Pharmacokinetics

1
Pharmacokinetics

• Study of process of drug absorption, metabolism
  and excretion, distribution, biotransformation,
  excretion and half-life

2
Absorption

• Process by which drug is made available for use
  in the body.
• Transfer drug from the body fluids to the tissue
  sites-

3
Absorption (Cont)

• Factors that influence the rate of absorption
• Route of administration
• IV- most rapid- immediate onset
• IM- short onset w/in minutes- about 20 min
• SubQ- rapid- e.g. insulin
• Oral- takes 30-60 minutes before absorption from
  GI tract onset of drug action thus delayed

4
Absorption (Cont)

• Solubility of drug
• More soluble, more rapidly absorbed
• Most drugs are Water-sol (most readily absorbed)-
  and partially lipid soluble
• Law of Diffusion- drug molecules pass from an
  area of high concentration to an area of low
  concentration
• Concentration of drug on each side differs so
  will equal out with transport

5
Absorption (Cont)

• Drugs pass through cell membranes through
• Filtration
• Passive transport- most pass this way
• Active transport

6
Absorption (Cont)

• Presence of certain body conditions
• Development of lipodystrophy
• Orally, food delays drug absorption
• Some drugs irritate stomach

7
Absorption (Cont)

• Factors that influence distribution
• Systemic circulation distributes drugs to various
  body tissues or target sites (receptor sites)
• Interact w/ specific receptors during
  distribution
• Some bind to protein or albumin in the blood
  plasma

8
Absorption (Cont)

• Blood levels must be maintained for drug to be
  effective Therapeutic level
• Blood flow needs to be adequate
• Blood-brain barrier lipid barrier
• Blood-brain barrier lipid barrier
• Drugs need to be lipid soluble to get into brain
  cells.

9
Biotransformation

• Metabolism
• Process by which drug is converted to a substance
  that can be eliminated
• Drug is converted by the liver to inactive
  compounds
• DMMS- drug microsomal metabolizing system
• Drugs such as barbiturates and sedatives
  stimulate the DMMS when taken frequently

10
Excretion

• Inactive compounds of drugs excreted by the
  kidneys- must be water- soluble
• Some drugs excreted w/o being changed by the
  liver
• Caution for pts w/ kidney disease
• lower doses in infants and children as immature
  kidney function. And in older age pts w/
  diminished kidney function

11
Half-life

• Time required for body to eliminate 50 of drug
  or for the concentration in blood to fall to half
  of the original level.
• Affects timing/frequency of drug dosage
• Drug w/ short half-life of 2-4 hours need freq
  adm
• Drug w/ long half-life (20-24 hrs) req less freq
  dosing.
• Rate of metabolism and excretion affects
  half-life.

12
Drug Reactions / Interactions

• Adverse drug reactions
• Undesirable drug effects which may be common or
  infrequently occurring
• May be mild, severe or life threatening.
• May occur after first dose, after several doses,
  or after many

13
Drug Reactions / Interactions (Cont)

• Reporting adverse drug reactions
• Drugs used, studied for many yrs and may take
  that long for adv rxns to become known.
• Reporting mechanisms to help ID adv rxns

14
Allergic drug reactions

• Allergic reaction
• Hypersensitivity reaction
• Allergy to drug begins to occur after more than
  one dose given.
• Occ may occur the first time a drug is given e.g.
  penicillin so need to monitor pt carefully w/
  first dose.

15
Allergic drug reactions(Cont)

• immune system views drug as an antigen or foreign
  body which then stimulates the antigen-antibody
  response that prompts body to produce antibodies
  and release histamine from the cell against the
  drug.
• Allergy SXS itching, skin rashes, hives
  (urticaria), incr nasal secretions, diff
  breathing and wheezing due to bronco-constriction,
  cyanosis, sudden loss of consciousness, swelling
  of eyes, lips or tongue.

16
Allergic drug reactions(Cont)

• Anaphylactic shock- extreme serious allergic drug
  rxn occurs shortly after adm of drug w
  sensitivity
• TX raise BP, improve breathing, restore cardiac
  function, tx symptoms as arise.

17
Allergic drug reactions(Cont)

• Angioedema angioneurotic edema collection of
  fluid in subq tissue.
• Eyelids, mouth, lips, throat.
• Dangerous when mouth affected. Swelling may
  block airway and result in asphyxia or difficult
  breathing or inability to breath

18
Drug idiosyncrasy

• Any unusual or abnormal rxn to a drug different
  from the one expected.
• Cause due to genetic deficiency making pt unable
  to tolerate certain drugs and chemicals.

19
Drug tolerance/ dependence

• Body adapts to presence of certain drugs
• Also sign of drug dependence
• Some users experience discomfort when drug
  w/drawn- with physical or psychological symptoms

20
Drug Reactions / Interactions

• Cumulative drug effect
• Seen most commonly w/ liver or kidney disease as
  organs are major sites of detox and excretion.
• Body is unable to metabolize and excrete a normal
  dose of drug before next dose occurs. Serious as
  can lead to toxic effects.

21
Drug Reactions / Interactions (Cont)

• Toxic reactions
• Levels build up to toxic when lgr doses given.
• Some drugs such as digoxin have very, very narrow
  margin of safety before toxic

22
Drug Reactions / Interactions (Cont)

• Can be reversible or irreversible
• Liver damage reversible as liver cells can
  regenerate.
• Hearing loss due to damage to 8th cranial nerve
  permanent- due to streptomycin or gentimicin.
• Can reverse w/ administration of antidote,
  digitalis toxicity can give Digibind, Narcan for
  narcotic overdose.
• monitor blood level for certain drugs
  gentimicin, theophylline, digitalis

23
Drug Reactions / Interactions (Cont)

• Drug Interactions
• Drug-drug interactions and food-drug
  interactions.
• Occurs when one drug interacts w/ action of
  another.
• antacids interact w drugs like tetracycline
• Know interactions
• oral anticoagulants
• anti-infectives, antiarrhythmics, alcohol

24
Drug Reactions / Interactions (Cont)

• Additive drug reaction when combined effect of
  the two drugs equal to sum of each drug given
  alone
• Synergistic drug reaction drugs interact w/ each
  other and produce effect greater than sum of
  separate actions.
• Antagonistic drug reaction one drug interferes
  w/ action of another and neutralizes or decreases
  effects

25
Drug Reactions / Interactions (Cont)

• Drug-food interaction food impairs or enhances
  drug given orally.
• Some req food
• Some antibiotics

26
Factors influencing drug response

• Age
• Infants and children req smaller doses
• Dose varies for age and wt.
• Elderly also need lower doses
• Polypharmacy- taking numerous drugs that can
  potentially react.

27
Factors influencing drug response(Cont)

• Weight based on wt of 150 average wt
• Gender women in general require smaller dose of
  some drugs as smaller ratio of body fat and water
• Genetic variations- some inherit protein or
  enzyme patterns that influence absorption
• Emotional state
• Patient expectations placebo affect

28
Factors influencing drug response(Cont)

• Disease presence of disease may influence
  action
• Liver disease alters ability to metabolize or
  detoxify drugs.
• Kidney disease impairs excretion.

29
Route of administration

• Local and systemic effects
• LOCAL topical application affects the skin, eye,
  ear, mucous membranes creams, ointments,
  suppositories
• SYSTEMIC absorbed and distributed throughout
  system via blood stream

30
Route of administration (Cont)

• Oral- slowest, and most convenient
• Parenteral any route that does not involve GI
  tract or inhalation
• IV- most rapid drug absorption
• IM- into muscles
• SubQ- into the subcutaneous tissues of the skin

31
Nursing Implications

• Many factors influence drug action
• Need to know routes, factors, dosages, other
  drugs, if oral can be give w/ or w/o food.
• Observe reactions, responses, adv rxns drug
  tolerance.
• Report and record observations.
• Know when to w/hold drug and notify MD.

32
Drug legislation / regulations

• Federal legislation- describes conditions under
  which certain meds may be given and distributed.
• State legislation- describes who may prescribe,
  dispense and administer certain drugs and under
  what conditions.

33
Drug legislation / regulations (Cont)

• Pure Food and Drug Act (FDA) first act passed
  in 1906,
• Harrison Narcotic Act 1914
• Pure Food, Drug and Cosmetic Act 1938
• Comprehensive Drug Abuse Prevention and Control
  Act 1970
• Drug Enforcement Agency (DEA)

34
Pregnancy Categories

• Drugs carry risk of causing birth defects
• Teratogen any substance that causes abnormal
  development of the fetus leading to a severely
  deformed fetus.
• Five categories of potential for causing birth
  defects.

35
Drug Development

• FDA approval required for use, monitoring for
  adverse or toxic reactions
• Investigational new drugs/ release of drugs for
  use.