1493-1541(1493-1541))

3. 3

4. 44
PHARMACOKINETICSPHARMACOKINETICS
PROCESSESPROCESSES::
►► AbsorptionAbsorption
►►DistributionDistribution
►►Binding /Localization /StorageBinding /Localization /Storage
►►BiotransformationBiotransformation
►►EliminationElimination

5. 55

6. 66

7. 77
For most majority of drugsFor most majority of drugs
BBIOAVAILABILITYIOAVAILABILITY is equalis equal toto
40-70%40-70% -- Average levelAverage level
IfIf BioavailabilityBioavailability
< 40%< 40% - Low level- Low level
< 70%< 70% - High level- High level

8. 8

9. 9

10. 10

11. 11

12. 12

13. 1313
VOLUME of DESTRIBUTIONVOLUME of DESTRIBUTION ((VVdd )) ––
a hypothetical volume of fluid into whicha hypothetical volume of fluid into which
the drug is disseminatedthe drug is disseminated
Water compartmentsWater compartments in the bodyin the body::
1).1). EXTRACELLULAR VolumeEXTRACELLULAR Volume -- 14 L14 L
a).a). PLASMA VolumePLASMA Volume -- 4 L4 L
b).b). INTERSTITIAL VolumeINTERSTITIAL Volume -- 10 L10 L
22)).. INTRACELLULAR VolumeINTRACELLULAR Volume -- 28 L28 L

14. 1414
VOLUME of DESTRIBUTIONVOLUME of DESTRIBUTION ((VVdd )) ––
a hypothetical volume of fluid into whicha hypothetical volume of fluid into which
the drug is disseminatedthe drug is disseminated
Water compartmentsWater compartments in the bodyin the body::
1).1). EXTRACELLULAR VolumeEXTRACELLULAR Volume -- 14 L14 L
a).a). PLASMA VolumePLASMA Volume -- 4 L4 L
b).b). INTERSTITIAL VolumeINTERSTITIAL Volume -- 10 L10 L
22)).. INTRACELLULAR VolumeINTRACELLULAR Volume -- 28 L28 L

15. 1515

16. 1616
VVdd is the ratio ofis the ratio of thethe total amounttotal amount of drugof drug inin
the body tothe body to the concentrationthe concentration of drug in plasma:of drug in plasma:
VVdd = D/C= D/C oror C = D/VC = D/Vdd
DD – t– total amount of drug in the bodyotal amount of drug in the body
CC – plasma concentration of drug– plasma concentration of drug
VVdd = 100= 100 mgmg//2525 mg/Lmg/L == 4 L4 L
VVdd = 100= 100 mgmg// 77 mg/Lmg/L == 14 L14 L
VVdd = 100= 100 mgmg//0.250.25 mg/Lmg/L == 400 L400 L

17. 17

18. 1818
PPhase Ihase I ––
LLipophilic moleculesipophilic molecules =>=> Polar MoleculesPolar Molecules
by introducing or unmasking a polarby introducing or unmasking a polar
functional group, such asfunctional group, such as –OH or –NH–OH or –NH22
a)a) UUtilizing thetilizing the Cytochrome P-450Cytochrome P-450
b)b) Not involving theNot involving the CYP-450CYP-450 systemsystem
►►OXIDATIONOXIDATION
►►REDUCTIONREDUCTION
►► HYDROLYSISHYDROLYSIS

19. 1919
Phase IIPhase II –– CONJUGATION REACTIONSCONJUGATION REACTIONS withwith
anan Endogenous substrateEndogenous substrate ::
 Glucuronic acidGlucuronic acid
 Sulfuric acidSulfuric acid
 Acetic acidAcetic acid
 Amino acidAmino acid
=>=> PPolarolar Water-SolubleWater-Soluble compoundscompounds thatthat
are most often therapeutically inactiveare most often therapeutically inactive

20. 2020
ENZYME INDUCTIONENZYME INDUCTION -- the ability of some drugsthe ability of some drugs
to induceto induce CYP-450CYP-450 by:by:
 the rate of its synthesis orthe rate of its synthesis or
 its rate of degradationits rate of degradation::
PhenobarbitalPhenobarbital
IsoniazidIsoniazid
GlucocorticoidesGlucocorticoides
AnticonvulsantsAnticonvulsants
Macrolid antibioticsMacrolid antibiotics
Chronic ethanol administrationChronic ethanol administration
SteroidsSteroids

21. 2121
ENZYME INHIBITIONENZYME INHIBITION -- the ability of drugsthe ability of drugs
to inhibitto inhibit CYP-450CYP-450 by:by:
 the rate of its synthesis orthe rate of its synthesis or
 its rate of degradation.its rate of degradation.
CimetidineCimetidine andand KetoconazolKetoconazol bind to thebind to the hemeheme
ironiron ofof CYP-450CYP-450 andand
MMETABOLISMETABOLISM ofof Endogenous SubstratesEndogenous Substrates andand
other coadministered drugs.other coadministered drugs.
EthinylestradiolEthinylestradiol
SpironolactonSpironolacton
AllobarbitalAllobarbital

22. 22

23. 23
CLEARANCE OF A DRUG
Cl = Rate of elimination / C
500 µg
per min
10 µg / mL
———►
DRUG IN
< 10 µg / mL
———►
PLASMA
ORGANS OF
DRUG
ELIMINATION
(kidney, liver etc)
500 µg / min
CL = ————— = 50 mL/ min
10 µg /ml
FIRST-ORDER (EXPONENTIAL ) KINETICS
Rate of elimination = Cl x C

24. 24
STEADY STATE plasma concentration (Css)
Dose
Css = ———— or Dose = Css x Cl
Cl
Doubling the Dose rate would double the Css

25. 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
25

26. 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 = ———— = Vmax
C
26

27. 27

28. 28

29. 29

30. 3030
50 %50 % of the drug is lost after one Tof the drug is lost after one T1/21/2
75%75% -- after 2 Tafter 2 T1/21/2
> 90%> 90% -- after 4 Tafter 4 T1/21/2

31. 3131

32. 3232

33. 3333

34. 3434

35. 3535

36. 3636

37. 3737

38. 3838

39. 3939

40. 4040

41. 4141
PlaceboPlacebo is an inert substance whichis an inert substance which
is given in the garb of a medicine.is given in the garb of a medicine.
PlaceboPlacebo causes some effects up tocauses some effects up to 20-40%20-40% ofof
cases. It can becases. It can be::
1)1) Positive placebo effectPositive placebo effect - 84%- 84%
2)2) Negative placebo effectNegative placebo effect 5-7%5-7%
3)3) Mix placebo effectMix placebo effect --
9-12%9-12%