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					   Pharmacology

The Study of Drugs and Their
    Actions on the Body
      Topic to be Discussed:
 Pharmacology, a historical perspective
 Drug sources
 Drug legislation
 Drug names
 Drug forms
       Historical Perspective
 Drugs were used
  to treat common
  ailments as far
  back as the earliest
  written documents.
 The Egyptians and
  Greeks were the
  first to use plant
  and animal
  sources of drugs
                   Drug Sources
   Plant
       Alkaloids (“ine”)
          Morphine   from the
           opium poppy
          Atropine from the
           Nightshade plant
           (Belladonna alkaloid)
     Glycosides (“in”)
     Gums
     Resins
     Oils
                Drug Sources

   Animal
     Hormones
        Insulin
        Oxytocin
     Oils and fats
     Enzymes
     Vaccines
                  Drug Sources
   Mineral
       Sodium Bicarbonate
       Magnesium Sulfate
       Iron
       Iodine
       Epson salts
                    Drug Sources
   Synthetic
       Lidocaine
       Diazepam
              Drug Legislation
   1906, the Pure Food and Drug Act
     Prohibited the sale of medicinal preparations
      with little or no use
     Restricted the sale of drugs with potential for
      abuse
   Named the United States Pharmacopeia
    (USP) and the National Formulary (NF) as
    official drug standards.
             Drug Legislation
   1914, The Harrison Narcotic Act
     Served to control the importation,
      manufacture, and sale of opium and it’s
      derivatives.
     Control the importation, manufacture, and
      sale of derivatives of the coca plant
     These drugs could only be obtained legally by
      a physician who qualified and attained a
      special narcotic license.
                   Drug Legislation
   1938, the Federal Food, Drug, and Cosmetic
    Act
     Truth-in-labeling clause
     Directions for use
     Labels must indicate if habit forming drugs are
      present and in what percentage.
     Durham-Humphrey Amendments, 1951.
         Drewclearer distinction between prescription-only and
          OTC medications.
       Kefauver-Harris Drug Amendments, 1962.
         Thalidomide, birth defects
         Required that drugs be proven effective for intended use
          Drug Legislation
 The Comprehensive Drug Abuse
  Prevention and Control Act of 1970
  (The Controlled Substance Act)
 Classified drugs into 5 schedules based
  on potential for abuse.
              Drug Schedule
   Schedule I, high potential for abuse with no accepted
    medical use. Heroin, marijuana, LSD
   Schedule II, high potential for abuse with medical
    uses. Morphine, cocaine, some amphetamines are in
    this group.
   Schedule III, lesser potential for abuse. Codeine as in
    Tylenol 3.
   Schedule IV, drugs with low potential for abuse, but
    which may cause physical or psychological
    dependence. Valium.
   Schedule V, low potential for abuse. Cough
    medicines with codeine or narcotic anti-diarrheal
    medicines.
                Drug Names
   Drugs are identified by 4 different names:
     Chemical names, the chemical composition
     Generic names, an abbreviated of the
      chemical name
     Trade name, the name given to a drug by the
      manufacturer (always capitalized)
     Official name, as listed in the United States
      Pharmacopeia or National Formulary and will
      always include either USP or NF
              Drug Classification
   Based on:
       The chemical structure
       The main effect
       The therapeutic use
       The mechanism of
        action
            Drug Names
Chemical  Name: 2-(diethylamino)-2’,6’-
acetooxylid monohydrochloride
monohydrate.
            Drug Names
 Generic Name: lidocaine hydrochloride
 Official Name: Lidocaine Hydrochloride,
  USP
 Brand (Trade) Name: Xylocaine®
                     Drug Forms
   Liquid
       Solutions, drug dissolved in a solvent
       Tinctures, drug extracted chemically with alcohol
       Suspensions, drugs do not remain dissolved and will
        separate after sitting for even short periods
       Spirits, solutions that contain volatile chemicals
        dissolved in alcohol
       Emulsions, oily preparations mixed with a solvent into
        which it does not dissolve
       Elixirs, preparations that contain a drug in an alcohol
        solvent, often flavored to improve taste
       Syrups, drugs suspended in sugar and water to
        improve taste
                     Drug Forms
   Solids
       Pills, drugs that are pressed and shaped into form that
        makes them easy to swallow
       Powders, drugs that are mixed with a solvent like water
        and drank
       Capsules, gelatin containers into which a drug is
        placed.
       Tablets, like pills, but are usually coated to improve
        taste and facilitate swallowing
       Suppositories, drugs mixed with a base that remains
        solid at room temperatures, but dissolved when placed
        rectally or vaginally and are absorbed by surrounding
        tissue.
      What is Pharmacology ?
Pharmacokinetics                  Pharmacodynamics
What the body does to drug        What the drug does to body



                      Pharmacology

  Pharmacotherapeutics                  Pharmacocognosy
The study of the use of drugs   Identifying crude materials as drugs


                           Toxicology
             Pharmacokinetics
   How a drug enters the body, reaches the site
    of action, and is eventually eliminated.
   Basically, what the body does to the drug.
                           Liberation
   Applies to drugs given orally
   Components
       Release of drug from pill, tablet, or capsule
       Dissolving of active drug in GI fluids
            Enteric coated aspirin slow absorption
                  Absorption
   Movement from administration site into
    circulation
           Drug Absorption
 Solubility of the drug. The tendency of a drug
  to dissolve.
 Concentration of the drug. Affects rate of
  absorption.
 pH of the drug. Acidic drugs more rapidly
  absorbed in an acidic environment.
 Site of absorption. Biologic membranes to
  pass through.
 Absorbing surface area. Large or small,
  smooth or rough.
 Blood supply to the site of absorption
  Membranes and Absorption
                           Lipid Bilayer
             Hydrophilic
             Heads                         Hydrophobic
                                           Tails
Small,       H2O, urea,
uncharged                                   Inside the
             CO2, O2, N2                    cell

Large,      Glucose                         DENIED!
uncharged   Sucrose
Small
charged     H+, Na+, K+,
ions        Ca2+, Cl-,                      DENIED!
            HCO3-
  LaChatlier’s Principle

                  A reaction at equilibrium
                   responds to stress in a
                    way to best return to
  System
                        equilibrium
    at
Equilibrium

4 Na+   + 4 Cl_             4 NaCl
            Ionization


Acids     Release/Donate H+
                                  Ionized
HA              H + + A-           form

Bases     Bind/Accept H+

H+ + B-           HB          Non-ionized
                                 form
         pH and the Environment
   Acidic drugs are best absorbed from acidic
    environments.
       To increase absorption of an acidic drug,
        acidify the environment. Or to decrease the
        absorption of an acidic drug alkalinize the
        environment.
   Base drugs are best absorbed from
    alkaline environments.
             Blood-Brain Barrier
   Central administration is necessary for
    drugs that cannot cross the blood-brain
    barrier.
       Over 100 years ago, blood-brain barrier
        discovered when blue dye injected into
        cadavers. Everything in the body turned blue,
        except the brain and spinal cord.
          The Blood-Brain Barrier
   Not fully
    formed at
    birth
   Consists of
    tight
    junctions of
    endothelial
    cells.
Functions of the Blood-Brain Barrier
 Protects the brain from ‘foreign
  substances’ in the blood that may injure
  the brain.
 Protects the brain from hormones and
  neurotransmitters in the rest of the body.
 Maintains a constant environment for the
  brain.
                     Distribution
The transportation of a drug from the site of
  absorption to the site of action.
Dependent on:
 Cardiovascular function
 Regional blood flow
 Drug storage reservoirs
 Physiologic barriers
      Lipid-soluble drugs easily pass through cell
       membranes, water soluble drugs do not.
      Lipid-soluble drugs can cross the blood-brain barrier
      Only free drugs can produce a therapeutic effect.
          Biotransformation
 The process by which drugs are converted
  to an inactive, more water-soluble form
  that can be excreted.
 Some drugs (prodrugs) are inactive when
  administered, and are converted to an
  active form after metabolized in the body.
 Also called drug metabolism.
          Drug Metabolism
 The majority of drugs are metabolized in
  the liver.
 Some drugs are metabolized in the
  plasma, kidneys, or intestines.
 Drug metabolism can be affected by: liver
  disease, heart failure, genetics,
  environment, and developmental changes.
Hepatic ‘First Pass’ Metabolism
 Affects orally administered drugs
 Metabolism of drug by liver before drug
  reaches systemic circulation
 Drug absorbed into portal circulation, must
  pass through liver to reach systemic
  circulation
 May reduce availability of drug
           Elimination / Excretion
 Drugs are eliminated in their original form or
  as metabolites.
 Drugs are excreted by the kidneys in urine,
  by the liver in bile, by the intestines in feces,
  by the skin, and by the lungs with expired air.
 The rate of elimination varies with the
  medication and the general health of the
  body.
 Half-life (t1/2)
       The time required for the plasma concentration
        of a drug to be reduced by 50%
     Onset, Peak, and Duration
 Onset of action - the time interval that starts
  when a drug is administered and ends when
  the therapeutic effect actually begins.
 Peak concentration - reached when the
  absorption rate equals the elimination rate
  (not always the same time of peak
  response).
 Duration of action - the length of time the
  drug produces its therapeutic effect.
           Pharmacodynamics
   What the drug does to the body. The study
    of the drug mechanisms that produce a
    biochemical and / or physiologic change.
     Drug receptors
     Effects of the drug
     Responses to the drug
     Toxicity and adverse effects to the drug
            Pharmacodynamics
 A drug can modify cell function or the rate of
  function, but it cannot impart a new function
  to a cell or tissue.
 A drug alters target cells by:
     Modifying the cell’s physical or chemical
      environment.
     Interacting with a receptor.
     Second messengers
         Relay signals received at receptors on the cell
          surface.
         Serve to amplify the strength of the signal.
     Receptor Interactions
          Lock and Key Mechanism




Agonist      Receptor




                           Agonist-Receptor
                              Interaction
       Receptor Interactions


Induced Fit
(Ligand Docking)


                   Receptor




   Perfect Fit!
          Receptor Interactions

Competitive
Inhibition




     Antagonist   Receptor




                               Antagonist-Receptor
                     DENIED!
                                    Complex
       Receptor Interactions

Non-competitive          Antagonist
Inhibition




  Agonist         Receptor




                         DENIED!
        Non-receptor Mechanisms
   Actions of Enzymes
       Enzymes = Biological catalysts
          Speed  chemical reactions
          Are not changed themselves

     Drugs altering enzyme activity alter processes
      catalyzed by the enzymes
     Examples
                        inhibitors
          Cholinesterase
          Monoamine oxidase inhibitors
        Non-receptor Mechanisms
   Changing Physical Properties
       Mannitol
          Changes osmotic balance across membranes
          Causes urine production (osmotic diuresis)
        Non-receptor Mechanisms
   Changing Cell Membrane Permeability
       Lidocaine
          Blocks   sodium channels
       Verapamil
          Block   calcium channels
       Bretylium
          Blocks   potassium channels
       Adenosine
          Opens    potassium channels
         Pharmacodynamics
 Agonist drugs - when a drug displays an
  infinity or attraction for a receptor and
  stimulates it.
 Intrinsic activity - the drug’s ability to
  initiate a response after binding with the
  receptor.
 Antagonist drugs - A drug that has an
  affinity for a receptor but displays no
  intrinsic activity
         Pharmacodynamics
 Competitive antagonist - competes with
  the agonist for receptor sites. Giving larger
  doses of the agonist can overcome the
  antagonist effects.
 Noncompetitive antagonist - binds to
  receptor sites and blocks the effects of the
  agonist. Giving larger doses of the agonist
  can’t reverse its action.
        Pharmacodynamics
 Some drugs act on a variety of receptors,
  therefore are nonselective and can cause
  multiple and widespread effects.
 Some receptors are classified by their
  specific effects.
 Drug potency - refers to the relative
  amount of a drug required to produce its
  desired response.
         Pharmacodynamics
 Dose-response curve - used to graphically
  represent a relationship between the dose
  of a drug and the response it produces.
 Maximum effectiveness - when an
  increase in dose yields little or no increase
  in response.
 Margin of safety (therapeutic index) - the
  relationship between a drug’s desired
  therapeutic effects and its adverse effects.
           Pharmacodynamics
 Therapeutic index - measures the
  difference between an effective dose for
  50% of the patients treated and the
  minimal dose at which adverse reactions
  occur.
 Drugs with a low therapeutic index have a
  narrow margin of safety.
     Digitalis has a TI of 2
     PCN has TI of > 100
Pharmacodynamics
Time Response Relationships

                     Maximal (Peak) Effect



Effect/
Response



           Latency   Duration of Response
                       Time
Time Response Relationships



           IV   IM
                            SC
Effect/
Response



                     Time
                   Potency

                      A               B
                                          Therapeutic
                                          Effect

Effect




                     Dose
         Which drug is more potent?
  Dose Response Relationships
                                  B

                       A
                                      Therapeutic
                                      Effect
     Effect




                     Dose
Which drug has the lower threshold dose?
Which has the greater maximum effect?
    Dose Response Relationships
   Loading dose
       Bolus of drug given initially to rapidly reach
        therapeutic levels
   Maintenance dose
       Lower dose of drug given continuously or at
        regular intervals to maintain therapeutic levels
      Pharmacotherapeutics
 The use of drugs to treat disease.
 Acute therapy - critical illness.
 Empiric therapy - based on practical
  experience not scientific data.
 Maintenance therapy - chronic illness.
 Supplemental (replacement) therapy -
  replenish or substitute for missing
  substances in the body.
      Pharmacotherapeutics
 Supportive therapy - doesn’t treat the
  cause of disease but maintains other
  threatened body systems until the condition
  resolves.
 Palliative therapy - comfort care for end-
  stage or terminal diseases.
 Factors affecting drug response - age,
  cardiovascular, gastrointestinal, hepatic,
  and renal function, diet, disease, drug
  interactions, infection, sex.
      Pharmacotherapeutics
 Drug tolerance - a decreased response to
  a drug over time requiring larger doses to
  produce the same response.
 Drug dependence - a physical or
  psychological need for a drug. Physical
  dependence produces withdrawal
  symptoms when the drug is stopped and
  psychological dependence results in drug-
  seeking behaviors.
          Drug Interactions
 Occur between drugs or between drugs
  and food.
 Additive effect - can occur when two drugs
  with similar actions are administered
  resulting in an effect equivalent to the sum
  of the effects of either drug administered
  alone in higher doses.
          Drug Interactions
 Synergistic effect (potentiation) - occurs
  when two drugs that produce the same
  effect are given together and one drug
  potentiates or enhances the effect of
  another drug resulting in a greater effect
  than if the drugs were taken alone.
 Antagonistic effect - occurs when the
  combined response of two drugs is less
  than the response produced by either drug
  alone.
           Drug Interactions
 Two drugs given together can affect the
  absorption of one or both drugs by
  changing the acidity of the stomach or
  forming insoluble compounds.
 When two drugs are given together, they
  can compete for protein-binding sites,
  leading to an increase in the effects of the
  drug that becomes a free unbound drug.
          Drug Interactions
 Drug metabolism and excretion can be
  inhibited by other drugs.
 Drug interactions can alter some lab
  studies.
 Interactions between drugs and food can
  alter the therapeutic effects of the drug.
 Food can alter the rate and amount of
  drug absorbed from the GI tract affecting
  bioavailability (the amount of drug
  available to the systemic circulation).
     Adverse Drug Reactions
 Dose-related or patient-sensitivity-related.
 A harmful, undesirable response (side
  effect or adverse effect).
 Dose-related reactions: secondary effects,
  hyper-susceptibility, overdose, iatrogenic
  (caused by medical personnel) effects.
 Secondary effects - a drug producing not
  only a therapeutic effect but also a
  secondary effect as well.
     Adverse Drug Reactions
 Hyper-susceptibility - experiencing an
  excessive therapeutic response or
  secondary effects.
 Overdose - occurs when an excessive
  dose is taken either intentionally or
  unintentionally resulting in an exaggerated
  response to the drug.
 Iatrogenic effects - mimic pathologic
  disorders.
     Adverse Drug Reactions
 Patient-sensitivity-related adverse
  reactions: drug allergy or idiosyncratic
  response.
 Drug allergy - occurs when a patient’s
  immune system identifies a drug as a
  dangerous foreign substance that must be
  neutralized or destroyed.
 Allergic reactions range from rash and
  itching to anaphylactic shock.
       Adverse Drug Reactions
   Idiosyncratic
    response - specific
    to the individual
    patient sometimes
    having a genetic
    cause.
        Weights and Measures
   Metric conversions
     Kilo = 1000
     Hecto = 100
     Deka = 10
     Fundamental unit = 1 (gram, liter, meter)
     Deci = 1/10
     Centi = 1/100
     Milli = 1/1000
     Micro = 1/1,000,000
                 Apothecary System
   Grains to milligrams
     1 grain = 60 milligrams
     1/2 grain = 30 milligrams
     1/4 grain = 15 milligrams
     1/8 grain = 7.5 milligrams

    A physician has ordered you to
    give 1/8th grain MSO4 to a
    patient with a fractured hip. You
    have 10mg/10ml. How many ml
    will you administer?
              Apothecary System
   Volume
       16 minims = 1 ml
       1 fluid dram = 4 ml
       1 oz = 30 ml
       1 pint = 16 oz or 480 ml
       1 quart = 32 oz or 960 ml
   Weight
       1/60 grain = 1 mg
       1 grain = 60 mg or 0.06 grams
       15 grains = 1 gram, 1000 mg
       2.2 pounds = 1 kilogram
       1 mg = 1000 µg (microgram)
          Drug Formulation
 Dosage = the amount of drug to be
  administered. (usually based on weight)
 Concentration = how much drug is there in
  relationship to volume. (mg/ml)
 Injection volume = a volume measurement
  based on weight. (ml/kg)
     Six Rights of Medication
          Administration
 Right Medication
 Right Dose
 Right Time
 Right Route
 Right Patient
 Right Documentation
              Drug Administration
   Enteral (Alimentary Tract)
       Oral
       Sublingual
       Rectal
   Parenteral (Not within the alimentary canal)
       Topical, intradermal, subcutaneous
       Inhalation, sublingual injection
       IM, IV, IO, ETT, IC
       Vaginal
   Central
       Directly into the brain or spinal cord
        Routes of Administration
   Common abbreviations
     PO = per os = oral
     IV = intravenous = into the vein
     IM = intramuscular = into the muscle
     SC = subcutaneous = between the skin and
      muscle
     IP = intraperitoneal = within the peritoneal cavity
     icv = intracerebroventricular = directly into the
      ventricle of the brain
              Drug Calculations
Injections:
Amount to be given = (volume on hand)(desired dose)
                           concentration


Infusions:
(volume on hand) (desired dose) x drip set = gtts/min
           concentration
        Pregnancy Considerations
   Increased maternal HR, CO and blood
    volume
       May affect absorption, distribution,
        effectiveness
 Drugs may cross placenta
 Drugs may cross into breast milk
 Tertatogens
       Pregnancy Categories
 A: controlled studies in pregnancy (<1 %).
 B: animal studies show no risk;
  Inadequate human data.
 C: animal studies show risk, inadequate
  human data.
 D: human data show risk, benefit may
  outweigh risk.
 X: animal or human data positive for risk.
  Use unwarranted.
         Pediatric Considerations
  Oral absorption
 Thinner skin ( topical absorption)
  Plasma protein concentration
        Free protein-bound drug availability
  Extracellular fluid in neonate
 Altered metabolic rates
  Elimination/metabolism
 BSA/weight based dosing important!
     Geriatric Considerations

  Oral absorption
  Plasma protein concentration
  Muscle mass,  body fat
  Liver/renal function
 Multiple drugs
 Multiple diseases
         Some Terminology
 Receptor affinity      Inhibition
 Efficacy                (antagonism)
 1st vs. 2nd               Competitive vs.
  messengers                 noncompetitive
 Up vs. down
                             vs. irreversible
  receptor regulation    Allergic reaction

 Agonist vs.            Idiosyncrasy
  antagonist             Tolerance
 -lytic vs. -mimetic
         More Terminology
 Cross tolerance      Synergism
 Tachyphylaxis        Potentiation
 Cumulative effect    Interference
 Dependence           Untoward effect
 Drug interactions    Latency
 Summation
   Additive effect
Questions?

				
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