This document discusses pharmacodynamics and pharmacokinetics. Pharmacodynamics is the mechanism of drug action and the relationship between drug concentration and the body's response. Most drugs act by binding to receptors on cells. Pharmacokinetics involves the absorption, distribution, metabolism and excretion of drugs in the body. Drugs can be administered through various routes including oral, intravenous, intramuscular and others. Factors like age, liver and kidney function impact how drugs are processed in the body.

1. Pharmacodynamics
& Pharmacokinetics
Mr. JHONEE BALMEO

2. Pharmacodynamics
 Pharmacodynamics is the mechanism of drug
action and relationships between drug
concentration and the body’s responses.
Such responses require that the drug interact
with specific molecules and chemicals
normally found in the body (Adams & Koch,
2010).

3. Pharmacodynamics
 A receptor is the drug’s specific target,
usually a protein located on the surface of
a cell membrane or within the cell. As the
drug binds to the receptor, it enhances or
inhibits the normal cellular function.
 The binding is usually reversible and the
action of the drug terminated once the
drug leaves the receptor (Adams & Koch,
2010, p. 60).

4. Pharmacodynamics
 Most drugs exert their effects by
chemically binding with receptors at the
cellular level. When a drug binds to its
receptor, the pharmacologic effects are
either agonism or antagonism.

5. Agonist
 When a drug produces the same
type of response as the
physiological or endogenous
substance, it is referred to as an
agonist.

6. Antagonist
 Conversely, a drug that inhibits cell
function by occupying receptor sites is
called an antagonist.
 The antagonist prevents natural body
substances or other drugs from
activating the functions of the cell by
occupying the receptor sites.

7. PARTIAL AGONISTS
 Some drugs combine with receptors and
activate them, but are incapable of
eliciting a maximal response, no matter
how high their concentration may be.
These are known as partial agonists, and are
said to have low efficacy.

8. Efficacy (Emax)
when this magnitude of effect
is reached, increasing the dose
will not produce a greater
magnitude of effect

9. RECEPTORS AND SIGNAL TRANSDUCTION
 Drugs are often potent (i.e. they produce
effects at low concentration) and specific
(i.e. small changes in structure lead to
profound changes in potency).

10. Potency
 "[Potency is] an expression of the activity of a drug, in
terms of the concentration or amount needed to produce
a defined effect."

11. RECEPTORS AND SIGNAL TRANSDUCTION
 Receptors were originally classified
by reference to the relative
potencies of agonists and antagonists
on preparations containing different
receptors.

12. RECEPTORS AND SIGNAL TRANSDUCTION
 Despite this complexity, it turns out that receptors fall
into only four ‘superfamilies’ each linked to distinct types
of signal transduction mechanism (i.e. the events that link
receptor activation with cellular response)

13. RECEPTORS AND SIGNAL TRANSDUCTION
 Three families are located in the cell membrane, while the fourth is
intracellular (e.g. steroid hormone receptors). They comprise:
 • Fast (millisecond responses) neurotransmitters (e.g. nicotinic receptors), linked directly
to a transmembrane ion channel.
 • Slower neurotransmitters and hormones (e.g. muscarinic receptors) linked to an
intracellular G-protein (‘GPCR’).
 • Receptors linked to an enzyme on the inner membrane (e.g. insulin receptors) are slower
still.
 • Intranuclear receptors (e.g. gonadal and glucocorticosteroid hormones): ligands bind to
their receptor in cytoplasm and the complex then migrates to the nucleus and binds to
specific DNA sites, producing alterations in gene transcription and altered protein
synthesis. Such effects occur over a time-course of minutes to hours.

14. RECEPTORS AND SIGNAL TRANSDUCTION
 1. ligand-gated ion channels
 2. G protein-coupled receptors
 3. enzyme-linked receptors
 4. intracellular receptors

16. SLOW PROCESSES
 Prolonged exposure of receptors to agonists, as frequently
occurs in therapeutic use, can cause down-regulation or
desensitization.
 Desensitization is sometimes specific for a particular
agonist (when it is referred to as ‘homologous
desensitization’), or there may be cross-desensitization to
different agonists (‘heterologous desensitization’).
 That’s why most doctor begins prescribing medications that are in low dosage

18. Pharmacokinetics
 is the study of drug absorption, distribution, metabolism
and excretion (ADME) – ‘what the body does to the drug’.
 Understanding pharmacokinetic principles, combined with
specific information regarding an individual drug and
patient, underlies the individualized optimal use of the
drug (e.g. choice of drug, route of administration, dose
and dosing interval).

19. Liberation
 Liberation is the first step in the process by which
medication enters the body and liberates the
active ingredient that has been administered.
The pharmaceutical drug must separate from
the vehicle or the excipient that it was mixed with
during manufacture.

20. Absorption
 Absorption is the process by which a drug passes
into the bloodstream.
 Unless the drug is administered directly into the
bloodstream, absorption is the first step in the
movement of the drug through the body.
 For absorption of a drug to occur, the correct form
of the drug must be administered through the
correct route.

21. 1. ABSORPTION
 Drug absorption, and hence the routes by which a particular
drug may usefully be administered, is determined by the rate
and extent of penetration of biological phospholipid membranes.
These are permeable to lipid-soluble drugs, whilst presenting a
barrier to more water-soluble drugs.
 The most convenient route of drug administration is usually by
mouth, and absorption processes in the gastro-intestinal tract
are among the best understood.

23. BIOAVAILABILITY, BIOEQUIVALENCE
 Drugs must enter the circulation if they are to exert a systemic effect.
Unless administered intravenously, most drugs are absorbed
incompletely.
 There are three reasons for this:
 1. the drug is inactivated within the gut lumen by gastric acid,
digestive enzymes or bacteria;
 2. absorption is incomplete; and
 3. presystemic (‘first-pass’) metabolism occurs in the gut wall and liver.

25. GENERIC VS. PROPRIETARY PRESCRIBING
 Many factors in the manufacture of the drug formulation
influence its disintegration, dispersion and dissolution in the
gastrointestinal tract.
 Pharmaceutical factors are therefore important in
determining bioavailability. It is important to distinguish
statistically significant from clinically important differences
in this regard

26. GENERIC VS. PROPRIETARY PRESCRIBING
 This raise the question of whether prescribing should be
by generic name or by proprietary (brand) name. When a
new preparation is marketed, it has a proprietary name
supplied by the pharmaceutical company, and a non-
proprietary (generic) name.
 The formulation of a drug (i.e. excipients, etc.) differs
between different manufacturers’ products of the same
drug, sometimes affecting bioavailability

27. ROUTES OF ADMINISTRATION
 ORAL ROUTE
FOR LOCAL EFFECT
Oral drug administration may be used to produce local
effects within the gastro-intestinal tract.
Examples include antacids, and sulphasalazine,

28. ROUTES OF ADMINISTRATION
 FOR SYSTEMIC EFFECT
Oral administration of drugs is safer and more convenient for
the patient than injection. There are two main mechanisms
of drug absorption by the gut:
Passive diffusion
Active transport

30. Other factors that influence absorption
include:
 1. surgical interference with gastric function – gastrectomy
reduces absorption of several drugs;
 2. disease of the gastro-intestinal tract (e.g. coeliac disease,
cystic fibrosis) – the effects of such disease are unpredictable, but
often surprisingly minor;
 3. the presence of food – the timing of drug administration in
relation to meal times can be important. Food and drink dilute the
drug and can bind it, alter gastric emptying and increase
mesenteric and portal blood flow;

31. Other factors that influence absorption
include:
 4. drug metabolism by intestinal flora – this may affect
drug absorption. Alteration of bowel flora (e.g. by
concomitant use of antibiotics) can interrupt
enterohepatic recycling and cause loss of efficacy of oral
contraceptives;
 5. drug metabolism by enzymes in the gastro-intestinal
epithelium;
 6. drug efflux back into the gut lumen by drug transport
proteins (e.g. P-glycoprotein (P-gp), ABCB1).

32. ROUTES OF ADMINISTRATION
 BUCCAL AND SUBLINGUAL ROUTE
Drugs are administered to be retained in the mouth for local
disorders of the pharynx or buccal mucosa.
Sublingual administration has distinct advantages over oral
administration (i.e. the drug to be swallowed) for drugs with
pronounced presystemic metabolism, providing direct and rapid
access to the systemic circulation, bypassing the intestine and
liver.

34. ROUTES OF ADMINISTRATION
 RECTAL ROUTE
Drugs may be given rectally for local effects. The
following advantages have been claimed for the
rectal route of administration of systemically active
drugs:
1. Exposure to the acidity of the gastric juice and to
digestive enzymes is avoided.
2. The portal circulation is partly bypassed, reducing
presystemic (first pass) metabolism.
3. For patients who are unable to swallow or who
are vomiting.

35. ROUTES OF ADMINISTRATION
 SKIN
Drugs are applied topically to treat skin disease. Systemic absorption via the
skin can cause undesirable effects.
Some Factors affecting percutaneous drug absorption include:
 skin condition – injury and disease;
 age – infant skin is more permeable than adult skin;
 hydration of the stratum corneum – this is very important. Increased
hydration increases permeability.
 Physical properties of the drug – penetration increases with increasing lipid
solubility.

36. ROUTES OF ADMINISTRATION
 LUNGS
Drugs, notably steroids, β2-adrenoceptor agonists and
muscarinic receptor antagonists, are inhaled as aerosols or
particles for their local effects on bronchioles.
Nebulized antibiotics are also sometimes used in children
with cystic fibrosis and recurrent Pseudomonas infections.

37. ROUTES OF ADMINISTRATION
 NOSE
Nasal mucosal epithelium has remarkable absorptive
properties, notably the capacity to absorb intact
complex peptides that cannot be administered by
mouth because they would be digested.
Systemic absorption may result in undesirable
effects, such as hypertension

38. ROUTES OF ADMINISTRATION
 EYE, EAR AND VAGINA
Drugs are administered topically to these sites for their
local effects (e.g. gentamicin or ciprofloxacin eyedrops
for bacterial conjunctivitis).
Occasionally, they are absorbed in sufficient quantity
to have undesirable systemic effects.

39. ROUTES OF ADMINISTRATION
 INTRAMUSCULAR INJECTION
Many drugs are well absorbed when administered intramuscularly.
The rate of absorption is increased when the solution is distributed
throughout a large volume of muscle.
Transport away from the injection site is governed by muscle blood
flow, and this varies from site to site.

40. ROUTES OF ADMINISTRATION
 Intramuscular injection has a number of disadvantages:
 1. pain – distension with large volumes is painful, and injected volumes should
usually be no greater than 5mL;
 2. sciatic nerve palsy following injection into the buttock – this is avoided by
injecting into the upper outer gluteal quadrant;
 3. sterile abscesses at the injection site.
 4. severe adverse reactions may be protracted because there is no way of
stopping absorption of the drug;
 5. for some drugs, intramuscular injection is less effective than the oral route;
 6. haematoma formation.

41. ROUTES OF ADMINISTRATION
 SUBCUTANEOUS INJECTION
This is influenced by the same factors that affect
intramuscular injections.
Cutaneous blood flow is lower than in muscle so absorption
is slower.

42. ROUTES OF ADMINISTRATION
 INTRAVENOUS INJECTION
This has the following advantages:
 1. rapid action (e.g. morphine for analgesia and furosemide in
pulmonary oedema);
 2. presystemic metabolism is avoided
 3. intravenous injection is used for drugs that are not absorbed by
mouth (e.g. aminoglycosides (gentamicin) and heparins).
 4. intravenous infusion is easily controlled, enabling precise titration
of drugs with short half-lives.

43. ROUTES OF ADMINISTRATION
 The main drawbacks of intravenous administration are as follows:
 Once injected, drugs cannot be recalled.
 2. High concentrations result if the drug is given too rapidly –
the right heart receives the highest concentration.
 3. Embolism of foreign particles or air, sepsis or thrombosis.
 4. Accidental extravascular injection or leakage of toxic drugs
(e.g. doxorubicin) produce severe local tissue necrosis.
 5. Inadvertent intra-arterial injection can cause arterial spasm
and peripheral gangrene.

44. ROUTES OF ADMINISTRATION
 INTRATHECAL INJECTION
This route provides access to the central nervous system for drugs that
are normally excluded by the blood–brain barrier.
This inevitably involves very high risks of neurotoxicity, and this route
should never be used without adequate training.

45. ?
 Which of the following is/are useful in emergencies for
most rapid and predictable action, but too rapid
administration is potentially very dangerous?
a. Subcutaneous
b. Intravenous.
c. Intrathecal
d. Intramuscular

46. ?
 Route of administration that is/are useful for insulin and
heparin in particular?
a. Subcutaneous.
b. Intravenous
c. Intrathecal
d. Intramuscular

47. 2. Distribution
 Distribution is the transportation of a drug from its
site of absorption to its site of action.
 When a drug enters the bloodstream, it is carried
to the most vascular organs—that is, liver, kidneys,
and brain. Body areas with lower blood supply—
that is, skin and muscles—receive the drug later.

48. 3. Metabolism
 metabolism is a process by which a drug is
converted to a less active form. Most
biotransformation takes place in the liver, where
many drug-metabolizing enzymes in the cells
detoxify the drugs.

49. 3. Metabolism
 Biotransformation may be altered if a person is
very young, is older, or has an unhealthy liver.
Nurses must be alert to the accumulation of the
active drug in these clients and to subsequent
toxicity.

50. 4. Excretion
 Excretion is the process by which metabolites and drugs are
eliminated from the body.
 Most drug metabolites are eliminated by the kidneys in the
urine; however, some are excreted in the feces, the breath,
perspiration, saliva, and breast milk.
 *Does older patient needs more dosage?
Or less?

51. 4. Excretion
 The kidneys are involved in the elimination of virtually
every drug or drug metabolite. The contribution of renal
excretion to total body clearance of any particular drug is
determined by its lipid solubility (and hence its polarity).
 Elimination of non-polar drugs depends on metabolism to
more polar metabolites, which are then excreted in the
urine.

53. 4. Excretion
 1. GLOMERULAR FILTRATION
Glomerular filtrate contains
concentrations of low-molecular weight
solutes similar to plasma. In contrast,
molecules with a high molecular weight
(including plasma proteins and drug–
protein complexes) do not pass through
the glomerulus.

54. 4. Excretion
 2. PROXIMAL TUBULAR SECRETION
There are independent mechanisms for
active secretion of organic anions and
organic cations (OAT and OCT) into the
proximal tubule.

55. 4. Excretion
 3. PASSIVE DISTAL TUBULAR
REABSORPTION
The renal tubule behaves like a lipid
barrier separating the high drug
concentration in the tubular lumen and
the lower concentration in the
interstitial fluid and plasma

56. 4. Excretion
 4. ACTIVE TUBULAR REABSORPTION
This is of minor importance for most
therapeutic drugs.

57. 4. Excretion
 1. GLOMERULAR FILTRATION
 2. PROXIMAL TUBULAR SECRETION
 3. PASSIVE DISTAL TUBULAR REABSORPTION
 4. ACTIVE TUBULAR REABSORPTION

59. ?
 Which would be absorbed the fastest:
a. pill
b. capsule, or
c. Liquid.

60. ?
 A client is experiencing diarrhea. How could this affect
absorption of an oral drug?

61. ?
 How does the presence of food in the stomach affect the
rate of absorption?

62. ?
 How is distribution of the oral medication affected if a
client has less than normal cardiac output (e.g., low BP,
prolonged capillary refill)?

63. Factors Affecting Medication Action
 A number of factors other than the drug itself can affect
its action.
 A person may not respond in the same manner to
successive doses of a drug. In addition, the identical drug
and dosage may affect different clients differently.

64. Factors Affecting Medication Action
 Developmental Factors

65. Factors Affecting Medication Action
 Sex

66. Factors Affecting Medication Action
 Cultural, Ethnic, and Genetic Factors

67. Factors Affecting Medication Action
 Diet

68. Factors Affecting Medication Action
 Environment

69. Factors Affecting Medication Action
 Psychological Factors

70. Factors Affecting Medication Action
 Illness and Disease

71. Factors Affecting Medication Action
 Time of Administration

72. ?
 Why would the very young and very old clients need to be
closely monitored by the nurse for signs and symptoms of
drug toxicity?

73.  An older client with renal insufficiency is to receive a
cardiac medication. Which is the nurse most likely to
administer?
1. A decreased dosage.
2. The standard dosage
3. An increased dosage
4. Divided dosages

74. References:
• Audrey Berman . . . [et al.]. – 9th
ed. (2012) KOZIER & ERB’S
Fundamentals of NURSING
Concepts, Process, and Practice.
• James M Ritter, L.Lewis, T. Mant
and A.Ferro. 5th ed. (2008) A
Textbook of Clinical
Pharmacology and Therapeutics