ABSORPTION & INTERACTION OF MEDICATIONS 2012/2013 Pharmacokinetics

Student Learning Outcomes See outline for SLO's

Overview This week we will start by tracing the path a medication takes to enter the body, how it travels to the site of action, is broken down and excreted Then how the medication produces its effects at the site of action How to safely administer medications following the 8 (10 rights) Conclude with Surgical Asepsis ( safe delivery of parental medications)

Introduction Over 11,000 brand name and generic medications available Each medication requires distinct  Application  Indications  Observation for adverse effects  Mechanism of actions  Some are prescribed for more then one illness The RN must have an understanding of each medication prior to its administration

Introduction Pharmacology – is the study of medication Pharmacotherapy - / Pharmacothetreputics -application of a drug for the purpose of diagnosis, prevention or treatment of suffering (Adams & Urban) Pharmacokinetics – absorption, distribution, metabolism, (biotransformation), excretion

What Are the Benefits of This Info? Assists us to:

Introduction Passage of drugs across membranes Medications must get into the body Diffusion  Takes into account  Membrane structure Drugs must pass thru cells vs. between

Drugs Cross Membranes By: Traveling via channels and pores  Must have small ions  Sodium & potassium are examples Transport systems – carriers that move drugs from one side of the cell membrane to the other  Transportation depends on the structure of the drug molecule

Diffusion

Drugs Cross Membranes By: Direct penetration of the membrane  Most drug use this route  These drugs must be lipid soluble  Remember cell membrane walls consist of lipids Other  Polar molecules – uneven distribution of electrical charges therefore do not penetrate cells  Kanamycin (antibiotic)

Ions Molecules that have a net electrical charge pH dependent ionization  Many drugs weak acids or weak bases  Acid may give up (H+) ions  Bases may take up (H+) ion

Note Acids tend to ionize in basic solutions Bases tend to ionize in acidic media Ionization – any process by which a neutral atom gains or loses electrons thus developing a net charge ASA (acidic) is absorbed better in stomach acid then in base lower GI environment  Remaining non ionized and therefore absorption is increased

Ion Trapping Drugs will be trapped on the side that favors their ionization  Acidic drugs will accumulate on the alkaline side  Alkaline drugs will accumulate on the acidic side  Treatment for poisoning an example we can change the pH of urine thus enhancing excretion

Factors That Affect Absorption Absorption – “movement of medication from its site of administration into the blood stream ” Rate of dissolution  Drug must first dissolve before it can be absorbed  Drugs that dissolve faster are absorbed faster  Repository

Factors That Affect Absorption Absorption dependent on the properties of the drug and on the physiological & anatomical attributes of the surface Surface area  The larger the surface area the faster the absorption  Anesthesia delivered via the lungs

Factors That Affect Absorption Blood flow  Drugs absorbed most rapidly from sites with the most blood flow  IV – directly into the blood stream  IM – muscles have a good blood supply Any thing that impedes or enhances blood supply can impact absorption  Heating pad vs. ice pack

Factors That Affect Absorption Drug Solubility  Lipid soluble drugs can readily cross the cell membranes  pH Partitioning  Just addressed

Routes IV - no barriers to absorption - Immediate & complete absorption - Disadvantages - Incontinent, costly, medication irretrievable - Fluid overload - Infection - Emboli

Routes IM  Only barrier – capillary wall  Drug can easily pass thru tissue  Absorption depends on  Water soluble will be absorbed more rapidly  Blood flow  Disadvantages  Discomfort  Nerve damage

Routes Subcutaneous  Nearly identical to IM

Oral Barriers 1. Lining of GI tract 2. Capillary wall 3. Absorption pattern solubility stability gastric & intestinal ph. gastric emptying food in GI Other meds special medication coatings

Oral Absorption takes place along the GI mucosa either in the stomach or lower GI tract Absorbed meds enter blood stream and go directly to the liver  Hepatic first pass effect  Hepatic microsomal enzymes  Advantages  Easy & inexpensive (relatively)  Safer – potentially reversible  Good choice for senior citizens

Oral Disadvantages  Variable absorption rate  Inactivation of certain medications  Requires a conscious & cooperative client  Age  Change in gastric pH can affect medication absorption

Pharmaceutical Preparation Tablets Enteric coating (do not crush) Sustained release preparations

Additional Routes Topical  Skin, eyes, ears, nose, mouth, & vagina Inhalation Rectal suppositories – cut in half length wise

Distribution “Movement of drugs throughout the body’’ Affected by Blood flow to the tissues - Exiting the vascular tissue - to site of action Drug Solubility Lipid soluble drugs are not limited by the barriers that normally limit water soluble drugs (Adams & Urban)

Distribution Tissue storage  Some tissues have a greater ability to accumulate and store drugs  Bone marrow  Teeth  Eyes  Adipose tissue

Distribution Determined:  Protein binding  Bonds reversible  Albumin – large molecule that remains in the blood stream & therefore amount of med available to the site of action may be limited  Only a few molecules will bind at any one time  Multiple Meds may compete at binding sites – resulting in Over dose Special Barriers  Blood brain & placental barriers

Distribution

Distribution Entering the cells.  Ph., lipid solubility etc.  Drugs may produce effects by.  Binding with receptors.

Metabolism Also known as “Biotransformation” “Enzymatic alteration of the drug structure Most often takes place in the liver Multiple enzymes  Hepatic microsomal enzymes –  Latest research is focusing on identifying individual characteristics and specific function of these enzymes

Consequences of Metabolism Accelerated renal excretion Drug inactivation Increased therapeutic action Activation of “prodrugs” (inactive substance changed to active substance) Increased toxicity Decreased toxicity

Factors Impacting Drug Metabolism Age Induction of drug metabolizing enzymes  Stimulates liver to breakdown itself faster or this change may affect other medications Hepatic First pass effect Nutritional status Competition between drugs

Question? List three problems you would see for a client with decreased liver function when it comes to metabolizing drugs ?

Excretion “Removal of drugs from the body.” Options - glomerular filtration - Drugs removed from blood & discarded into the urine - Passive tubular reabsorption - Frequently occurs with lipid soluble drugs - Active tubular secretion – active pumping of drug into tubular urine

Modifiers of Renal Excretion pH – dependent ionization  > excretion rate Competition for active tubular transport  Competition between drugs for active transport Age Lab test

Nonrenal Routes of Drug Excretion Breast milk Bile Lungs Sweat Saliva

Plasma Drug Levels Minimum effective concentration  Below MEC therapeutic effects of med will not occur Toxic concentration Therapeutic Range Drug half life (t5) Loading & maintenance doses Peak & Trough

Time Response

Pharmacodynamics Drug receptor interactions  Functional macromolecule in a cell to which a drug binds to produce its effects

Pharmacodynamics 1. Receptors are normal points of control 2. Receptor function regulated by body 3. Meds only Mimic, block, normal functions 4. Can not confer new functions

Pharmacodynamics 5. Meds Therapeutic effects due to body’s preexisting capabilities. 6. Research – ongoing

2 Agonists

Medication Interactions Agonist - medication that produces the same response as the endogenous substance – (actual molecule in the body that produces the desired effect) (some times these substances produce a great erect then the endogenous substance) partial agonist - medication that produces a weaker effect Antagonist - drug that prevents the agonist from producing the desired effect

Medication Interactions Drug may enhance or inhibit drug action  Additive  Two drugs from a similar therapeutic class produce a combined summative effect  Synergistic effect - medications acting together produce a greater effect them each of them alone 1+1 += 3  Medication manufactured as a combination drug Synercid – comb antibiotic – effective against “Staph infections ”

Remember Medication interactions : Meds  Enhance absorption  Decrease absorption  Reverse the effects Foods  All of the above  OJ + Iron

Determinants that Affect Drug Therapy Clinical Factors  Age, weight  Present health disorder  Other disease entities  Client drug compliance Pharmacokinetics  Absorption  Distribution  Metabolism (t1/2)  Excretion Administration  Drug form  Route of administration  Multiple drug therapy.  Drug interactions Pharmacodynamics  Onset, peak, & duration  Therapeutic range  Side effects and adverse effects Pharmacogenitics

Practice Question Mr. T has liver and kidney disease he is administered a medication that is manufactured to have a 30 hour half life. You expect the duration of this mediation for him to: A. B. C. D.

Answer

Example Digoxin  Effects  OD  Nursing assessments  Nursing interventions

Nursing Process Assessments Nursing Interventions Cultural considerations Evaluation

Nursing Process Transcultural Considerations Assessment  Cultural & ethnic background  Time away from country of origin  Travel history & language ability  Nonverbal communication patterns  Food preferences and health practices  Traditional health practices

Nursing Diagnosis Knowledge deficit: food and drug interactions related to new prescription as evidenced by “I do not understand this why I can not eat a lot of bananas”

Nursing Diagnosis Planning  Assist clients to develop a dietary plan that optimizes health focused on decreasing or eliminating interactions with medications Interventions  Client teaching  Teaching the family  Optimizing dietary intake and decreasing chance for food and drug interactions  Provide information in client’s preferred language Evaluation

Conclusion Remember the nurse is the client’s last line of defense when it comes to administration of medication

References Adams, M.P., & Urban, C.Q., (2013) Pharmacology: connections to nursing practice (2 nd ed.) Boston: Pearson Potter, P.A., Perry, A. G., Stockert, P. A., Hall, A.M. (2013) Fundamentals of nursing (8 th ed.) St. Louis: Elsevier