2. Pharmacologic Principles
• Drug
Any chemical that affects the physiologic processes of a
living organism
• Pharmacology
The study or science of drugs
3. • Therapeutic ratio
– is the number indicating the ratio between lethal or toxic dose
and effective dose.
• Critical concentration
– Amount of drug that is needed to cause therapeutic effect
– Must be maintained in order for the drug to produce the desired
therapeutic effect in the body.
4. • Loading dose
– The starting dose that is higher than the dose usually used for tx
– Given so that the time for a drug to reach its critical conc will be hasten
• Dynamic equilibrium
– Result when drug reaches in the body and actual conc of the drug is
achieved involving the process of absorption, distribution, metabolism
and excretion
5. Pharmacologic Principles
• Knowledge of pharmacologic principles:
» why a drug is ordered
» how to administer drugs
» assessment of therapeutic benefits
» how to deal with toxic adverse effects
• The nurse with a sound knowledge base in pharmacology is better
equipped to implement the nursing process
7. Pharmacologic Principles
1) Pharmaceutics
The study of various drug forms
Deals with the delivery system
IV, PO, IM
Injection, capsule, timed-release, topical
Determines the rate at which the drug will dissolve and be absorbed
8. Pharmacologic Principles
1) Pharmaceutics
• The pharmaceutical phase is
concerned with the disintegration of the
dosage form or dissolution of the drug
in the body
• How the dosage forms affect the way
the body metabolizes the drug and how
the drug affects the body
9. Pharmacologic Principles
1) Pharmaceutics
The dosage form determines the rate at which a drug
enters the body
A variety of dosage forms are available to increase the
accuracy of dosing and to obtain therapeutic
responses with the least amount of adverse effects
11. Pharmacologic Principles
2) Pharmacokinetics
– The study of what actually happens to a drug from the time it enters the body until it
has left the body
a. Absorption
movement of a drug from the site of administration
b. Distribution
transport of a drug in the bloodstream
c. Metabolism
alteration of a drug in the body
d. Excretion
elimination of the drug or its compound from the body
12. 2) Pharmacokinetics
a. Absorption
• What happens to a drug from the time it is introduced to the body until it
reaches the circulating fluids and tissues.
Areas in the body where drug can be absorbed
• GI tract either oral/rectal
• Mucous membranes
• Skin
• Lungs
• Muscle
• Subcutaneous tissues
13. 2) Pharmacokinetics
a. Absorption
• The route of administration affects the rate and extent of absorption of that
drug
A. Enteral (GI tract)
B. Parenteral
C. Topical
• The extent of absorption is called BIOAVAILABILITY
– portion of the drug that reaches the systemic circulation
KEY POINT: not all drug formulations are equally absorbed
14. Oral Drugs
• Dosage
– determined by how much of the drug is
required to be taken by mouth to reach
desired effect.
15. Mechanism of Drug Absorption
• Passive Diffusion
– movement of a drug from higher to lower concentration.
• Carrier Mediated Absorption(Facilitated diffusion)
– no cellular energy. Drug molecules combine with a carrier substance such as
enzyme or other protein.
• Active Transport
– drug molecules move from an area of low concentration to an area of high
concentration; transported by the carrier molecules as cellular energy.
• Pinocytosis
– occurs when a cell engulfs drug particles and moves them across the cell
membrane and into the inner cell.
16. a. Absorption of oral drugs
Factors that affect absorption
varies according to the dosage form and route
1. Food or fluids administered with the drug
– help or hinder absorption
– food may delay transit to the intestines
– high fat foods may help some fat soluble drugs
2. Dosage formulation
– determined by how much of the drug is required to be taken by mouth to given the
desired affect.
– tablets, capsules- some dissolve in the stomach, others in the intestine.
– Certain types are coated to dissolve slowly and have timed release.
– Some types are formulated with small particles that dissolve super fast- ie: micronized
glyburide
20. a. Absorption of oral drugs
Factors that affect absorption
varies according to the dosage form and route
3. Status of the absorptive surface
– portions of the small intestine may be missing or damaged
4. Rate of blood flow to the small intestine
– blood flow may be decrease to the intestine in certain instances
– i.e. sepsis, exercise, labor
5. Acidity of the stomach
– food increases gastric acid production leading to decreased stomach pH. Drugs are formulated to dissolve at a specific pH
level.
6. Status of GI motility
– Fast or slow transit time due to pathology, conditions, or other medications change transit time
21. a. Absorption of oral drugs
Some drugs need to be taken on an empty stomach
with a full glass of water
Other drugs should be taken on a full stomach or
with food to enhance absorption or minimize gastric
irritation
22. • + food in stomach
– usually decreases absorption of drugs, but it may increase absorption for a few
specific medications.
• pH of the stomach
– Alkaline drugs are absorbed more readily in an alkaline environment
– acid drugs are absorbed more readily in an acid environment.
• form of the drug
– liquid drugs being absorbed the fastest and enteric-coated tablets the slowest.
23. a. Absorption of oral drugs
Drugs are absorbed into the mesenteric blood system and go to the liver for
biotransformation before traveling on to the general systemic circulation.
This is called the
FIRST PASS EFFECT
• Therefore some of the drug is inactivated and not all will be available for use
at its intended site of action.
• Drugs are formulated to account for this difference in availability to the
tissues- called (bioavailability)
• This is why different forms of drugs are not equal
24. First-Pass Effect
The metabolism of a drug and its passage from the
liver into the circulation.
• oral route may be extensively metabolized by the liver before
reaching the systemic circulation (high first-pass effect).
• The same drug—given IV—bypasses the liver, preventing the
first-pass effect from taking place, and more drug reaches the
circulation.
25. First-Pass Effect
• Routes that bypass the liver:
– Sublingual Transdermal
– Buccal Vaginal
– Rectal* Intramuscular
– Intravenous Subcutaneous
– Intranasal Inhalation
*Rectal route undergoes a higher degree of first-pass effects than the other
routes listed.
26. What else might influence oral drug
absorption?
• Food in stomach
• Certain juices – grapefruit juice
• Milk – binds with molecules of some drugs so that the drug is never
absorbed
• Orange juice – enhances absorption of iron taken orally
• The coating on the tablet: chewable, enteric coated (breakdown
occurs in small intestine), slow release capsules
27. a. Absorption of parenteral
drugs
Parental drugs have no first pass effect
• Intravenous
– rapid and 100% bioavailable
– Avoids problems with stomach acid and intestinal absorption issues
• Intramuscular
– not as rapid as IV- will absorb better if there is a good blood supply
• Some IM medications are in DEPOT form- have a very slow absorption time (even
months)- due to the formulation
– these drugs should not be given IV- can cause an embolus
28. a. Absorption of parenteral
drugs
Parenteral Route
• Intravenous*
• Intramuscular
• Subcutaneous
• Intradermal
• Intrathecal
• Intraarticular
*Fastest delivery into the blood circulation
29. a. Absorption of topical drugs
• Many different formulations of topical drugs
• May be given for local or systemic effect
30. a. Absorption of topical drugs
Topical Route
• Skin (including transdermal patches)
• Eyes
• Ears
• Nose
• Lungs (inhalation)
• Vagina
31. a. Absorption of oral drugs
sublingual and buccal
Avoids the first pass effect
• Absorbed into the highly vascularized tissue under the tongue or between
the cheek and the gum- the oral mucosa
• Bypass the liver
• Rapidly absorbed
32. a. Absorption
• The ROUTE of administration affects
the rate and extent of absorption
of that drug
33. 2) Pharmacokinetics
The transport of a drug in the body by the
bloodstream to its site of action
a. Absorption
b. Distribution
c. Metabolism
d. Excretion
34. b. Distribution
• Drugs are distributed first to areas that have extensive blood
supplies
heart liver kidneys brain
• Areas of slower distribution are
muscles skin fat
• Sites like bone and brain may be very difficult for drugs to reach due
to either poor blood supply or barriers
35. b. Distribution of drugs
Factors that affect distribution
1. Protein-binding
• Many drugs bind to proteins in the bloodstream
-Albumin is the main protein to bind with drugs
-Drugs bound to proteins are not available for use in other tissues & organs called protein bound
-Drugs not bound to protein are available to act at
the intended site of action and exert their effects
*called free drug
• Drug companies adjust drug dosages to allow for protein binding
36. b. Distribution of drugs
Factors that affect distribution
• If a patient has low albumin more free drug is available and the
patient may have increased adverse effects (toxicity)
• If 2 drugs are given that are highly protein bound they compete for
binding sites on the albumin.
– The drugs will have higher levels of ―free‖ drug and the patient may have
increased adverse effects
• This fact is significant because only the unbound or free drug is able
to reach the target tissue and exert its pharmacologic effect.
37. b. Distribution of drugs
Factors that affect distribution
2. Water soluble vs fat soluble
• Water soluble drugs
– tend to stay in the bloodstream and have slow absorption into the tissues.
• Fat soluble drugs
– are distributed to the tissues more quickly
– the more lipid soluble the drug is, the higher its ability to reach all cells in the body.
38. b. Distribution of drugs
Factors that affect distribution
3. Blood Flow
a. Blood-brain barrier
– network of capillaries that makes it more difficult for drugs to pass through--will
allow some fat soluble drugs to pass through
– Brain capillary endothelium have special characteristics that limit the passage of
drugs
b. Placental barrier
– in general whatever mom gets the fetus gets
39. b. Distribution of drugs
Factors that affect distribution
4. Blood Flow
– If drug is circulating in the bloodstream, it will gain greater access to tissues that
are highly perfused.
– Therefore, if the blood circulation is poor, the result is insufficient drug
distribution.
5. Binding to sub-cellular components
– There are drugs that are bound within specific cells in which they are causing
their effect and are unable to leave the cell to be carried in the blood stream.
40. 2) Pharmacokinetics
a. Absorption
b. Distribution
c. Metabolism
d. Excretion
41. c. Metabolism of drugs
• Also Known as Biotransformation
• Drugs are changed into new, less active chemicals
• It takes place mainly in the liver and produces
1. An inactive metabolite
2. A more soluble compound
3. A more potent metabolite
42. c. Metabolism
(biotransformation)
Organs or body tissues responsible for
metabolism:
– Liver (mainly)
– Skeletal muscle
– Kidneys
– Lungs
– Plasma
– Intestinal mucosa
43. c. Metabolism (biotransformation)
Hepatic Cytochrome P-450 enzyme system
• These enzymes control a variety of biochemical reactions that aid in
metabolism
• These enzymes are largely targeted against lipid-soluble and
nonpolar (no charge) drugs which are difficult to eliminate
• These include the majority of medications
44. c. Metabolism (biotransformation)
The capability of the liver to metabolize drugs varies widely between patients
• Age
Elderly have decreased hepatic enzymes
Neonates have immature liver functions
• Genetics
certain genetic groups metabolize drugs at
different rates
• Foods
Grapefruit and certain other foods
• Concurrent use of other medications
Tylenol and many other drugs
• Diseases
Cardiovascular or Renal dysfunction
45. c. Metabolism
(biotransformation)
Factors that decrease (delay) metabolism
• Cardiovascular dysfunction
• Renal insufficiency
• Starvation
• Obstructive jaundice
• Slow acetylator (metabolism of drug)
• Erythromycin or ketoconazole drug therapy
46. c. Metabolism
(biotransformation)
Decreased drug metabolism
results in:
• Accumulation of drugs
• Prolonged action of the drugs
• Possible toxic levels
47. c. Metabolism
(biotransformation)
Factors that increase (stimulate) metabolism
• Fast acetylator
• Drugs that stimulate the formation of new enzymes
Barbiturate therapy
Rifampin therapy
49. c. Metabolism (biotransformation)
FIRST PASS EFFECT
• The initial metabolism of a drug and its passage from the liver into the
circulation
– A drug given via the oral route may be extensively metabolized (inactivated or
changed) by the liver before reaching the systemic circulation high first-pass effect
• Oral drugs ( because they go through the liver) may not be 100% available
to reach the intended sites of action
50. c. Metabolism (biotransformation)
FIRST PASS EFFECT– routes of administration
• The same drug—given IV—initially bypasses the liver, getting to it’s
intended site of action more quickly and preventing the first-pass effect
from taking place.
• IV drugs are 100% available to the body (bioavailability)
Cefuroxime:
IV = 750mg/ml
oral = 500 mg/ml
51. c. Metabolism (biotransformation)
FIRST PASS EFFECT– routes of administration
• The first-pass effect is one reason why drug dosages and frequency
of administration are different depending on the route of
administration
IV DOSE is not always equal to an ORAL DOSE
52. 2) Pharmacokinetics
a. Absorption
b. Distribution
c. Metabolism
d. Excretion
53. d. Excretion
The elimination of drugs from the body
• Kidneys (main organ)
Whether the drug is an original compound
(parent compound), an active or an inactive
metabolite----
• Liver
• Bowel
– Biliary excretion
– Enterohepatic recirculation
54. d. Excretion
The kidneys remove the drugs that are unbound
(free) in the plasma
Certain drugs (like highly protein bound drugs)
can’t be excreted and are reabsorbed back into
the system
55. d. Excretion
• Patients with renal failure will not be able to
excrete drugs efficiently
• Drug levels will increase
• Patients may experience more adverse effects
and toxicity
56. Pharmacokinetics
Onset, Peak, Duration and Trough
Onset
• The time it takes for the drug to elicit a therapeutic
response
INSULIN ONSET PEAK DURATION
Ultra rapid acting 15 mins. 2-4 hrs. 6-8 hrs.
Insulin analog
(Humalog)
57. Pharmacokinetics
Onset, Peak, Duration and Trough
Peak
• The time it takes for a drug to reach its maximum therapeutic
response
• Oral = 1-3hrs
• IV = 10mins
• good time for a dressing change or other painful procedure
• Good time to draw blood
INSULIN ONSET PEAK DURATION
Ultra rapid acting 15 mins. 2-4 hrs. 6-8 hrs.
Insulin analog
(Humalog)
58. Pharmacokinetics
Onset, Peak, Duration and Trough
Duration
• The time a drug concentration is sufficient to elicit a therapeutic
response
how long is it going to last- (anticipate the next dose)
INSULIN ONSET PEAK DURATION
Ultra rapid acting 15 mins. 2-4 hrs. 6-8 hrs.
Insulin analog
(Humalog)
59. Pharmacokinetics
Onset, Peak, Duration and Trough
Trough
• Lowest blood level of a drug
Note:
If either the peak or trough levels is too high, toxicity can occur.
If the peak is too low, no therapeutic effect is achieved.
61. Laboratory Values
• Laboratory values reflecting function of liver and kidneys need to be
looked at:
– BUN and Creatinine – kidney function
– LFT or liver function tests:
• ALT – alanine aminotransferase (elevated in hepatitis)
• AST or SGOT– aspartate aminotransferase – elevated in liver disease
• ALP – elevated in biliary tract disease
• Bilirubin levels – infants – gallstones in adults
62. Serum Drug Levels
• Laboratory measurement of the amount of drug
in the blood at a particular time
• A minimum effective concentration (MEC) must
be present before a drug exerts its action on a
cell.
63. Toxic Levels
• Excessive level of a drug in the body
– Single large dose
– Repeated small doses
– Slow metabolism which allows drug to accumulate in
the body
– Slow excretion from the body by the kidneys or
gastrointestinal tract
64. Yes, laboratory values are
important!
• Serum drug levels indicate the onset, peak
and duration of the drug action
65. Do we do serum drug levels for all
drugs?
• No
• When do we need them?
– Drugs with narrow margin of safety (digoxin, aminoglycoside
antibiotics, lithium)
– To check to see if the drug is at therapeutic levels – seizure
medications
– When drug overdose is suspected
67. Pharmacokinetics
• Half-life
• The time it takes for one half of the original amount of a drug in the
body to be removed
• A measure of the rate at which drugs are removed from the body
• Most drugs are considered to be effectively removed after about five
half-lives**
68. Why is this important?
• Half-life determines how often a drug is given
– Daily in the morning
– At bedtime
– Q.I.D - four times a day
– T.I.D – three times a day
– Q4 hours – every four hours
– Q 12 hours – 9 am and 9 pm
69. Pharmacokinetics
Short ½ life– need to take frequently
compliance may be a problem
example: acyclovir 5 times daily
Long ½ life- pt has an adverse reaction
the drug will be in the body for
hours or days
example: Cialis T1/2 = 17 hours
(Viagra might have been a better choice for this pt with a T1/2 of 4 hours)
70. Pharmacokinetics
• Steady state
• Where the amount of drug excreted is equal to the amount of drug absorbed
with each dose
• Giving more drug could cause toxicity
• Giving less drug would not be therapeutic
• Typically occurs after 4-5 half-lives of administration
71. Pharmacokinetics
Steady state
• Drugs with a very long half-life make take a longer time to reach a steady
state
- some antidepressants
• With certain drugs, to reach a steady state more quickly, a LOADING
DOSE may be ordered
This is a higher initial dose
