Pharm E2- Ortho/Pain

What is the most reliable indicator of pain?

patient’s description (subjective experience)

What kind of pain is a burning, tingling, or shooting pain sensation caused by nerve damage?

Neuropathic pain

What kind pain is sharp, dull, aching, or throbbing and can be somatic (skin/bone/joint/CT) or visceral (internal organs, mucosal lining)?

Nociceptive pain

What kind of morbidity do half of chronic pain patients experience?

Psychiatric comorbidity

What is the first line therapy for low back pain and OA?

APAP

What drug?

• analgesic & antipyretic used for mild-mod pain

• no anti-inflammatory properties

• more potent centrally; inactivated by peroxides in inflamed tissue

• opioid sparing (need fewer opioids to tx pain)

Acetaminophen (APAP)

What is the max dose of Acetaminophen (APAP) a patient can receive per day?

4 g

What SE is seen with APAP?

dose dependent hepatic necrosis

What drugs?

• analgesic, antipyretic, & anti-inflammatory

• inhibit COX 1 & 2 enzymes; decrease PG synthesis

• ex: ibuprofen, naproxen, indomethacin, ketorolac, tolmetin, ASA

NSAIDs

What SEs are seen with NSAIDs?

GI ulcers, bleeding, hypersensitivity rxns, asthma / bronchospasm

prolonged gestation & premature closure of ductus arteriosus

increase liver enzymes & dec renal function

What drug?

• salicylate; antiplatelet (irreversible)

• nonselective COX 1 & 2 (more dangerous than other NSAIDs)

• oral absorption, crosses placenta & breast milk; modified in liver & excreted through kidneys

ASA

What SEs are seen with salicylates (ASA)?

bleeding, GI upset, tinnitus, hypersensitivity, etc

preeclampsia & growth retardation in pregnancy, reye’s syndome

What are contraindications to ASA?

bleeding disorders, pregnancy, children w/ fever associated with viral dz (chicken pox/influenza)

What condition?

• fatty liver encephalopathy - vomiting, progressive CNS damage (stupor → convulsions & coma), hepatic injury

• hypoglycemia, metabolic acidosis, inc aminotransfersase, ammonia, & prothrombin time

• can be seen in children with viral illness who were given ASA

Reye’s Syndrome

What is the treatment for Reye’s syndrome?

glucose and mannitol

What drugs are propionic acid derivatives?

Ibuprofen, Naproxen, Ketoprofen, Fenoprofen, Flurbiprofen, Oxaprozin

What drugs?

• category of nonselective NSAIDs

• orally absorbed, hepatic conjugation & renal excretion

  • Less severe GI SEs but more severe renal & hepatic toxicity

• high protein binding & more potent

Proprionic acid derivatives

Which propionic acid derivative would be ideal for chronic pain patients due to the long half life of 40-60 hours?

Oxaprozin (Daypro)

What drug?

• slowly reversible & noncompetitive NSAID; mos potent CNS & peripheral

• closes ductus arteriosus

• higher incidence of SEs- GI, HAs, dizzy, hematologic toxicity

• decrease effects of diuretics

Indomethacin (Indocin)

What drug?

• slowly reversible noncompetitive IV NSAID; less effective anti-inflammatory agent

• go to for acute pain

• opioid sparing

Ketorolac (Toradol)

What BBW is associated with Ketorolac?

GI effects

How many days should the use of Ketorolac be limited to?

(** Test Q)

5 days

What drug?

• analgesic, antipyretic, & anti-inflammatory

• more potent than ASA

• SEs- GI, anticoagulant effects

Tolmetin (Tolectin)

What drug?

• rapidly reversible & competitive NSAID

• used to tx arthritis

• equipotent to ASA & Naproxen

• fewer & mild GI SEs

Piroxicam (Feldene)

What NSAID has a 10 fold selectivity for COX 2 & less GI toxicity?

Meloxicam (Mobic)

What drug?

• prodrug & active metabolite used to tx RA & OA pain

• some COX 2 seletivity

• SE: stomach cramps, diarrhea

Nabumetone (Relafen)

What drug?

• anti-inflammatory w/ some COX 2 selectivity used to tx RA pain

• topical formula available

• SE: bleeding, ulcers

Diclofenac (Voltaren)

What SEs are associated with COX-2 inhibitors (except celecoxib)?

CV events, heart attack, stroke, hypersensitivity & skin rxns

less risk for GI ulcers**

What agents are COX-2 inhibitors?

Etoricoxib, Celecoxib (go to), Etodolac

Valdecoxib & Rofecoxib removed from market

What drugs inhibit PG12 production more than TXA2 production in epithelial cells of blood vessels, increasing the risk for MIs & strokes?

Cox-2 inhibitors

What opioid receptor affects afferent neurons in dorsal spinal cord to inhibit transmission & dec cAMP, & also is associated with analgesia, respiratory depression, & euphoria?

Mu

What term is being described?

• occurrence of withdrawal syndrome when stopping opioids (N, V, dysphoria, sweating) that is not fatal & not correlated with addiction

• every experiences this if on opioids long enough

Physical dependance

What term is being described?

• psychological dependence to opioids

• cravings (DA reward system in brain), compulsive & impaired control of drug use

• continued use despite known harm/consequences

Addiction

What term is being described?

• state of adaptation where drug’s effectiveness diminishes over time

  • (get used to drug & need more to maintain effectiveness)

Tolerance

What is pseudotolerance?

change in pain state due to increased activity or disease progression, NOT because the meds aren’t working as well

What term is being described?

• usually due to undertreatment

• can be confused with drug seeking behavior, but behaviors will stop once dose is increased because pain is better

Pseudoaddiction

Pseudoaddiction or addiction?

• drug seeking behaviors go away once the dosage is increased

• individual regains function

Pseudoaddiction

Pseudoaddiction or addiction?

• constant drug seeking behavior, no change with increased dose

• individual loses function

Addiction

What is the limit for prescribing opioids for acute pain?

3 days (can extend to 7 days if written “acute pain exemption”)

What is the limit to prescribing opioids for chronic pain?

no refills but can write for total of 90 days with 3 separate scripts (must write “non acute pain”)

What drug?

• converted to morphine via CYP2D6 in liver

• less potent then morphine; weakest opioid; used for mild-mod pain

• CV or CIII**

Codeine (Tylenol #3)

What is the BBW associated with Codeine?

ultra rapid CYP2D6 metabolizing in children w/ T&A (risk resp depression)

What opioid is NOT a CII?

Codeine

How would a patient deficient in CYP2D6 enzyme respond to Codeine?

less effective; more resistance to the dangerous SEs

What drug?

• opioid available IV, PO, IR, & ER

• hepatic metabolism via glucuronidation

• renal excretion (*caution w/ elderly & renal failure pts)

• can cause pruritus from significant histamine release

Morphine (MS Contin, Duramorph)

What should be done for a patient who experiences pruritus after receiving morphine?

switch agent or pretreat with antihistamines

What drug?

• semisynthetic opioid

• converted to hydromorphone (Dilaudid) via CYP2D6

• usually in combo w/ APA but can be used alone (Zohydro ER)

• frequently #1 prescribed med in US

Hydrocodone (Norco, Lortab)

What drug?

• 2x as potent as PO morphine bc of improved bioavailability

• only PO dosages - long acting (Oxycontin), short acting, or with APAP (Percocet)

• metabolized to oxymorphone via P450 2D6

Oxycodone (Roxicodone)

What drug?

• metabolized via glucuronidation

• very potent but shorter half life than morphine

• less histamine please = less pruritus

Hydromorphine (Dilaudid)

What drug?

• synthetic opioid 100x more potent than morphine

• IV for acute pain or long acting for chronic pain

  • also TD, TM, IN

Fentanyl (Sublimaze)

What drug is useful for pain patients who have true allergies to phenanthrene opioids (ex- morphine, oxycodone)?

Fentanyl

What drug?

• opioid receptor full agonist; NMDA receptor antagonist; inhibit reuptake of NE & 5HT

• long acting - 50+ hr half life

• not used for breakthrough pain

• used for chronic pain & opioid addiction (can prevent withdrawal sx)

• multiple conversion ratios

Methadone

What SE is associated with Methadone?

prolong QTc (check elytes & EKG!)

What drug?

• metabolized to normeperidine (a toxic metabolite that’s renally cleared)

• drug interaction d/t MAO inhibition

• pts can develop tolerance quickly

• avoid use in elderly & renal imapired (should almost never be used)

Meperidine (Demerol)

What drug can be used for rigors (shivers) in a surgical setting?

Meperidine (Demerol)

What drug?

• partial agonist - tight binding affinity at Mu receptors

• available SL (37 hr half life), TD, & implant

• used in opioid addiction

  • start once withdrawal sx begin & full agonist out of system (can induce withdrawal if taken w/ full agonist or opioids due to potential to displace from receptor)

Buprenorphine (Suboxone, Subutex)

What should Buprenorphine be compounded with to deter IV abuse (counter reacts & opioids don’t work as well)?

Naloxone

When converting opioids, why would you want to start at 50-75% of the dosage of medication a patient is currently on?

incomplete cross tolerance (not as tolerant to the drug they are switching to, need to work them back up)

What must all opioids be converted to first when switching drugs?

PO morphine

What device provides a continuous hourly infusion (basal rate) of opioids & allows additional dosage when a patient pushes a button?

IV patient controlled analgesia (PCA)

What PCA dosage setting is most effective for persistent pain?

basal rate + on demand dose (1/4-1/3 of basal rate)

What SEs are seen with opioids?

MC: constipation, N, V, sedation, histamine release (pruritus)

LC: delirium, resp Depression, abuse & diversion

What opioid SE would a patient NEVER be able to develop a tolerance to?

Constipation

How can constipation as an SE of opioids be treated (start prophylactically)?

Mush & push - stool softener & stimulant laxative

(fiber, fluid, Senna + Docusate, etc)

What drug?

• Mu opioid receptor antagonist - reverse opioid induced resp/CNS depression

• crosses BBB

• IV, IM, or IN (no oral bioavailability)

• fast onset & short half life

• can induce withdraw if too much

Naloxone (Narcan)

What drugs?

• Mu receptor antagonist - peripherally acting agents

• does not cross BBB; works at GI tract for constipation

  • reverse GI SEs but won’t block analgesic effects on brain

Alvimopan (Entereg)

Methylnaltrexone (Registor)

Naloxegol (Movantik)

What SEs are seen with anti epileptics?

sedation, mental clouding, dizziness, N, unsteadiness

What agents are antiepileptics that can be used to treat neuropathic pain?

Carbamazepine, Gabapentin, Lamotrigine, Pregabalin

What drug blocks the reuptake of NE to modulate pain & is the gold standard for neuropathic pain management?

TCAs

What SEs are seen with TCAs?

anticholinergic, cardiac abnormalities, sexual dysfunction, wt gain

How to local anesthetics work to treat neuropathic pain like in post herpetic neuralgia?

Block neuronal Na channels preventing signal conduction

What are examples of topical local anesthetics used for neuropathic pain?

EMLA cream (lido + prilocaine) & 5% lidocaine patch

What epidural / local anesthetic blocks that are opioid sparing?

Ropivacaine, Bupivacaine

What drugs are skeletal muscle relaxants?

Baclofen (Lioresal)

Cyclobenzaprine (Flexeril)

Metaxalone (Skelaxin)

Methocarbamol (Robaxin)

Tizanidine (Zanaflex)

Carisoprodol (Soma)

How do skeletal muscle relaxants work to treat pain associated with muscle spasms?

agonizes GABA-B receptors centrally & increase Cl- flow

(doesn’t directly inhibit muscles, turns down CNS signal telling them to spasm)

What SEs are associated with muscle relaxants?

drowsiness & sedation (don’t give w/ opioids), dizziness, light headedness, fatigue

What drug?

• topical cream for analgesia

• have to apply consistently → activates pain fibers to release substance P & desensitizes them once substance P runs out

• use for minor aches & pains of muscles/joints, localized neuropathic conditions (postherpetic neuralgia)

Capsaicin

What SEs are associated with Capsaicin?

temporary burning/stinging after application that resolves in few days-wks

lipophilic → stays on hands; with soap and water!

What drug?

• partial opioid Mu agonist & weak inhibition of NE & 5HT

• use for mod-severe pain

• better tolerated than opioids but still abuse potential (Mu binding)

• C-IV

• combine w/ APAP → Ultracet

Tramadol (Ultram)

What SEs are associated with Tramadol (Ultram)?

dizziness, N, constipation, somnolence

Is Tramadol fully reversible with Naloxone (opioid antagonist)?

No

What is the main psychoactive compound in medical marijuana?

THC

Which cannabinoid receptor is primarily in CNS?

CB1

Which cannabinoid receptor is in peripheral tissues?

CB2

What SEs are associated with medical marijuana?

acute: impaired short term memory, motor coordination, judgement (no driving)

chronic: can affect developing brain (impaired memory, low IQ)

rare: paranoia, psychotic sx

worsen pulm sx (bronchitis, PNA), MI, stroke, PVD possible

What must an appropriate candidate for medical marijuana have?

debilitating metical condition

multiple failed trials of 1st & 2nd line agents

failed FDA approved cannabinoid (dronabinol, nabilone)

no active substance abuse, psychotic disorder, unstable mood/anxiety disorder

Patient presents with 10/10 pain after MVA & needs pain relief but has a morphine allergy (anaphylaxis). What treatment choice do you go with?

(*example test Q)

Fentanyl

Which manifestation of a venous thromboembolism is more likely to be fatal, PE or DVT?

Pulmonary embolism

What are risk factors for venous thromboembolisms (VTE)?

age, previous hx VTE,

venous stasis (obesity/paralysis/immobile),

vascular injury (hip/knee replacement)

hypercoagulable state (factor def, pregnancy)

drugs (estrogen containing)

How do you prevent a VTE?

physical activity, compression, early ambulation after surgery, Unfractionated Heparin / Enoxaparin / Fondaparinux

VTE algorithm