Pharmacologic Principles Chapter 2

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Pharmacologic
Principles Chapter 2

• Catherine Luksic BSN, RN
• Level I

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Pharmacology

• DRUG
• Any chemical that affects the physiologic
  processes of a living organism
• PHARMACOLOGY
• Study (science) of drugs
• Includes
• Absorption
• Distribution
• Metabolism
• Excretion
• Mechanism of Action
• Therapeutic effects
• Adverse effects

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Pharmacology

• Subspecialty Areas of Pharmacology
• Pharmaceutics
• Pharmacokinetics
• Pharmacodynamics
• Pharmacotherapeutics
• Pharmacognosy
• Toxicology
• NURSES MUST UNDERSTAND BASIC PRINCIPLES OF
  PHARMACOLOGY
• Therapeutic and Toxic
• SAFETY !

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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

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Pharmacology Drug Development
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Pharmaceutics

• Process of turning chemicals into safe
  medications
• Science of dosage form design
• ie tablet, capsule, liquid, powder, etc.
• Study of how various dosage forms/designs
  influence a drugs metabolism and use in the body
• Design that will allow drug molecules to bind to
  a target site

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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

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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)

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Pharmaceutics

• Topical
• Ointments, creams, pastes, powders, patches
• Mucosal
• eye, ear, nasal, vaginal
• Inhaled

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Pharmaceutics

• Drug Dissolution Absorption
• Drugs must dissolve 1st (before absorbed)
• Oral Preparations
• Liquids, elixirs, syrups FastestSuspension
  solutions êPowders êCapsules êTablets êEnteric
  coated tablets êExtended release
  tablets Slowest
• Extended Release (forms) SR (slow release), CR
  (controlled release), XL (extended length)

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Pharmaceutics

• Drug Dissolution Absorption
• Parenteral Preparations
• Do NOT have to dissolve 1st
• Subcutaneous, Intramuscular
• Intravenous
• directly into bloodstream
• immediate absorption

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Pharmacokinetics

• Study of what happens to a drug from entrance
  into body until it leaves the body
• 4 phases
• Absorption
• Distribution
• Metabolism
• Excretion

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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.)

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PharmacokineticsAbsorption

• Factors That Affect Absorption
• Administration route
• Dosage formulation
• Food or fluids administered with the drug
• Grapefruit, fruit juices, antacids, fat soluble
  vitamins, iron
• Rate of blood flow to the small intestine
• Acidity of the stomach
• Status of GI motility

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Pharmacokinetics - Absorption

• Bioavailability
• Extent of drug absorption
• Amount of drug actually available to circulation
• Depends upon first pass effect
• Example Aspirin
• Has high first pass effect

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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
  Liver
• Hepatic vein Circulation
  (distribution)
• Liver may metabolize drug into smaller
  metabolites
• Therefore, less amount of drug will pass into
  circulation
• Intravenous drugs no first pass in liver

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PharmacokineticsAbsorption

• 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

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Pharmacokinetics Absorption

• Routes that bypass the liver
• Sublingual Transdermal
• Buccal Vaginal
• Rectal Intramuscular
• Intravenous Subcutaneous
• Intranasal Inhalation
• Rectal drugs may have some degree of first-pass
  effect

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PharmacokineticsAbsorption

• Parenteral Route
• No first pass effect
• Intravenous
• Intramuscular
• Subcutaneous
• Intradermal
• Intraarticular (physician)
• Fastest delivery into the blood circulation

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PharmacokineticsAbsorption

• 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

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Pharmacokinetics Distribution

• Transport of drug by bloodstream to site of
  action
• Areas of rapid distribution
• Heart
• Liver
• Kidneys
• Brain
• Areas of slower distribution
• Muscle
• Skin
• Fat
• Areas difficult to reach
• Bone
• Blood brain barrier

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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

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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, Digoxin

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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

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Pharmacokinetics Metabolism

• Factors that decrease metabolism
• Cardiovascular dysfunction
• Kidney failure
• Liver failure
• Genetics
• Starvation
• Factors that increase metabolism
• Certain drugs (dilantin, barbiturates, rifampin)

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Pharmacokinetics Metabolism

• Delayed drug metabolism results in
• Accumulation of drugs (toxicity)
• Prolonged action of the effects of drugs

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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

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Pharmacokinetics Half-Life

• Time required to eliminate (½) 50 of a drug
• Example
• Digoxin - 36 hr. half-life
• Takes 7.5 (up to 9) days to clear
• Takes 56 half-lives to eliminate 98 of a drug
• Liver or kidney disease
• Can prolong half-life
• Increases risk of toxicity

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of half lives remainder of drug
1 50
2 25
3 12.5
4 6.25
5 3.125
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Pharmacokinetics OnsetPeakDuration

• 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

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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

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Onset-Peak-Duration(Vancomycin example)
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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,
  91-99
• 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

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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

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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

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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

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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)

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Pharmacotherapeutics

• Types of therapy
• Acute
• Maintenance
• Supplemental
• Palliative
• Supportive
• Prophylactic
• Empiric

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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

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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
• Goal is to provide comfort
• Used in end stage illnesses
• Usually all other therapy has failed
• Example Morphine for pain

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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

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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

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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

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Adverse Effects Monitoring

• Patients condition - Physiological
• Age
• Infants children need ? dose
• Immature organ function
• Elderly may require ? dose
• Decreased gastric acidity
• Dry mouth/decreased saliva
• Decreased liver blood flow/mass
• Increased body fat, decreased muscle mass
• Decreased kidney function

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Adverse Effects Monitoring

• Patients condition - Physiological
• Weight
• Average 150lb
• Dosage adjustments
• Large weight differences
• Gender
• Women
• Smaller
• Different fat/water ratio
• May need dosage adjustments

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Adverse Effects Monitoring

• Patients 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

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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

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• 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 ?

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• A 78 y.o. man who has been diagnosed with a URI
  tells the nurse that he is allergic to Penicillin
  (PCN). Which is the most appropriate response by
  the nurse ?
• 1. thats to be expected, lots of people are
  allergic to penicillin
• 2. this allergy is not a big concern right now
• 3. what type of reaction did you have when you
  took penicillin ?
• 4. drug allergies dont usually occur in older
  individuals

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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

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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, coumadin)
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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

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Drug Classifications

• Place drugs in similar categories
• Similar general use
• Similar mechanisms of actions
• Similar contraindications
• Similar precautions
• Similar nursing implications

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Drug Classifications

• Examples
• Antibiotics
• Antihypertensives
• Antiepileptics
• Sedatives
• Anesthetics
• Decongestants
• Antineoplastics
• Etc.

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Drug References

• Physicians Desk Reference (PDR)
• U.S. Pharmacopia
• National Formulary
• Various Nursing Drug Handbooks/References
• Davis Drug Guide