Transcript Introduction to Pharmacology NAPNES Guidelines

Pharmacologic
Principles
Chapter 2
Cristen Walker, MS, CRNP
Level I
Pharmacology
• DRUG
– Any chemical that affects the physiologic processes of
a living organism
• PHARMACOLOGY
– Study (science) of drugs
– Includes:
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Absorption
Distribution
Metabolism
Excretion
Mechanism of Action
Therapeutic effects
Toxic effects
Pharmacology
• Subspecialty Areas of Pharmacology
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Pharmaceutics
Pharmacokinetics
Pharmacodynamics
Pharmacotherapeutics
Pharmacognosy
Toxicology
– NURSES MUST UNDERSTAND BASIC PRINCIPLES OF
PHARMACOLOGY
– Therapeutic and Toxic
Pharmacology –
Drug development
Drugs will acquire 3 names
CHEMICAL (N-4 hydroxyphenyl acetamide)
Drugs chemical composition, molecular structure
GENERIC (acetaminophen)
Shorter than chemical name
Used as official listing of drugs
TRADE (Tylenol)
Registered trademark, “brand” name
Name is restricted to “owner” (company, ie, Merck)
**Patent lasts 17 years
- 10 years for research and development
- 7 years of marketability
Pharmacology –
Drug Development
Pharmaceutics
• Process of turning chemicals into safe
medications
• Science of dosage form & design
– ie – tablet, capule, liquid, powder, etc.
– Study of how various dosage forms/designs
influence a drugs metabolism and use in
the body
Pharmaceutics
• Drug routes
– Oral
• Via mouth
• Includes sublingual, buccal
– Enteral
• Via intestine
• Via NG tube, feeding tube (or rectal)
– Rectal
– Parenteral
• Intramuscular, Subcutaneous, Intravenous,
– Topical
• Directly applied to skin
– Mucosal
Pharmaceutics
**Forms/designs of drugs:
• Oral
– Tablets, capsules, powder, liquid, elixir, suspension
– EC, ER, SR
• Enteral
– Meds given via NG or feeding tube (solid or liquid)
– Crushed meds – must be dissolved
• Rectal
– Suppositories, creams, enema
– Also considered as ENTERAL route
• Parenteral
– Injections (solutions, powder)
Pharmaceutics
• Topical
– Ointments, creams, pastes, powders,
patches
• Mucosal
– eye, ear, nasal, vaginal
• Inhaled
Pharmaceutics
Drug Dissolution & Absorption
**Drugs must dissolve 1st (before absorbed)
Oral Preparations
Liquids, elixirs, syrups
Suspension solutions
Powders
Capsules
Tablets
Enteric coated tablets
Extended release tablets
Fastest
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Slowest
*Extended Release (forms) = SR (slow release), CR
(controlled release), XL (extended length)
Pharmaceutics
• Drug Dissolution & Absorption
• Parenteral Preparations
»Do NOT have to dissolve 1st
»Subcutaneous, Intramuscular
»Intravenous
*directly into bloodstream
*immediate absorption
Pharmacokinetics
Study of what happens to a drug from
entrance into body until it leaves the body
4 phases
 Absorption
 Distribution
 Metabolism
 Excretion
Pharmacokinetics - absorption
Absorption
 Occurs after dissolution of drug
 Drug → GI tract → blood/body fluids → tissue
 Affected by form of drug
 Affected by ROUTE of administration (oral,
parenteral,etc.)
Pharmacokinetics—Absorption
Factors That Affect Absorption
• Administration route
• Dosage formulation
• Food or fluids administered with the drug
• Grapefruit, fruit juices, antacids, fat soluble vitamins
• Rate of blood flow to the small intestine
• Acidity of the stomach
• Status of GI motility
Pharmacokinetics - Absorption
Bioavailability
 Extent of drug absorption
 Amount of drug actually available to circulation
 Depends upon “first pass effect”
Pharmacokinetics - absorption
First Pass effect
 Drugs must dissolve & be absorbed by GI tract
 Must pass through LIVER before reaching circulation
(bloodstream)
 Drug
GI system
Portal vein
Hepatic vein
Heart (distribution)
Liver
 Liver may metabolize drug into smaller metabolites
 Therefore, less amount of drug will pass into
circulation
 Intravenous drugs = no “first pass” in liver
Pharmacokinetics—Absorption
Oral/Enteral Route
• Drug is absorbed into the systemic circulation
through the oral or gastric mucosa, the small intestine, or
rectum
– Oral – high “first pass” effect
– Sublingual – dissolve under tongue, highly vascular
area, these drugs bypass liver, no “first pass” effect
– Buccal – same as sublingual
– Rectal (suppository or topical) – rectal drugs have
SOME “first pass” effect
Pharmacokinetics — Absorption
• Routes that bypass the liver:
– Sublingual
– Buccal
– Rectal*
– Intravenous
– Intranasal
Transdermal
Vaginal
Intramuscular
Subcutaneous
Inhalation
*Rectal drugs may have some degree of first-pass
effect
Pharmacokinetics—Absorption
Parenteral Route
*No “first pass” effect
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Intravenous*
Intramuscular
Subcutaneous
Intradermal
Intraarticular (physician)
*Fastest delivery into the blood circulation
Pharmacokinetics—Absorption
Topical/Mucosal Route
Skin
 Includes transdermal route, patches
Eyes
Ears
Nose
Vagina
Topicals = slower onset, longer duration
No “first pass” effect, bypass liver
Exception = rectal
Pharmacokinetics —Distribution
Transport of drug by bloodstream to site of
action
Areas of “rapid” distribution
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Heart
Liver
Kidneys
Brain
Areas of “slower” distribution
 Muscle
 Skin
 Fat
Areas “difficult” to reach
 Bone
 Blood brain barrier **
Pharmacokinetics - distribution
• BLOOD BRAIN BARRIER
– Restricts passage of various chemicals between
the bloodstream and the central nervous system
– CNS = brain, spinal cord
– BBB
» allows oxygen to pass
» may restrict certain bacteria & viruses
» Not all meds can pass through
Pharmacokinetics - distribution
• Distribution depends upon protein-binding
• Albumin = most common blood protein,
carries protein-bound drug molecules
• “bound” portion of drug =
pharmacologically inactive
• “unbound” portion = pharmacologically
active
– Easily distribute to body tissues (outside of
blood
vessels) and reach site of action
• Lasix, Coumadin, Aspirin
Pharmacokinetics —Metabolism
• aka “Biotransformation”
• Process by which a drug is biochemically
altered
– inactive metabolite (compound)
– more potent, active metabolite
– Less potent, active metabolite
• LIVER – most responsible for metabolism of
drugs
• Also involved = kidneys, lungs, skeletal
muscle, intestines
Pharmacokinetics — Metabolism
Factors that decrease metabolism:
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Cardiovascular dysfunction
Kidney failure
Liver failure
Genetics
Starvation
Factors that increase metabolism:
• Certain drugs (dilantin, barbiturates, rifampin)
Pharmacokinetics —Metabolism
Delayed drug metabolism results in:
• Accumulation of drugs (toxicity)
• Prolonged action of the effects of drugs
Pharmacokinetics — Excretion
• Elimination of drugs from the body
• All drugs must eventually be excreted
• Kidney = organ most responsible for
excretion of drugs (urine)
• Also, liver (bile), bowel (feces), sweat
glands
• Liver metabolizes most drugs, kidney
excretes what is “left behind”
• Kidneys can also metabolize certain drugs
– insulin
Pharmacokinetics — Half-Life
• Time required to eliminate (½) 50% of a drug
• Example:
• Digoxin - 36 hr. half-life
• Takes 7.5 days to clear
• Takes 5–6 half-lives to eliminate ~ 98% of a
drug
• Liver or kidney disease
– Can prolong half-life
– Increases risk of toxicity
Pharmacokinetics –
Onset—Peak—Duration
Onset
• The time it takes for the drug to elicit a
therapeutic response
• Insulin: 10-20 min
Peak
• The time it takes for a drug to reach its maximum
therapeutic response
• 30-60 min
Duration
• The time a drug concentration is sufficient to elicit a
therapeutic response
• 2-4 hours
PHARMACOKINETICS –
ONSET-PEAK-DURATION
• Peak
– Peak effect, maximum therapeutic
response
– Highest blood level of the drug
– If too high = toxicity of drug
• Trough
– Lowest blood level of the drug
– If too low, then may not be therapeutic
Onset-Peak-Duration
Pharmacokinetics: Example
• Furosemide (LASIX)
• Pharmaceutics: Tablet, Oral solution, Injection
• Pharmacokinetics:
– Absorption: Bioavailability = 64% tablet, 60% oral
soln, 100% IV
• Tablet, oral soln – 60 min. delay if taken w/ food
– Distribution: highly protein bound to albumin, 9199%
– Metabolism: metabolized in liver
– Elimination: excreted by kidneys
– Onset: 1 hr. (oral)
5 minutes (IV)
*store
– Peak:
1-2 hr. (oral) ½ hr. (IV)
room
– Duration: 6-8 hrs. (oral) 2 hrs. (IV)
temp
Pharmacodynamics
 Mechanism of drug action - how drugs act at
sites of activity
 Involves receptors and enzymes
 Not all drugs have a known mechanism of action
 Most drugs produce more than one effect
Therapeutic effect – desired or primary effect
Secondary effect – may be desirable or not
1. Drug-receptor interaction: drug binds to a receptor
site on cell surface, causes or blocks an action
2. Enzyme interaction: drug binds to enzyme molecule &
either enhances or inhibits its action
3. Nonselective interactions: do not bind to enzyme or
receptor, act on cell membrane or cell wall
Pharmacodynamics
• Drug-Receptor Interaction
– Drug binds to specific receptor
• Alters cell function
• Produces desired effect
• Can bind completely or partially
– Agonists
• Drugs that bind and produce desired effect
– example, Morphine
– Antagonist
• Drugs that block agonist effect at binding site
– example, Narcan, reverses effect of narcotic
– Example, Toprol, beta-blocker, lowers HR
Pharmacodynamics
• Enzyme Interaction
– Drug interacts with enzyme system
• Inhibits the action of the enzyme
• The action of the cell is changed or altered
» Example: ACE inhibitor (Lisinopril)
» Inhibits conversion of angiotensin I to
angiotensin II
Pharmacotherapeutics
• The treatment of pathologic conditions
through the use of drugs
“drug therapy”
• Desired therapeutic outcome
– Should be established before drug started
– What is expected ?
• Must be measurable and realistic
• Progress must be monitored (example =
antibiotics)
Pharmacotherapeutics
• Types of therapy
– Acute
– Maintenance
– Supplemental
– Palliative
– Supportive
– Prophylactic
– Empiric
Pharmacotherapeutics
• Acute therapy
– Involves more intensive drug therapy
– Used in the acutely or critically ill
– Example: to maintain heart rate or BP
– Usually needed to maintain life
– ie – dopamine (vasopressor to maintain BP)
• Maintenance therapy
– May not cure but prevents progression of disease
• May prevent progression
– Used in chronic illnesses (example: hypertension, diabetes)
– ie – lisinopril, oral contraceptives
Pharmacotherapeutics
• Supplemental therapy
– Replaces body substances needed to maintain normal
functioning
• May not be produced by the body
• Produced in insufficient amounts
• Example: Insulin
• Palliative therapy
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Goal is to provide comfort
Used in end stage illnesses
Usually all other therapy has failed
Example: Morphine for pain
Pharmacotherapeutics
• Supportive therapy
– Maintains integrity of body functions while
patient recovering from illness
– Examples
• Providing fluids/electrolytes to prevent
dehydration
– In vomiting or diarrhea
• Blood products or blood volume expanders
– Blood loss during surgery
Pharmacotherapeutics
• Prophylactic therapy
– Used to prevent illness
– Example: pre-op antibiotics, vaccines
• Empiric therapy
– Use of a drug based on probability, certain
illness/disease has likelihood of occurrence
– Example: Antibiotic for UTI before actual
diagnosis
Adverse Effects - Monitoring
• Adverse effects – unintended effects
• Side Effects
• Therapeutic index – ratio of toxic level to
therapeutic level
– Low therapeutic index: difference between toxic
and therapeutic dose is low – dangerous !
– Example: coumadin (anticoagulant)
• Tolerance – Pts. decreasing response to
repeated doses
– ie – valium, pain meds
• Dependence – Physiologic or psychologic need
for drug
• addiction
Adverse Effects – Monitoring
Patient’s condition - Physiological
• Age
– Infants & children need ↓ dose
• Immature organ function
– Elderly may require ↓ dose
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Decreased gastric acidity
Dry mouth/decreased saliva
Decreased liver blood flow/mass
Increased body fat, decreased muscle mass
Decreased kidney function
Adverse Effects – Monitoring
Patient’s condition - Physiological
• Weight
– Average = 150lb
– Dosage adjustments
• Large weight differences
• Gender
– Women
• Smaller
• Different fat/water ratio
• May need dosage adjustments
Adverse Effects – Monitoring
Patient’s condition - Pathological
• Liver/kidney disease
– Inability to metabolize/excrete one normal dose
before next drug given
– Leads to drug toxicity
– Lower doses are frequently given
• Liver disease
• Kidney disease
Adverse Effects
• Allergic Reactions (hypersensitivity)
– Usually begins after 2nd dose or more
– May occur within minutes or delay for hours or
even days
– Immune system views “drug” as foreign
substance
– Histamine is released
– S/S = skin rashes, hives, itching (urticaria or
pruritis), facial swelling, difficulty breathing,
sudden LOC, throat swelling (angioedema),
wheezing
– Anaphylactic Shock
• Severe allergic rx, severe respiratory distress, life
threatening
• Mr. Carter has a rash and pruritis. You suspect
an allergic reaction and immediately assess
him for other more serious symptoms. What
question would be most imortant to ask Mr.
Carter ?
Adverse Effects
• Idiosyncratic reaction: unexpected reaction in a
particular patient, not common reaction
• Pharmacogenetics: study of genetic traits that
result in abnormal metabolism of drugs
• ie: coumadin, codeine, psych drugs (chap. 5)
• Teratogenic effects: result in structural defects of
in fetus
• FDA – 5 categories (A,B,C,D,X) of teratogens
– Category A – studies show NO risk (multivitamin)
– Category X – Completely contraindicated in
pregnancy, HIGH fetal risk
Teratogens
Category A
No risk to fetus in first, second or third trimesters
Category B
Studies have not shown fetal risk in animals, but no controlled studies in
pregnant women
Considered safe in all trimesters (benadryl,tylenol,PCN)
Category C
Animal studies have revealed adverse effects on fetus
Drugs should be given only if benefit outweighs risk
Category D
Positive evidence of harm to fetus
Use may be acceptable absolutely necessary (life threatening situations)
Category X
Studies have shown fetal abnormalities, drug is completely contraindicated
(acutane)
Pharmacognosy
• The study of natural drug sources
– Plants
– Animals
• Four main sources of drugs
– Plants
– Animals
– Source of many hormone drugs (premarin – urine of pregnant
mares; insulin – pigs & humans; heparin – pigs)
– Minerals (salicylic acid, sodium chloride)
– Laboratory synthesis
Drug Classifications
• Place drugs in similar categories
– Similar general use
– Similar mechanisms of actions
– Similar contraindications
– Similar precautions
– Similar nursing implications
Drug Classifications
• Examples:
– Antibiotics
– Antihypertensives
– Antiepileptics
– Sedatives
– Anesthetics
– Decongestants
– Antineoplastics
– Etc.
Drug References
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Physicians Desk Reference (PDR)
U.S. Pharmacopia
National Formulary
Various Nursing Drug
Handbooks/References
– Davis Drug Guide