PHARMA-PHARMACOKINETICS

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PHARMA-PHARMACOKINETICS

  1. 1. PHARMACOKINETICS
  2. 2. Pharmacologic Principles• Drug Any chemical that affects the physiologic processes of a living organism• Pharmacology The study or science of drugs
  3. 3. • Therapeutic ratio – is the number indicating the ratio between lethal or toxic dose and effective dose.• Critical concentration – Amount of drug that is needed to cause therapeutic effect – Must be maintained in order for the drug to produce the desired therapeutic effect in the body.
  4. 4. • Loading dose – The starting dose that is higher than the dose usually used for tx – Given so that the time for a drug to reach its critical conc will be hasten• Dynamic equilibrium – Result when drug reaches in the body and actual conc of the drug is achieved involving the process of absorption, distribution, metabolism and excretion
  5. 5. Pharmacologic Principles• Knowledge of pharmacologic principles: » why a drug is ordered » how to administer drugs » assessment of therapeutic benefits » how to deal with toxic adverse effects• The nurse with a sound knowledge base in pharmacology is better equipped to implement the nursing process
  6. 6. Pharmacologic Principles1) Pharmaceutics2) Pharmacokinetics3) Pharmacodynamics4) Pharmacotherapeutics5) Pharmacognosy6) Toxicology
  7. 7. Pharmacologic Principles1) Pharmaceutics The study of various drug forms Deals with the delivery system IV, PO, IM Injection, capsule, timed-release, topical Determines the rate at which the drug will dissolve and be absorbed
  8. 8. Pharmacologic Principles1) Pharmaceutics• The pharmaceutical phase is concerned with the disintegration of the dosage form or dissolution of the drug in the body• How the dosage forms affect the way the body metabolizes the drug and how the drug affects the body
  9. 9. Pharmacologic Principles1) Pharmaceutics The dosage form determines the rate at which a drug enters the body A variety of dosage forms are available to increase the accuracy of dosing and to obtain therapeutic responses with the least amount of adverse effects
  10. 10. Pharmacologic Principles1) Pharmaceutics2) Pharmacokinetics3) Pharmacodynamics4) Pharmacotherapeutics5) Pharmacognosy6) Toxicology
  11. 11. Pharmacologic Principles2) Pharmacokinetics – The study of what actually happens to a drug from the time it enters the body until it has left the bodya. Absorption movement of a drug from the site of administrationb. Distribution transport of a drug in the bloodstreamc. Metabolism alteration of a drug in the bodyd. Excretion elimination of the drug or its compound from the body
  12. 12. 2) Pharmacokineticsa. Absorption• What happens to a drug from the time it is introduced to the body until it reaches the circulating fluids and tissues.Areas in the body where drug can be absorbed• GI tract either oral/rectal• Mucous membranes• Skin• Lungs• Muscle• Subcutaneous tissues
  13. 13. 2) Pharmacokineticsa. Absorption• The route of administration affects the rate and extent of absorption of that drug A. Enteral (GI tract) B. Parenteral C. Topical• The extent of absorption is called BIOAVAILABILITY – portion of the drug that reaches the systemic circulation KEY POINT: not all drug formulations are equally absorbed
  14. 14. Oral Drugs• Dosage – determined by how much of the drug is required to be taken by mouth to reach desired effect.
  15. 15. Mechanism of Drug Absorption• Passive Diffusion – movement of a drug from higher to lower concentration.• Carrier Mediated Absorption(Facilitated diffusion) – no cellular energy. Drug molecules combine with a carrier substance such as enzyme or other protein.• Active Transport – drug molecules move from an area of low concentration to an area of high concentration; transported by the carrier molecules as cellular energy.• Pinocytosis – occurs when a cell engulfs drug particles and moves them across the cell membrane and into the inner cell.
  16. 16. a. Absorption of oral drugsFactors that affect absorption varies according to the dosage form and route1. Food or fluids administered with the drug – help or hinder absorption – food may delay transit to the intestines – high fat foods may help some fat soluble drugs2. Dosage formulation – determined by how much of the drug is required to be taken by mouth to given the desired affect. – tablets, capsules- some dissolve in the stomach, others in the intestine. – Certain types are coated to dissolve slowly and have timed release. – Some types are formulated with small particles that dissolve super fast- ie: micronized glyburide
  17. 17. Amoxicillin Suspension
  18. 18. Amoxicillin Chewable Tablets
  19. 19. Amoxicillin Tablets
  20. 20. a. Absorption of oral drugsFactors that affect absorption varies according to the dosage form and route3. Status of the absorptive surface – portions of the small intestine may be missing or damaged4. Rate of blood flow to the small intestine – blood flow may be decrease to the intestine in certain instances – i.e. sepsis, exercise, labor5. Acidity of the stomach – food increases gastric acid production leading to decreased stomach pH. Drugs are formulated to dissolve at a specific pH level.6. Status of GI motility – Fast or slow transit time due to pathology, conditions, or other medications change transit time
  21. 21. a. Absorption of oral drugsSome drugs need to be taken on an empty stomach with a full glass of waterOther drugs should be taken on a full stomach or with food to enhance absorption or minimize gastric irritation
  22. 22. • + food in stomach – usually decreases absorption of drugs, but it may increase absorption for a few specific medications.• pH of the stomach – Alkaline drugs are absorbed more readily in an alkaline environment – acid drugs are absorbed more readily in an acid environment.• form of the drug – liquid drugs being absorbed the fastest and enteric-coated tablets the slowest.
  23. 23. a. Absorption of oral drugsDrugs are absorbed into the mesenteric blood system and go to the liver for biotransformation before traveling on to the general systemic circulation. This is called the FIRST PASS EFFECT• Therefore some of the drug is inactivated and not all will be available for use at its intended site of action.• Drugs are formulated to account for this difference in availability to the tissues- called (bioavailability)• This is why different forms of drugs are not equal
  24. 24. First-Pass EffectThe metabolism of a drug and its passage from the liver into the circulation.• oral route may be extensively metabolized by the liver before reaching the systemic circulation (high first-pass effect).• The same drug—given IV—bypasses the liver, preventing the first-pass effect from taking place, and more drug reaches the circulation.
  25. 25. First-Pass Effect• Routes that bypass the liver: – Sublingual Transdermal – Buccal Vaginal – Rectal* Intramuscular – Intravenous Subcutaneous – Intranasal Inhalation *Rectal route undergoes a higher degree of first-pass effects than the other routes listed.
  26. 26. What else might influence oral drug absorption?• Food in stomach• Certain juices – grapefruit juice• Milk – binds with molecules of some drugs so that the drug is never absorbed• Orange juice – enhances absorption of iron taken orally• The coating on the tablet: chewable, enteric coated (breakdown occurs in small intestine), slow release capsules
  27. 27. a. Absorption of parenteral drugs Parental drugs have no first pass effect• Intravenous – rapid and 100% bioavailable – Avoids problems with stomach acid and intestinal absorption issues• Intramuscular – not as rapid as IV- will absorb better if there is a good blood supply• Some IM medications are in DEPOT form- have a very slow absorption time (even months)- due to the formulation – these drugs should not be given IV- can cause an embolus
  28. 28. a. Absorption of parenteral drugsParenteral Route• Intravenous*• Intramuscular• Subcutaneous• Intradermal• Intrathecal• Intraarticular *Fastest delivery into the blood circulation
  29. 29. a. Absorption of topical drugs• Many different formulations of topical drugs• May be given for local or systemic effect
  30. 30. a. Absorption of topical drugsTopical Route• Skin (including transdermal patches)• Eyes• Ears• Nose• Lungs (inhalation)• Vagina
  31. 31. a. Absorption of oral drugs sublingual and buccal Avoids the first pass effect• Absorbed into the highly vascularized tissue under the tongue or between the cheek and the gum- the oral mucosa• Bypass the liver• Rapidly absorbed
  32. 32. a. Absorption• The ROUTE of administration affects the rate and extent of absorption of that drug
  33. 33. 2) Pharmacokinetics The transport of a drug in the body by the bloodstream to its site of action a. Absorption b. Distribution c. Metabolism d. Excretion
  34. 34. b. Distribution• Drugs are distributed first to areas that have extensive blood supplies heart liver kidneys brain• Areas of slower distribution are muscles skin fat• Sites like bone and brain may be very difficult for drugs to reach due to either poor blood supply or barriers
  35. 35. b. Distribution of drugsFactors that affect distribution1. Protein-binding• Many drugs bind to proteins in the bloodstream -Albumin is the main protein to bind with drugs -Drugs bound to proteins are not available for use in other tissues & organs called protein bound -Drugs not bound to protein are available to act at the intended site of action and exert their effects *called free drug• Drug companies adjust drug dosages to allow for protein binding
  36. 36. b. Distribution of drugsFactors that affect distribution• If a patient has low albumin more free drug is available and the patient may have increased adverse effects (toxicity)• If 2 drugs are given that are highly protein bound they compete for binding sites on the albumin. – The drugs will have higher levels of ―free‖ drug and the patient may have increased adverse effects• This fact is significant because only the unbound or free drug is able to reach the target tissue and exert its pharmacologic effect.
  37. 37. b. Distribution of drugsFactors that affect distribution2. Water soluble vs fat soluble• Water soluble drugs – tend to stay in the bloodstream and have slow absorption into the tissues.• Fat soluble drugs – are distributed to the tissues more quickly – the more lipid soluble the drug is, the higher its ability to reach all cells in the body.
  38. 38. b. Distribution of drugsFactors that affect distribution3. Blood Flowa. Blood-brain barrier – network of capillaries that makes it more difficult for drugs to pass through--will allow some fat soluble drugs to pass through – Brain capillary endothelium have special characteristics that limit the passage of drugsb. Placental barrier – in general whatever mom gets the fetus gets
  39. 39. b. Distribution of drugsFactors that affect distribution4. Blood Flow – If drug is circulating in the bloodstream, it will gain greater access to tissues that are highly perfused. – Therefore, if the blood circulation is poor, the result is insufficient drug distribution.5. Binding to sub-cellular components – There are drugs that are bound within specific cells in which they are causing their effect and are unable to leave the cell to be carried in the blood stream.
  40. 40. 2) Pharmacokinetics a. Absorption b. Distribution c. Metabolism d. Excretion
  41. 41. c. Metabolism of drugs • Also Known as Biotransformation• Drugs are changed into new, less active chemicals• It takes place mainly in the liver and produces 1. An inactive metabolite 2. A more soluble compound 3. A more potent metabolite
  42. 42. c. Metabolism (biotransformation)Organs or body tissues responsible for metabolism:– Liver (mainly)– Skeletal muscle– Kidneys– Lungs– Plasma– Intestinal mucosa
  43. 43. c. Metabolism (biotransformation)Hepatic Cytochrome P-450 enzyme system• These enzymes control a variety of biochemical reactions that aid in metabolism• These enzymes are largely targeted against lipid-soluble and nonpolar (no charge) drugs which are difficult to eliminate• These include the majority of medications
  44. 44. c. Metabolism (biotransformation)The capability of the liver to metabolize drugs varies widely between patients• Age Elderly have decreased hepatic enzymes Neonates have immature liver functions• Genetics certain genetic groups metabolize drugs at different rates• Foods Grapefruit and certain other foods• Concurrent use of other medications Tylenol and many other drugs• Diseases Cardiovascular or Renal dysfunction
  45. 45. c. Metabolism (biotransformation)Factors that decrease (delay) metabolism• Cardiovascular dysfunction• Renal insufficiency• Starvation• Obstructive jaundice• Slow acetylator (metabolism of drug)• Erythromycin or ketoconazole drug therapy
  46. 46. c. Metabolism (biotransformation)Decreased drug metabolismresults in:• Accumulation of drugs• Prolonged action of the drugs• Possible toxic levels
  47. 47. c. Metabolism (biotransformation)Factors that increase (stimulate) metabolism• Fast acetylator• Drugs that stimulate the formation of new enzymes Barbiturate therapy Rifampin therapy
  48. 48. c. Metabolism (biotransformation)Increased drug metabolismresults in:• Drugs may leave the system more quickly• Diminished pharmacologic effects
  49. 49. c. Metabolism (biotransformation) FIRST PASS EFFECT• The initial metabolism of a drug and its passage from the liver into the circulation – A drug given via the oral route may be extensively metabolized (inactivated or changed) by the liver before reaching the systemic circulation high first-pass effect• Oral drugs ( because they go through the liver) may not be 100% available to reach the intended sites of action
  50. 50. c. Metabolism (biotransformation)FIRST PASS EFFECT– routes of administration• The same drug—given IV—initially bypasses the liver, getting to it’s intended site of action more quickly and preventing the first-pass effect from taking place.• IV drugs are 100% available to the body (bioavailability)Cefuroxime: IV = 750mg/ml oral = 500 mg/ml
  51. 51. c. Metabolism (biotransformation)FIRST PASS EFFECT– routes of administration• The first-pass effect is one reason why drug dosages and frequency of administration are different depending on the route of administration IV DOSE is not always equal to an ORAL DOSE
  52. 52. 2) Pharmacokinetics a. Absorption b. Distribution c. Metabolism d. Excretion
  53. 53. d. Excretion The elimination of drugs from the body• Kidneys (main organ) Whether the drug is an original compound (parent compound), an active or an inactive metabolite----• Liver• Bowel – Biliary excretion – Enterohepatic recirculation
  54. 54. d. Excretion The kidneys remove the drugs that are unbound (free) in the plasma Certain drugs (like highly protein bound drugs) can’t be excreted and are reabsorbed back into the system
  55. 55. d. Excretion• Patients with renal failure will not be able to excrete drugs efficiently• Drug levels will increase• Patients may experience more adverse effects and toxicity
  56. 56. Pharmacokinetics Onset, Peak, Duration and TroughOnset• The time it takes for the drug to elicit a therapeutic response INSULIN ONSET PEAK DURATIONUltra rapid acting 15 mins. 2-4 hrs. 6-8 hrs. Insulin analog (Humalog)
  57. 57. PharmacokineticsOnset, Peak, Duration and TroughPeak• The time it takes for a drug to reach its maximum therapeutic response• Oral = 1-3hrs• IV = 10mins• good time for a dressing change or other painful procedure• Good time to draw blood INSULIN ONSET PEAK DURATIONUltra rapid acting 15 mins. 2-4 hrs. 6-8 hrs. Insulin analog (Humalog)
  58. 58. PharmacokineticsOnset, Peak, Duration and TroughDuration• The time a drug concentration is sufficient to elicit a therapeutic responsehow long is it going to last- (anticipate the next dose) INSULIN ONSET PEAK DURATIONUltra rapid acting 15 mins. 2-4 hrs. 6-8 hrs. Insulin analog (Humalog)
  59. 59. PharmacokineticsOnset, Peak, Duration and TroughTrough• Lowest blood level of a drugNote:If either the peak or trough levels is too high, toxicity can occur.If the peak is too low, no therapeutic effect is achieved.
  60. 60. INSULIN ONSET PEAK DURATIONUltra rapid acting 15 mins. 2-4 hrs. 6-8 hrs. Insulin analog (Humalog)Rapid acting: ½-1 hr 2-4 hrs. 6-8 hrs. Regular (Semilente)Intermediate: 1-2 hrs. 7-12 hrs. 24-30 hrs. NPH (Lente)Long acting: 4-6 hrs. 18 + hrs 30-36 hrs. Protamine Zinc (Ultralente)
  61. 61. Laboratory Values• Laboratory values reflecting function of liver and kidneys need to be looked at: – BUN and Creatinine – kidney function – LFT or liver function tests: • ALT – alanine aminotransferase (elevated in hepatitis) • AST or SGOT– aspartate aminotransferase – elevated in liver disease • ALP – elevated in biliary tract disease • Bilirubin levels – infants – gallstones in adults
  62. 62. Serum Drug Levels• Laboratory measurement of the amount of drug in the blood at a particular time• A minimum effective concentration (MEC) must be present before a drug exerts its action on a cell.
  63. 63. Toxic Levels• Excessive level of a drug in the body – Single large dose – Repeated small doses – Slow metabolism which allows drug to accumulate in the body – Slow excretion from the body by the kidneys or gastrointestinal tract
  64. 64. Yes, laboratory values are important!• Serum drug levels indicate the onset, peak and duration of the drug action
  65. 65. Do we do serum drug levels for all drugs?• No• When do we need them? – Drugs with narrow margin of safety (digoxin, aminoglycoside antibiotics, lithium) – To check to see if the drug is at therapeutic levels – seizure medications – When drug overdose is suspected
  66. 66. PharmacokineticsHalf-lifeHow do pharmaceutical companies determine how often a drug needs to be given to remain in a therapeutic range?
  67. 67. Pharmacokinetics• Half-life• The time it takes for one half of the original amount of a drug in the body to be removed• A measure of the rate at which drugs are removed from the body• Most drugs are considered to be effectively removed after about five half-lives**
  68. 68. Why is this important?• Half-life determines how often a drug is given – Daily in the morning – At bedtime – Q.I.D - four times a day – T.I.D – three times a day – Q4 hours – every four hours – Q 12 hours – 9 am and 9 pm
  69. 69. PharmacokineticsShort ½ life– need to take frequently compliance may be a problem example: acyclovir 5 times dailyLong ½ life- pt has an adverse reaction the drug will be in the body for hours or days example: Cialis T1/2 = 17 hours(Viagra might have been a better choice for this pt with a T1/2 of 4 hours)
  70. 70. Pharmacokinetics• Steady state• Where the amount of drug excreted is equal to the amount of drug absorbed with each dose• Giving more drug could cause toxicity• Giving less drug would not be therapeutic• Typically occurs after 4-5 half-lives of administration
  71. 71. PharmacokineticsSteady state• Drugs with a very long half-life make take a longer time to reach a steady state - some antidepressants• With certain drugs, to reach a steady state more quickly, a LOADING DOSE may be ordered This is a higher initial dose

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