MSK Pharm 1 Flashcards
Arachidonic acid results in
Cox-1 and Cox-2
Cox-1 leads to
prostaglandin (PG) and Tranexamic acid (TXA)
Cox-2 leads to
prostaglandin (PG)
Cox-1 PG is responsible for
mucosal protection
Cox-1 TXA is responsible for
platelet aggregation, vasoconstriction
Cox-2 PG is responsible for
pain, inflammation, fever, uterine contraction, vasodilation, inhibition of platelet aggregation
Three types of endogenous adrenal hormones
mineralocorticoids, androgens, glucocorticoids
Ex of mineralocortiocids
aldosterone
Ex of androgens
DHEA
Ex of glucocorticoid
cortisol, corticosterone
6 effects of glucocorticoids
1) increase blood sugar via catabolism of protein and conversion into sugars and fats (gluconeogenesis) 2) enhance sympathetic response 3) stimulate CNS (irritabiilty, insomnia) 4) decrease WBCs 5) stabilize intracellular lysosomes (decrease cell energy) 6) inhibit synthesis of histamin, kinins, prostaglandins
Prednisolone/prednisone mimics actions of
cortisol
Prednisolone/prednisone inhibits
phospholipase
Uses for prednisolone/prednisone (4)
1) immunosuppressant 2) decrease cellular injury 3) anti-inflammatory 4) inhibit collagen synthesis (decrease scar tissue formation)
What drug is most like cortisol?
hydrocortisone
AE of corticosteroids
Cushing’s syndrome, muscle atrophy, osteoporosis, decreased immune response, GI bleeding and ulcers, hyperglycemia, sodium retention (increased BP), hypokalemia, insomnia, irritability/instability, increased appetite, hirsuitism, amenorrhea, adrenal suppression
Symptoms of adrenal suppression
weakness, lethargy, anorexia, nausea, myalgia
What is adrenal suppression?
atrophy of adrenal cortex
Why does adrenal suppression occur?
glucocorticoids suppress pituitary release of ACTH, zona fasiculata (cells that produce cortisol in the adrenal gland) does not receive stimulation, adrenal atrophy occurs
How long does it take for adrenal suppression to occur?
several weeks of treatment; long acting and high dose preparations have highest risk
What can we do to prevent adrenal suppression?
Do not abruptly discontinue; gradually taper doses over weeks to months
What’s the preferred treatment for adrenal insufficiency
hydrocortisone
What conditions require caution with corticosteroids?
infection (predisposes to infection, don’t give with live vaccines), diabetes, peptic ulcer disease, osteoporosis, Myasthenia gravis, cataracts/glaucoma, pregnancy, CNS disorders
Using corticosteroids in pregnancy can cause?
cleft palate, hypoadrenalism
Mechanism of action of NSAIDs
block the production of prostaglandins via cyclooxygenase inhibition (COX)
What’s the original, prototypical NSAID?
Aspirin
Function of NSAIDS (2)
antipyretic and anti-inflammatory
Dosing of ASA for antiplatelet
<300 mg/day
Dosing of ASA for analgesia, antipyretic?
300-2400 mg/day
Dosing of ASA for anti-inflammatory?
2400-4000 mg/day
ASA impacts bleeding time, but not?
PT or PTT
Does ASA reversibly or irreversibly inhibit cox-1?
irreversibly
What are the most common side effects of ASA use?
GI upset and ulcer
What are SE of ASA use?
GI upset and ulcer, bleeding, salicylism, increased risk of gout attack
Symptoms of salicylism?
vomitting, tinnitus, hearing loss, vertigo
What’s the weirdness with gout and ASA?
increased risk of gout attack (doses over 3 gm/day increase uric acid excretion however)
Overdose levels of ASA
20-35 tablets of 325 mg
Symptoms of ASA overdose
respiratory alkalosis and metabolic acidosis, hyperthermia, seizures/coma/death
How is an ASA overdose treated?
activated charcoal (if ingestion is recent), hemodialysis if very severe or worsening
What do we worry about with ASA and asthma?
Samter’s Triad
Why don’t we use ASA with children and teens?
Reye’s syndrome
What’s Reye’s Syndrome?
swelling in brain and liver
Ecotrin is an example of ?
ASA
motrin is an ex of?
ibuprofen
anaprox is an ex of?
naproxen
bufferin is an ex of?
ASA
advil is an ex of?
ibuprofen
Naprelan is an ex of?
naproxen
indocin is an example of?
indomethacin
Toradol is an ex of?
ketorolac
celebrex is an ex of?
celecoxib
mobic is an ex of?
meloxicam
Do NSAIDs (other than ASA) reversibly or irreversibly bind to cox-1?
reversibly
What med is used to close patent ductus arteriosus?
indomethacin
What’s a short-term NSAID used for opiod level pain?
ketorolac
What’s the issue with ketorolac?
high rate of GI events and renal toxicity; poor anti-inflammatory effects
How are NSAIDs excreted?
renal predominately; some undergo enterohepatic recycling
Metabolism of NSAIDs
phase 1, phase 2 or both
How is absorption of NSAIDs?
well absorbed, no interference from food
Repeated dosing of NSAIDS is detectable in?
synovial fluid
SE of NSAIDS
GI (N/V, GI bleed/ulcer), fluid retention, anemia/dyscrasias, allergy, tinnitus, MI/CHF, HTN
Ibuprofen dosing for inflammation
600 mg qid
ASA dosing for inflammation
1200-1500 mg tid
Naproxen dosing for inflammation?
375 mg bid
What class is acetaminophen?
para-aminophenols
Acetaminophen AKA
n-acetyl-para-aminophenol (APAP)
MOA of acetaminophen
blocks central (not peripheral) prostaglandin production; mechanism not fully understood
Uses for acetaminophen
antipyretic, analgesic NOT anti-inflammatory
Advantages of acetaminophen
No GI irritation, almost no allergy, no bleeding issues
SE of acetaminophen use
methomoglobinemia, leukopenia, liver toxicity
What’s the dangerous metabolite of acetaminophen?
N-acetyl-p-benzoquinone imine
Regular strength acetaminophen
325 mg
extra strength acetaminophen
500 mg
arthritis formulation acetaminophen
650 mg
Excedrin of 2 tablets = pain relief of x tablets of APAP or ASA
4 tablets
Excedrin consists of
APAP 250 mg, ASA 250 mg, caffeine 65 mg
Max daily dose for children for acetaminophen
75 mg/kg/day
Max daily dose for adults for acetaminophen
4000 mg
minimum hepatotoxic single dose of acetaminophen for children
150 mg/kg
minimum hepatotoxic single dose of acetaminophen for adults
7.5-10 grams
What is the crude resin from opium poppies containing several alkaloids, one of which is morphine?
opium
what is the natural compound structurally related to those found in opium?
opiate
An synthetic agent with the same functional and pharmacological properties of opiates ?
opioid
How do opiates work?
activates mew receptors in thalamus and limbic system
Common SE of opiates?
sedation, lethargy, muscle relaxation, amnesia, respiratory depression and euphoria
What are results of using opiates?
suppression of cough reflex and stimulation of CTZ (emesis); miosis; histamine release (bronchoconstriction and hypotension); decreased GI motility and urinary retention
Routes of administration of opiates?
oral, transdermal, parenteral, sublingual/buccal, subQ, insufflation, epidural, itrathecal, rectal
Bio-availability of opiates
is a problem and oral doses are often much higher than other routes
What will highly lipophilic opioids do?
accumulate in fatty tissues
How do opioids distribute out of the blood?
quickly to high perfused tissues
Metabolism of opiods
glucuronidation
which opioids utilize the cytochrome system?
meperidine, fentanyl, alfentanil, sufentanil
Excretion of opioids?
primarily renal
Clinical effects in CNS of opioids
analgesia, euphoria/dysphoria, sedation without amnesia/disrupted sleep architecture, respiratory depression, cough suppression, miosis, truncal rigidity, N/V
No tolerance develops with the opiod SE of?
miosis and constipation
Clinical effects of opioids in the periphery
minor bradycardia, constipation, urinary retention, itching, sweating, flushing
Therapeutic uses of opioids
analgesia, acute cardiogenic pulmonary edema, cough suppression, non-infectious diarrhea, shivering, anesthesia
What type of analgesia use is appropriate for opioids?
- severe, chronic pain
- sharp, intermittent pain
What’s the assumed mechanism for opioid use in treatment of acute cardiogenic pulmonary edema/
decreased anxiety
Describe tolerance of opioids
decrease in apparent effectiveness of a drug; reversible; surmountable; shift in dose curve to the right
What’s dependence?
neuronal adaptation to repeated drug exposure leading to a withdrawal syndrome upon cessation
What will precipitate withdrawal of opioids?
IV naloxone
Symptoms of opiate withdrawal?
rhinorrhea, lacrimation, yawning, chills, goosebumps, hyperventilation, hyperthermia, mydriasis, aching, vomiting, diarrhea, anxiety, hostility
Which opiates are more likely to foster addiction?
short acting opiates
What diseases should be cautioned if using opioids?
respiratory disase, gallbladder disase, depression, history of drug abuse, epilepsy, diabetes, pregnancy, use of other narcotics or CNS depressants
Mechanism of action of local anesthetics
work on afferent nerve fibers; LA given in unionized form, enters neuron, ionizes and cannot leave cell, binds to NA channel, stops Na from entering neuron and prevents generation and conduction of action potential
Membrane penetration and LA? Unionized.
penetrate membranes
Membrane penetration and LA? Ionized.
do not penetrate membranes well
Membrane penetration and LA? weak bases
if enters a slightly acidic area, it becomes unable to cross barriers
Which type of administration of LA has the lowest systemic absorption?
SC Injections
What does an Epi additive do to LA?
vasoconstrictor (keeps drug in area for a longer period of time); prolongs block
What are issues to an Epi additive do to LA?
skin necrosis; some people are sensitive and will become tachycardic
What does a base additive do to LA?
maintain unionized form for a quicker onset of action but decreases duration of action
Opioid additive to LA?
neuraxial synergy
Alpha-2-adrenergic agonists additive to LA?
inhibit peripheral nerve conduction
How are ester LAs hydrolized?
hydrolized by pseudocholinesterases to PABA
What’s the cause of ester LA allergy?
PABA; some people lack pseudocholinesterase activiity
How are amide LAs metabolized?
in liver by cytochroms
SE with LA?
HA, dizziness, confusion, CNS depression (except cocaine), vasodilation (except cocaine)
Describe lidocaine
rapid, moderate acting, also an antiarrythmic
When is lidocaine beneficial?
when intubating and extubating
Describe bupivicaine
slow onset, long lasting, cardiotoxic
What is a huge issue with LA?
methemoglobinemia
Prilocaine is a problem in?
neonates and patients with poor heart or lung function (MetHb)
Benzocaine oral prepration use over time may cause?
MetHb
How is methemoglobinemia treated?
IV methylene blue
What is methemoglobinemia?
higher than normal levels of ferric hemoglobin; can’t bind oxygen normally; can’t transport oxygen/starving tissues
Describe toxicity issues with LA?
a progression may occur as more nerves are affected; lightheadedness, tinnitus, periorbital numbness, seizures, coma, respiratory arrest, cardiovascuar collapse; rare neural toxicity; transient neurological symptoms
Describe transient neurological symptoms (TNS)
pain in lower extremities (gluteus and moving down), resolves within a week
What’s a likely culprit of TNS?
lidocaine
Which LAs are often culprits of arrhythmias?
bupivacaine and ropivacaine
What do you use to combat seizures from LA?
benzos
What do you use to combat arrhythmias from LA?
amiodarone
What’s used to manage cardiovascular collapse?
IV lipid
What is the most common cause of pyogenic osteomyelitis?
s. aureus
What is the most common cause of non-pyogenic osteomyelitis?
mycobacterium tuberculosis
What’s the most common cause of osteomyelitis in those with sickle cell?
s. aureus, salmonella
What are the four routes of infection of osteomyelitis?
hematogenous ,contiguous spread, direct inocluation
approach to osteomyelitis treatment?
empiric therapy, must identify organism and primary site, acute v.s chronic, treatment for 4-6 weeks
What route of administration is preferred for osteomyelitis treatment?
parenteral
When do you collected bone sample?
before you treat
Oral treatment of osteomyelitis may be appropriate after identification of organism if,
confirmed infection, initial response to parenteral therapy, suitable oral medication available, pt will be compliant
If vertebral, hematogenous osteomyelitis treat with:
vancomycin + [ceftriaxone OR cefipime OR levofloxacin]
If extremity, hematogenous osteomyelitis treat with:
vanco + [ceftazidime OR cefipime]
If confirmed MRSA, hematogenous osteomyelitis treat with:
vanco +/- rifampin
If confirmed MSSA hematogenous osteomyelitis treat with:
nafcillin OR oxacillin OR cefazolin
If confirmed salmonella hematogenous osteomyelitis treat with:
ciprofloxacin or levofloxacin
If osteomyelitis with contiguous spread without vascular insufficiency and thinking MRSA treat with:
vanco + ceftazidime OR cefepime
If osteomyelitis with contiguous-spread without vascular insufficiency and thinking p. aeruginosa treat with:
ciprofloxacin OR levofloxacin OR cefepime
Who do you suspect has pseudomonas osteomylitis?
IV drug abuse, puncture wounds of the foot, long bone internal fixation
How do you treat osteomyelitis that’s contiguous with vascular insufficiency?
debridement, bone sample, treated based on C&S for 6 weeks
Who should be treated for osteoporosis?
postmenopusal women and men 50 years and older who have: a hip or vertebral fracture, t-score <2.5 at hip or lumbar spine, osteopenia and FRAX-calculated 10 year hip fracture risk of 3% or major fracture risk of 20%
If you initiate treatment for osteoporosis, what should be corrected first?
hypocalcemia
x mg of calcium per day for women 51 and older and men 71 and older?
1200 mg
Men 50-70 should consume x mg of calcium?
1000 mg
x IU of vitamin D per day for patients 50 and older
800-1000 IU
% daily value of calcium based on?
1000 mg calcium per day
No more than x mg per dose of calcium due to saturation of transporters
500 mg
What are the two calcium supplements available?
calcium carbonate, calcium citrate
Which is less expensive: calcium carbonate or calcium citrate?
calcium carbonate
Calcium carbonate require?
acidic environment for absorption, must be taken immediately after a meal
SE of calcium carbonate
gas and bloating
What’s unique about calcium citrate?
contains less calcium per dose, can be taken with or without food, no GI problems
What are lifestyle changes that are important in osteoporosis?
weight-bearing exercise
What improves spine BMD?
non-weight bearing when combined with weight bearing
Bisphosponates MOA
decrease bone turnover; inhibit remodeling of bone (osteoblasts have time to work); inhibit resorption; slows but does not stop bone formation
Bisphosphonate instructions
take first thing in the day, empty stomach, 8 oz of water, no other food/drink for 30 minutes, remain upright for 30-60 minutes
Serious SE of bisphosphonate?
erode the esophagus
Examples of bisphosphonates
alendronate and ibandronate and risedronate and zoledronic acid
Alendronate dosing
10 mg daily OR 70 mg weekly
Who is alendronate approved for?
postmenopausal women, men, steroid-induced osteoporosis
What is binosto?
An alendronate; dissolved in 4 oz room temp water, wait 5 min after fizzing stops then stir 10 seconds then drink
What’s a con of binosto?
1500 mg of sodium
Dosage of ibandronate
150 mg monthly or 3 mg IV every 3 months
Who is ibandronate approved for?
postmenopausal women only
Dosing for risedronate
5 mg daily OR 35 mg weekly OR 75 mg two consecutive days each month OR 150 mg monthly
Who is risedronate approved for?
postmenopausal women, men, steroid-induced osteoporosis
Zoledronic acid dosage
5 mg IV oncea year
Who is zoledronic acid approved for?
postmenopausal women, men, steroid-induced osteoporosis; secondary prevention s/p hip fracture given within 90 days of fracture
SE of osteoporosis meds?
GI (pain, nausea, dyspepsia, esophageal ulceration and possible perforation), muscle pain, hypocalcemia, osteonecrosis of the jaw
When is osteonecrosis likely in treating osteoporosis?
cancer patients after receiving invasive dental work
Criteria for drug-induced osteonecrosis of the jaw?
-the patient has taken or is taking antiresporptive or antiangiogenic agents -for 8 weeks, there has been exposed bone or bone that is able to be probed through a fistula in the maxillofacial area -there is no history of radiation or metastatic disease to the jaw area
Controversy with osteoporosis med?
esophageal cancer risk, increased atypical (sutrochanteric, diapheeal) fractures–maybe associated with steroid or PPI use
What’s the benefit of IV osteoporosis meds?
bypasses GI effects; but reserve for pts who can’t tolerate oral, are n on-compliant or unable to follow directions
Raloxifene dose
60 mg qd
Raloxifene indication
postmenopausal women
Raloxifene class
selective estrogen receptor modulation (SERM); agonist at bone receptor, antagonist in breast and uterine tissue
Results of raloxifene?
increases BMD in hip and spine and decreased vertebral fractures (not shown to decrease nonvertebral or hip fx)
SE of raloxifene
hot flashes, leg cramps, increased DVT/PE
What’s a good choice if you think a patient has risk of estrogen dependent cancer and osteoporosis?
raloxifene
Route of calcitonin
injectable and nasal spray
What’s the indication of calcitonin?
prevention of fx in postmenopausal women
Calcitonin and fracture risk
has not demonstrated reduced fx risk
Recommendations for calcitonin
for use only as an alternative to other therapies in women who have been postmenopausal for at least 5 years; use only when other therapies are not tolerated or patient insists on using this product
SE of calcitonin
rhinitis, epistaxis, nose bleeds, allergic reactions, cancer risk
What is teriparatide?
amino acids 1-34 of human PTH
How does teriparatide work?
anabolic–increases bone formation; stimulates osteoclast maturation, regulates calcium and phosphate reabsorption in kidneys, increases calcium absorption in gut
What happens when teriparatide is given intermittently?
osteoblasts are stimulated over osteoclasts
SE of teriparatide?
nausa, insomnia, hypercalcemia, increased risk of osteosarcoma
contraindications of teriparatide
bone cancer, paget’s disease, hyperparathyroidism, hypercalcemia
Who is teriparatide approved for?
severe osteoporosis (osteoporosis with fracture)
teriparatide dose?
Sq 20 mcg per day
Denosumab what is it?
monoclonal antibody against RNKL
What does denosumab do?
decreases osteoclast formation and function; blocks RANKL from binding to RANK
Dose of denosumab
60 mg Sq every 6 months
SE of denosumab
increased risk of skin infections, increased risk of hypocalcemia, osteonecrosis of jaw, arthraliga, back pain
