Pharm Review

Question 1

Most preferred NSAIDs for pts?

Answer 1

• Naproxen and ibuprofen

- most can be dosed w/ loading dose if needed

Question 2

Diff classes of NSAIDs?

Answer 2

• Salicylate (acetylated)
• Salicylate (nonacetylated)
• Propionic acids
• acetic acids
• oxicams
• fenamates
• nonacidic
• selective COx 2 inhibitors

Question 3

MOA of NSAIDs?

Answer 3

• inhibit Cox which impairs transformation of: arachadonic acid - to prostaglandins - prostacyclin and thromboxanes
• Cox 1 enzymes: regulates normal cellular processes (gastric cycytoprotection, vascular homeostasis, platelet aggregation, kidney fxn)
• Cox 2: expression of this is increased during states of inflammation, effects of Cox-2 inhibition on inflammation isn’t completely understood

Question 4

Adverse effects of NSAIDs?

Answer 4

• GI
• Renal
• CV
• liver
• pulm
• heme
• malignancy
• derm
• healing of MSK injuries
• up to 12% of hosp admissions for adverse drug runs are NSAID related

Question 5

Renal adverse rxns of NSAID use?

Answer 5

• renal vasoconstriction, acute renal failure, HTN, hyperkalemia, hyponatremia, edema, increased risk of Renal cell cancer

Question 6

Hepatic adverse rxns of NSAIDs?

Answer 6

• can cause elevation of liver transaminases
• actual NSAID assoc liver injury is rare
• may be disease specific (more common in SLE and RA)

Question 7

Pulm adverse rxns of NSAIDs?

Answer 7

• adverse events seem to be more likely to be related to nonselective COX 1/2 inhibitors and less likely w/ selective COX 2 inhibition
• bronchospasm
• pulm infiltrates w/ eosinophilia

Question 8

Heme adverse rxns of NSAIDs?

Answer 8

• neutropenia
• antiplatelet effects due to inhibition of COX1:
  for most NSAIDs - platelet fxn normalizes w/in 3 days of d/c of drug (24 hrs for ibuprofen)
• but still need to continue ASA for cardioprotection if using NSAID therapy
• interaction w/ warfarin, may increase INR
• higher risk of bleeding w/ anticoag. use

Question 9

CNS adverse effects of NSAIDs?

Answer 9

• Aseptic meningitis
• tinnitus: usually w/ salicylates but can occur w/ all NSAIDs, usually reversible upon d/c
• ## psychosis and cog impairment: more common w/ indomethacin, elderly

Question 10

Skin adverse effects of NSAIDs?

Answer 10

• drug rash or pseudoporphyria (blistering w/ sun exposure)
• blistering skin lesions that may be potentially life threatening:
  TENS
  SJS

Question 11

NSAIDs effects on fx healing?

Answer 11

• may cause non-union (approx 1%)
• may want to avoid NSAIDs for up to 90 days post fx
• data isn’t clear, more studies needed

Question 12

NSAID CIs mnemonic?

Answer 12

• Nursing or preg
• Serious bleeding
• Allergy/asthma/angioedema
• Impaired renal fxn
• Drug (anticoag)

Question 13

NSAIDs: salicylates?

Answer 13

• Acetylated
• ASA only one in this group
• diff from other classes by irreversible platelet inhibition for the life of the platelet
• don’t use to tx pain, just use for its CV protective effects
• other NSAIDs may dampen it’s anti-platelet effects
• usually continue chronic aspirin use if adding another NSAID for pain management

Question 14

Propionic acids?

Answer 14

• Naproxen

- Ibuprofen

Question 15

Naproxen pros, formulations and dosages?

Answer 15

• available OTC
• long acting
• less CV risk compared to others
• 2 formulations: naproxen base and naproxen sodium
• dose: 200 mg naproxen base = 220 mg naproxen sodium (has quicker onset of action than base)
• max daily dose: Day 1- 1250 mg naproxen base, subsequent daily doses shouldnt exceed 1000 mg naproxen base (or 1100 mg naproxen sodium)
• take q 12 hrs
• good choice for tx of acute or chronic pain if NSAID is indicated
• may give loading dose of 500 mg naproxen base or 550 mg naproxen sodium

Question 16

Use of ibuprofen, dosing?

Answer 16

• available OTC
• short duration of effect
• alt to naproxen
• max dose: 2400 mg/day (up to 3200 mg on day 1 if loading dose used)
• may give loading dose up to 1600 mg
• usual analgesic dose is 400 mg q 4-6 hrs

Question 17

Acetic acids class?

Answer 17

• IV ketorolac (toradol)

- Indomethacin (Indocin)

Question 18

Use of Ketorolac (toradol)?

Answer 18

• optional loading dose: 30 mg (usually just need 15 mg)
• adjust dose based on age and wt
• tx of moderate to severe postop pain
• risk of gastropathy when used more than 5 days
• not for oral use
• don’t use for chronic pain or inflammation
• make sure pts are well hydrated and w/o sig kidney disease

Question 19

Use of Indomethacin (indocin)?

Answer 19

• optional loading dose 75 mg
• comes in an immediate release and extended release
• max dose per day: 150 mg
• used for tx of acute gout and pericarditis mainly**
• not for chronic daily use: higher risk of GI bleed, adverse effects
• may be assoc w/ aplastic anemia

Question 20

Oxicams class?

Answer 20

• meloxicam (mobic)

- prioxicam (feldene)

Question 21

Use of Meloxicam?

Answer 21

• long duration of effect (qday dosing): 7.5-15 mg qday
• slow onset of action
• max daily dose: 15 mg
• relatively COX2 selective at lower total dose of 7.5 mg

Question 22

Use of Piroxicam (feldene)?

Answer 22

• an option for tx of chronic pain and inflammation poorly responsive to other NSAIDs
• daily dose of more than 20 mg increase risk of serious GI complications
• usual daily dose is 10-20 mg once daily

Question 23

Use of celecoxib (celebrex)?

Answer 23

• selective COX-2 inhibitor
• optional loading dose of 400 mg
• max daily: 400 mg
• usual dose is 100 mg BID or 200 mg daily
• no effect on platelet fxn
• decreased GI toxicity
• dose related renal and CV effects
• sulfa allergy - CI to celebrex use

Question 24

How do you judge who needs narcotics?

Answer 24

• sig soft tissue swelling or ecchymosis suggests sig injury
• pain at rest
• night pain
• pain uncontrolled by NSAIDs or APAP
• anyone who has had surgery
• sometimes may just need narcotics at night

Question 25

Narcotic pain relief used in ortho pain?

Answer 25

- codeine - hydrocodone - oxycodone

Question 26

Use of Codeine?

Answer 26

- considered weak opioid - for mild-moderate pain - schedule III - met. to morphine: if not properly metabolized it isn't effective - if metabolized too quickly = initial overdose, shorter duration of action, more SEs - 5-10% of pts have genetic variation fo metabolism and may have only limited or no benefit from codeine

Question 27

Use of hydrocodone?

Answer 27

- lorcet, lortab, norco, vicodin - Schedule III - for moderate to severe pain - onset of action: 10-20 min - duration: 4-8 hrs - in combo w/ acetaminophen

Question 28

Use of oxycodone?

Answer 28

- percocet, roxicet, endocet - schedule II - moderate to moderately severe pain - onset of action: 10-30 min - in combo w/ APAP - avoid long acting combos for acute pain (MS contin)

Question 29

Use of Naloxone?

Answer 29

- reverses resp depression, sedation and analgesia - 0.04mg-0.08 mg IV push q 1 min x 2 - may need to repeat dosing as half life is short

Question 30

Extended release and long acting opioid analgesics - when should these never be used?

Answer 30

- NEVER for acute pain | - NEVER in narcotic naive pt

Question 31

Toxicities of all opioids in general?

Answer 31

- sedation and resp depression: drugs that act on CNS potentiate effects, EToH, sedative-hypnotics, TCAs, BZDs, MAOIs - constipation: worse w/ sustained release morphine compared to fentanyl patch, stool softners alone are not enough (need laxative) - decreased effectiveness of diuretics: induce release of ADH and counteracts effect of diuretics - QT prolong

Question 32

When may opioid drug levels decrease or increase?

Answer 32

- if used concomitantly w/ cytochrome P450 inhibitors or inducers - inhibitors: buproprion, fluoxetine, paroxetine, cimetidine, acyclovir, duloxetine, fluoroquinolones, ketoconazole, PPIs, verapamil, diltiazem, grapefruit juice - inducers: carbamazepine, isoniazid, tobacco, rifampin, St. John's wort

Question 33

Extended relief and long acting opioid analgesics?

Answer 33

- morphine sulfate ER: MS contin, kadian, Embeda, Avinza - buprenorphine transdermal: butrans - methadone: dolophine - fentanyl transdermal: duragesic - hydromorphone: Exalgo

Question 34

Rules for transdermal admin?

Answer 34

- never cut or tear patch - heat exposure can increase release and absorption of transdermal opioid analgesics - application: chest, side of waist, upper arm, avoid hairy areas but if not clip the hair, rotate sites, wash site w/ water only

Question 35

Use of Tramadol? MOA? Metabolism? Caution?

Answer 35

- not a controlled substance (schedule IV), but has high potential for physical and psych dependence - works at mu receptors and also inhibits NE and serotonin - effective for relief of neuropathic pain - improved fxnl outcomes in pts w/ fibromyalgia - may be no more effective than NSAIDs or nortryptyline for chronic pain - extensively metabolized in the liver - use w/ caution in elderly and w/ renal insufficiency

Question 36

Skeletal muscle relaxants used?

Answer 36

- cylcobenzaprine (flexeril) - tizanadine (zanaflex) - metaxalone (skelaxin) - diazepam (Valium)

Question 37

Use of muscle relaxants?

Answer 37

- short course of therapy only - most benefit is w/in 1st 1-2 wks of therapy - very sedating w/ anticholinergic SEs - not generally for long term use unless neuromuscular problems that cause spasticity

Question 38

Risk of abuse of muscle relaxants?

Answer 38

- diazepam (valium) and carisoprodol (soma) should be used only briefly (few days) - high potential for abuse

Question 39

Use of muscle relaxants and NSAIDs?

Answer 39

- may have synergistic effect for tx of acute low back pain | - pts more likely to improve when used in combo

Question 40

What offers the best pain relief?

Answer 40

- NSAIDs or APAP in combo w/ narcotics

Question 41

How do you avoid bowel obstruction if tx w/ narcotics?

Answer 41

- tx w/ stool softeners and gentle stimulant laxatives prn