Transcript Nursing Process and Drug Therapy. Basic Pharmacology Principles

Pharmacology
Ideal Drug
Effectiveness
Safety
Selectivity
Reversible
Predictability
Ease of administration
Freedom from drug interactions
Ideal Drug
Low cost
Chemical Stability
Possession of a simple generic name
Therapeutic Objective
Maximum benefit with minimum harm
The intensity of the response to a drug is
directly related to the concentration of the
drug at its site of action
Intensity of Drug responses
Administration – dosage and route
Pharmacokinetics
Pharmacodynamics
Individual variation
Nursing Responsibilities
Last line of defense against errors!!!!!!!!!
Patient education
Utilize the nursing process
Drug Legislation
1906 – drugs should be free of adulterants
1938 – testing for toxicity
1962 – proof of effectiveness
1970 – Controlled Substance Act –
Scheduled drugs
1997 – Food and Drug Administration
Modernization Act
New Drug Development
Preclinical testing – prior to testing on
humans
Clinical testing
I – normal volunteers – except maybe
patients who have disease
II and III – patients
IV – released for general use
Be neither the first to adopt the new nor the
last to abandon the old!
Drug Names
Chemical
Generic Name
Trade Name
OTC drugs
Pharmacokinetics
 Drug movement throughout the body
 Absorption – movement of drug from its site of
administration into blood
 Dissolve – must dissolve before being absorbed
 Surface area – the larger the faster
 Blood flow – most rapid where blood flow is
high
 Lipid solubility - the higher the faster
 pH partitioning
Absorption - Routes
 IV – no barriers to absorption
 Intramuscular – good for poorly soluble drugs,
“time released”
 Subcutaneous – again no significant barriers
 Oral – must pass through cells of epithelium,
enteric coating
 Safer but highly variable absorption – enteric,
sustained-release, tablets
Routes of Drug
Administration
Robert L. Copeland, Ph.D.
Department of Pharmacology
www.med.howard.edu/pharmacology
202.806.6311
Drug Absorption
Absorption is the process by which
a drug enters the bloodstream
without being chemically altered or
The movement of a drug from its
site of application into the blood or
lymphatic system
Drug Absorption
Factors which influence the rate of
absorption
–
–
–
–
–
–
–
types of transport
the physicochemical properties of the drug
protein binding
routes of administration
dosage forms
circulation at the site of absorption
concentration of the drug
Drug Absorption
The rate at which a drug reaches it site
of action depends on:
– Absorption - involves the passage of
the drug from its site of
administration into the blood
– Distribution - involves the delivery of
the drug to the tissues
Drug Absorption
Mechanisms of solute transport
across membranes
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–
–
–
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passive diffusion
filtration and bulk flow
endocytosis
ion-pairing
active transport
– Drug Absorption animation
Ion Trapping cont:
Body fluids where a pH difference from
blood pH will favor trapping or
reabsorption: stomach contents
small intestine
breast milk
aqueous humor (eye)
vaginal secretions
prostatic secretions
Ion Trapping:
Kidney:
Nearly all drugs filtered at the glomerulus:
Most drugs in a lipid-soluble form will be absorbed
by passive diffusion.
To increase excretion: change the urinary pH to favor
the charged form of the drug:
• Weak acids: excreted faster in alkaline pH (anion
form favored)
• Weak bases: excreted faster in acidic pH (cation
form favored)
Lipid-Water Partition Coefficient
– The ratio of the concentration of the
drug in two immiscible phases: a
nonpolar liquid or organic solvent
(representing the membrane); and
an aqueous buffer, pH 7.4
(representing the plasma)
Lipid-Water Partition Coefficient
The higher the lipid/water p.c. the greater
the rate of transfer across the membrane
–
polarity of a drug, by increasing ionization
will
the lipid/ water p.c.
–
polarity of a drug, suppression of ionization
will
the lipid/ water p.c.
Routes of Drug
Administration
Important
Info
The route of administration (ROA)
that is chosen may have a profound
effect upon the speed and efficiency
with which the drug acts
The possible routes of drug entry
into the body may be divided into
two classes:
–Enteral
–Parenteral
Enteral Routes
Enteral - drug placed directly in the GI tract:
– sublingual - placed under the
tongue
– oral - swallowing (p.o., per os)
– rectum - Absorption through the
rectum
Sublingual/Buccal
Some drugs are taken as smaller tablets
which are held in the mouth or under the
tongue.
Advantages
– rapid absorption
– drug stability
– avoid first-pass effect
Sublingual/Buccal
Disadvantages
– inconvenient
– small doses
– unpleasant taste of some drugs
Oral
Advantages
– Convenient - can be self- administered, pain
free, easy to take
– Absorption - takes place along the whole
length of the GI tract
– Cheap - compared to most other parenteral
routes
Oral
Disadvantages
– Sometimes inefficient - only part of the
drug may be absorbed
– First-pass effect - drugs absorbed orally
are initially transported to the liver via
the portal vein
– irritation to gastric mucosa - nausea and
vomiting
Oral
Disadvantages cont.
– destruction of drugs by gastric acid and
digestive juices
– effect too slow for emergencies
– unpleasant taste of some drugs
– unable to use in unconscious patient
First-pass Effect
The first-pass effect is the term used for
the
hepatic
metabolism
of
a
pharmacological agent when it is
absorbed from the gut and delivered to
the liver via the portal circulation. The
greater the first-pass effect, the less the
agent will reach the systemic circulation
when the agent is administered orally
First-pass Effect cont.
Magnitude of first pass hepatic effect:
Extraction ratio (ER)
ER = CL liver / Q ; where Q is hepatic
blood flow (usually about 90 L per hour.
Systemic drug bioavailability (F) may be
determined from the extent of absorption
(f) and the extraction ratio (ER):
F = f x (1 -ER)
First-pass Effect
Rectal
1. unconscious patients and children
2. if patient is nauseous or vomiting
3. easy to terminate exposure
4. absorption may be variable
5. good for drugs affecting the bowel such
as laxatives
6. irritating drugs contraindicated
Parenteral Routes
– Intravascular (IV, IA)- placing a drug
directly into the blood stream
– Intramuscular (IM) - drug injected into
skeletal muscle
– Subcutaneous - Absorption of drugs from the
subcutaneous tissues
– Inhalation - Absorption through the lungs
Intravascular
Absorption phase is bypassed
(100% bioavailability)
1.precise, accurate and almost immediate onset of
action,
2. large quantities can be given, fairly pain free
3. greater risk of adverse effects
a. high concentration attained rapidly
b. risk of embolism
c. OOPS factor or !@#$%
Intramuscular
1. very rapid absorption of drugs in aqueous
solution
2.repository and slow release preparations
3.pain at injection sites for certain drugs
Subcutaneous
1. slow and constant absorption
2. absorption is limited by blood flow,
affected if circulatory problems exist
3. concurrent administration of
vasoconstrictor will slow absorption
Inhalation
1.gaseous and volatile agents and aerosols
2.rapid onset of action due to rapid access to
circulation
a.large surface area
b.thin membranes separates alveoli from
circulation
c.high blood flow
Particles larger than 20 micron and the particles impact
in the mouth and throat. Smaller than 0.5 micron and
they aren't retained.
Inhalation cont.
 Respiratory system. Except for IN, risk hypoxia.
 Intranasal (snorting) Snuff, cocaine may be partly oral via post-
nasal dripping. Fairly fast to brain, local damage to septum.
Some of the volatile gases also appear to cross nasal membranes.
 Smoke (Solids in air suspension, vapors) absorbed across lung
alveoli: Nicotine, opium, THC, freebase and crack cocaine,
crystal meth.Particles or vapors dissolve in lung fluids, then
diffuse. Longer action than volatile gases. Tissue damage from
particles, tars, CO.
 Volatile gases: Some anaesthetics (nitrous oxide, ether) [precise
control], petroleum distillates. Diffusion and exhalation
(alcohol).
 Lung-based transfer may get drug to brain in as little as five
seconds.
Topical
•Mucosal membranes (eye drops, antiseptic,
sunscreen, callous removal, nasal, etc.)
•Skin
a. Dermal - rubbing in of oil or ointment
(local action)
b. Transdermal - absorption of drug through
skin (systemic action)
i. stable blood levels
ii. no first pass metabolism
iii. drug must be potent or patch
becomes to large
Route for administration
-Time until effect-
 intravenous 30-60 seconds
 intraosseous 30-60 seconds
 endotracheal 2-3 minutes
 inhalation 2-3 minutes
 sublingual 3-5 minutes
 intramuscular 10-20 minutes
 subcutaneous 15-30 minutes
 rectal 5-30 minutes
 ingestion 30-90 minutes
 transdermal (topical) variable (minutes to hours)
Time-release preparations
Oral - controlled-release, timed-release,
sustained-release
– designed to produce slow,uniform
absorption for 8 hours or longer
– better compliance, maintain effect over
night, eliminate extreme peaks and
troughs
Time-release preparations
Depot or reservoir preparations -
parental administration (except IV), may
be prolonged by using insoluble salts or
suspensions in non-aqueous vehicles.
Distribution
Blood flow to tissues
Exiting the vascular system once it has
been delivered – pass through pores in
capillary wall
Protein - binding
Drugs can bind with proteins
Parts of drugs will be bound during any
given time period
Impedes drug’s ability to reach sites of
action, metabolism, or excretion
Metabolism
LIVER
Enzymatic alteration of drug structure
Consequences of metabolism
Accelerated renal excretion – kidney
cannot excrete highly lipid soluable
Drug inactivation
Increased therapeutic action
Activation of prodrugs
Increased or decreased toxicity
Considerations in Metabolism
Age
Induction of drug metabolizing enzymes
First-pass effect – Nitroglycerin
Nutritional status
Competition between drugs
Excretion
KIDNEY
Glomerular filtration – blood to tubular
urine
Tubular reabsorption
Active tubular secretion – pumps for
organic acids and organic bases – to urine
Monitoring drug levels
Plasma drug levels
Therapeutic range
Drug Half-life
Time requires for the amount of drug in the
body to decrease by 50%
Will determine dosing requirements
Goal - plateau
Dosing
Loading doses – when plateau must be
achieved quickly
Routine smaller doses – maintenance doses
Peak and trough levels
Maximal efficacy – largest effect a drug
can produce
Potency – one that produces its effects at
lower dosages
Receptors
Drugs bind to receptors to produce effects
Reversible
All that drugs can do is mimic the
physiological activity of the body’s own
molecules
Block the physiological activity of the
body’s own molecules
Agonists
Mimic the body’s own regulatory
molecules
Antagonists
Drugs that block the actions of endogenous
regulators
Partial agonists
Mimic the actions but with reduced
intensity
Drug Interactions
Can have varying effects
Direct chemical or physical – IV
preparation
Drug – Food Interactions
Frequently decreased rate of absorption
Grapefruit juice can inhibit metabolism
“with food” – with or shortly after meal
“empty stomach” – one hour prior to meal
or two hours after
Adverse drug reactions
Side effect
Toxicity
Allergic reaction
Idiosyncratic effect
Iatrogenic disease
Physical dependence
Carcinogenic effect
Teratogenic effect – induce birth defect
Ways to minimize
Variation in drug responses
 Age
 Body composition
 Gender
 Pathophysiology
 Tolerance
 Placebo effect
 Genetics
 Variability in absorption – bioavailability – oral –
ability to reach circulation
 Compliance
What does the term adverse reaction refer
to?
A. A life-threatening response to a
response to a drug
B. A drug-induced allergy
C. A harmful, undesirable response to a
drug
D. An unpredictable response to a drug
What is an idiosyncratic response?
A. a toxic reaction
B. an allergic reaction
C. a reaction peculiar to the patient
D. an anaphylactic reaction
 Which statement accurately characterizes
geriatric patients’ compliance with prescribed
drug regimens?
 A. compliance decreases with age
 B. compliance increases with age
 C. compliance increases with multiple health
problems
 D. compliance decreases when more than three
drugs are prescribed
END