Its all about the pharmacokinetic of drugs..

1. Submitted By:-
Mukesh Jaiswal
APGDCR
Dehradun

2.  Defined as the study of ADME of drugs and their
relationship with its therapeutic and toxic effects.
 The use of pharmacokinetic principles in
optimizing the drug dosage for the patient need
and achieving maximum therapeutic utility is called
Clinical pharmacokinetics.

4. Routes can be broadly classified in to:-
 Local Routes.
 Systemic Routes.

5.  Topical Route.
a. Skin.
b. Mucous Membrane.
√Mouth and Pharynx.
√Eyes, Ear and Nose.
√Bronchi and Lungs.
√Urethra.
√Vagina.
√Anal canal.
 Deeper Tissue.
 Arterial Supply.

6.  Oral Route.
 Sublingual Route.
 Rectal Route.
 Cutaneous.
 Inhalation.
 Nasal.
 Parenteral.
√Subcutaneous.
√Intramuscular.
√Intravenous.
√Intradermal Injection.

7.  Defined as the process of movement of unchanged
drug from the site of administration to systemic
circulation.
 Absorption of drug is directly proportional to drug
concentration at the site of action.
 Drug concentration at the site of action is directly
proportional to therapeutic response.
 Therefore Absorption of drug is directly
proportional to the therapeutic response of drug.

10.  Cmax:- The point of maximum concentration of
drug in plasma is called as peak and the
concentration of drug at peak is known as peak
plasma concentration.
 tmax:- The time for drug to reach peak
concentration in plasma.
 AUC:- It represents the total integrated area under
the plasma level-time profile and expresses the
total amount of drug that comes in to systemic
circulation after administration.AUC is expressed in
mcg/Ml.

11.  The velocity with which a reaction or a process
occurs is called as its Rate.
 The manner in which the concentration of drug
influence the rate of reaction or process is called as
the Order of reaction.
If C is the conc. Of drug A, the rate of decrease in C
of drug A as it is changed to B can be described by a
general expression as a function of time t.
dC= -KCn
dt

12. Where, K= rate constant
n= order of reaction
 If n=0, it’s a zero order kinetics, if n=1 it is a first
order kinetics and so on.
 The three commonly encountered rate processes in
physiologic systems are:-
√Zero order kinetics
√First order kinetics
√Mixed order kinetics

13.  Defined as the one
whose rate is Steady drug loss
independent of the
concentration of drug
undergoing reaction
i.e. the rate of reaction
cannot be increased
further by increasing
the concentration of
reactants. Slope= -k0
 Eg. Administration of
a drug as a constant
rate i.v. infusion.

14.  Defined as whose rate is
directly proportional to
the concentration of the
drug undergoing reaction dC
dt
i.e. greater the
concentration faster the
reaction.
 It is also called as
monoexperimental rate
process.
c

15.  Itis a mixture of both first order and zero
order kinetics.
 It is also known as dose dependent kinetics.

16.  Since oral route of drug administration is most
common for systemically acting drug.
 GIT plays important role in absorption of drug.
 The GI lining constituting the absorption barrier
allows most nutrients like glucose, amino
acids, fatty acids, vitamins etc to pass rapidly
through it in to the systemic circulation but
prevents the entry of certain toxins and
medicaments.

17.  The principal mechanism for transport of drug
molecules across the cell membrane are:-
1. Passive Diffusion.
2. Pore Transport.
3. Facilitated Diffusion.
4. Active Transport.
5. Electrochemical Diffusion.
6. Ion Pair Transport.
7. Endocytosis.

18.  Also called non ionic Diffusion.
 Major Process for absorption of more than 90% of the
drugs.
 Here Drug molecules diffuses from a region of higher
concentration to one of lower concentration until
equilibrium is attained and the rate of diffusion is directly
proportional to the concentration gradient across the
membrane.
 Also known as FICK’S LAW.

19. dQ/dt=DAKm/w /h (CGIT –C)
Where:-
dQdt= rate of drug diffusion.
D= Diffusion Coefficient of the drug through the membrane.
A= Surface area of absorbing membrane.
Km/w= Partition Coefficient of the drug b/w the lipoidal
membrane and aqueous GI fluid.
h= thickness of the membrane.

20.  It is also known as convective transport, bulk flow
of filtration.
 Important in the absorption of low molecular
weight, low molecular size, and water soluble drug
through narrow, aqueous-filled channels or pores
in the membrane structure.
 Examples are urea, water, and sugars.

22.  It is carrier mediated transport system that
operates the concentration gradients.
 Much faster than passive diffusion.
 Examples include entry of glucose into RBCs and
intestinal absorption of vit B1 and B2 .
B1 +IF(intrinsic Factor)= B1-IF Complex (in intestine)
B1-IF Complex= B1 +IF (in Blood)

24.  Here drug is transported from a region of lower to
one of higher concentration i.e. against the
concentration gradient.
 Required energy.
 Can be inhibited by metabolic poisons that
interfere with energy production.
 Examples includes absorption of 5-fluorouracil, 5-
bromouracil, methyldopa, levodopa.

26. Carrier

27.  Also known as ionic diffusion.
 Here the charge on the membrane influences the
permeation of drugs.
 The rate of permeation is in the following order.
Unionized > anions> cations

28.  Here the cationic drugs or anionic drugs penetrates
the membranes by forming reversible neutral
complexes. Such phenomena is called ion pair
transport.
In GI Lumen
Cationic drug + Endogenous anion=neutral ion pair complex
In Blood
Endogenous anion+ Free Drug

30.  It is a minor transport mechanism which involves
engulfing extracellular materials with in a segment
of cell membrane to form a vesicles which then
pinched off intra cellularly.
 Endocytosis includes two types of processes:-
√ Phagocytosis (cell eating)
√ Pinocytosis (cell drinking)

31. Process of Endocytosis

32.  Physicochemical properties of drug substances.
 Dosage form characteristics and pharmaceutical
ingredients.
 Patient related factors.

33.  Drug solubility and dissolution rate.
 Particle Size and effective surface area.
 Polymorphism and amorphism.
 Lipophilicity of the drug.
 Salt form of drug.
 Drug stability.

34.  Disintegration time.
 Dissolution time.
 Manufacturing variables.
 Pharmaceuticals ingredients.
 Nature and type of dosage form.
 Product age and storage condition.

35.  Age.
 Gastric emptying time.
 Gastrointestinal pH.
 Disease state.
 Blood flow through GIT.
 Gastrointestinal contents.
 Pre systemic metabolism.

36.  Defined as the process which involves the reversible
transfer of a drug b/w one compartments and another.
Drug
distributed
Drug metabolized
in the body
Drug in
Plasma
Drug
Excreted

37.  Tissue Permeability of the drug.
 Organ/tissue size and perfusion rate.
 Binding of drug to tissue components.
 Miscellaneous factors.

38.  The tissue permeability of a drug depend upon the
physicochemical properties of drug as well as the
physiological barrier that restrict diffusion in to
tissue.
 Drug having molecular weight less than 500 to
600 Daltons easily cross the barriers and
distributes easily.
 Unionized drugs cross the barriers more easily
than ionized one.

39.  Lipophillic drugs are easily cross the barriers than
hydrophillic drugs.
 Weaker acids distributes more fasters than strong
acids.
 Thiopental distributes in CSF at a rate 80 times
faster than salicylic acid.

40.  Perfusion rate is defined as the volume of blood
that flows per unit time per unit volume of the
tissue.
 Drug distribution also depend upon the size of the
organ/tissue.
 Lists of organs in decreasing perfusion rate.
lungs > kidney > adrenals > liver > heart > brain > muscles >
skin > fat > bone

41.  The phenomena of complex formation with
proteins is called as protein binding of drug.
 Binding of drugs falls in to 2 classes:-
1. Binding of drugs to blood components.
√ Plasma Proteins
√ Blood cells
2. Binding of drugs to extra vascular tissue
protein, fats, bones etc.

42.  The binding of drugs to various plasma proteins is
reversible.
 The order of binding of drugs to various plasma
proteins is:-
albumin > α-1 acid glycoprotein > lipoprotein >
globulins
 For majority of drugs that bind to extra vascular
tissues, in order of binding is:-
liver > kidney > lungs > muscles

43.  Age.
 Pregnancy.
 Obesity.
 Diet.
 Disease State.
 Drug interaction.

44.  Defined as the hypothetical volume of body fluid in to which a
drug is dissolved or distributed.
 Since the concentration of drug in plasma (C) is directly
proportional to amount of drug in body (X),
XαC
or X = Vd C
Where Vd is apparent volume of distribution.
Vd = X/C
Volume of
= Amount of drug in the body
Distribution Plasma Concentration of drug

45.  Defined as the conversion of drug from one
chemical form to another.
 The term metabolism is different from chemical
instability.
 For e.g. conversion of penicillin to penicilloic acid
by the bacterial pencillinase and mammalian
enzymes is metabolism but its degradation by the
stomach acid to penicillenic acid is chemical
instability.

46.  It is also known as detoxification process
 It normally results in p’cologic inactivation of drugs.
 Sometimes yield the metabolites with equal activity. e.g.
Prodrugs .
 The decreasing order of drug metabolizing ability of
various organ is:-
liver > lungs > kidneys > intestine > placenta > adrenals > skin
 Brain, testes, muscles, spleen, etc also metabolize
drugs to a small extent.

47.  These are the enzymes which helps in the
metabolism of drugs.
 Divided in to 2 categories:-
√ Microsomal
√ non-microsomal
 The microsomal enzymes catalyze a majority of
drug biotransformation reactions.
 The no. of lipid soluble substrates can interact
nonspecifically with the microsomal enzymes.

48.  R.T.Williams divided the pathways of drug
metabolism reactions into 2 general categories:-
√ Phase I
√ Phase ll
 Phase l reactions are also known as
Functionalization reactions or Transformation
Reactions and Phase ll reactions also known as
Conjugation reactions.

49.  These reactions generally precedes phase ll
reactions.
 It includes Oxidative, Reductive, and Hydrolytic
reactions.
 In these reactions a polar group is either
introduced or unmasked if already present.
 The resulting product of phase l reaction is
susceptible to phase ll reactions.

50.  Oxidative reactions increases hydrophilicity of xenobiotics by
introducing polar functional groups such as –OH.
 Cytochrome P-450 is the enzyme which transfers an oxygen atom to
a substrates RH and convert it to ROH.
 Reductive reactions are also capable of generating polar functional
groups such as hydroxy and amino in to substrates.
 Hydrolytic reactions makes a large chemical change in the substrates
brought about by loss of relatively large fragments of the molecules.

51.  These reactions are also known as conjugation
reactions.
 These reactions generally involves covalent
attachment of small polar endogenous molecules
such as glucuronic acid, sulfates, glycine etc.
 Attachment are either on the unchanged drugs or
phase I products and form highly water soluble
conjugates.
 Also known as true detoxification reactions.

52.  The enzymes involved in these reactions are called
as transferases.
 The phase ll reactions involved:-
√ conjugation with glucuronic acid.
√ conjugation with sulfate moieties.
√ conjugation with alpha amino acids.
√ conjugation with glutathione.
√ Acetylation reactions.
√ Methylation reactions.

53.  Physicochemical properties of drugs.
 Chemical factors.
√ enhance or inhibits by enzymes.
√ environmental chemicals.
 Biological Factors . Physiologic factors.
√ Species difference. √ pregnancy.
√ Strains difference. √ Hormonal Imbalance.
√ Sex Difference. √ Disease State.
√ Age.
√ Diet.

54.  Defined as the process whereby drug or their
metabolites are irreversibly transferred from
internal to external environment.
 Principal organs of excretion are kidneys is known
as renal excretion.
 Other organs which are involved in excretion of
drugs are lungs, biliary system, intestine, salivary
glands and sweat glands is known as non renal
excretion.

55.  Almost all drugs and their metabolites are excreted by
the kidneys.
 The basis functional unit of kidney involved in excretion
is the naphron.
 Each kidney comprises of one million naphrons.
 Each naphron is made up of :-
√ Glomerulus
√ Proximmal tubule
√ Loop of henle
√ Disttal tubule
√ Collecting tubule

57.  Theprincipal processes that determine the
urinary excretion of a drug are:-
√ Glomerular Filtration
√ Active tubular Secretion
√ Active or Passive Tubular Reabsorption
Rate of = Rate of + Rate of - Rate of
Excretion Filtration secretion Reabsorption

58.  The sum of individual clearances by all eliminating
organs is called as Total body clearance or Total
systemic clearance.
 Clearance is defined as the hypothetical volume of
body fluids containing drug from which the drug is
removed or cleared completely in a specific period
of time.
Clearance(CL) = Elimination rate
Plasma drug concentration

59.  Defined as the volume of blood or plasma which is completely
cleared of the unchanged drug by the kidney per unit time.
ClR = Rate of urinary excretion
Plasma drug concentration
 Renal Clearance is the ratio of “sum of rate of glomerular
filtration and active secretion minus rate of reabsorption” to
“plasma drug concentration”.
ClR = rate of filtration + rate of secretion + rate of reabsorption
plasma drug concentration

60.  Physicochemical properties of the drug.
 Plasma concentration of the drug.
 Distribution and binding characteristics of the drug.
 Urine pH.
 Blood flow to the kidneys.
 Biological factors.
 Drug interactions.
 Disease states.

61.  The dose required in patients with renal failure can
be calculated by:-
Normal Dose x Renal Failure
 The dosing interval in hours can be computed from
the following equation:-
Normal interval (in hours)
RF

62.  When the drug is eliminated by both renal and non
renal mechanisms, the dose to be administered in
patients with renal failure is obtained from:-
Normal dose [RF x Fraction excreted + Fraction eliminated]
in urine nonrenally

63.  It is also known as extra renal routes.
 The various non renal routes are:-
√ Biliary Excretion.
√ Pulmonary Excretion.
√ Salivary Excretion.
√ Mammary Excretion.
√ Skin/Dermal Excretion.
√ Gastrointestinal Excretion.
√ Genital Excretion.