Summer Pharmacology

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ckitejr
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Summer Pharmacology
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2015-06-29 21:06:46
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pharmacology medical physician assistant
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PAP570 Pharmacology I for midlevel providers
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  1. Prescription Components
    • Heading (name, address, phone, DEA #)
    • Pt Information (name address, age date)
    • Inscription (drug)
    • Subscription (quantity)
    • Signa (patient directions)
    • Prescriber (with credentials)
    • Substitution level (DAW or blank)
    • Refills
  2. Verbal orders
    • cannot be called in for controlled substances in NYS
    • Pharmacist can add pt. age & address, but nothing else.
  3. Appropriate dosing assurance
    • one refill on PRN orders
    • strength of dose and units of measure
    • zeros before decimal points, but not after
  4. Needles and syringes
    • regulated by Bureau of Narcotics Enforcement
    • More than 10 requires a prescription
  5. Exceptions to childproof containers
    • sublingual nitro
    • steroid dose packs
    • OCP
    • other patient requests
  6. Controlled substances
    • Schedule I-V
    • I-Stop Prescription Drug Reform Act
    • Hydrocodone is leading controlled substance prescribed--high street value
  7. Schedule I
    high potential for abuse, not legal, no medicinal use (LSD)
  8. Schedule II
    • potential for abuse, can prescribe (codeine)
    • anabolic steroids in NYS are II, but Federally considered III
  9. Schedule III
    • less potential for abuse (hydrocodone)
    • can be prescribed for 30days with 5 renewals in a 6 month period
  10. Schedule IV
    • low potential for abuse (phenobarbital, benzodiazepines)
    • benzodiazepines are treated as schedule II for refills and quantities
    • can be prescribed for 30days with 5 renewals in a 6 month period
  11. Schedule V
    • very low potential for abuse (codeine used for anti-tussive purpose)
    • can be prescribed for 30days with 5 renewals in a 6 month period
  12. Rules for Schedule II and Benzos
    • require a DEA number
    • valid for 30 days after date written
    • maximum of 30days for Rx
    • No refills
    • Emergency orally transmitted allow for 5 day Rx and require 72 written follow up
  13. Exceptions for up to 3 month supply
    • Codes
    • A--painc disorders
    • B--ADHD
    • C--Chronic debilitating neurological
    • D--Relief of pain known to be chronic or incurable
    • E--Narcolepsy (only legal Tx for amphetamines)
  14. DM 1
    • loss of insulin production from pancreatic beta cells
    • Tx with subcutaneous insulin
  15. DM 2
    • insulin insufficiency
    • typically associated with obesity
    • Tx with diet exercise, oral hypoglycemics, insulin as needed
    • Exercise enhances insulin sensitivity and blood glucose control
  16. lispro, aspart, glulisine
    • rapid acting
    • lasts 2-4 hours
  17. NPH
    • intermediate acting
    • protamine complexes with insulin
    • 10-16 hour duration
  18. insulin glargine, detemir
    • long acting
    • 24 hour duration
  19. Tx of diabetes in pregnancy
    insulinis preferred Tx
  20. U-500
    Tx severe insulin resistence
  21. Total Daily Dosing
    • weight in kg x 0.2
    • basal 30-50% of daily dose
    • bolus 10-20% at each meal
  22. Carb counting and insuling
    • 1 unit insulin per 10g of carbs
    • correction factor of 50 (1 unit insulin to lower blood glucose 50 points)
    • Target blood glucose is 100mg/dL
  23. Insulin regimes
    • conventional (1-2 injections a day, with NPH regulators
    • basal/bolus therapy 3 or more injections with basal insulin and premeal short acting insulins
    • CSII (continuous subcutaneous insulin infusion or insulin pump that mimics basal bolus therapy)
  24. Sulfonylureas
    • glyburide, glipizide, glimepiride
    • bind to K channels on beta cells affecting membrane potential and stimulating insulin release
    • SE--hypglycemia, skin rash, weight gain
    • Metabolized in liver
  25. Meglitinides
    • repaglinide, D-phenylalanine, nateglinide
    • also binds to K channels, but in different location than sulfonylureas-->shorter duration and rapid onset
    • SE--weight gain, diarrhea
  26. Biguanides
    • cAMP driven decrease of hepatic gluconeogenisis
    • enhances peripheral insulin sensativity
    • SE--weight LOSS, lowers serum triglycerides, diarrhea
    • CI--renal failure
    • Lactic acidosis is rare, but lethal SE
  27. thiazolidinedones (TZDs)
    • pioglitazone
    • bind to PPAR-y that enhances enzymes and proteins needed to respond to insulin
    • useful with sulfonylureas
    • SE--weight LOSS, lower extremity edema, and possible bladder cancer risk
  28. alpha-glucosidase inhibitors
    • acarbose, miglitol
    • inhibitors of enzyme needed for complex carb breakdown
    • SE--flatulance and diarrhea
  29. SGTL 2 inhibitors
    • canagliflozin, dapagliflozin, empagliflozin
    • inhibit renal Na/glucose transporter --> increased secretion of glucose
    • SE--UTIs, osmotic diuresis
  30. glucagons-like peptide 1 (GLP 1)
    • exenatide, liraglutide
    • enhance oral glucose induced insulin release
    • possible risk of medullary thyroid cancer
  31. dipepetidyl peptidase inhibitors
    • increase glucose secretion by inhibiting enzymes that degrade GLP-1
    • second line therapy
    • Sitagliptin, saxagliptin
    • "stop the glistens"
  32. amylin analogues
    • enhance oral glucose release
    • SC injections before meals
    • Pramlinitide
    • hypoglycemia, and weight loss
    • can be used for DM1 and DM2
  33. Two main glucocorticoids
    • cortisol
    • aldosterone (mineral corticoid)
    • made on demand (no reserves)
    • delayed onset and require liver to clear
  34. Glucocorticoids
    • control normal metabolism
    • inhibit inflammation
    • diabetogenic (increase A1C)
    • long term osteoporosis
    • taper to avoid Addisonian adrenal
    • Cushinging's syndrom with prolonged use
  35. Mineralcorticoids
    • aldosterone
    • leads to salt and fluid retention & K secretion
  36. Glucocorticoid examples
    • cortisone-short acting
    • prednisone-intermediate acting
    • beclomethasone-long acting & aerosolized
  37. Mineralcorticoid example
    fludrocortisone
  38. Cortisol
    acts as mineralcorticoid as well as glucocorticoid
  39. Drug interactions with mineral cortocoids
    • NSAIDs--produce decrease renin
    • ACEs--inhibit release of Ang II
    • these both lead to decreased Aldosterone secretion
  40. Spironolactone
    K sparring diuretic as it antagonizes aldosterone
  41. Ketoconazole (role in glucocorticoids)
    antifungal that inhibits gonadal and adrenocortical synthesis
  42. Potentiation
    • inactive drug that causes an active drug to have a greater response
    • increase blood levels of active drug by an inactive drug
  43. Heparin OD Tx
    protamine sulfate
  44. Drug absorption issues
    • TCAs chelated from dairy products
    • Tyramine and MAOIs can lead to hypertensive crisis
    • Cimitidine--known inhibitor of CYP450
    • Rifampin--known inducer of CYP450
  45. Log kill
    cancer drugs kill a fraction of the cancer cells so there is an ever shrinking number of cells that remain
  46. Cell cycle
    G1-S-G2-M
  47. Alkalayting agents
    examples and site of action
    • Busulfan, cyclophosphomide, melphalan
    • non-specific cell cycle
  48. Antimetabolites
    target what cell cycle phase and examples
    • S-phase - attacking DNA synthesis
    • 5FU (prymadine antagonist for colon cancer)
    • Methotrexate (inhibits dihydrofolate reductase & reversed with leucovorin)
    • cytarabine (prymadine antagonist Tx leukemia)
    • 6-mercaptopurine (purine analogue)
  49. Vinca alkaloids
    cell cycle phase and examples
    • attack M phase via mitotic spindle disruption
    • vinblastine--Tx Hodgkin's lymphoma, CYP450 metabolized-->requires dose adjustment if reduced liver function
    • vincristine--known adverse effect of SIADH
  50. Methods of Resistence
    • Efflux pump (for drugs entering cell)
    • Beta-Lactamases 
    • Typically from multi drug resistance protein 1
  51. Cancer Chem Toxicity Sites
    Bone Marrow & GI epithelium--as these are highly mitotic sites with lots of cell division--the target for cancer drugs
  52. Drugs that lack myelosuppression
    • Bleomycin (lung toxicity)
    • L-asparaginase (Tx ALL)
    • hormones
  53. Agents to resist GI toxicity of cancer theraputics
    • chlorpromazine (DA receptor blocker)
    • metoclopramide (cholinergic agonist)
    • lorazepam (GABA agonist)
    • ondansetron (5HT receptor antagonist)
    • dexamethasone (anti-inflammatory steroid)
  54. Renal Toxicity
    • cisplatin  "piss platin"
    • high dose methotrexate
    • cyclophosphamide (alkalayting agent Tx lymphoma, multiple myeloma)
    • high-dose methotrexate
  55. Cardiotoxicity
    • doxorubicin (adrianmycin)
    • daunorubicin
  56. Neurotoxic agent
    vincristine (dose limited)
  57. Alkylating agents
    MOA, toxicity and examples
    • bind directly to DNA--> breaking it (S phase typically)
    • bone marrow suppression
    • mechlorethamine, cyclophosphamide, nitrourease, melphalan, busulfan, cisplatin
  58. Plant products
    MOA toxicity cell cycle phase
    examples
    • attack microtubules
    • peripheral neuropathy
    • M-phase specific (cell division)
    • vinblastine, vincristine, paclitaxel (breast cancer), etopside (breast cancer Tx)
  59. Hormones and Hormone Antagonists
    for cancer
    • prednisone (antiinflammatory with Cushing syndrome SE)
    • leuprolide (GnRH analogue long-term use will suppress LH & FSH, chemical castration)
    • flutamide (inhibits androgen uptake, used to Tx prostate cancer along with leuprolide)
    • tamoxifen (estrogen antagonist, Tx breast cancer--menopasual side effects)
  60. Neuro transmission
    • EPSP and IPSP felt at dendrites
    • summed in axon hillock AP down axon
    • at terminal Ca influx causes release of NTs through vesicle excytosis
  61. Acetylcholine
    major NT at NMJ in ANS and cleared through AcH esterases (thus AChE inhibitors prolong ACh effects)
  62. Glutamate
    • Major excitatory NT in CNS as well as GABA precursor
    • Astrocytes in CNS are responsible for reuptake
  63. Tyrosine
    • precursor for Epi, NorEpi, & DA
    • Tryptophan is precursor for 5HT
  64. Neuropeptides
    • volume transmission
    • cleared by diffusion
    • release is frequency dependent
  65. Local ansesthetices
    • Work on Na channel from inside of cell
    • ionized end is active and blocks channels
    • work on channels being activated
    • 3-4 nodes are required to be blocked to stop an AP
    • co-administered with epi to vasoconstrict and decrease washout
  66. Local anesthetics
    adverse reactions
    • seizures
    • respiratory failure
  67. Amides
    • Two Is in the name
    • chemically stable highly protein bound
    • metabolized in liver
  68. Esters
    • metabolized by esterases in plasma
    • can create allergic reaction via PABA metabolism
    • useful in CSF where no esterases exist
  69. Local anesthetics
    pH
    • most are weak bases and so in acid environment get shifted to unprotanated form (unactive form) a condition found with necrotic tissues or infections.
    • Coadministration of a base can raise pH and shift equation to favor HB+ the active phase
  70. Ester examples
    • procaine,
    • chlororprocaine
    • tetracaine
    • benzocaine
    • cocaine
  71. Amide 
    examples
    • lidocaine
    • articaine
    • mepivacaine
    • bupivacaine
    • articaine
  72. Epilepsy Tx
    • monotherapy
    • titraition from one medication to another
  73. Seizure types
    • local -- simple or partial
    • Generalized -- generalized or absance
  74. Seizure type signs & symptoms
    and Tx
    • simple partial--pt is conscious
    • complex partial--localized but spreads (limb weakness) aura
    • generalized (grand mal) --convulsions, jerking dramatic tonic/clonic activity
    • absence (petit mal) --- sudden onset, short duration Tx w/ ethosuximide
    • All others lamotrigine and valproic acid
  75. Seizure meds
    • carbamazepine--induces liver metabolism
    • phenytoin--hirutism and gingival hyperplasia
    • lamotrigine--idiosyncratic rash may be fatal
    • valproic acid--induces liver metabolism and can be fatal
    • ethosuximide--for absence seizures--GI upset
  76. status epilepticus
    • diazepam
    • lorazepam
    • propofol
    • with phenytoin given for longer 1/2 life
  77. seizure Tx stratagies
    • prevent spread
    • reduction of activity
  78. Seizure meds MOA
    • lengthening refractory period
    • phenytoin, carbamazepine, lamotrigine, topiramate, oxcabazepine
    • decrease Ca2+ influx into axon terminal reducing NT release
    • ethosuximide and phenytoin
  79. Parkinsons Disease
    • loss of DA in substantia nigra
    • two pathways
    • direct--go pathway increase in pathway leads to increase activity
    • indirect--stop pathway increased activity leads to decreased movement
  80. Parkinson Tx stratagies
    • replace DA (L-Dopa)
    • dopamine agonists (ropinirole and pramipexole)
    • anticholinergics (benstropine, biperiden, amantidine)
  81. Postural tremor Tx
    • propanolol
    • primidone for hand tremors
  82. Huntington's Tx
    • Fluoxetine (for depression as there is no Tx)
    • diazapam for antispasmodic
  83. Wilson's disease
    • penicillamine as chelator for metabolising excess cooper
    • Zu acetate blocks Cu absorption
  84. Tourette's Tx
    • resperine (DA depleting)
    • haloperidol
    • Botulinum toxin for focal dystonias
  85. Opioids act on what receptors
    • mu--euphoria, respiratory depression, decreased GI motility
    • kappa-dysphoria, miosis, respiratory depression
    • delta--peripheral analgesia
  86. Opioid antagonists, agonists and mixed antagonist/agonists
    • antagonist--naloxone & naltrexone (longer acting)
    • mixed--pentazocine, buprenorphine, butorphanol, nalbuphine
    • agonists--everything else
  87. Mu receptors and side effects
    • in Gut create constipation
    • in CTZ cause nausea on initial dose
    • cough suppressant in with medullary effect
    • CPYinducers--lessen opioid affects (phenobarbitol, carbamazepine, rifampin)
    • CYP inhibitors--increase the effects (cimetidine, ritanovir)
  88. Morphine key points
    • large 1st pass effect
    • mu agonist
    • potent metabolite is morphine-6-glucuronide (phase 2 rxn) "conjugation reactions"
  89. heroine
    key features
    • lipophilic so crosses BBB
    • active metabolite is 6-monoacetylmorphine
  90. codeine
    key features
    • weak mu and delta agonist
    • used as antitussive
    • morphine is major metabolite
  91. dextromethorphan
    key features
    • analogue of codeine that antagonizes NMDA receptors
    • used as oral antitussive with no opioid effects
  92. tramadol 
    features
    codine analogue with good bioavailability
  93. oxycodone
    mu agonist with good oral bioavailability
  94. meperidine
    • mu agonist
    • can interact with MAOIs leading to toxic levels of metabolite normoperidine that can lead to miosis and convulsions
  95. pentacozine
    • kappa agonist/mu antagonist
    • used for pain, but can cause increased myocardial consumption so CI in CHF
  96. buprenorphine
    • mu partial agonist
    • used for opioid addition treatment
  97. methadone
    mu partial agonist with long 1/2 life used to treat withdrawal
  98. Opioids potentiate
    • CNS depressants (EtOH)
    • Hypotensive drops
  99. opiod withdrawl
    • 7-10 days duration
    • early finding--lacrimation, rhinorrhea, yawning, salivation
    • later--irritability, chills/sweating
    • NOT life threatening
  100. leading cause of death, disease, and disability in US?
    substance abuse
  101. Define
    drug abuse
    self-administered in an unapproved manner
  102. define
    addiction
    • the seeking of substances despite consequences
    • addictiveness of a drug is based on how quickly is makes DA levels rise
  103. define
    craving
    intense desire to experience psycho active aspects of drug
  104. define
    sensitization
    • increased physiological or behavioral response to repeated administration of a drug
    • dose response curve shifts to left
  105. define tolerance
    • diminished response to repeated administration of a drug
    • dose response curve shifts to right
    • cross tolerance is tolerance to all drugs of a class
  106. define physical dependence
    • development of withdrawal sypmtoms when drug is stopped
    • can be rapid with antagonist induced or longer with partial agonist
  107. EtOH
    key features
    • zero order kinetics so time only to eliminate
    • modulates GABA and ACh (depression and memory)
    • associated with liver disease and thiamine deficiency, megaloblastic anemia and Wernicke-Korsakoff syndrome
    • withdrawl can be fatal
    • disulfram to Tx withdrawal symptoms
  108. Barbiturates and benzos
    key features
    • modulate GABA
    • enhance opioid euphoria
    • OD--coma respiratory depression, 
    • flumazenil is benzo antagonist
    • Airway support
    • withdrawl can be fatal
  109. Stimulants
    key feautres
    • nicotine--head and neck cancers
    • vareniciline (partial agonist) used in patch treatment as well as buproprion
  110. cocaine 
    key features
    • blocks DA, NE 5HT reuptake
    • vasoconstrictor
    • associated with Hep B Hept C and endocarditis
  111. amphetamines MOA
    increase catecholamine release 5HT and inhibit reuptake
  112. Hallucinogens
    • LSD--5HT agonist, benzo to Tx bad trip, sweating and lacrimation for sings
    • PCP--blocks glutamate receptors
    • Tx with urine acidification
    • marajuana--CB 1 receptors for euphoria
  113. Cidal vs static ABX
    • cidal kills (DNA or cell wall MOAs)
    • static (ribosomal activity)

    • static + static = additive
    • cidal + cidal = synergistic
    • cidal + static = antagonistic
  114. cell wall is preferential target for gram = or - organisms
    +  want to hit the thick cell wall
  115. Cell wall synthesis and inhibition
    • cephlosporins and penicillins
    • mainly for G+ organisms
    • resistance is via betalactamase
  116. cephlopsorin
    generations
    • 1--narrow and sensative to beta lactamases
    • 2-extended spectrum, broader G- activity
    • 3-more resistant to cephlosporinases and enter CSF
    • 4-additional G- coverage (pseudomonas)
  117. clavulanic acid
    added to penicillin as it inhibits the action of beta lactamases
  118. Carbapenems
    MOA and examples
    • Attack cell wall with increased side chains to hide from beta lactamase activity
    • imipenem azotreonam
    • good G+ and G- coverage
    • linked to hypersensativty reaction
  119. azotreonam
    G- coverage, but no anaerobic or G+ coverage
  120. Vancomycin
    • interrupts cell wall synthesis in G+ bacteria
    • used for pseudomembranous colitis (c diff) and MRSA
    • VRE has resurfaced
  121. Bacitracin
    • acts on ribsomes interferring with transfer of materials for cell wall synthesis
    • ototoxicity and nephrotoxicity--so topical use
  122. polymixins
    • act as detergent for cell membranes
    • Colistin is last ditch effort for Klebsiella
    • affect host membranes as well making them less popular
  123. Aminoglycocides
    • irreversibly bind to 30s subunits making them bacterialcidal
    • getamicin and tobramycin
    • since they have to make it through the cell wall to work they are often combined with penicillins amp and gent
  124. Tetracyclines
    • broad spectrum interferr with tRNA and ribosome binding
    • Ca chelators thus side effects are on bone and teeth and thus CI in pregnancy and young children
    • Doxycycline used for chlamydia, micoplasma and tick-born as well as acne
  125. Chloramphenicol
    • blocks peptide elongation on 50s ribosome
    • rare side effecrt is aplastic anemia
    • used for bacterial meningitis or brain abscess when penacillin allergic
  126. Erythormycin
    • macrolide that blocks peptide elongation on 50s ribosome
    • cardiac toxicity
  127. clindamycin
    • works on G+ anerobe
    • induce colitis
    • 50s ribosome
  128. linezolid
    blocks 50s complexing to form function 70s
  129. Quinolones
    MOA example and CI
    • accumulate in cartilage so not good for children and cardiac toxicity
    • MOA is interfering with DNA gyrase and topoisomerase IV
    • ciprofloxin and levofloxin
  130. Metronidazole
    • disrupts bacterial DNA
    • targets anaerobes
    • targets protozoa
    • disulfuram-type reaction
  131. Antimetabolites
    • sulfa- drugs
    • prevent synthesis of folic acid
    • Tx giardia and trichomonas
  132. Trimethoprim
    interfers with folic acid synthesis at different point in pathway from sulfa and so can be combined to Tx UTI
  133. Rifampin
    • TB drug
    • mycolic acid cell wall with slow growth rate
    • MOA is inhibition of mRNA synthesis
    • turns secretions orange
  134. Isoniazid
    • alters synthesis of mycolic acid
    • bacterialcidal for mycobacterium
    • resistence issues mean always taken in combination
    • neural and hepatic toxicity
  135. Resistance strategies for cell wall synthesis drugs
    • insensitive peptidoglycan precursors
    • altered penicillin-binding proteins
    • beta-lactamases
  136. Resistance strategies for protein synthesis disruption drugs
    • methylating enzyme acetyltransferase
    • increased efflux
    • decreased ribosomal binding
    • modifying enzymes
  137. Resistance strategies for nucleic acid synthesis inhibition
    • altered gyrase/altered enzymes
    • reduced binding to the bacterial DNA RNA polymerase
  138. Acyclovir
    nucleoside analogue DNA chain terminator that is incorporated well in thymidine kinase of HSV and VZV
  139. Valcyclovir
    Tx herpes
  140. Ganciclovir
    used to Tx CMV
  141. Ribavirin
    • used to Tx RSV in babies
    • MOA nucleoside analogue
  142. Foscarnet
    • binds to DNA viral polymerase
    • toxic to host with many side effects (electrolyte disorders)
    • Tx resistant poxviruses
  143. Trifluridine
    Tx herpetic keratoconjunctivitis
  144. Amantadine
    viral
    • treats influenza A 
    • prevents viral shedding
  145. Relenza oseltamivir
    • neuraminidase inhibitors
    • shorten course of flu
  146. HAART for HIV
    • 2 NRTIs
    • NNRTI
    • or 
    • 2 NRTIs
    • PI
    • or INSTI
    • 2 NRTIs
  147. NRTI
    • AZT
    • binds to reverse transcriptase
  148. NNRTI
    • efavirenz
    • binds to reverse transcriptase interfering with cDNA
  149. Protease Inhibitors
    • indinavir
    • interferes with an HIV-I protease
    • Ritonovir is CYPbooster to increase bioavailabiity and decrease dosing frequency
  150. Amphotericin B
    • binds to ergosteral in fungal cell wall
    • renal toxicity
  151. nystatin
    Candida infections
  152. ketoconazole
    • affects ergosterol synthesis (needed for fungal cell wall)
    • less side effects than Amp B
  153. Terbinafine
    used for cutaneous mycotic infections
  154. Griseofulvin
    • treat nails
    • attacks microtubules --> peripheral neuropathy
  155. TMP-SMX
    • bactrim 
    • prophylaxis in AIDS against trichomonas
  156. paromomycin
    aminoglycocide for entomeba cysts
  157. primaquine
    anti malarial
  158. chloroquine
    antimalarial
  159. quinine
    antimalarial with specific treatment for p faciparum
  160. atovaquone
    disrupts electron chain transport in malarial mitochondria
  161. praziquantel
    • increases Ca influx to paralize worm
    • used on Flat worms or tape worms
  162. albendazole
    inhibits microtuble assembly in roundworms
  163. pyrantal pamoate
    paralizes round worms
  164. Side effects of COX inhibition
    • ulceration
    • renal injury
    • idiosyncratic hypersensitivity reactions bronchospasm, angioedema
  165. ASA
    key features
    • irreversibly blocks COX-1
    • Associated with Reye's syndrome in children who are recovering from viral illness
    • zero order kinetics
    • aspirine hypersensitivity reactions
  166. diflunisal
    longer acting than ASA
  167. ibuprofen
    better tolerated for RA
  168. naproxen
    stronger than ibuprofen Tx anklyosing spondylitis, OTC use limited to 10 days
  169. indomethacin
    • strongest NSAID Tx acute gouty artheritis
    • liver, bone marrow and CNS toxicities
  170. ketrolac
    injectable NSAID
  171. celecoxib
    • COX-2 selective inhibitor
    • associated with increased risk of CVA and MI
  172. caffeine and NSAIDs
    potentates NSAID with his phosphodisesterase activity
  173. acetaminophen
    • inhibits prostoglandin synthesis in the CNS
    • analgesic and antipyretic, but NOT anti-inflammatory
    • can cause fatal liver damage, which can be treated with N-acetylcystine

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