Module 2 Flashcards
Define pharmacodynamics
The study of the biochemical and physiologic effects of drugs (what drugs do to the body and how they do it)
What does pharmacodynamics include?
- Dose-response relationships
- Drug-receptor interactions and drug responses that do not involve receptors
- Interpatient variability in drug responses
- the therapeutic index
What is dose-response relationships?
The relationship between the size of an administered dose and the intensity of the response produced
What does the dose response determine?
- The minimum amount of drug to be used
- The maximum response a drug can elicit
- How much to increase the dosage to produce the desired increase in response
As the dosage increases, what happens to the response?
It becomes larger
How is treatment adjusted regarding dose-response relationships?
Adjusted by increasing or decreasing the dosage until the desired intensity of response is achieved
What three phases occur in dose-response relationships?
Phase 1: occurs at low doses
Phase 2: an increase in the dose elicits a corresponding increase in the response
Phase 3: when the curve flattens and a point is reached at which an increase in dose is unable to elicit a further response
What two properties of drugs are revealed in dose-response curves?
Maximal efficacy
Relative potency
What is maximal efficacy?
The larges effect that a drug can produce
What is relative potency?
The amount of drug that must be given to produce an effect
(Implies nothing about maximal efficacy)
Define drugs
Chemicals that produce effects by interacting with other chemicals
Define receptor
Functional macromolecule in a cell to which a drug binds to produce its effects
What are we typically referring to when using the term “receptor”?
The body’s own receptors for hormones, neurotransmitters, and other regulatory molecules
Is the binding of a drug to its receptor reversible?
Usually
What happens when a drug binds to a receptor?
It will mimic or block the action of the endogenous regulatory molecules
And increase or decrease the rate of physiologic activity normally controlled by the receptor
What does it mean that drugs can only mimic or block the body’s own regulatory molecules?
Drugs cannot give cells new functions
(Drugs cannot make the body do anything it’s not already capable of doing. They can only alter the rate of pre-existing processes)
What are the four primary receptor families?
Cell membrane
Ligand-gated ion channels
G protein
Transcription factors
How does the cell membrane receptor family work?
Embedded enzymes, on the surface of the cell
How does the ligand-gated ion channels receptor family work?
Regulate the flow of ions into and out of the cells
How does the G protein-coupled receptor systems receptor family work?
With the receptor
How does the transcription factors receptor family work?
Intracellularly
What occurs if a drug is more selective?
Fewer side effects
How do receptors make selectivity possible?
By the existence of many types of receptors.
Each type of receptor participates in the regulation of just a few processes
Why does the lock and key mechanism of receptors not guarantee safety?
- The receptor can still produce non-selective results if it is responsible for regulating several processes
- Drugs that interact with it will also influence several processes
The body has receptors for each type of?
Neurotransmitter
Hormone
What are agonists?
Molecules that activate receptors
What qualities do agonists have?
Affinity
High intrinsic activity
What do agonists do?
**Can make processes go “faster” or “slower”
What are endogenous regulators considered?
Agonists
What do antagonists do?
At the receptor site, they prevent some kind of action from occuring
How do antagonists work?
By preventing receptor activation by endogenous regulatory molecules and drugs
Do not cause receptor activation but cause pharmacologic effects *by preventing the activation of receptors by agonists
Qualities of antagonists
Affinity
No intrinsic activity
In which ways can receptors build sensitivity?
The number of receptors on the cell surface
The sensitivity to agonists can change
How can the number of receptors on the cell surface and the sensitivity to agonists change?
In response to:
Continuous activation (making things happen)
Continuous inhibition (stopping things from happening)
What happens with continuous exposure to an agonist?
Desensitized or refractory
Or undergo downregulation
What happens with continuous exposure to an antagonist?
Becomes hypersensitive, or supersensitive
Examples of drugs that do not work by using receptors:
Antacids
Antiseptics
Saline laxatives
Chelating agents
What does interpatient variability in drug responses mean?
The dose required to produce a therapeutic response can vary among patients
How is the measurement of interpatient variablity found?
Through a formula called ED50
What is the ED50?
Formula that finds the dose required to produce a therapeutic effect in 50% of the population
What is the therapeutic index?
Measure of a drug’s safety
How is a drug’s therapeutic index found?
Ratio of the drug’s LD50 (average lethal dose to 50% of the animals treated) to its ED50
What does a high therapeutic index mean, vs. a low therapeutic index?
*The larger/higher the therapeutic index, the safer the drug
*The smaller/lower the therapeutic index, the less safe the drug is
What are drug-drug interactions?
Interactions that occur when a patient is taking more than one drug. Some are intended and some are not
What are the consequences of drug-drug interactions?
Intensification of effects:
- increased therapeutic effects
- increased adverse effects
Reduction of effects: (block each other out)
- decreased therapeutic effects
- decreased adverse effects
Or creation of a unique response
Example of drug-drug interaction that increases the therapeutic effects
Ampicillin and sulbactam (antibiotics)
Example of drugs-drug interaction the increases adverse effects
Aspirin and warfarin (both thin the blood)
Example of drug-drug interaction that decreases therapeutic effects
Propranolol and albuterol (propranolol is a beta blocker and albuterol blocks receptors in the lung)
Example of drug-drug interaction that decreases adverse effects
Narcan and morphine (narcan blocks receptors from morphine to prevent adverse effects from it)
Example of drug-drug interaction resulting in a unique response
Alcohol with Antabuse/disulfiram (makes you really sick)
Four basic mechanisms of drug-drug interactions:
- Direct chemical or physical interaction
- Pharmacokinetic interaction
- Pharmacodynamic interaction
- Combined toxicity
Why should you never combine drugs in the same container without establishing compatibility?
They could have a direct chemical or physical interaction
What should you do if you’re unsure if drugs are compatible?
Need to call the pharmacy to make sure they’re compatible before mixing them together
What’s important to know about mixing intravenous solutions?
Chemical or physical interactions are most common in intravenous solution
If they cause precipitation - do not mix
Types of pharmacokinetic drug-drug interactions:
Altered absorption
Altered distribution
Altered renal excretion
Altered metabolism
Cytochrome P450 (CYP) group of enzymes
What can cause altered absorption in pharmacokinetic interactions?
Elevated gastric pH
Laxatives
Drugs that depress peristalsis
Drugs that induce vomiting
Adsorbent drugs
Drugs that reduce regional blood flow
What can cause altered distribution in pharmacokinetic interactions?
Competition for protein binding
Alteration of extra cellular pH
What can cause altered renal excretion in pharmacokinetic interactions?
Drugs can alter:
Filtration, reabsorption, active secretion
What can cause altered metabolism in pharmacokinetic interactions?
Most important and complex mechanism in which drugs interact,
The cytochrome P450 (CYP) group of enzymes can really impact a lot of medications, taking multiple meds together can affect this group
What is p-glycoprotein?
Transmembrane protein that transports a variety of drugs out of cells
What happens to the intestinal epithelium if there is recused or increased PGP?
Affects absorption
What happens to the placenta if there is reduced or increased PGP?
Affects drug export from placental cells to maternal blood
What happens to the blood-brain barrier if there is reduced or increased PGP?
Affects drug export from the cells of the brain capillaries into the blood
What happens to the liver if there is increased or decreased PGPs?
Affects drug export from liver into bile
What happens to kidney tubules when there is an increase or decrease of PGPs?
Affects drug export from renal tubular cells into the urine
What pharmacodynamic interactions occur if there is a drug-drug interaction at the same receptor?
Almost always inhibitory (antagonist/agonist)
(They constantly fight each other and we don’t get a response)
What pharmacodynamic interactions occur if there is a drug-drug interaction at separate receptor sites?
May be potentiative (work well together Ex: morphine and diazepam)
Or
Inhibitory (hydrochlorothiazide and spironolactone)
What is combined toxicity?
Drugs with overlapping toxicities should not be used together
How can we minimize adverse drug-drug interactions?
- Minimize the number of drugs a patient receives
- ** Take a drug history
- Be aware of the possibility of illicit drug use
- Adjust the dosage when metabolizing inducers are added or deleted
- Adjust the timing of administration to minimize interference with absorption
- Monitor the patient for early signs of toxicity
- Be especially vigilant when a patient is taking a drug with a low therapeutic index
What is a drug-food interaction?
Impact of food on drug absorption
What can drug-food interactions cause?
Decreased absorption rate
Increased absorption
Example of decreased absorption due to a drug-food interaction
Milk and tetracycline (tetracycline not effective)
Fiber and digoxin
Drug-food interaction involving the P450 enzymes
**Grapefruit juice effect
What occurs with the grapefruit juice effect?
Inhibits the metabolism of certain drugs
Or
Raises/increases the drugs’ blood levels
Examples of the grapefruit juice effect increasing a drug’s blood levels
Felodipine
Lovastatin
* Cyclosporine (given for organ transplant patients)
Midazolam
What do drug-food interactions have an impact on?
Drug toxicity
Drug action
Timing of drug administration
Examples of drug-food interactions impacting drug toxicity?
Monoamine oxidase inhibitors (MAOIs) and tyramine-containing foods
Ex: theophylline and caffeine
Potassium-sparing diuretics and salt substitutes
Aluminum-containing antacids and citrus beverages
Examples of drug-food interactions impacting drug action?
Warfarin and foods rich in vitamin K
(Vitamin K counteracts Warfarin)
Examples of drug-food interactions impacting timing of drug administration
- **Some drugs are better tolerated on an empty stomach
- others should be taken with food, especially for nausea
If a drug is supposed to be taken on an empty stomach, what does this mean?
Should take drug 1 hour before a meal or 2 hours after
Example of a known drug-herb interaction
*St. John’s wort
Induces drug-metabolizing enzymes and reduces the blood levels of many drugs
Two issues related to drug safety
Adverse drug reactions (adverse drug events)
Medication errors
How are adverse drug reactions defined by the world health organization?
** Any harmful, UNINTENDED, and undesired effect that occurs at normal drug doses
(Excludes excessive dosages)
Can range from annoying to life threatening
What are examples of a mild adverse drug reaction?
Drowsiness
Nausea
Itching
Rash
Examples of severe drug reactions?
Respiratory depression
Neutropenia
Hepatocellular injury
Anaphylaxis
Hemorrhage
Death
Which groups of people are adverse drug reactions most common in?
Elderly
Very young
Patients with chronic disorders
Risk is also increased by severe illness
Define side effect
A nearly unavoidable secondary drug effect produced at therapeutic doses
When might a side effect develop?
Soon after drug is initiated or
Not until drug has been taken for weeks or months
Define toxicity
Adverse drug reaction caused by excessive dosing
How can toxicity occur even with normal dosing?
If pt has neutropenia (risk for infection) or with anticancer medications
How can we try to avoid toxicity?
The dosing and keeping up with plasma levels can help
Define allergic reaction
Immune response determined by the degree of sensitization of the immune system, rather than by drug dosage
Most common drug that causes allergic reactions
Penicillins
Define idiosyncratic effect
An uncommon drug response resulting from a genetic predisposition
Example of an idiosyncratic effect
Succinylcholine-induced paralysis
(Usually brief, but may last hours in genetically predisposed patients)
Define paradoxical effect
The opposite of the intended drug response
Example of a paradoxical effect
When using benzodiazepines for sedation to treat insomnia, excitement may occur instead (esp in children and older adults)
Define iatrogenic disease
A disease produced by a physician (or by drugs prescribed by a physician)
Define physical dependence
A state in which the body has adapted to drug exposure in such a way that an abstinence syndrome will result if drug is discontinued
How does physical dependence develop?
During long-term use of certain drugs (opioids, alcohol, barbiturates, amphetamines)
Examples of drugs that have a carcinogenic effect
A few therapeutic agents
Several drugs used to treat cancer
Diethylstibestrol (DES)
Define teratogenic effect
A drug-induced birth defect
Example of organ-specific toxicity to the kidneys
Amphotericin B (antifungal)
Example of organ-specific toxicity to the heart
Doxorubicin (anticancer)
Example of organ-specific toxicity to the lungs
Amiodarone (antidysrhythmic)
Example of organ-specific toxicity to the inner ear
Aminoglycoside (antibiotic)
What are QT interval drugs?
Drugs that cause the QT interval of the heartbeat to elongate
Leading cause of liver failure in the US
Hepatotoxic drugs
How do hepatotoxic drugs cause damage?
As they are metabolized, they are converted to toxic products that can injure liver cells
Combining hepatotoxic drugs may increase the risk for liver damage
If we are giving a drug that has the potential of causing liver side effects, what do we need to do?
- Monitor liver enzymes
If enzymes are elevated, need to get pt off of that drug
**What are the signs of liver injury we need to educate our patient about?
Jaundice
Dark urine
Light-colored stools
Nausea
Vomiting
Malaise
Abdominal discomfort
Loss of appetite
Which liver enzymes should be monitored for liver injury?
Aspirate aminotransferase (AST)
Alanine aminotransferase (ALT)
What is the QT interval?
Measure of the time required for the ventricles to depolarize after each contraction
What are QT drugs?
Drugs that prolong the QT interval on an ECG
What can QT interval drugs create the risk for?
Life-threatening dysrhythmias
Examples of life threatening dysrhythmias
Tornadoes de pointes
Ventricular fibrillation
Which patients are at higher risk of being affected by a QT drug?
Women
Older adults
Patients with:
- bradycardia
- congestive heart failure
- congenital QT prolongation
- low potassium
- low magnesium
How can a nurse minimize adverse drug reactions?
Evaluate the patient for ADRs, educate patients and families about how to minimize harm
How to monitor the liver for toxicity
Look for signs of jaundice
Monitor liver function tests
How to monitor the kidney for signs of toxicity
Routine urinalysis
Serum creatinine level (with periodic creatinine clearance testing)
How to monitor bone marrow for signs of toxicity
Periodic blood cell counts
Define *black box warnings
- Strongest safety warning a drug can carry and still remain on the market
What is the purpose of black box warnings?
- to alert prescribers to:
- potentially severe side effects
- ways to prevent or reduce harm
Examples of potentially sever side effects that black box labels alert prescribers of:
- Life-threatening dysrhythmias
- Suicidality
- Major fetal harm
Examples of ways to prevent or reduce harm that black box warnings alert prescribers of
- Avoiding a teratogenic drug during pregnancy
What is a Risk Evaluation and Mitigation Strategy (REMS)?
A plan to minimize drug-induced harm
What is iPLEDGE?
An example of an REMS
It was designed to ensure that those who are pregnant or who may become pregnant will not have access to Isotretinoin
What are the most common human factors that cause medication errors?
Performance deficits (most common)
Knowledge deficits
* Miscalculation of dosage
90% of all med errors are due to:
Human factors
Communication mistakes
Drug name confusion
Factors that influence individual variation in drug responses:
Body weight and size (how big someone is)
Age
Pathophysiology of the individual
Drug tolerance
Variability in absorption
Genetics and pharmacogenomics
How does kidney disease affect drug responses?
Reduced excretion and increased toxicity
How does liver disease affect drug responses?
Reduced metabolism and increased toxicity
How does acid-base imbalance affect drug responses?
PH changes alter absorption, distribution, metabolism, and excretion of drugs
How does altered electrolyte status affect drug responses?
It is rare for electrolyte changes to have a significant impact on drug responses
What is tolerance?
Decreases responsiveness to a drug as a result of repeated administration
What are three types of drug tolerance?
Pharmacodynamic tolerance
Metabolic tolerance
Tachyphylaxis
What does pharmacodynamic tolerance result from?
Associated with long-term administration of drugs (such as morphine and heroin)
What does metabolic tolerance result from?
Accelerated drug metabolism
What does tachyphylaxis result from?
Repeated dosing over a short time causes a reduction in drug responsiveness
Define bioavailability
The ability of the drug to reach the systemic circulation from its site of administration
Which types of medications does bioavailability occur with?
Only oral medications
What affects bioavailability of a medication?
Tablet disintegration time
Enteric coatings
Sustained-release formulations
Define pharmacogenomics
Study of how genes affect individual drug responses
Ways genetic variations can affect individual drug responses:
Examples of genetic variations that affect individual drug responses:
- Alter the structure of drug receptors
- Alter drug metabolism
- Gender
- Race
- Comorbidities
- Diet
- Psychosocial factors
Examples of how gender affects drugs
Alcohol is metabolized more slowly in women
Certain opioids are more effective in women
Quinidine causes greater QT interval prolongation in women than in men
How does diet affect drug response?
Starvation can reduce protein binding of drugs
Define genetics
The passing of genetics traits from one generation to another through human genes
The examination of the effects of genes
What is a genome?
All of a person’s genes
How the genes interact with each other and the environment
Involves investigating diseases
Define pharmacogenomics
- The study of how genes affect a person’s response to drugs
Benefits of pharmacogenomics
- Combines genomics and pharmacology to provide individualized and more specific drug therapies
- Reduces adverse drug reactions
Explain the categorization of the FDA pregnancy risk factors
Category A is safest for pregnant people
Category X is most dangerous and is known to cause fetal harm
Which age group is considered to be pediatric patients?
All patients younger than 16 years old
Which pharmacokinetic responses does the immaturity of kids’ organs put them at risk for?
Elevated drug levels = more intense response
Delayed elimination = prolonged response
Which 5 pharmacokinetic processes are immature and cause infants have such an increased sensitivity of drugs?
Absorption
Protein binding of drugs
Blood-brain barrier
Hepatic metabolism
Renal drug excretion
What is one important difference in children vs. adults regarding metabolism of drugs?
Children 0-2 yrs metabolize drugs faster than adults
Age-related adverse drug reactions in children
Growth suppression
Discoloration of developing teeth
Kernicterus
What is dosing most commonly based on in children?
Body surface area
Why do older adult patients experience more adverse drug reactions and drug-drug interactions than younger patients?
Prescribed more drugs
Altered pharmacokinetics (more sensitive to drugs)
Multiple and severe illnesses
Poor adherence
Goals of treatment of older adult patients
Reduce symptoms and improve quality of life
How does altered GI absorption in older adults affect pharmacokinetics?
- Not a major factor in drug sensitivity
- % of oral dose absorbed is not affected
- Rate of absorption slows
- Delayed gastric emptying and reduced splanchnic blood flow occur
Characteristics of older adults that affect distribution.
How is distribution affected in older adults?
Increase in body fat percentage
Decrease of lean body mass
Decrease in total body water
Reduced concentration of serum albumin causes decreased protein binding of drugs and increased levels of free drugs
How is metabolism affected in older adults?
Hepatic metabolism declines with age
Responses of drugs are prolonged
Responses to oral drugs may be enhanced
How is excretion affected in older adults?
Renal function declines (renal blood flow, glomerular filtration rate, active tubular secretion, and number of nephrons)
Most important cause of adverse drug reactions in older adults
** Drug accumulation due to reduced renal excretion
How should excretion me monitored to be sure older adults do not have an adverse drug reaction?
Renal function should be assessed
** Creatinine clearance rather than serum clearance
Why should a creatinine clearance test be done for older adults rather than serum creatinine?
Lean muscle mass (source of creatinine) declines in parallel with kidney function
Creatinine levels may be normal even though kidney function is greatly reduced
Why are beta blockers less effective in older adults?
Reduction in number of beta receptors
Reduction in the affinity of beta receptors for beta-receptor blocking agents
Symptoms of ADRs in older adults that are nonspecific
Dizziness and cognitive impairment
Measures used to reduce ADRs in older adults
Thorough drug history
Monitor the patient’s response and *plasma drug levels
Use simple regimen
Monitor for drug-drug interactions
Review need for drug therapy
Dispose of old medications
Take steps to promote adherence
Avoid drugs on the Beers list
Reasons older adults may intentionally not adhere to drug therapy
High cost of drugs
Side effects
Pt’s believe that the drug is unnecessary or the dosage is too high
