Concept of pharmacokinetic and pharmacodynamic in nursing.

1. NRS431 - Pharmacology In
Nursing

3. • The study of the absorption,
distribution, metabolism and
excretion of the drugs.
i.e The movement of the drugs
into,within and out of the
body.

4. • Once drug is administered, it is
absorbed, i.e enters the blood, it is
distributed to different parts of the
body, reaches the site of action, is
metabolized and excreted.
• All these processes involve passage
of the drug molecules across
various barriers - like the intestinal
epithelium,cell membrane,renal
filtering membrane,capillary barrier.

5. • Drugs may be transported across
the membrane by passive or
active transport.
• Passive transport ; the drug
moves across a membrane
without any need for energy.

6. • It is the transfer of drugs against a
concentration of drugs against a
concentration gradient and needs
energy.
• Only drugs related to natural
metabolites are transported by this
process.
• e.g Levodopa, iron, aminoacids,
penicillin and probenecid are given
together,the excretion of penicillin is
delayed by probenecid.

7. • Defined as the passage of the drug
from the site of administration into
the circulation. In order for a drug
to reach its site of action,it must
pass through various membranes
depending on the route of
administration.

8. • Absorption occurs by one of the
processes i.e .passive diffusion or
active transport.Thus except for
IV route, absorption is important
for all other route of
administration .

9. • Several factors influence the rate
and extent of absorption of a drug.
They are :-
• 1. Disintegration and dissolution
time : The drug taken orally should
break-up into individual particles
to be absorped.then it has to
dissolve in the GI fluids.In case of
drugs given SC or IM ,the drug
molecules have to dissolve in the
tissue fluids,liquids are absorped
faster than solids.

10. • Delay in disintegration and
dissolution result in delayed
absorption.
• 2. Formulation : Inert substance
used with drugs as diluents like
starch and lactose may sometimes
interfere with absorption.

11. • 3. Particle size: small particle size is
important for better absorption of
drugs.Drugs like corticosteroids,
griseofulvin,digoxin ,asprin and
tolbutamide are well absorped
when given as small particles.
• 4. Lipid solubility: lipid soluble
drugs are absorbed faster and
better by dissolving in the
phospholipids of the cell
membrane.

12. • 5. pH and ionization : Ionized
drugs are poorly absorbed while
unionized drugs are lipid soluble
and are well absorbed.
• Acidic drugs remain unionized in
acidic medium of the stomach and
are rapidly absorbed,e.g
aspirin,barbiturates.
• Basic drugs are unionized when
they are reach the alkaline medium
of intestine from where they are
rapidly absorbed,e.g pethidine,
ephedrine.

13. • strong acid and bases are highly
ionized and therefore poorly
absorbed ,e.g heparin, streptomycin.
• 6. Area and vascularity of the
absorbing surface : larger area of
the absorbing surface and more the
vascularity – better is the
absorption.Thus most of the drug
absorbed from the small intestine.

14. • 7. Gastrointestinal motility:
Gastric emptying time-if gastric
emptying is faster ,the passage of
the drug to the intestines is quicker
and hence absorption is faster.
• Intestinal motility – when motility is
highly increased as in diarrhea,drug
absorption is reduced.

15. • 8. Presence of food : Drugs may form
complexes with food,
• such complexes are poorly
absorbed.e.g. Tetracycline chelate Ca2+
present food ,so absorption reduced.
• 9. Metabolism : Some drugs may be
degraded in stomach, e.g.nitroglycerin,
insulin.
• 10. Diseases : The disease of the
stomach like malabsorption and
achlorhydria result in reduced
absorption of drugs.

16. • First pass metabolism is the metabolism
of the drug during its passage from the
site of absorption to the systemic
circulation.It is also called presystemic
metabolism or first pass effect.
• Drugs given orally may be metabolized
in the gaster wall and in the liver before
reaching the systemic circulation.The
extent of FPM differs from drug to drug
and person to person.

17. • FPM may result in partial to total
inactivation of the drug.When it is
partial , it can be compensated by
giving higher dose of particular
drug,e.g nitroglycerin,salbutamol.

18. • Bioavailability is the fraction of
the drug that reaches the systemic
circulation following administration
of any route. IV -100%
Bioavailability , chlortetracycline
30%, chloroquin 80% , diazepam
100%.
• Bioequivalence : It is the study of
comparison bioavailability of
different formulation of the same
drug.

19. • After a drug reaches the systemic
circulation ,it gets distributed to
various tissues . It should be cross
several barriers before reaching the
site of action.
• Like absorption, distribution also
involves the same process, i.e
filtration,diffusion and specialized
transport.

20. • Various factors determine the rate
and extent of distribution, they are
lipid solubility,ionization,blood
flow and binding to plasma
proteins and cellular protein.
• Unionized and lipid soluble drugs
are widely distributed through out
the body.

21. • Upon reaching the circulation,most
of the drug bind to plasma protein;
acidic drug mainly bind with
albumin and basic drugs to α-acid
glycoprotein.The free or unbound
fraction of the drug is the only form
available for action,metabolism and
excretion,

22. • The protein bound form serves as a
reservoir . PB prolongs the duration
and action of drug.e.g warfarin
99%,morphine 35%,ethosuximide
and lithium 0%.
• One drug may displaces another
binding site and result in
displacement interaction,warfarin
99% PB indomethacin reduces its
binding to 95%.Free warfarin level
increased it produce toxicity.

23. • Tissue binding : some drugs get
bound to certain tissue constituent
because of special affinity for them.
TB delays excretion and thus
prolongs the duration of drug.
• Lipid soluble drug like thiopentone
sodium are bound to adipose
tisssue, bone-tetracycline,retina-
chloroquine,thyroid-iodine.

24. • Blood brain barrier (BBB) :
• The endothelial cells of the brain
capillaries have tight junctions.
Moreover glial cells envelope the
capillaries and together these form
the BBB. Only lipid soluble and
unionized drugs can cross BBB.
• E.g. Penicillin readily penetrates
BBB.

25. • Placental barrier :
• Lipid soluble ,unionized drugs
readily cross the placenta.

26. • Metabolism or biotransformation is the
process of biochemical alteration of the
drug in the body.Body treats most of the
drugs as foreign substance and tries to
inactivate and eliminate them by various
biochemical reactions.
• These processes convert the drugs into
more polar ,water soluble compounds so
that they are easily excreted through the
kidneys.

27. • Some of the drugs are largely
unchanged in urine, e.g frusemide,
and atenolol. Mainly drugs are
metabolized in liver some are
metabolized in kidneys, lungs,
blood and skin.

28. • The chemical reactions of biotrasformation can
take place in two phases,
• 1. Phase I (Non-synthetic reactions) : convert
the drug to more polar metabolite by
oxidation,reduction,or hydrolysis.if the
metabolites are not water soluble it undergoes
phase II reactions.
• 2. Phase II (Synthetic reaction) : in this
reactions water soluble substance present in
the body like glucuronic acid,sulfuric acid or an
aminoacid combine with the drug to form a
highly polar compounds it excreted by the
kidneys.large molecules are excreted through
the bile.

29. • The major organs of excretion are
the kidneys, intestine, biliary
system and the lungs. Drugs of
small amounts are excreted in
saliva, sweat and milk.

30. • Kidney is the most important organ of drug
excretion. Highly lipid soluble drugs are
reabsorbed in the renal tubules ,so their
excretion is slow.
• Unabsorbed portion of the orally
administered drugs are eliminated through
the feces. Large water soluble conjugates are
excreted in the bile.
• The lungs are the main route of elimination
for gases and liquids, e.g. GA , Alcohol.

31. • Plasma half-life is the time taken for the
plasma concentration of a drug to be reduced
to half its value.
• Minimum dose is the smallest dose required
to produce a desired therapeutic effect of the
drug.
• Maximum dose is the largest dose of the drug
that can be safely given to a patient without
producing harmful effect.
• Toxic dose is the dose of the drug which
produce undesirable effects in majority of the
patients
• Lethal dose is the dose of the drug which can
cause death. E.g lethal dose of phenobarbitone
is 6-10gm.

33. • Pharmacodynamics is the study of
actions of the drugs on the body and
their mechanism of action, i.e to know
what drugs do and how they do it.
• Drugs produce their effects by
interacting with the physiological system
of the organisms. By such interaction
drugs can only modify the rate of
function of various systems.
• e.g drugs may ↑es or ↓es the
secretions.But they cannot change the
basic funtion of any physiological
system.

34. • Thus drugs act by :
• 1. Stimulation
• 2.Depression
• 3.Irritation
• 4.Replacement
• 5.Anti-infective or cytotoxic action
• 6.Modification of the immune status

35. • Stimulation is the ↑es in activity
of the specialized cells, e.g
adrenaline stimulates the heart.
• Depression is the ↓es in activity of
the specialized cells, e.g quinidine
depresses the heart.
• Irritation : This can occur on all
types of tissues in the body and
may result in inflammation,
corrosion and necrosis of cells.

36. • Replacement : drugs may be used
for replacement when there is
deficiency of natural substances
like hormones ,metabolites or
nutrients ,e.g insulin in diabetes,
iron in anemia ,vit C in scurvy.
• Anti –infective and cytotoxic
action: drugs may act by
specifically destroying infective
organism,e.g penicillin ,cytotoxic
effect on cancer cells.

37. • Modification of immune status:
• Vaccines and sera act by
improving our immunity while
immunosuppressants act by
depressing immunity,e.g
glucocorticoids.
• *Sera - Plural serums or sera. Blood serum
extracted from an animal that has immunity to
a particular disease. The serum contains
antibodies to one or more specific disease
antigens, and when injected into humans or
other animals, it can transfer immunity to
those diseases.

38. • Sites : drugs may produce their
effects by locally or systematically.
• Local : drugs may act at the site
of application. e.g
antibiotics,antifungal agent.

39. Drugs may act by one or more
complex mechanism of action.
fundamental mechanism of drug
action may be:
• Through receptor
• Through enzymes and pumps
• Through ion channel
• By physical action
• By chemical interaction
• By altering metabolic processes

40. • Through receptor
• Drugs may interact specific receptor in
the body.
• Through enzymes and pumps
• Drugs may act by inhibition of various
enzymes,thus altering the enzyme –
mediated reaction ,e.g . Allopurinal
inhibits the enzyme xanthine oxidase ;
acetazolamide inhibit carbonic
anhydrase.
• Through ion channel
• Drugs may interfere with the movement
of ions across specific channels, e.g . Ca
channel blocker , K channel blocker.

41. • Physical action
• The action of drug could result from its
physical properties. E.g .absorption
–activated charcoal in poisoning.
• Chemical interaction
• Drugs may act by chemical reaction.
– Antacids - Neutralize gastric acids
– Oxidising agents - KMno4 (germicidal)
• Altering metabolic processes
• Drugs like antimicrobial alter the
metabolic pathway in the micro
organism resulting destruction of
microb. e.g sulfonamides interfere with
bacterial folic acid synthesis.

42. • A receptor is a site on the cell
with which an agonist binds to
bring about a change. Receptor
are proteins.They may be present
in the cytoplasm or on the
nucleus.

43. • The receptor has to identify the
compound, and when the compound
binds to the receptor ,it has convey the
message to bring about a response.
• Agonist : Substance that binds to the
receptor and produce a response.
• Antagonist : Substance that binds to
the receptor and prevents the action of
agonist on the receptor.
• Partial agonist : It binds to the receptor
but has low intrinsic activity that is ,
produce partial response.

44. When two or more drugs are given
concurrently ,the effect may be additive,
synergistic or antagonistic.
• Additive effect : The effect of two or more drugs
get added up and the total effect is equal to the
sum of their individual actions. e.g . Ephedrine
with theophylline in bronchial asthma.
• Synergism : When action of one drug is
enhanced or facilitated by another drug the
combination is synergistic.Here the total effect
of the combination is greater than the sum of
their independent effect.It is often called
‘potentiation’ or supra-additive effect.e.g
acetylcholine + physostigmine.

45. One drug opposing or inhibiting the
action of another drug is
antagonism.Based on the mechanism,
antagonism may be :-
• Chemical antagonism ,
• Physiological antagonism ,
• Antagonism at the receptor level
• -Reversible (competitive)
• -Irreversible
• Non- competitive antagonism

46. • Chemical antagonism: Two substances
chemically interact to result in
inactivation of the effect,e.g . Antacid like
aluminium hydroxide neutralize gastric
acids.
• Physiological antagonism : Two drugs
act at different sites to produce
opposing effect. E.g . Insulin and
glucagon have opposite effects on the
blood sugar level.
• Antagonism at the receptor level
– The antagonist inhibits the binding of the
agonist to the receptor .Such antagonism
may be reversible or irreversible.

47. • Reversible competitive antagonism : The
agonist and antagonist compete for the same
receptor . By increasing the concentration of
the agonist,the antagonism can be overcome.It
is thus reversible antagonism.Acetylcholine and
atropine compete at muscarinic receptor .The
antagonism can be overcome by increasing the
concentration of ACh at the receptor.
• Irreversible antagonism : The antagonist
binds so firmly by covalent bonds to the
receptor that it is slowly not dissociate at all. It
block the agonist,and the blockade cannot be
overcome by increasing the dose of agonist
hence it is irreversible antagonism,e.g.
Adrenaline and phenoxybenzamine at α-
adrenergic receptor.

48. • Various factor modifying the drug
action.They are
• 1. Body weight : The
recommended dose is calculated
for medium and built persons.For
the obese and underweight
persons,the dose has to be
calculated individually.

51. • 2. Age : In the new born ,the liver
and kidney are not fully mature to
handle the drugs,e.g barbiturates
which produce sedation in adults
may produce excitation in
children.

53. • 3. Sex : The hormonal effects and
smaller body size may influence drug
response in women.special care is
necessary while prescribing for
pregnant and lactating women during
menstruation.
• 4. Species and race : response to drug
may vary with species and race.e.g.
Rabbits are resistant to atropine need
more dose to produce mydriasis.
• 5. Diet and environment : food
interfere with the absorption of the
drugs. e.g.tetracycline form complexes
with Ca present in the food and are
poorly absorbed.

54. • 6. Route of administration : route of
administration may modify the
pharmacodynamic response.e.g. Mgso4 given
orally it is a purgative,in IV it causes CNS
depression and has anticonvulsion
effects.applied topically it reduce local edema.
• 7. Genetic factor : the enzyme production are
genetically controlled. The responce of the
drugs differ according to the metabolizing
enzymes.
A. Acetylation of drugs : the rate of drug acetylation differs
among individuals people may be fast or slow acetylators.
e.g. INH,sulfonamides and hydralazine.
B.G6PD deficiency : primaquine,sulphones and quinolones
can cause hemolysis in such people.

55. • 8. Dose : it is interesting to know the response
of the drug, the dose is increased the response
also increased till the maximum
reached .incase some drugs further increased
the drug response is lowered.e.g. Myasthenia
gravis ,neostigmine enhance the muscle power
in therapeutic doses if the dose higher it'll
produce muscle paralysis.
• 9. Diseases : presence of certain disease can
influence drug responses,e.g . Malabsorption
–drugs are poorly absorbed ,liver diseases-rate
of metabolism reduced.

56. • 10. Repeated dosing : Can result in
cumulation,tolerance,tachyphylaxis.
Cumulation : Drugs like digoxin which
are slowly eliminated may cumulate
resulting in toxicity.
Tolerance :Tolerance is defined as the
capacity of the body to become less
responsive to a substance.
– Lethal dose of Morphine is 250 mg, but
drug addict can tolerate morphine in gm.

57. Trachy phylaxis : is the rapid development of
tolerance.When some drugs are administered
repeadly at short interval ,tolerance develops
rapidly and is known as tachyphylaxis or acute
tolerance.
• 11. Psychological factor : The doctor
patient relationship as well as the nursing
care influence the response to a large
extent by acting on the patient psychology.
The patients confidence in the doctor may
be adequate enough to relieve a
suffering ,particularly the psychosomatic
disorder.Placebo is the inert dosage form
with no biological activity but only
resembles the actual preparation in
appearance.

58. • 12. Presence of other drugs :
• The concurrent use of two or
more drugs can influence the
response of each other.

59. • Karch, A. (2008). Focus on:
nursing pharmacology. New York,
NY: Lippincott Williams & Wilkins.
• Goodman & Gilman's The
Pharmacological Basis of
Therapeutics,11th Ed., Mcgraw-hill
Medical Publishing Division, New
York, 2006
• en.wikipedia.org