nurs 323 quiz 1

drug

Any chemical that can affect a living process

pharmacology

The study of drugs and their interactions with living systems

clinical pharmacology

The study of drugs in humans

therapeutics

(aka pharmacotherapeutics) the use of drugs to diagnose, prevent, or treat disease or to prevent pregnancy

effectiveness

Does it cause the response for which it is given

safety

There is no such thing as a safe drug

selectivity

1. Causes only the response for which it is given
2. There is no such thing as a selective drug

reversible action

Do drug actions subside after a certain amount of time?

ease of administration

is it simple to administer

predictability

How will the patient respond?

drug interactions

are there many interactions?

cost

is it expensive?

chemical stability

does the drug have a long shelf life?

goal of drug therapy

to provide maximum benefit with minimum harm

nursing and pharmacology

1. Last line of defense against medication errors
2. Beyond administration
3. Evaluation of response
4. Education/safety

beyond administration

1. Assessment prior to administration


1. Baseline data
2. Dosage and administration


1. Appropriate indications
2. The R’s
3. Evaluating effects


1. Is the drug doing what it is intended to do?
2. Continuous/ongoing assessment
4. Minimizing adverse effects
5. Minimizing adverse interactions


1. Drugs
2. Food
6. PRN medications
7. Toxicity


1. Knowing what to look for
2. Knowing who is at risk

patient education -- what we teach

1. Drug name
2. Indication
3. Dosage and administration
4. Duration o use
5. Storage
6. When to expect therapeutic effects
7. Minimizing adverse effects and interactions
8. Who to contact
9. Questions about medications
10. Adverse reactions

absorption

movement of a drug from the site of administration into the blood

rate of absorption

how quickly the drug moves into the bloodstream

amount of absorption

how much of the drug moves into the bloodstream

factors affecting absorption

1. Rate of dissolution
2. Surface area
3. Blood flow
4. Lipid solubility
5. pH partitioning

parenteral

outside of the GI tract

IV, IM, and Sub-Q

IV

1. Barriers to absorption


1. None
2. Patterns of absorption


1. Direct
3. Advantages


1. Rapid onset, control of the level of drug, ability to administer large volumes of fluid
4. Disadvantages


1. Expensive, inconvenient, cannot take it back, infection, fluid overload, embolism

IM and Sub-Q

1. Barriers to absorption


1. None easily passes through spaces of the capillary wall
2. Patterns of absorption


1. Rapid or slow
2. The water solubility of the drug
3. Blood flow to the site of injection 
3. Advantages


1. Good for meds with poor water solubility
2. Used for the administration of depot preparations
4. Disadvantages


1. Discomfort, inconvenient, can be painful, infection, nerve damage

enteral

using the GI tract

oral drugs

1. Barriers to absorption


1. Epithelial cells lining the GI tract
2. Patterns of absorption


1. Highly variable


1. Solubility/stability of the drug
2. Gastric and intestinal pH
3. Gastric emptying time
4. Presence of food
5. Co-administration of other drugs
6. Coating of the drugs
3. Advantage


1. Easy, convenient, and safe
4. Disadvantages


1. Variability of absorption
2. Requires patient cooperation

pharmacokinetics

1. **Drugs move in different ways**


1. **Extent of movement depends on the ability of drugs to pass to and from the major spaces of the body: intracellular, intravascular, and interstitial.**
2. **In many cases, drugs can pass freely between wide junctions, or gaps, in a capillary wall**
2. At other times drugs must pass across membranes via


1. Channels or pores
2. Transport systems
3. Direct membrane penetration


1. For direct penetration, drug must be lipid soluble, nonpolar, or nonionized

pharmacokinetics absorption

1. Chemical equivalence
2. Bioavailability


1. The amount of active drug that reaches the system circulation from its site of administration
3. Oral preparations


1. Tablets
2. Enteric-coated
3. Sustained release


2. Additional routes of administration


1. Topical


1. Transdermal
2. Sublingual
2. Inhalation
3. Suppository
4. Direct injection to the site of action

pharmacokinetics distribution

1. The movement of drugs throughout the body
2. 3 factors


1. Blood flow


1. To the tissues


1. 2 pathologic conditions in which low regional blood flow can affect drug therapy


1. Abscesses
2. Tumors
2. Ability to exit the vascular system


1. Exiting the vascular system


1. Capillary beds
2. Blood-brain barrier


1. Tight junction
2. Not fully developed in infants
3. Placental drug transfer


1. Not an absolute barrier
4. Protein binding


1. Plasma albumin
2. Drugs can form reversible bonds
3. Bound molecules cannot reach their sites of action, metabolism, or excretion
4. Drugs with the ability to bind to albumin will compete for sites and may displace other drugs causing increased levels of the free drug
3. The ability of the drug to enter the cells


1. Entering cells


1. Some drugs must enter cells to reach their sites of action, and MOST must enter to undergo metabolism and excretion


1. Lipid solubility
2. Transport system

pharmacokinetics metabolism

1. The enzymatic alteration of drug structure
2. Main site of metabolism is the liver


1. Cytochrome P450 system

therapeutic consequences of drug metabolism

1. Accelerated renal excretion
2. Drug inactivation
3. Increased therapeutic action
4. Activation of prodrugs
5. Increased toxicity
6. Decreased toxicity

special considerations

1. Age


1. Infants – liver is not fully developed
2. Induction of drug-metabolizing enzymes


1. Some drugs can cause the liver to synthesize more drug-metabolizing enzymes


1. Increases metabolism of the drug
2. Increases metabolism of other drugs
3. Inhibition of drug-metabolizing enzymes


1. Decreases rates of drug metabolism
4. First pass effect


1. Rapid inactivation of some oral drugs as they pass the liver after being absorbed
2. Parenteral administration will bypass this effect
5. Nutritional status


1. Adequate nutritional status provides the required cofactors for the hepatic drug-metabolizing enzymes to function
6. Competition between drugs


1. Two or more drugs that use the same metabolic pathway may cause a decrease in the metabolism of one or more

pharmacokinetics excretion

1. The removal of drugs from the body
2. Renal drug excretion


1. Glomerular filtration
2. Passive tubular reabsorption
3. Active tubular secretion
3. Factors that modify renal drug excretion


1. pH-dependent ionization
2. Competition for active tubular transport
4. Non-renal routes of drug excretion


1. Breast milk
2. Bile
3. Lungs
4. Sweat and saliva

pharmacodynamics

The study of biochemical and physiological actions of drugs and the molecular mechanisms by which those effects are produced

plasma drug levels

Plasma drug levels are highly predictive of therapeutic and toxic responses

minimum effective concentration (MEC)

The minimum plasma drug level at which therapeutic effects will occur

toxic concentration

The level at which toxic effects occur

therapeutic range

1. Falls between the MEC and toxic concentration
2. Enough drug is present to produce a therapeutic response

drug half-life

The time required for the amount of drug in the body to be decreased by half

plateau

1. When a steady level of the drug has been achieved
2. When the amount of drug eliminated between doses equals the dose administered
3. It takes four to five half-lives to achieve a plateau
4. Reducing fluctuations in drug levels


1. Administer a continuous infusion
2. Administer a depot preparation
3. Reduce the size of a dose and the dosing interval

peak

the highest level of a drug

trough

1. the lowest level of drug


1. For trough lab, draw serum level immediately before administration of next dose

loading dose

used when plateau must be achieved quickly

maintenance dose

smaller doses used once plateau is achieved

dose relationships

1. The relationship between the size of an administered dose and the intensity of the response produced


1. The minimum amount of drug needed to elicit a response
2. The maximum response a drug can elicit
3. How much to increase the dosage to increase the response
2. Drug responses are graded – patient response gets more intense with increased dosing

maximal efficacy

largest effect that a drug can produce

potency

1. Amount of drug given to elicit an effect
2. A potent drug produces its effect at low doses

Two drugs can be equally effective but have different potency

receptors

1. Chemical sites in the body that drugs interact with to produce effects


1. Make selective drug action happen
2. Drugs either mimic or block the action of the body’s own regulatory molecules; do NOT give cells new functions


1. Drugs produce their therapeutic effects by helping the body use its pre-existing capacities

drug receptors and selectivity

1. If a drug interacts with only one type of receptor that regulates only a few processes the effects of the drug will be limited
2. If a drug interacts with a receptor type that regulates multiple processes, the drug is likely to elicit a variety of responses
3. If a drug interacts with multiple receptors, it will elicit a variety of responses

affinity

1. Strength of attraction between a drug and its receptor


2. High-affinity drugs have a strong attraction to receptor sites


1. Drugs with high affinity are very potent
2. Drugs with low affinity need to be present in high concentrations to elicit a response

intrinsic activity

1. The ability of a drug to activate a receptor upon binding


2. Drugs with high intrinsic activity have high maximal efficacy


1. Produce an intense response

agonists

1. Activate receptors; have high affinity and intrinsic activity
2. Mimic action of endogenous regulators

antagonists

1. Prevent receptor activity


1. Have high affinity, but no intrinsic activity
2. Bind to receptors but do not cause receptor activation
2. Block actions of endogenous regulatory molecules or drugs


1. Response to an antagonist is determined by how much agonist is present
3. Noncompetitive antagonists


1. Bind irreversibly to receptors
2. Decrease the total number of receptors available for binding
4. Competitive antagonists


1. Produce receptor blockade by competing with agonists
2. If both have equal affinity then the receptor is occupied by whichever agent is higher in concentration

partial agonists

1. An agonist with moderate intrinsic activity
2. Produces less effect than a full agonist


1. Pentazocine (a partial agonist) and meperidine (a full agonist) – better pain relief with meperidine

regulation of receptor sensitivity

1. Desensitization (refractoriness) results from continuous exposure of cell receptors to an agonist


1. The cell is less responsive
2. Implications for drug tolerance
2. Hypersensitivity results from continuous exposure of cell receptors to antagonist


1. The cell is hypersensitive

drug responses without a receptor

1. React through physical or chemical reactions


1. Antacids
2. Saline laxatives
3. Chelating agents

average effective dose

ED 50


1. The dose required to produce a defined therapeutic response in 50% of the population


1. Patients must be evaluated individually for the proper dosing – many variables

therapeutic index

ED 50 : LD 50

Ratio between average effective dose and average lethal dose


1. Wide therapeutic index is relatively safe
2. Narrow therapeutic index is relatively unsafe

variations in drug responses

1. Body surface area is more precise than body weight


1. The percentage of body fat can change drug distribution
2. Extremes of age are more sensitive
3. Gender-related differences


1. Most research previously performed on male subjects
4. Pathophysiology


1. The renal disease affects excretion
2. Liver disease affects the metabolism


1. Dosage adjustment is required for both
3. Acid-base imbalance (pH partitioning)
4. Altered electrolytes

tolerance

1. Decreased responsiveness to a drug as a result of repeated drug administration
2. Patients who are tolerant to a drug require higher doses to produce the same effects that were achievable with lower doses before tolerance had developed

pharmacodynamic tolerance

1. Associated with the long administration of drugs
2. Adaptive processes occur in response to chronic receptor activation
3. Increased drug levels are required to produce the same effects

metabolic tolerance

1. Related to accelerated drug metabolism
2. Certain drugs can induce the synthesis of drug-metabolizing enzymes causing increased metabolism of other drugs

tachyphylaxis

A form of tolerance where the reduction in drug responsiveness is brought on by repeating dosing over a short time (within hours) instead of days to weeks

placebo effect

Caused by psychological factors not chemical properties of the drug

bioavailability

1. The amount of active drug that reaches the systemic circulation from its site of administration
2. Different forms of the same drug can vary in bioavailability
3. Primarily occur in oral preparations
4. Highest concern in drugs with narrow therapeutic range

pharmacogenetics

The study of genetically inherited conditions that affect the way drugs act on the body and modify the way the body acts on drugs

i.e., Rapid metabolizers of INH


1. Altered immune response to drugs
2. Variants in genes that code for beta-blocker


1. Hyperresponsive
3. Variant in genes for Coumadin


1. Excessive anticoagulation

gender and drugs

1. Men and woman can respond differently to drugs 
2. Examples


1. Digoxin


1. may increase in mortality in women when used to treat heart failure
2. Alcohol


1. Metabolized more slowly by women
3. Opioids 


1. Some are more effective in women than in men

race and drugs

1. Not a predictor
2. How do we define it?
3. Focus on genetic and psychosocial factors


1. Genetic variation

diet and drugs

1. Malnutrition


1. Lower amounts of plasma proteins (albumin) causing levels of free drug to rise – more intense effects, possible toxicity
2. Decreased oxidative metabolism & decreased glomerular filtration rate
2. Intake of Vitamins 
3. Urinary pH
4. Timing of meals

drug therapy and pregnancy

1. Err on the side of caution, any drug taken during pregnancy will reach the fetus
2. Physiologic changes during pregnancy can alter the pharmacokinetics of drugs


1. Renal
2. Liver
3. Gastrointestinal
3. Placental drug transfer
4. Pregnancy Categories


1. Based on research for risks posed to the fetus (teratogenic effects)


1. Category A and B (remote risk)
2. Category D (proven risk)
3. Category X (proven risk)
5. Adverse Effects


1. Up to day 60 after implantation – organogenesis – result in gross malformations
2. Exposure later in pregnancy results in functional impairment (i.e. cognitive deficits
6. Lactation 
7. Avoid drugs known to be harmful during breastfeeding

drug therapy in pediatric patients

1. osage based on weight in kilograms or more precisely body surface area (expressed in square meters)
2. Differences in Absorption


1. Enteral, Parenteral, Topical
3. Differences in Distribution


1. Higher water concentration, lower fat
2. Immature blood brain barrier
3. Limited protein binding capacity
4. Differences in Metabolism


1. Liver
2. Respiratory Rate
5. Differences in Excretion
6. Adverse Effects 


1. Age related effects
7. Dosage determination
8. Neonates (first 4 weeks of life) and  Infants (weeks 5-52 of life) are at risk for the most intense adverse effects
9. Pharmacokinetic action is more similiar to adults after 1 year

drug therapy in geriatric patients

1. Challenges of drug therapy in older adults


1. Pharmacokinetic changes
2. Multiple and severe illnesses
3. Multidrug therapy
4. Poor adherence
2. Pharmacokinetic changes in older adults


1. Absorption
2. Distribution


1. Increased percent of body fat
2. Decreased percent of lean body mass
3. Decreased total body water
4. Reduced concentration of serum albumin
3. Metabolism
4. Excretion


1. Creatinine clearance rather than serum creatinine is a better indicator in older adults of renal function
3. Monitoring and preventing adverse drug reactions and drug-drug interactions
4. Promote adherence
5. Environmental influences
6. Assessment of the home


1. Patient’s ability for self care
2. Family support
3. Risk factors
4. Financial, Transportation Issues
7. Drug storage


1. Stability
2. Proper disposal

drug-drug interactions

1. Three possibilities


1. One drug intensifies the effects of the other
2. One drug reduces the effects of the other
3. The combination produces a new response not seen with either drug alone
2. Intensification (potentiative) effects


1. Increased therapeutic effects
2. Increased adverse effects
3. Reduction (inhibitory) effects


1. Reduced therapeutic effects
2. Reduced adverse effects
4. Creation of a new response

mechanisms of drug-drug interactions

1. Direct chemical or physical interactions
2. Pharmacokinetic interactions


1. Altered Absorption
2. Altered Distribution 


1. Competition for protein binding
3. Altered Metabolism


1. Enzyme induction or Enzyme inhibition
4. Altered Renal excretion
5. Drugs act at the same site
6. Drugs act at separate sites
3. Combined toxicity
4. The more drugs a patient receives, the greater the chance there will be an interaction

drug-food interactions

1. Food and drugs may interact to alter the effect of pharmacotherapy


1. Decreased absorption
2. Increased absorption
2. The risk for toxicity may increase with drug-food interactions
3. Drug action may be decreased

timing with respect to meals

1. Administration on an empty stomach


1. 1 hour before or 2 hours after eating
2. Administration with food


1. With food or shortly after

grapefruit juice effect

1. Grapefruit juice inhibits an isoenzyme responsible for the intestinal metabolism of multiple drugs
2. This inhibitory effect is dependent on the amount of juice consumes and can persist for up to 3 days
3. Increases the amount of drug available for absorption, which increases the blood level of drugs
4. Patient teaching point

drug-herb interactions

1. Drug interactions may also result from herbal supplements interacting with drugs
2. They can impact the therapeutic outcome of prescribed agents


1. Increased toxicity
2. Reduced therapeutic outcomes

adverse effect

An effect other than the desired therapeutic effect that may occur during drug therapy

side effect

Usually refers to a minor effect, such as nausea, nearly unavoidable secondary drug effect produced at therapeutic dosing

toxicity

caused by excessive dosing

allergic reactions

1. An immune response


1. Must have had prior sensitization
2. Allergic reactions are not determined by the size of the dose, but by the degree of sensitization

anaphylaxis

1. Anaphylaxis is the most serious of allergic reactions… it is a medical emergency
2. A systemic reactions


1. Contraction of smooth muscles – airway closes
2. Increased vascular permeability – swelling
3. So, it looks like


1. Dyspnea, bronchospasm, laryngeal edema, cardiac dysrhythmias, and occasionally seizures

idiosyncratic response

1. Unusual, abnormal or peculiar response to a drug
2. Idiosyncratic responses are thought to occur because of genetic enzymatic deficiencies that alter the drug’s metabolism

paradoxical response

Opposite of an intended drug response

iatrogenic disease

1. A disease that occurs as a result of medical care or treatment
2. Can be the result of drugs

drug toxicity

Toxicity results when the dosage of drug or drugs exceeds the amount the body can eliminate through metabolism and excretion

physical dependence

A state in which the body has adapted to prolonged drug exposure in such a way that abstinence syndrome will result if drug use is discontinued

abstinence syndrome

1. Varies depending on the drug

Patient teaching related to abrupt discontinuation

carcinogenic effect

The ability of certain medications and environmental chemicals to cause cancer

teratogenic effect

drug-induced birth defects

neurotoxicity

1. The brain is sensitive to small amounts of toxic substances
2. Neurotoxicity can occur after exposure to drugs and other chemicals and gases
3. Signs and symptoms of neurotoxicity


1. Changes in level of consciousness (drowsiness, restlessness)
2. Auditory and visual disturbances, nystagmus
3. Tonic-clonic (grand mal) seizures

hepatotoxicity

1. Primary side of drug metabolism


1. The liver of high susceptible to toxicants due to direct exposure to ingested drugs and other toxicants
2. Manifestations of hepatotoxicity


1. Hepatitis
2. Jaundice
3. Elevated liver enzymes (laboratory values)
4. Fatty infiltration of the liver

nephrotoxicity

1. High susceptibility due to high vascularity


1. Chemically induced kidney damage is typically manifested as acute tubular necrosis
2. Laboratory values to assess


1. Blood urea nitrogen (BUN)
2. Creatinine
3. Creatinine clearance

immunotoxicity

1. A wide variety of drugs can affect the immune system
2. Some may cause immunosuppression (decreased ability to fight infection), whereas others may directly destroy immune system components (i.e., leukocytes)

cardiotoxicity

1. Irregularities in cardiac rhythms and conduction and possibly heart damage may result from an adverse effect known as cardiotoxicity
2. Cause unknown
3. Characteristics of cardiotoxicity include transient cardiac arrhythmias and depression of the myocardial function
4. Prolonged QT interval

ototoxicity

1. Many drugs can produce ototoxicity, which affects the eighth cranial nerve and results in inner ear or auditory nerve damage
2. Structures of the inner ear that may be affected include the cochlea, vestibule, and semicircular canals
3. Ototoxicity may or may not be reversible

identifying adverse drug reactions

1. Did symptoms appear when the drug was first used?
2. Did the symptoms go away when the drug was stopped?
3. Did the symptoms come back when the drug was reintroduced?
4. Does the illness itself explain the event?
5. Could any other drugs be the cause?

minimizing adverse drug reactions

1. Medication guides


1. FDA approved documents
2. Boxed warnings/black box warning


1. The strongest safety warning a drug can carry and still remain on the market

medication errors

1. Types of medication errors


1. There are 13 types
2. Causes of medication errors
3. Ways to reduce medication errors
4. Reporting medication errors
5. Medication reconciliation