Pharm exam 1: Section 1 Flashcards
Goals for drug therapy
safety, appropriateness, effectiveness
- is the regimen easy?
- Will pt follow regimen?
- Does regimen have least amount of side effects?
US FDA
regulate whether drug can be on the market; regulate if off label use is ok
National Provider Identifier
Anyone using electronic prescribing system needs NPI #
Pre-clinical trials
lab and animal studies
Clinical trials - phase 1
small safety study with healthy people
20-80 people
Clinical trials - phase 2
Safety study
People with illness that med will be used for
100-300 people
Determine side effects
Clinical trials - phase 3
Determines effectiveness of drug and side effects
Trial is double blind with placebo
People with illness for meds use
1k-3k people
Clinical trials - post phase 3
Approved or rejected
If approved - med is marketed
Clinical trials - phase 4
long term monitoring of drug side effects
post marketing studies
Controlled substances Act of 1970
FDA determines potential for drug to cause addiction and dependency (physiologic or psychological)
Schedule 1 drug
High potential for abuse, no therapeutics use
Ex: heroin, lsd, cocaine, marijuana
Schedule 2 drug
Valid for medical use High potential for abuse No prescription refills Must write number of pills prescribed on paper prescription with signature Ex: methadone, opioids
Schedule 3 drug
Potential for abuse, moderate to low risk for dependence
Prescription refills 5 times over 6 months
Ex: Percocet, Vicodin
Must write number of pills prescribed on paper prescription with signature
Schedule 4 drug
Low potential for abuse unless used everyday
Physiologic dependence possible
Ex: anti-anxiety medication, non-narcotic pain meds
Schedule 5 drug
Lowest potential for abuse
Ex: cough medicine with codeine, antitussives, antidiarrheals
Drug Enforcement Agency (DEA)
Determines what drugs are required to be scheduled
Brand vs generic
Generic can be made and marketed when patent expires for brand medication
Generic must undergo clinical trials
Generic must be similar in how well they work to brand
Must be within close percentage of bioequivalence of brand
Safe because of oversight
Foreign medication
Not regulated, may be counterfeit
May be different dose or have different ingredients
Unsafe
Complimentary and Alternative medicine (CAM)
Sold as food, no FDA approval required
Ex: St. Johns Wort interferes with many meds
Fox glove is digitalis
Medication disposal
Contaminate environment if not disposed via community drug take back program
Can put meds in cat litter and dispose in closed container
Who regulates APN prescribing?
States, not federal government
Board of nursing with some medical board
Cert and license determine scope of practice
22 states and DC allow APN to prescribe independently
General principles of prescribing meds
Collect data and assess pt (med hx, sx hx, allergies, hx and physical exam)
Formulate differential dx
Select appropriate therapy (don’t duplicate therapy, cost effective therapy)
Patient education: therapeutic effects, side effects, how to deal with adverse drug reactions, how to deal with adverse reactions, readable instructions, easily understood language, pharmacy preference)
Causes of Adverse Events
Lack of knowledge:
prescriber must educate pt, if unfamiliar with pt medical issue, refer
Lack of communication
Illegible, incomplete, or wrong medication use
Lack of allergy medication
Overuse, underuse, misuse, inadequate history
If don’t know meds pt is taking, look it up
Prescription requirements
Name and title Practice address and phone License (state) and NPI # DEA # if a controlled substance (print and sign prescription) Billing medicare needs NPI #
Prescription requirement
Pt information Medication and formulation Strength and frequency Quantity - spell out (thirty not 30) # of refills - refills last 6 months; if pt doesn't fill a prescription within 6 months - need to write another prescription (controlled substances) Signature
Monitor medication adherence
Lab testing: blood level of medication
Pill count: ask pt bring pill box
Patient diary
Patient relationship with provider helps to increase compliance; talk to pt, listen to pt
Factors that influence adherence
Cost
Side effects: if not ok with pt life, pt will not take medication
Perception of whether needs/values are met
Perception of efficacy of med (belief that med works/is beneficial)
Perception of side effects
Cultural influences
Approachability of provider
Compatibility with lifestyle (pt won’t follow complicated regimen)
Understanding of treatment
Pharmacogenomics
Study of pharmacology and genes Personalized medicine How genetic variations impact response to therapy Enables targeted therapy/focus resources Expedites clinical improvement Target risk reduction strategies
Drug
any substance that modifies at least one function in a living organism
Toxicology
study of dangerous of harmful chemicals or drugs
Pharmacotherapeutics
use of drugs to dx, prevent, treat disease or illness
Includes pharmacodynamics and pharmacokinetics
Pharmacokinetics
what the body does to the drug
how a drug is administered, absorbed, distributed, and eliminated
Purpose: get drug to site of action where it can produce pharmacodynamic effect
Pharmacodynamics
what the drug does to the body
how the drug initiates therapeutic or toxic effect
Enteral route: lipid soluble
Absorption: first pass
Per orum, PO, Oral
Absorbed enterally via GI tract - via active or passive transport
Most subject to hepatic first pass: metabolized in liver.
In liver, hepatic enzymes reduce amount of ACTIVE drug reaching blood –> decreased amount of drug available in body
PO doses are higher to account for loss of meds in liver extraction
Enters bloodstream and impacts organs + tissues
Passive Diffusion
Method of enteral route absorption
Movement of molecules from an area of higher concentration to lower concentration
Greater distance to travel; larger molecules –> slower diffusion
Active transport
Method of enteral route absorption
Membrane proteins act a carrier molecules to transport substances across cell membrane
Absorption time
Depends on gastric emptying time
Presence/absence of food
Gastric or GI pH
Enteral route
Skips first pass
Buccal: nicotine gum, fentanyl lollipop, orally dissolving meds
Sublingual: nitroglycerin, immitrex: veins carry drug to superior vena cava and eventually the heart
Rectal: suppositories, enemas - less effective due to bowel irrigation, early evacuation
Parenteral route
skips first pass
IV: immediate serum levels; no first pass effect; fastest method
IM: slower onset than IV; absorption required; depends on vascularity of area. Highly vascular areas with big surface area increases absorption
SubQ: absorption required; slower onset than IM
Epidural: injected into spinal cord but outside of dura
Intrathecal: injected into CSF
Intra-articular: injected into joint
Intra-arterial: injected into artery; dangerous bc connected to organ
Intra-osseus: injected into bone
Inhalation delivery
Drug delivered to lung
Rapid absorption into bloodstream
Can reduce GI side effects in some instances
Topical delivery
Drug applied to skin surface and/or mucous membranes
Not absorbed systemically; low dose or not well absorbed dermal
Mucous membrane: potential for systemic activity or interaction; eye drops
Skin surface: mostly local effect; topical steroids
Creams are H2O soluble: washed easier than ointment
Creams are preferred over hairy areas bc they are hydrophilic
Transdermal: crosses dermis
Drugs get absorbed systemically over a period of time
Controlled slow release of a drug - maintains constant blood level of drug (put on regularly)
Ex: Nitro patch or fentanyl patch
Exercise increases absorption - may lead to side effects from more rapid absorption
* Pt instructed not to open patch bc rapid release
Bioavailability
First pass effect
First pass effect: hepatic metabolism before reaching the bloodstream
Some drugs are very highly metabolized (up to 70%)
Prodrugs (precursor to active drug) depend on hepatic metabolism to become active
Increased metabolism –> decreased bioavailability
Bioavailability Impact of formulation Like dissolves like Acidic drugs absorbed in stomach Basic drugs absorbed in intestine
Immediate release: absorbed in stomach bc stomach acidic and drug is acidic
Extended release: dissolve slowly; absorbed in intestine
Enteric coated: slows drug to be dissolved in the intestine rather than the stomach;
intestines have higher pH
preserves gastric mucosa.
Intestine provides more surface area for drug absorption
diarrhea decreases absorption
Faster action on empty stomach; faster gastric emptying
Slower action after meal; slower gastric emptying
Laxative (cathartics) increase peristalsis –> less absorption and less bioavailability
Bioavailability
Blood flow
Meds reach well perfused areas in higher supply
Decreased blood flow –> decreased absorption
Distribution depends on adequate blood flow to area, lipid/water solubility, protein binding
Distribution impacted by obesity –> lipid soluble drugs distribute into fatty tissues to be stored and concentrated
H2O soluble drugs stay in vascularized areas
Pharmacokinetics
Protein binding - usually reversible
Primary plasma protein - albumin
Drug bound to protein is inactive; serves as storage site for drug; can’t leave bloodstream or bind to enzyme to exert action
Drug unbound to albumin is considered “free drug” and is biologically active
Low albumin states –> more drug availability and activity; more free drug –> more exaggerated response to drug
Factors affecting albumin levels: nutritional status, renal status
Basic drugs bind to alpha1 acid glycoprotein / lipoprotein
Acidic drugs bind to albumin
Protein binding
Drug interactions
Drugs with higher affinity to receptor site of protein will push drug with low affinity off site. Drug with low affinity will have more free drug in bloodstream –> more exaggerated drug response
Ex of drugs with low protein affinity: warfarin, ibuprofen, OCP, seizure medication
Pharmacokinetics
Entering cell
Lipid and water soluble drugs
Lipophilic drugs cross blood brain barrier (Diazepam)
- penetrate cell membrane quickly
Hydrophilic drugs can’t cross blood brain barrier; not good for central disorder (PCN)
Pharmacokinetics
Entering cell
Acidity
pH: absorbed in similar pH
Stomach = low pH
Intestines = high pH
non-ionized cross membrane more easily (passive diffusion)
Strong ionized drugs need to be actively transported via Na+ or K+ pump; require energy; decreased rate of entry into cell
Pharmacokinetics
Metabolism
Change of substances into H2O soluble to prepare for excretion
Liver is major organ that metabolizes drugs; liver has high concentration of metabolic enzymes
Prodrugs: administered in inactive form; become active once metabolites are cleaved
Ex: prednisone, enalapril, acyclovir, morphine, oxypurinol
Pharmacokinetics
Metabolism
Preparation for excretion
Drugs go through hydrolysis to be H2O soluble for excretion
Excretion occurs: renally or in the feces
Drugs must be less lipid soluble to excrete
Once hydrolyzed, can’t cross membranes and gets excreted
Metabolism
Phase 1
Drug is changed from lipophilic to hydrophilic via
* oxidation, reduction, and hydrolysis: drug is changed from more polar/H2O soluble compound
Mainly through Cytochrome P450 and its isoenzymes
Metabolism
Phase 2
Further prepares for elimination
Poor liver function increases concentration of drug
Decreased blood flow to liver = decreased delivery of drug to liver
Cigarette smoking = increased metabolic rates -> need for increased doses of med
Elimination
Combo of metabolism and excretion
Half life
Half life: time required for 50% of drug to be eliminated from body
Drug is considered fully clear after 4-5 half lives of drug
5 half lives = 97% of drug elimination
Longer half life: difficult to reach steady state
Loading dose required to reach desired blood concentration quickly
Loading dose: based on volume of distribution of drug, not based on half life
Maintenance dose scheduled in intervals based on half life or amount of drug eliminated
Elimination
Biliary excretion: drugs excreted by liver into gallbladder
Renal: 90% of drugs
GFR must be evaluated
Low GFR: Rx low dose bc not easily excreted by kidneys
GI tract: drugs excreted to the bile and then to feces
Breast milk, exhalation, saliva, skin, perspiration, tears
Factors that interfere with Elimination
Renal failure: increases half life, need downward dose adjustments
Hepatic disease: prodrug not broken down to active metabolite; increases half life
Exercise: impacts blood flow, GI motility, body temp
Decreased blood flow to liver -> increased half life and decreased clearance
Clearance: removal of drug from plasma or organ; last step in elimination
High clearance rate: drug removed rapidly
Low clearance rate: drug removed slowly
Larger volume of distribution (drug plasma): faster half life
pts > 65 or serum creatinine > 1.5 at risk for toxicity bc of decreased renal function
Pharmacdynamics
Impacted by:
Receptor abundance Older people have less receptors Young children have less receptors Receptor affinity: decreases with age Low affinity requires high concentration of drug to attach to receptors High affinity requires less concentration to attach to receptors More dose=bigger response Antagonists: compete for receptor sites Ex: Narcan; Carbon monoxide
Receptors
Autonomic NS: involuntary functions thermoregulation vascular contractility heart and respiratory rate digestion
Somatic NS: Voluntary functions
movement
speech
Autonomic NS
Sympathetic NS: fight or flight response Neurotransmitters is norepinephrine alpha 1 receptors: smooth muscle alpha 2: brainstem, spinal cord, eye beta 1: heart beta 2: lungs
Parasympathetic: cholinergic, muscarinic receptors
Neurotransmitter: acetylcholine
Agonists: prolong acetylcholine activity; cause contraction, increase secretion, increased sweating, increased urination
Antagonist: anticholinergics block effects of acetylcholine. Urinary retention, xerostomia, increased HR
Efficacy and toxicity
ED50 drug dose -> therapeutic effects in 50% of pts
LD50 drug dose -> lethal in 50% of recipients
Potency: amount of drug needed to produce a response
Narrow window between toxicity and therapeutic range
-> increased risk for toxicity
Therapeutic index
Dose
TI = LD50/ED50
lethal dose = 100; effective dose = 25; 100/25 =4
Therapeutic Window
Range
Range from desire effect to dangerous dose
Ex: med effective in 50% at 1mg but is lethal in 50% at 100mg
Therapeutic window = 1-99 (lower than dose that produces toxicity)
Adverse drug reactions
unintended effect at a commonly used dose
can be expected/anticipated: abx -> diarrhea
excludes overdose, errors, non-adherance
Adverse reaction
Type A
Correct response; wrong area of body
Mu sites in gut cause constipation with opioid use
mild hypersensitivity reaction
related to pharmacologic actions of med
AA.- nitroglycerin causes stronger effect (increased vasodilation)
Adverse reaction
Type B
More dangerous
Unusual or unanticipated actions of the drug
Hypersensitivity reactions
Ex: pt lacks P450 enzyme, takes beta blocker and BP drops bc not metabolizing drug
Neonatal absorption
< 1 month old
75-80% body is water: hydrophilic drugs exit body quickly
Weakly alkaline gastric: don’t absorb acidic medications well
Gastric motility differs: breast fed babies have faster peristalsis
Very thin stratum corneum: faster absorption of meds
Poor muscle mass but great capillaries: lots of perfusion to tissues
Low serum albumin: more free drug, exaggerated drug response
GI enzymes: low P450; poor metabolism of meds
Phase I and II metabolism delayed: drugs remain active longer and take longer to convert to H2O soluble form to be excreted
Lower GFR: poor kidney function to eliminate drug
Absorption: Infants
1 month - 1 year
Body water content decreases
Body fat increases
CYP450 enzymes start to work; metabolize drugs better
GFR increases after 2 weeks - 5 months: < 2 yrs be careful with drug administration d/t kidney development
Thin stratum corneum: increased topical absorption
Absorption: Children
1 - 12 yrs
> 2 yrs: kidneys are mature
Adherence = parent + child (child likely won’t take med alone)
Weight based dosing until 88 lbs or 18 yo
Total daily dose: mg/kg/day
Dose per day: mg/kg
Obese children: consider increasing or decreasing dose if response not adequate to normal dose
Physiologic changes in pregnancy
increased blood volume: 30-50%
increased circulation
decreased serum albumin percentage: bc more dilute
gastric pH increases: decreased absorption of acidic drugs
increased body water
progesterone and GI motility: decreased GI motility
* consider increasing or decreasing dose if desired response not adequate
Medication response may be lower due to changes
Teratogenic meds
Thalidomide: sz med used in pregnant women for migraine, anxiety, and sedative properties -> birth defects
Taken off market
Began inquiry into placental transfer of drugs
Pregnancy
Factors promoting transfer across placenta
Lipid solubility
Smaller, lighter molecules
Unbound “free” drug
Pregnancy
Factors inhibiting transfer across placenta
Highly ionized molecules (+ or - charge requires energy to cross placenta)
Larger, heavier molecules
Drugs with high protein binding (drugs have high affinity to protein)
Teratogenicity
likelihood a drug will cause structural or functional abnormalities to fetal organs
Psych meds cause cardiac problems in babies
FDA Categories
A & B usually ok to give to mothers
C & D usually not ok to give
Category X never ok to give
Category A: controlled trials in 1st trimester without fetal harm
Ex: Folic acid, thyroid hormones (thyroid hormones need to be high enough to maintain pregnancy)
Category B: No RCT in humans, animal RCT show no risk in 1st or later trimesters (no harm presented after taking med)
Ex: PCN, axythromycin, metformin, cyclobenzaprine, pantoprazole
Category C: No RCT in women or animal, or animal studies show some adverse effect
Ex: ACEI, Labetolol, Amlodipine, Gabapentin, Tramadol, Trazadone, Prednisone
Category D: Evidence of human risk. Benefits must be high to warrant use
Ex: Sulfa drugs, ASA, Losartan, Benzos
Category X: studies in women and animals demonstrate abnormalities. C/I in anyone who may become pregnant
* routine pregnancy screens if on med to prevent pregnancy
Ex: Retinoins, statins, warfarin, methotrexate
Breastfeeding
Breast milk is 80% water: hydrophilic meds pass more easily
Need high enough serum concentration to enter breastmilk
Pump and dump to prevent med transfer
Highly protein bound meds not as likely to pass
Look up meds to be sure
Elderly
Lean muscle mass, less water content Muscle is where water is stored
Increased risk of dehydration, decreased drug absorption
More body fat
Less CYP450: slower drug metabolism
Lower GFR: decreased drug excretion
Longer half life: longer clearance
Slower elimination
Elderly
Polypharmacy: med reconciliation to prevent med duplication (diff med, same class)
Cost of medication: decreases compliance; choose generic
Adherence and memory
OTC products: herbal meds, do they interact
Side effects: normal part of aging or med interaction
Sedation, falls, stability: don’t over sedate -> decreased functional capacity, can cause falls
Beers Criteria
For potentially inappropriate medication use in older adults >65
Developed by American Geriatric Society
Commonly prescribed meds on list, some are necessary to give
Medicare Part D plans may not pay for some of these medications
