Pharm Exam 1

  1. FDA drug definition
    a chemical used to treat, cure, prevent or diagnose a disease or medical condition
  2. what is the FDA responsible for
    • assuring the safety, efficacy, and security of drugs
    • facilitating innovations that make drugs safer, more effective, and less expensive
    • helping the public get info on medicines
  3. CDER
    • center for drug evaluation and research: the branch of the FDA that reveiws drugs
    • theyll call specialists for the condition that a proposed drug treats
  4. pre-clinical laboratory research
    • identified a candidate drug molecule and purifies and synthesizes it
    • demonstrate in vitro, then animal testing if promisint
  5. pre clinical animal research
    • helps predict safety, eficacy and dosing in humans
    • must ensure humane and proper care of animals
    • typically at least 2 different species
    • goal is to determine if safe to test in humans
  6. IND
    • if pre clinical results are promising, an investigational new drug IND application is submitted to the FDA
    • if approved, begin human tests
  7. phases of clinical trials
    • phase 1: small trials (20-80) in healthy subjects, determines best dose
    • phase 2: small trials in subjects with disease of interest, refines dosing regimen. patients may be more vulnerable to side effects than healthy
    • phase 3: large randomized control trials with disease of interest, allows more robust comparison of risks vs benefits and tells about long term safety
  8. NDA
    If clinical research results are positive, a new drug application (nda) is submitted to the FDA. if approved, marketing can begin
  9. how long from drug birth to FDA approval
    • 8-15 years
    • 1 in 5,000 will graduate to clinical trials
    • 1 in 5 clinical trail drugs will become fda approved
  10. phase 4 trials
    • occur after fda approval
    • aka post marketing studies
    • evaluate long term safety and efficacy
    • may also look at alternate administration techniques, different dosing regimens, usefullness in other disesaese, and cost effectiveness
  11. how do generic drugs get FDA approval
    by proving bioequivelance: which is the same rate and extent of absorption of the active ingredient

    new/costly drug trials not needed, leading to cheaper price
  12. what drugs can get nonprescription  (otc) status
    • benefits strongly outweigh risks, low potential for misuse
    • consumer can self diagnose the condition/symptom
  13. pharmacokinetics
    what the body does to the drug
  14. pharmacodynamics
    what the drug does to the body
  15. 4 steps of pharmacokinetics
    • absorption
    • distribution
    • metabolism
    • excretion
  16. absorption
    • the movement of drug from site of administration to systemic circulation
    • can be from fat, gi tract, sub q tissue, muscle, bone
  17. bioavailability
    • the proportion of drug that enters the bloodstream and has an active effect
    • intravenous drugs are always 100% bioavailable
    • can range from 0-100% for other routes
  18. what factors influence peripheral absorption
    • regional blood flow
    • type of tissue
    • drug chemical properties
    • limitation of physiologic transport- ie proteins that carry the drug across a membrane
  19. why dont we give everything IV if its 100% bioavailable
    there are benefits to slow absorption, ie insulin
  20. cell membranes and drugs
    • cell membranes divide the bodys compartments from eachother.
    • drugs must cross the cell membrane to move from one body compartment to the next
  21. Types of drugs for membrane transport
    • lipophilic drugs: fat soluble. cross cell membranes easily
    • hydrophilic drugs: water soluble. Polar/ionized. dont cross easily
    • soooo hydrophillic drugs in the peripheral will be absorbed more slowly than lipophilic
    • nonpolor/nonionized drugs: these are neutral and cross easily unlike polar ionized that are charged
  22. characteristics of the drug in influencing bioavailability
    • chemical properties
    • sustained-release vs immediate release
  23. what factors influence bioavailability
    • characteristics of the drug, dose, form
    • extent of metabolism occuring prior to systemic circulation
    • capacity of intestines to absorb drug
    • presence of interacting substances (other drugs, food)
    • blood flow
  24. extent of metabolism occuring prior to systemic circulation in influiencing bioavailability
    • FIRST PASS EFFECT: Liver chews up and destroys drug molecules leaving less drug in the systemic circulation
    • all drugs taken orally have the first pass effect.
  25. capacity of intestines in influencing bioavailabilyt
    • if the intestines cant absorb as much drug. 
    • ie saturated protens for transport, gastric motility is too fast, or not enough surface area
  26. drug acidity
    • pH can affect drug absorption from the GI tract
    • drugs are best absorbed in the neutral/non ionized state
  27. acidic drugs
    • remain non-ionized in acidic environments, like the stomach, but become ionized in basic environments, like the small intestine
    • absorption therefore high in stomach, low in small intestine.
    • in basic environments, the drug will dissociate and be charged and therefore have a harder time moving across the membrane. 

    this is why some drugs are taken with or without food
  28. basic drugs
    • opposite of acidic
    • better absorbed in small intestine than the stomach.
  29. best absorption in small intestine and stomach
    • stomach: weak acids
    • small intestine weak bases
  30. example of an acid drug and what if a patient is on a basic drug
    • reyataz (atazanavir) requires an acid ph for absorption
    • what if they take zantac (acid suppressant)

    take them at least 2 hours apart
  31. first pass effect
    • drugs absorbed by the GI tract pass through the liver first
    • reduces drug availability in certain drugs
    • ie met 25mg po is the same potency as 5mg iv- metoprolol has rapid and complete absorption, but first pass effect reduces it to 40-50%
  32. distribution
    • the movement of drug from the systemic circulation to the peripheral tissues
    • ie the visceral organs, interstitial tissue, CNS, bone, fat
  33. interstitial fluid
    • appx 20% of body weight
    • a 70kg patient has about 14 liters
  34. total body fluid
    • 2/3 intracellular fluid
    • 1/3 extracellular fluid
  35. vD
    • volume of distribution: the relative extent to which a drug moves to other body compartments
    • small vd: the drug tends to stay within the bloodstream (<0.25L/kg)
    • mid-range Vd: 0.25-0.7L/kg
    • large vD: it doesnt stay, youre giving the dose and it leaves the blood and goes to other parts of the body
  36. distribution compartments
    • some compartments are more difficult to distribute into than others: ie the BBB in the cns has a very tight formation of capillary epithelial cells and an astrocystic sheath beneath the basement membrane
    • water soluble drugs poorly absorbed to the CNS
    • propofol enters more readily than lorazepam bc its more fat soluble
  37. Vd is increase for drugs that have.... (3 things)
    • higher lipid solubility
    • lower extent of serum protein (albumin) binding
    • greater affinity for peripheral tissue binding

    • if you have to give a lot of a drug frequently, it likely has a high VD
    • drugs can also bind peripheral proteins or peripheral binding sites
  38. volume of distribution calculation
    vd = drug dose in mg / plasma concentration after absorption has occurred (if not IV) in mg/L

    • ie 50mg metoprolol that you know 60% gets lost in the first pass effect
    • vd = 50mg/ 50*0.4 mg/L = 2.5L
  39. how long does distribution take
    appx 1 hour
  40. population based pharmacokinetics to estimate starting dose
    dose = vd x concentration in plasma
  41. your patient is seizing! calculate a phenytoin loading dose
    cp desired: 15mg/L
    vd: 0.7L/kg
    Pt weight: 70kg
    • 0.7L/kg*70kg = 4.9L
    • 15mg/L*4.9L= 73.5mg
  42. tigecycline has a very large vd 600L
    Daptomycin has a small vd 7L
    what abx is better for treating endocarditis?
    • DAPTOMYCIN- it will stay in the blood stream and go to the heart
    • drugs with a large VD leave
  43. biotransformation
    • the chemical alteration of a drug to form a metabolite that is (usually) less active and more "excretable" than the parent drug
    • occurs as part of metabolism
  44. Process of rational prescripting
    • define the patients problem
    • specify the therapeutic objective
    • verify wheather your p treatment is suitable for this patient, is it effective and safe?
    • start the treatment
    • give information, instructions, and warnings
    • monitor the tx, stop if needed
  45. what is the WHO guide to good prescribing? how can it be used to help with prescribing decisions?
    • a manual to prescribing to tell you what to prescribe for a patient. a six step approach to prescribing that suggests physicians should
    • evaluate and clearly define the patients problems
    • specify the therapeutic objective
    • select the appropriate drug therapy
    • initiate therapy with the appropriate details and consider nonpharmacological therapy
    • give information, instrctions and warnings
    • evaluate the therapy regularly and consider d/cing
    • consider drug cost when prescribing
    • use computer and other tools to reduce prescribing error

    these 8 steps compose a systemic approach to prescribing that is efficient and practical. 

    also use a prescribing software and electronic drug references
  46. what factors influence adherence to med regimes
    • dose frequency
    • cost
    • interactions/side effects
  47. antagonists and agonists
    • agonists: bind the receptor and act as the drug or enhance its effect
    • antagonists: bind the receptor and block it or goes against the natural chemical
  48. where does metabolism primarily occur
    • liver
    • to a lesser extent, also occurs in the small intestine, kideny, lungs and brain
    • changes in liver (aging, hepatiits) can alter the rate of drug metabolism
  49. what can metabolism of a parent compound lead to
    • accelerated renal excretion
    • inactivation or weakend activity
    • increased therapeutic action (ie codeine is a prodrug of morphine, starts working after metaboliszed. same with protonix. inactive until metabolized bc its a prodrug)
    • formation of metabolites can be inert, active or toxic
  50. what are the 2 phases of metabolism that most (But not all) drugs go through
    • phase 1 reactions
    • phase 2 reactions
  51. phase 1 reactions
    • involve chemical reactions (oxydation, reduction, and hydrolysis) that often lead to drug inactivation.
    • these reations also introduce functional groups (OH, COOH, SH, O or NH2) to the partent compound, which facilitates Phase 2. 
    • oxidation is the most common phase 1 reaction
    • gets drugs ready for phase 2
    • mediated by the cytochrome p450 enzymes
  52. phase 2 metabolism
    • involves chemical processes that convert lipophillic drugs to hydrophillic drugs so they can be peed out.
    • produce a water-soluble metabolite
    • drug or metabolite is conjugated with a polar molecule (glucuronic acid, methyl, acetyl or sulfate group)
    • compared to phase 1, this function is much less susceptible to changes in liver function
  53. ie of drug choice with phase reactions
    • choose between diazepam and lorazepam
    • diazepam: undergoes phase 1 and phase 2 metabolism
    • lorazepam: undergoes phase 2 only

    so lorazepam may be preferred in those with liver issues bc phase 2 is not reliant on liver functions
  54. drug-drug interactions
    • metabolism accounts for most therapeutically improtant drug drug interactions
    • PK drug-drug interactions typically occur wen hepatic enzyme activity is either inhibited or induced
    • the enzymes have a certain baseline level of activity, and other drugs can slow them down or reve them up
  55. what can alter cyp450 enzymes
    • chemicals
    • food
    • drugs
  56. substrate
    a drug that is metabolized by a CYP450 enzyme
  57. inducers
    • molecules that increase cyp450 enzyme activity
    • enhance the metabolism and clearance of that enzymes substrate
    • potential consequence is therapeutic failure bc drug is metabolized to quickly
  58. inhibitors
    • moleculse that decrease CYP450 enzyme activity
    • slows the metabolism of that enzymes substrate, leading to greater drug exposure of what ever drugs are substarates of that enzyme
    • potential consequence is drug toxicity
  59. JT is a 60 year-old man with recently diagnosed atrial fibrillation (afib). He is prescribed warfarin, an anticoagulant, to reduce his risk of embolic stroke. He is also prescribed amiodarone to prevent further episodes of afib.

    Warfarin is a substrate of CYP450 2C9

    Amiodarone is an inhibitor of CYP450 2C9
    warfarin could get to toxic levels bc its not being metabolized since amiodarone inhibited its enzyme
  60. JT really likes grapefruit juice. Grapefruit inhibits CYP450 3A4

    Amiodarone is a substrate of CYP450 3A4
    Amiodarone’s metabolite (desethylamiodarone) inhibits CYP450 3A4

    Simvastatin is a substrate of CYP450 3A4
    Theres a Cascading effect.   Grapefruit increases body’s exposure to both amiodarone and simvastatin.  Long-term increase in amiodarone metabolite may further inhibit metabolism of amiodarone and simvastatin. 

    Too much simvastatin increases risk of hepatotoxicity and rhabdomyolysis

    Too much amiodarone increases risk of arrhythmia, liver toxicity, thyroid toxicity, and pulmonary toxicity.
  61. genetic polymorphisms and 2 examples
    • can also alter CYP450 enzyme activity, resulting in rapid or slow metabolism
    • 10% of codein is metabolized by CYP 2D6 to morphine. 10% of caucasians are poor metabolizer of 2D6, less than 2% of asians are- they dont have the capacity to metabolize the drug to its active form so it doesnt work
    • clopridigral is a prodrug that gets metabolized by CYP2C19 to its active metabolite for antiplatelet. a mutation in this can cause peple to get a heart attack after being on plavix bc you never convert it to its active metabolite bc the enzyme is mutated
  62. types of metabolizers of analgesics
    • ultrarapid metabolizer:1-2% of ppl (extra sensitive to drug effect)
    • normal metabolizer: 77-92% of patients
    • intermediate metabolizer: 2-11% of patients
    • poor metabolizer: 5-10% (poor analgesic response)
  63. inducers of CYP3A4
    • Rifampin/Rifabutin
    • Phenobarbital
    • Phenytoin
    • St. Johns Wort
    • Carbamazepine
  64. Inhibitors of CYP3A4
    • graprefruit juice
    • azole antifungals
    • cimetidine
    • macrolides (erythromycin/clarithromycin)
    • ritonavir (protease inhibitors)
  65. elimination
    • the removal of drug or metabolite from the body without further chemical change
    • now the drug has done its thing and needs to leave the body
    • most leave through the kidney
  66. GFR
    • glomerular filtration
    • blood flow forces non-protein bound drugs through glomeruli which filters out small molecules
    • tells us how good the kidneys are filtering substances from the blood into the urine. an indirect way of guessing how well drugs that are filtered through the glomerulus will be excreted
  67. passive tubular reabsorption
    • lipophilic drugs can be reabsorpbed.
    • hydrophilic (polar and ionized drugs) remain int he urine
    • once drugs pass into urine, if theyre lipophilic they can get reabsorbed thru the tubules, THIS is why phase 2 metabolism is so important bc it will stop this
  68. active tubular secrettion
    • only occurs rarely
    • tubular pumps secrete drugs directly into the proximal tubule
    • this happens with penicillin
    • instead of getting filtered thru the glomerulus, there is an acid exchange process wehre they get PUSHED INTO the glomerulus
  69. drug ionization in excretion
    • drugs that are ionized have a harder time crossing cell membranes, so drugs that are ionized are more likely to get peed out and not reabsorped
    • so we can make them ionized to get rid of them: ie if aspirin overdose, they therapeuitcally alkalinize the urine to enhance the elimination of salicyclic acid- raise ph of urine so the acid gets ionized and is less likely to get reabsorbed into the body and more likely to get peed out
  70. other less prominent modes of elimination
    • bile
    • feces
    • sweat
    • saliva
    • breast milk
    • breath
  71. clearance
    • clearance is the volume of blood that is cleared of drug per unit of time
    • any substance

    this concept is used to estimate GFR
  72. CrCl
    • creatinine clearance
    • gives us insite about renal drug clearance
    • cr is a breakdown product of muscle that is produced at a constant rate and eliminated exclusively via glomerular filtration
    • ClCr is appx the same as GFR, estimates how fast our glomerulus clears creatinine. the only way cr leaves the body is through glomerular filtration
  73. cockroft-gault formula
    estimates CrCl

    CrCl= (140-age in years) * (pt weight in kg)* (0.85 if a woman)/ 72* (serum cr in mg/dl)

    if you know a pt baseline GFR you can estimate how well they will clear drugs
  74. What Zosyn® (piperacillin/tazobactam) dose should our patient receive for her pneumonia?

    55 y.o. woman 50kg
    Height is 5’0”
    Serum creatinine (SCr) concentration from this morning is 1.7mg/dL.

    > 40 mL/min

    4.5g IV every 6 hours

    20-40 mL/min

    3.375g IV every 6 hours

    <20 mL/min

    2.25g IV every 6 hours
    • 140-55 = 85 
    • 85*50kg*.85 = 3612.5
    • 3612.5/ (72*1.7)= 295.14

    >40ml/min so 4.5
  75. half life
    the time necessary to remove 50% of the drug from blood
  76. how many half lives does it take to remove a drug from the body
    • about 4-5
    • half life is related to vd clearance
    • t1/2= 0.693(vd)/clearance
    • drugs with shorter half lives require more frequent dosing to maintain a clinical effect
  77. steady state
    • when the rate of drug going into the systemic circulation is in equilibrium with the amount of drug being eliminated
    • rate in = rate out
    • only applies when giving drugs at a regular interval, not as needed
  78. receptors
    • like dimmer switches for physiological funcitons
    • drugs can be agonists or antagonists to receptors
    • drugs can modify pre existing systems, not create new ones
  79. beta 1 receptors agonist and antagonist
    • they control hr
    • norepinepherine is an agonist, stimulates activity to raise bp and hr
    • metoprolol is an antagonist- binds receptor and blocks it from norepi, leads to slower hr
  80. four major types of drug receptors
    • ion channel linked: transmembrane proteins that surround a channel (pore), the drug binds receptor and the channel opens and ions move accros the channel altering the membrane potential and producing a physiolocial change
    • DNA Linked: intracellular receptors that affect gene transcritpion into RNA to up or down regulate expression of proteins that will change physiological functions
    • Transmembrane enzymes: drug binds and activates enzyme and cell physiology is changed, ie insulin
    • G protein coupled
  81. ligand receptors
    • react within seconds
    • albuteral uses this which is why it works so fast
  82. receptors and ligands
    • different receptors can be targeted by the same ligand
    • nicotinic receptors: are ion channel linked receptors- activation leads to skeletal muscle contraciton
    • muscarinic receptors: are g-protein coupled receptors- activation leads to smooth muscle contraction (ie bronchoconstriction)

    • both receptors are activated by acetylcholine
    • atropine can reverse the toxic effects of aceytlcholine muscarinic toxicity bc it acts on these receptors, but not nicotinic ones
  83. maximal therapeutic effect
    • most drugs have one
    • we cant create more receptors in the body, eventually they get saturated and giving more drug will do nothing
  84. potency
    • the amount of drug required to elicit an effect
    • not the same as therapeutic potential
    • a drug that you have to give a lot less of for an effect is more potent
    • but you can get a higher maximal therapeutic effect with a different drug that you give more of
  85. upregulation/downregulation of receptors
    • they can be upregulated or downregulated in response to stimuli
    • increased stimultation eventually will lead to down regulation. body will say woah i dont need all this stimulation, let me stop making those receptors. Decreased receptors leads to decreased response potential
    • opioid tolerance happens by downregulation of opiod receptors
    • we cant create more receptors, but our body can. as body is exposed to more stimulation, the body may say ya know what im too over stimulated im gonna downregulate poduction of receptors making you less susceptable to the drug over time, receptors get desensitized
    • in contrast, constant blocking will lead to UPREGULATION of receptors
  86. interpatient variability
    • results in different dosing requirements for different patients
    • some will have a different response when others
    • drugs can be dangerous if they have a narrow therapeutic range and high interpatient variabilty
  87. therapeutic index
    if lower than 2.5, need to monitor for toxicity
  88. things to ask all female patients of child bearing age
    • last menstraul period
    • contraception history
    • sexual history
    • pregnancy test
  89. what does embryonic and fetal exposure to teratogenic drugs depend on?
    • gestational age
    • route of administration
    • drug absorption
    • dose of drug
    • maternal serum levels
    • maternal and placental clearance system
    • placental passage is necessary for a medication to affec the kid
    • molecular weight is an important regulator of if drug will cross
    • ionization and high fat solubility
    • pH gradients
  90. when are moms usually not susceptable to teratogens
    weeks 1 and 2
  91. order of abnormalities in gestation
    • weeks 1 and 2: prenatal death
    • weeks 4-7: major structural abnormalities
    • weeks 8-38: physiological defects and minor structural abnormalities
  92. major drugs with significant adverse fetal effects (drug, when and damage)
    • ACE inhib: all trimesters, renal damage
    • TCAs: third tri, neonatal withdrawal
    • Barbituates: all tris, neonatal dependence with chronic use
    • carbamazepine: first tri, neural tube defects
    • cocaine, tamoxifen: all tri, risk of spontaneous abortion
    • ethanol: all tri, fetal alcohol syndrome
    • iodine: all tri, congenital goiter, hypothyroidism
    • lithium: first tri, increased ICP
    • tobacco: all tri, growth retardation
    • tetracycline: all tri, discolored teeth and altered bone
    • thalidomide and DES: first tri, limb malformation
    • warfarin: all tri, alters resp tract formation (first), CNS malformation (second), risk of bleeding (third)
  93. pharmacovigilance
    the science and activities related to the detection, assessment, understanding and prevention of adverse drug effects or any other possible drug related problems
  94. most common types of fetal disorders, most common to least
    • malformations
    • growth retardation
    • other fetal disorders
    • chromosomal abnormalities
  95. FDA pregnancy risk categories
    • A: adequate and well controlled studies have failed to show risk in the first tri, and theres no evidence in later trimesters
    • B: animal reproduction studies have not demonstrated a risk to fetus, but no adequate and well controlled human studies available
    • C: animal reproduction studies have shown an adverse effect on the fetus but theres no studies in human, but potential benefits may outweigh risks in certain women
    • D: there is positive evidence of human fetal risk based on adverse reaction data from investigations or marketing experience or studies in humans, but potential benefits may warrent use despie potential risk
    • X: studies in humans have demonstrated fetal abnormalities and/or there is evidence of human fetal risk. risks involved in use during pregnancy clearly outweigh the benefits
  96. critical factors affecting drug transfer and drug effects on the fetus
    • physiochemical properties of the drug
    • rate at which drug crosses placenta and amount that reaches fetus
    • duration of exposure to drug
    • distribution characteristics in different fetal tissues
    • stage of placental and fetal development at time of drug exposure
    • effects of drugs used in combination
  97. other drug effects to consider in pregnancy
    • vasoconstriction of placental vasculature: compromises blood flow to placenta and can cause abnormal effects on the preg- pre eclampsia and IUGR. ie nicotine does this
    • uterine contractions: ie prostaglandin influencing drugs
  98. principles of prescribing drugs for lactating women
    • 1. avoid drug therapy if possible
    • 2. topicals if possible
    • 3. med safe for infant are generally safe for lactating mom
    • 4. med safe in pregnancy are NOT always safe in lactation
    • 5. use reliable references
  99. what to consider with category b and c drugs
    • informed consent
    • recording patient characteristics
    • documenting dose and interval
    • measuring plasma drug levels
    • publishing case reviews
  100. big drugs to avoid in pregnancy
    • statins
    • halcion
    • coumadin
    • testosterone
    • sulfa drugs (3rd tri)
    • misoprostol
    • ribavarin
    • methotrexate
    • tinidazole
    • ocps
    • hrt
    • finasteride
    • dihydroergotamine mesylate
    • FSHs
    • clomid
  101. factors determining drug passage into milk
    • lipid solubility
    • its mostly passive diffusion
    • weak bases- become ionized in low ph, so weak bases have increased concentration in breast milk
    • maternal drug level
    • highly protein bound drugs are less likely to cross
    • milk to plasma ratio- drug concentration in breast milk to drug concentration in moms plasma. high M/P ratio = more drug in breast milk
  102. recommendation for lactating moms
    • most drugs given are detectable in breast milk, but concentration is usually lower than therapeutic amounts
    • safe drug: take 30-60 min after nursing and 3-4 hours before next feeding
    • no safety data drug: avoid use or discontinue breast feeding
  103. ADME Changes in pregnency
    • a: slower gastric emptying, slower bowel and colonic transit time
    • d:incr. volume distribution for lipophilic drugs
    • m: Sex steroid levels increase during pregnancy and increase the activity of enzymes in the cytochrome P450 (CYP) family and Phase 2 metabolic enzymes leading to clinically significant reductions in active drug levels.
    • e: increased renal blood flow so faster elimination
  104. absorption differences in pediatrics
    • oral: further reduced oral absorption bc infants have reduced gastric acidity or gastric dysmotility
    • percutaneous: babies have a higher surface area to weight ratio than adults so there is increased absorption of topical meds
  105. volume of distribution in pediatrics
    children have a higher proportion of body water and lower proportion of plasma proteins, so higher doses of water soluble drugs, but lower doses of protein bound drugs are required
  106. clearance in pediatrics
    • drug clearance is slower in young babies until renal function is equal to adults which happens at 6mo
    • children at higher risk for drug toxicity for renally cleared meds
    • new born rate is only 30-40% of adult levels, 3wks is 50%
    • drugs dependent on kidney excretion are slowly cleared in first weeks of life
  107. drug metabolism in kids
    liver metabolism is slower in babies than adults comparable by 2 years
  108. what drugs should be avoided in kids under 4
    • otc cough and cold meds
    • antihistamines
    • sympathomimetic decongestents
    • antitussives
  109. considerations for pediatric prescribing
    • why is it being given
    • which is the best drug
    • what is the dose
    • which route
    • consider and document history (problem list)
    • avoid use of meds that may interfere with dx (ie head trauma and meds that have sedating side effects)
  110. how can patient characteristics and development dictate drug choices
    • liquid vs tablet
    • allergies
    • PMH
    • developmental ability- inhaler vs nebulizer, is a spacer needed
  111. dosing in peds
    • individualized per patient based on..
    • disease
    • comorbidities
    • concomitant meds
    • age
    • size/weight
    • maturation or organ development
    • mg/kd dosing
  112. neonatal dosing
    • based on gestational or postnatal age and weight
    • maturation of drug elimination routes needs to be considered
  113. gi tract absorption in kids
    • affected by
    • gastric acid secretion
    • bile salt formation
    • gastric emptying time
    • intestinal motility
    • bowel length and absorptive surface area
    • microbiome

    • all these factors are reduced in neonates
    • all these factors may reduce or increase in an ill child of any age
  114. reduced gastric acid in kids
    • increases bioavailability of acid labile drugs (drugs easily destroyed by acid), ie penicilin
    • decreases bioavailability of weak acids (ie phenytoin)
  115. reduced bile salt formation in kids
    decreases bioavaiilability of lipophilic drugs like diazepam
  116. reduced gastric emptying and intestinal motility in kids
    increases the time it takes to reach therapeutic concentrations in infants under 3 months
  117. drug metabolizing enzymes in the intestine of infants
    results in reduced drug absorption
  118. congential atretic or surgically removed bowel in infants
    results in a range of absorptive defects
  119. metabolic drug degredation in kids
    immature systems in kids results in prolonged halflife of drugs and slower clearance rates. stays in body longer
  120. pediatric IV route
    • bolus: gives immediate effect
    • continuous infusions: looking for continuous therapeutic drug concentration, for drugs with short half life
    • intermittent: drugs requireing dilution in a moderate amount of volume
  121. pediatric PO route
    • absorption takes place in small intestine
    • villi and microvilli
    • need patient cooperation
    • anticipatory guidance regarding oral drug administration- no pill crushing!
  122. pediatric topical dosing
    • thinner stratum corneum in children- more rapidly absorbed creams and ointments
    • skin surface area is greater in infants than older children allowing for greater weight adjusted absorption of hydrophillic drugs. ie risk of od of benadryl 
    • occlusive dressings increase absorptions
  123. IM admin in children
    • children have less muscle mass
    • erratic blood flow to tissue- affects absorption rates
    • drugs should be water soluble
    • site needs adequate flow
  124. eye ointments in peds
    • more often used
    • liquids have pottential to irritate nasal mucosa as it drains through the lacrimal apparatus
  125. prescribing problems for older adults
    • overprescribing: excessive dose or duration
    • misprescribing: unfavorable med
    • underprescribing: not enough or no clinically relevant meds
  126. what puts elders at risk for polypharmacy
    • Multiple disease states
    • Multiple providers **
    • Setting changes, transitions of care ***
    • Minimal access to primary care
    • Sensory deficits leading to non-adherence/confusion regarding medication plan
    • Cognitive deficits
    • Low literacy/understanding
  127. what is the prescribing cascade
    interpreting a side effect as a new condition and prescribing a drug to treat it
  128. what puts elders at risk for adverse effects
    • > 6 concurrent chronic diagnoses
    • > 12 doses of medications/day
    • > 9 medications (includes OTCs) ***
    • Multiple prescribing providers
    • Prior ADE
    • Low body weight
    • Age = > 85 years old
    • Creatinine clearance = < 50mL/minute
  129. reasons for polypharmacy
    • multiple deasese
    • multiple doctors
    • setting changes of care
    • minimal access to care
    • sensory deficits leading to nonadherence/confusion
    • cognitive deficits
    • low literacy
  130. what to consider when evaluating a new sign/sx in an old person
    • first: is it a potential drug side effect
    • could it be caused by too much or too little of a drug or an interaction
    • could it be caused by the way the drug is taken
    • can the dosage be reduced?
  131. absorption in elderly
    • slower gastric motility
    • decreased HCl production
    • decreased effective absorption surface area in gut
    • co-admin of other drugs or food that affect absorption
  132. distribution in elderly
    • decreased muscle mass 20%
    • total body water decreased by 10-15%
    • increased body fat 15-20%
    • for meds distributed in muscle mass or body water- they may reach high serum concentrations
    • lipid soluble drugs tend to accumulate- low serum ocncentrations but prolonged duration due to longer half life- its stuck in the periphery
  133. factors affecting elder distribution
    • decreased blood supply to tissues
    • lower ablumin levels in illness and malnutrtion or polypharm
    • fewer available molecules for binding
    • higher levels of unbound drug now available to disperse- consider lower doses
  134. protein binding in elderly
    • albumin binds acidic drugs, and it decreases with aging
    • alpha-1 acid glycoprotein AAG binds basic drugs- lidocaine, propanoll, no change with healthy aging but can change in nonhealthy
    • get a free (unbound) drug level
    • patients on chronic acidic drugs may get TOXIC levels if albumin drops when they get sick or malnourished- watch them
  135. metabolism in elderly
    • altered hepatic metabolism in aging dpending on health and comorbidities
    • decreased hepatic mass with aging
    • decreased hepatic bloodflow
    • reduced first pass effect- leads to longer half life and more bioavailabiliyt
  136. cyp450 in elderly
    cyp3a4 involved in 50% of drugs
  137. excretion in elderly
    • changes in kidney function have the most profound effect on pharmacokinetics
    • decreased gfr of avg 1/3
    • decreased renal blood flow
    • decreased concentration of urine in the tubules
    • decreased in active tubular secretion
  138. more kidney considerations in elderly
    • kidney function declines starting at age 30- decrease in renal size, blood flow, and functioning of nephrons
    • cant use serum Cr as a measure- doesnt accurately reflect clearance
    • you need 5 different equations- egfr calculators- use cr. clearance calculation (cockcroft gault formula)
  139. anticholinergic meds
    • block acetylcholine
    • can cause confusion, urinary retention, constipation, dry mouth, tachycardia, ataxia, falls
    • counsel patients against PM products
  140. beers list
    • guides older people and HCP away from harmful meds
    • advises medications to be....
    • avoided by most older people outside of hospice and palliative care
    • avoided by older people with specific health concerns
    • avoided in combination with other treatments because of the risk for harmful drug-drug interactions
    • used with caution because of potential harmful side effects
    • dosed differently or avoided among people with reduced kidney function, which impacts pharmacokinetics
  141. informed prescribing
    • evaluate literacy
    • keep in mind burden of pils
    • avoid automatic refills- you want them back in to see you
    • med rec every visit
    • review med interactions carefully even if theyve been on it a while
    • ask pt how they take their meds
    • think is the drug needed at all
  142. Gram positive bacteria
    • streptococci
    • staphylococci
    • enterococci
  143. gram negative
    • neisseria
    • acinetobacter
    • moraxella
    • e.coli
    • klebsiella
    • enterobacter
    • proteus
    • shigella
    • salmonella
    • pseudomonus
    • haemophilus
  144. anaerobes
    • bacteroides fragilis
    • clostridium
  145. atypical bacteria
    • treponema
    • chlamydia trachomatis
    • chlamydia pneumonie
    • mycoplasma pneumoniae
    • mycobacterium tuberculosis
  146. common pathogens for meningitis
    • strep pneumo
    • neisseria meningitis
    • haemophilius influenzae
    • strep agalectiae
    • listeria monocytogenes
  147. common pathogens for eye infections
    • staph aureus
    • neisseria gonorrhoeae
    • chlamydia trachomatis
  148. common pathogens for sinusitis
    • strep pneumo
    • haemophilus influenzae
  149. common pathogens for otitis media
    strep pneumo
  150. common URT infection bacteria
    • strep pyogenes
    • haemophilus influenzae
  151. common pneumonia pathogens
    • community: strep pneumo, haemophilus influ, staph aureus
    • atypical: mycoplasma pneumoniae, chlamydia pneumoniae, legionella pneumophilia
    • tuberculosis: mycobacterium tuberculosis
  152. common skin infection bacteria
    • staph aureus
    • strep pyogenes
    • pseudomonus aeruginosa
  153. common UTI bacteria
    • e.coli
    • other enterobacteriaceae
    • staph saprophyticus
    • pseudomonus aeruginosa
  154. beta lactam antibiotics
    • all contain a beta lactam ring
    • inhibit bacterial cell wall biosynthesis
    • ie penicillins, cephalosporins (ie cefalexin)
  155. generations of cephalosporins
    • 1st: ampicillin, cephalexin, cefadroxil
    • 2nd: cefazolin, cefonicid, cefmetazole
    • 3rd: ceftriaxone, cefixime, moxalactam
    • 4th and 5th: cefpine, fefozopran, ceftaroline, fosamil
Card Set
Pharm Exam 1
Exam of 2/10/21