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I. PHARMACEUTICAL PHASE
A solid drug (tablet) has to disintegrate before it can be absorbed The process where a solid (tablet) goes into solution is known as dissolution ALL drugs must be in solution to cross biologic membranes
#1 ABSORPTION
Movement of a drug from the site of administration into the bloodstream. Absorption determines how long it takes for a drug to take effect. Usually the more rapid the absorption, faster the drug works Drugs can be absorbed through plasma membranes by various methods but primarily by: Diffusion (lipid soluble molecules) & Active transport (protein bound or water soluble molecules)
Additives: alter the location of disintegration of drugs as well as increase or decrease the rate of absorption Enteric coating allows a drug to dissolve only in an alkaline (pH greater than 7.0) environment such as the small intestine. Sustained release drugs:allow drugs to be released slowly over time, rather than quickly, like conventional tablets. SR, LA Size of drug particles: smaller the particle, faster the onset. Ex: The generic drug Glyburide has trade names Micronase and Glynase. Glynase (micronized) onset is faster than Micronase (nonmicronized)
Absorption:ENTERAL ROUTES
Mucous membranes of the mouth: Buccal or Sublingual forms of drugs Highly vascular absorbing surface Avoids first pass phenomenon that occurs in the liver Absorptive area is small therefore Only small amounts of drugs can be given
CONSIDER THIS
Alcohol is extremely lipid soluble Aspirin is a very weak acid Both are well absorbed in the stomach.
Absorption:ENTERAL ROUTES
Oral Route: Small Intestines Most important site for absorption of oral drugs as it has extensive absorptive surface due to many villi. Peristalsis and mixing encourage dissolution of drugs. Highly vascular and has a pH of 7.0 to 8.0 In what way will diarrhea affect absorption? Why?
Absorption:ENTERAL ROUTES
Mucus Membranes of the Lower Intestine: Rectal Route Avoids most first pass effects in the liver Has extensive vascularity. Limited surface area Drugs need to be in solution or absorption is erratic and unpredictable.
Absorption:PARENTERAL
intravenous subcutaneous intramuscular intradermal intraarticular synovial cavity intrathecal - spinal subarachnoid space or epidural space intraperitoneal
REMEMBER Parenteral meds retain 100% bioavailability THEREFORE smaller doses are appropriate
Absorption: PARENTERAL
Subcutaneous and intramuscular injections are affected by tissue composition Intramuscular route is more effective than the subcutaneous route because there is a greater blood supply in muscle tissue. Application of heat or massage can increase vasodilation and improve absorption
#2 Distribution
Distribution: the transport of drugs from the blood to the site of action. A drug must be distributed to its site of action to have an effect Drugs are also distributed to tissues where it has no effect. Competition for drug binding sites affects the amount of drug available for action in the body.
Critical Thinking
What effect would an albumin level of 2.8 have on distribution? What should the nurse be alert to happening ?
CONSIDER THIS
The elderly have less effective blood-brain barriers. Symptoms of dizziness and lightheadedness are more common as side effects to many drugs taken by the elderly.
#3
METABOLISM
Biotransformation: process by which the body changes the chemical structure of a drug to another form called a metabolite. Metabolite: a more water soluble compound that can be easily excreted. The major organ for this process is the liver
METABOLISM (BIOTRANSFORMATION) First Pass Phenomenon - Drugs are first absorbed through the small intestine than arrive at the liver via the portal circulation There they undergo considerable biotransformation before entering the systemic circulation. There will be less active drug available for action in the body cells after this first Pass through the Liver !
Consider this
Enzymes within the liver called cytochromes metabolize lipid soluble drugs. People with liver disease have a reduced amount of cytochromes What will the overall effect then be??
Variations in Metabolism
Pharmacogenetics - hereditary influences on drug responses, refers to variations in which individuals metabolize drugs. Remember our discussion of Acetylator Rates? Circadian Rhythms - the rate of drug absorption, hepatic clearance, half-life and duration of action, have all been shown to differ depending upon the time of day a drug is administered. Effects of Gender and Age BMR differences GERIATRIC CHGS
#4
Excretion
Excretion: process where drugs are removed from the body. Kidneys are the major organs of excretion. Lungs excrete gaseous drugs. Biliary excretion (bile & feces) is important for a few drugs. These drugs may be reabsorbed when passing through the intestines from the liver ( enterohepatic re-circulation ). Intestines, sweat, saliva and breast milk constitute minor routes of drug excretion.
Excretion
Clearance of drugs - elimination of drugs from circulation by all routes. It affects the time a drug remains in the body and the dosage required. Renal Clearance Hepatic clearance
PLASMA HALF-LIFE
The amount of time a drug stays in the body is measured by the elimination half-life. This is the time required for the concentration of drug in the blood to decrease by 50%. Half-life affects the frequency of administration Drugs with short half-lives are quickly eliminated from the body. ( Ex: PCN given several X per day ) Drugs with longer half-lives stay in the body longer (Ex: Digoxin given once a day )
Consider This
Bronchodilators (ie: albuterol ) used for asthma attacks are classified as betaagonists. They attach to adrenergic receptors in the sympathetic nervous system (SNS) and mimic the action of norepinephrine. Adrenergic antagonists such as betablockers (ie: atenolol) attach to the adrenergic receptors in the SNS and block the action of norepinephrine
Saturability
Drug receptor binding is saturable This occurs when all available receptors are occupied Once all available receptors are saturated, increasing the drug concentration WILL NOT increase therapeutic effect but it WILL increase the risk of adverse side effects
Onset of drug action is the time it takes after the drug is administered to reach a concentration that produces a response. Duration of action is the time during which the drug is present in a concentration large enough to produce a response. Peak effect is the time it takes for the drug to reach its highest effective action.
Trough level will occur immediately before a drug is given, or once sufficient drug is eliminated. This is the lowest point of drug concentration Plasma blood levels may be taken for peak and trough levels. The drug must be administered precisely as ordered and a blood sample must be taken just before the next drug dose is scheduled for an accurate trough level.
Consider this
Certain drugs, such as aminoglycoside antibiotics ( Gentamycin ) are extremely ototoxic and nephrotoxic and are administered once daily. It is the responsibility of the nurse administering these medications to utilize therapeutic drug monitoring procedures Check trough levels 18-24 hrs after previous dose for a < 1mcg/ml level ( or previously set # from MD / Lab / Pharmacy)
Therapeutic Responses
Toxicity studies of drugs determine two dosage levels for drugs. The effective dose is the dose of a drug necessary to produce the desired intensity of effect in one-half of all patients. The lethal dose is the dose of a drug that elicits an undesirable toxic or lethal reaction in one-half of all patients.
Therapeutic Index
A drug with a wide therapeutic index has a high safety margin and is relatively safe; the lethal dose is greatly in excess of the therapeutic dose. A drug with a narrow therapeutic index is more dangerous for the patient because small increases over normal doses may induce toxic reactions. Peak
and trough levels may need to be monitored
Therapeutic range: plasma drug concentration between minimum and toxic concentrations. Loading doses: higher amount of drug given once or twice to achieve maximum effective dose quickly Maintenance dose: intermittent doses given to maintain plasma levels.
ADR
Adverse Effects: are unwanted and/or unintended action that may occur during drug therapy. Every drug has the potential to produce adverse effects. Side Effects: Undesirable but mild unavoidable/predictable pharmacological effects of a drug.
ADR
Toxic Effects: More serious effect. Life threatening. Each drug has characteristic toxic effects. May be due to the accumulation of the drug in the body r/t decreased renal function Teratogenic Effects: Drug induced birth defects which follow drug therapy in pregnant women.
Drug Interactions
Occur when 1 drug and a 2nd drug or element such as food may have an effect on each other. These interactions may or the therapeutic effect of 1 or both drugs, create a new effect or incidence of adverse effects
Drug Interactions
Additive effects: 2 or more similar effect drugs are combined. The result equals the sum of the individual agents Each drug is given in a lower dose for an equal effect of either drug given separately. 1+1=2. Ex: Percodan ( oxycodone + acetominophen) improves pain relief Synergism: The harmonious action of two unlike drugs producing an effect which is greater than the total effects of each drug acting by itself. 1+1=3. Ex: Advicor ( niacin + statin drugs) improves lipid lowering action.
Drug Interactions
Potentiation: One drug improves the performance of the other drug. This is a particular type of synergistic effect. +1=2 Ex: amoxicillen + probenecid (anti-gout) prolongs serum levels of the antibiotic Idiosyncratic Reactions: Unusual, unexpected reactions to a drug, which may be genetically caused. Sometimes the person will react with the opposite effect to the desired one. (Also called paradoxical reaction) Ex: Genetic G6PD enzyme deficiency (prevents RBC hemolysis) idiosyncratic reactions to ASA, sulfonamides (African American and Kurdish Jewish populations)
Allergic Reactions
Increased reactions with repeated exposure to the drug. Hypersensitivity reactions are exaggerated in response to a drug. Anaphylaxis: A systemic reaction, the most severe of all the allergic reactions.
(edema of airways, severe hypotension, cardiac arrhythmia, death)
Case Study
After starting a new IV line, you administer the Lasix IV. The client almost immediately begins to experience an anaphylatic type reaction. He did not report any past allergies to Lasix, but he is allergic to sulfa drugs. Should this information have impacted your administration of the Lasix? Was this a preventable, predictable drug reaction? Was it a medication error?
Nursing Considerations
Take a careful drug history Know what interactions to anticipate Identify the drug reaction by monitoring the patient response to the drug. Educate the patient and the family re the risks and benefits of the drug. Document any drug reactions clearly and specifically