Chapter: Pain/ Gout/ Migraine

Question 1

What are the two main categories of pain, and how do they differ in terms of their underlying causes and mechanisms?

Answer 1

Pain is classified into two main categories: nociceptive pain and pathophysiologic pain, based on its underlying cause. Nociceptive pain arises from tissue damage, stimulating sensory nerves called nociceptors to send pain signals to the brain. It can stem from injuries to internal organs (visceral pain) or from injuries to the skin, muscles, bones, joints, or ligaments (somatic pain). On the other hand, pathophysiologic pain, also known as neuropathic pain, results from nervous system damage or malfunction rather than tissue injury. Conditions like fibromyalgia, diabetic neuropathy, chronic headaches, and drug-induced toxicities fall under this category.

Question 2

How is pain primarily assessed, and what factors should patients with chronic pain monitor and document?

Answer 2

Pain is subjective and primarily assessed through the patient’s description and observations. Patients with chronic pain should learn to monitor and document their pain by noting its level, type (using descriptors like burning or stabbing), and daily fluctuations. Recording factors that exacerbate or alleviate pain aids in evaluating pain management and guiding medication adjustments. Pain scales, such as numeric (ranging from 0 for no pain to 10 for worst pain) or visual analog scales, are commonly used to gauge pain severity. Hospital standards, as set by the Joint Commission (TJC), mandate the timely assessment and management of pain using both non-pharmacologic and pharmacologic interventions.

Question 3

Pain can be treated using a stepwise approach, where the choice of drug depends on the patient’s self-reported pain severity

Answer 3

Question 4

NON-OPIOID ANALGESICS

Acetaminophen: MOA

Answer 4

Acetaminophen is effective for reducing pain and fever, acting as an antipyretic. However, it lacks anti-inflammatory properties. Its exact mechanism of action is not fully understood, but it is believed to involve inhibiting the synthesis of prostaglandins in the central nervous system, thereby reducing the generation of pain impulses

Question 5

NON-OPIOID ANALGESICS

Acetaminophen: brand names/combination, max dose, BW, Reversal Agent

Answer 5

APAP Products:
- Only APAP: Tylenol (tab/cap), FeverAII (suppository), Ofirmev (inj)
- + hydrocodone (Lortab, Norco, Vicodin)
- + oxycodone (Endocet, Percocet)
- + codeine (Tylenol #3, 4)
- + caffeine (Excedrin)
- + aspirin/caffeine (Excedrin Extra, Excedrin Migraine)
- + caffeine/pyrilamine (Midol)
.
Max dose:
- Adult: Maximum < 4,000 mg/day from all sources
- Pediatrics (< 12 yrs): 10-15 mg/kg Q4-6H
.
BW:
Severe hepatotoxicity (can require liver transplant or resultin death), associated with doses > 4 grams/day total
.
Reversal Agent for OD: The antidote for acetaminophen overdosage is N-acetylcysteine (NAC, Acetadote).
■ Restores hepatic glutathione
■ Administered intravenously or orally

Question 6

NON-OPIOID ANALGESICS

NON-STEROIDAL ANTI-INFLAMMATORY
DRUGS (NSAID): What are the differences between traditional non-selective NSAIDs and selective COX-2 inhibitors in terms of their mechanisms of action and effects on gastrointestinal risk?

Answer 6

NSAIDs, including traditional non-selective ones like ibuprofen and aspirin, as well as selective COX-2 inhibitors, work by inhibiting the enzymes COX-1 and COX-2, which are responsible for producing prostaglandins and thromboxane A2. This inhibition reduces inflammation, relieves pain, and lowers fever. Non-selective NSAIDs block both COX enzymes, while COX-2 selective NSAIDs specifically target COX-2, which helps decrease gastrointestinal risks since COX-1 protects the stomach lining. Blocking COX-1 also reduces the formation of thromboxane A2, important for platelet function. Aspirin is unique as it irreversibly inhibits both COX-1 and COX-2 and is used as an antiplatelet agent, providing cardiovascular benefits known as cardioprotection.

Question 7

Non-Aspirin Boxed Warnings: All prescription, non-aspirin NSAIDs require a MedGuide due to these risks:

Answer 7

• GI Risk: NSAIDs pose a heightened risk of severe GI complications such as bleeding and ulceration. Elderly patients, those with a history of GI bleeding, and individuals taking systemic steroids, SSRIs, or SNRIs face the highest risk. Although aspirin and over-the-counter NSAIDs lack a boxed warning, they still carry this risk.
• CV Risk: NSAIDs elevate the likelihood of myocardial infarction (MI) and stroke. Their usage should be avoided in patients with cardiovascular disease or predisposing factors. This warning encompasses all over-the-counter non-selective NSAIDs except aspirin.
• Coronary Artery Bypass Graft (CABG) Surgery: NSAID administration is contraindicated following CABG surgery. Instead, antiplatelet therapy, typically aspirin, is recommended postoperatively.

Question 8

Side Effects of All NSAIDS

Answer 8

• Renal Effects: NSAIDs can reduce renal clearance by decreasing blood flow to the glomerulus. When combined with other nephrotoxic agents or in cases of dehydration, the risk is heightened. Caution should be exercised or NSAIDs should be avoided altogether in renal failure.
• Blood Pressure: NSAIDs have the potential to elevate blood pressure. They should be used cautiously in patients with controlled hypertension and avoided in those with uncontrolled hypertension.
• Effects on Pregnancy: NSAIDs can induce premature closure of the ductus arteriosus, leading to heart failure in the baby. Therefore, NSAIDs should not be used during the third trimester of pregnancy, approximately after 30 weeks.- IV NSAIDs (lndomethacln, Ibuprofen) can be used within 14 days
  of birth to close a patent ductus arterlosus !
• Nausea: NSAIDs, particularly salicylates, can cause nausea. This effect can be mitigated by taking the medication with food, switching to an enteric-coated or buffered product, or changing to a different NSAID.
• Photosensitivity: NSAIDs can induce photosensitivity reactions. Avoid sun exposure during mid-day hours, utilize sun-protective clothing, and apply broad-spectrum sunscreen with an SPF 30

Question 9

List all of the COX-1/COX-2 Non Selective NSAIDs

Answer 9

• Ibuprofen
• Indomethicin
• Naproxen
• Ketorolac
• Other: Piroxicam and Sulindac

Question 10

Non-Aspirin NSAIDs/ non-opioid

COX-1/COX-2 Non-selective NSAIDs: Ibuprofen - Brand, dosing/max, Notes

Answer 10

Brands: Advil, Motrin
Dosing:
- Adult: OTC: 200-400 mg Q4-6H/ Max: 1.2 grams/day
Rx: 400-800 mg Q6-8H/ Max: 3.2 grams/day
- Pediatric: 5-10 mg/kg/dose Q6-8H; Max: 40 mg/kg/day
Notes: OTC: limit self-treatment to < 10 days

Question 11

Non-Aspirin NSAIDs/ non-opioid

COX-1/COX-2 Non-selective NSAIDs: lndomethacin - Brand, Notes

Answer 11

Brands: Indocin
Notes: High risk for CNS side effects

Question 12

Non-Aspirin NSAIDs/ non-opioid

COX-1/COX-2 Non-selective NSAIDs: Ketorolac - Brand, warning, Notes

Answer 12

Brands: Toradol
Warnings: acute renal failure, liver failure
Notes: Nasal spray: prime five times before use.

Question 13

Non-Aspirin NSAIDs/ non-opioid

COX-1/COX-2 Non-selective NSAIDs: Naproxen - Brand, Notes

Answer 13

Brands: Aleve, + esomeprazole (Vimovo)
Notes: BID dosing

Question 14

Increased COX-2 Selectivity: List the medication and just come general notes

Answer 14

• Celecoxib (celebrex): Highest COX2 selectivity; Sulfonamide allergy is C/I!
• Diclofenac (volteran): avoid in women of childbearing potential
• Meloxicam (mobic) - some COX2 selectivity
• Nabumetone

Question 15

Salicylate NSAIDs: Asprin - brands, Cardioprotection dosing?, Warning, SEs, notes

Answer 15

- Brands: Ascriptin, Bufferin, Ecotrin, Bayer
- Cardioprotective dose: 81-162mg
- **Warnings: ** Avoid aspirin in children and teenagers with any viral infection due to potential risk of Reye’s syndrome
- SEs: Dyspepsia, heartburn, bleeding
- Notes: PPls may be used to protect the gut with chronic NSAID use; consider the risks from chronic PPI use (decrease bone density, increase infection risk); Salicylate overdose can cause tinnitus

Question 16

Opioid drugs interact in a variety of ways with the three primary types of opioid receptors:

Answer 16

• µ (mu), K (kappa) and δ (delta)
• Opioids are mu receptor agonists in the CNS, which primarily produce pain relief, but also cause euphoria and respiratory depression

Question 17

What are some general opioid boxed warnings?

Answer 17

Some other side effects: Constipation, nausea/vomiting (especially with acute, high-dose use), somnolence, dizziness/lightheadedness and risk of respiratory depression. Pruritus is common, especially in opioid-naive patients; diphenhydramine can be used (especially with morphine) to reduce rash and itching! All opioid at C-II unless stated otherwise!

Question 18

Common Opioid

Codeine: Some combination drugs/ schedule, BW, C/I, SEs, Note

Answer 18

- Drugs: Codeine (C-II); Codeine + APAP - Tylenol 3 and 4 (C-III); oral solution in cough products (C-V)
- BW: Resp depression, death has occured in children who were found to be ultra-rapid metabolizer of codeine (d/t CYP2D6 polymorph) after tonsillectomy and/or adenoidectomy
- C/I: Dont use in children < 12 y/o (any indication) and < 18y/o following tonsillectomy and/or adenoidectomy
- SE: high degree of GI uspet/ constipation
- Note: Codeine is prodrug and is metabolize to morphine via CYP2D6

Question 19

Common Opioid

Fentanyl:Brand names/ dosage form, BW, SEs, Notes, Fent patch

Answer 19

- Names: Duragesic, Sublimaze
- Doseage form: inj, patch (1 patch Q72 H but can be 48H), oral (Actiq): transmucosal lozenge on a stick “lollipop”
- BW: DO NOT use with strong or moderate CYP3A4 inhibitors
- SEs: application site redness/erythema (patch)
-Notes: Not use for opioid naive patient; A patient who has been using morphine 60 mg/day or equivalent for at least 7 days can be converted to a fentanyl patch.

Question 20

Common Opioid

Fentanyl Patch :important notes

Answer 20

• Apply to hairless skin (cut hair short if necessary)
• Do not apply more than 1 patch at a time
• Can be covered only with the permitted adhesive film dressings Biocfusive or Tegaderm
• Do not cover with a heating pad or any other bandage
• Some patches need to be removed before MRI. This is specific to each formulation and manufacturer. Check the individual manufacturer package insert
• Dispose of patch in toilet
• Keep away from children and pets

Question 21

Common Opioid

Hydrocodone IR (in combination product only): list product, BW, SEs

Answer 21

• +APAP: Norco (2.5/5/10 mg hydrocodone + 325 APAP)
• BW: Inititation of CYP3A4 inhibitors
• SE: dry mouth

Question 22

Common opioid

Hydromorphone: Brand, dosing, BW, Note

Answer 22

Hydromorphone (Dilaudid): PO: 2-4mg Q4-6H PRN; IV: 0.2-1mg Q2-3H PRN
.
BW: Risk of medication error with high potency (HP) injection (use in opioid-tolerant patients only!)
.
Note: Potent - so start low and convert carefully, high risk of OD

Question 23

Common Opioid

Methadone: Brand, BW, warning, note

Answer 23

- Methadone (Dolophine): 2.5-10mg
- BW: Life-threatening QT prolongation and serious arrhythmias (e.g., Torsades de Pointes)
- Warning: Combination with other serotonic drugs or MAO inhibitors can increase the risk of serotonin syndrome.
- NOTES:Due to variable half-life, methadone is hard to dose safely; Can decrease testosterone and contribute to sexual dysfunction; Methadone is a major CYP3A4 substrate; avoid use with inhibitors or lower methadone dose!!!

Question 24

Common Opioid

Meperidine: Brand, Dosage form, warning, Note

Answer 24

- Merperidine (Demerol): tab, solution, iv
- Warning: Renal impairment/elderly at risk for CNS toxicity (SZ), avoid with or within 2 weeks of MAO
inhibitor
- Notes:No longer recommended as an analgesic (especially in elderly and renally impaired); short duration; in combo with othe drugs it’s serotonergic and can increase of serotinin syndrome

Question 25

Common Opioid

Morphine: Brand, Dosage form, SEs, Note

Answer 25

Morphine: ER: MS Contin; Injection: Duramorph,Infumorph
.
SEs: Pruritus, dry mouth
.
Notes: Diphenhydrimine or similar can be given to block histamine-induced pruritus

Question 26

Common opioid

Oxycodone:Names, BW, SEs

Answer 26

- Names: IR: Roxicodone; CR: Oxycontin; +APAP Endocet, Perocet
- BW: Initiation of CYP3A4 inhibitors (or stopping CYP3A4 inducers) can cause fatal overdose!
- SEs: Pruritus, dry mouth

Question 27

Opioid DDI

Answer 27

• Using this medication alongside other central nervous system (CNS) depressants like alcohol, hypnotics, benzodiazepines, and muscle relaxants can lead to increased drowsiness, dizziness, confusion, and a higher risk of respiratory depression. It’s especially important to avoid alcohol when taking any opioid, particularly extended-release formulations.
• Increased risk of hypoxemia with underlying resp
  disease (e .g., COPD) and sleep apnea.
• Methadone: caution with agents that worsen cardiac function or increase arrhythmia risk. Caution with other serotonergic agents. Caution with agents that worsen renal function, elderly patients and those with seizure history.
• Hydrocodone, fentanyl, methadone and oxycodone are CYP3A4 substrates. Avoid use with CYP3A4 inhibitors.

Question 28

DOSING CONVERSIONS: IV vs PO options

Answer 28

Always round down when going from one opioid to another: rounding the dose down will reduce the risk of overdose

Question 29

Steps for opioid conversion

Answer 29

Question 30

A hospice patient has been receiving 12 mg/day of
IV hydromorphone. The pharmacist will convert the
hydromorphone to morphine ER, to be given Q12H. The hospice policy for opioid conversion is to reduce the new dose by 50%, and to use 5 -17% of the total daily dose for BTP.

Answer 30

Question 31

Conversion Exception: Fent Patches

Answer 31

Converting to a fentanyl patch typically involves using a dosing table provided in the package insert or following specific instructions. The process includes finding the total daily dose in milligrams (mg), converting it to micrograms (mcg) by multiplying by 1,000, and then dividing by 24 to determine the patch dose since fentanyl patches are dosed in mcg per hour. It’s important to note that fentanyl is not absorbed orally, so no oral dose conversion is listed on the conversion chart. Clinicians may also use an estimation method, such as morphine 60 mg total daily dose equals a 25 mcg/hr fentanyl patch, but different methods can yield different results. For accuracy, it’s crucial to follow the specific instructions provided when converting to or from fentanyl patches.

Question 32

Examples

Fent Patches: MJ is a 52-year-old male patient who has been using OxyContin 40 mg BID and Endocet 5-325 mg as needed for BTP. He uses the
BTP medication 2 - 3 times weekly. Using the OxyContin dose only, select the fentanyl patch strength that should be chosen for
this patient, using the following table:

Answer 32

Oxycodone 80 mg daily is in the range of 67.5 -112 mg daily which correlates to the 50 mcg/hr patch.

Question 33

Opioids an Non-Cancer Pain

Opioids are not first-line for chronic pain treatment and should not be used routinely. In some cases, they have benefit. When used, follow safe use recommendations:

Answer 33

• Establish and measure goals for pain and function.
  Reaching low pain rather than no pain may be reasonable.
• It using opioids, start with immediate release. Start low and go slow.
• Evaluate risk factors for opioid-related harm.
• Pharmacist should check their state’s Prescription Drug Monitoring Program (PDMP) database. Look for high dosages and multiple prescribers.
• Use urine drug testing, and watch for false positives and negatives.
• Use adjunctive medications to enable a lower opioid dose.
• Avoid benzodiazepines and opioids given together, except in rare cases. This quadruples the risk of overdose death.
• F/U, taper, consider D/C

Question 34

Opioid Allergy

Answer 34

Question 35

Opioid Side Effect: Opioid Induced Respiratory Depression (OIRD) Risks

Answer 35

Question 36

Opioid Side Effects: Constipation

Answer 36

Most opioid SEs lessen over time except constipation. If problem presist, can switch to another opioid. Additionally, all opioid (except oxymorphone) shoud be taken with food to lessen nausea

Question 37

Treatment for Opioid Induced Constipation

Peripherally-acting mu-opioid receptor antagonists (PAMORAs): MOA

Answer 37

Block opioid receptors in the gut to reduce constipation without affecting analgesia. PAMORAs are indicated for OIC and are only effective when constipation is secondary to use of an opioid!

Question 38

Treatment for Opioid Induced Constipation

Peripherally-acting mu-opioid receptor antagonists (PAMORAs): List the drug/brand, Warnings, SEs

Answer 38

- Drugs: Methylnaltrexone (Relistor); Naloxegol (Movantik)
- Warnings: Risk of GI perforation
- SEs: Abdominal pain, flatulence
- Notes: D/C all laxitives prior to use; for patients who failed OTC laxatives

Question 39

CENTRALLY ACTING ANALGESICS: What are they and how to they work?

Answer 39

Both tramadol and tapentadol are mu-opioid receptor agonists and inhibitors of norepinephrine reuptake. Tramadol also
inhibits reuptake of serotonin. Both tapentadol and tramadol have the same boxed warnings as opioids

Question 40

Centrally Acting Analgesics

Tramadol: Brand, schedule, BW, warning, C/I, SEs, Note

Answer 40

• Brand: Ultram
• Schedule: C-IV
• BW: Resp depression and death have occured in children following tonsilectomy and/or adenoidectomy found to have evidence of being ultra-rapid metabolizer of tramadol
• Warning: SZ risk, risk of serotonin syndrome, hypoglycemia
• C/I In children < 12 y/o or in children < 18 following tonsil/adenoi
• Note: Tramadol require conersion to active metabolite by CYP2D6

Question 41

Centrally Acting Analgesic Drug Interactions

Answer 41

■ Caution with other agents that lower seizure threshold
■ Caution with other serotonergic drugs.
■ Avoid tramadol with CYP2D6 inhibitors.

Question 42

Opioid OD

Answer 42

TX: Naloxone (Narcan): 1 spray (4mg) - repeat dose may be required. SE: can cause acute withdrawl symp

Question 43

Treatment for Opioid Use Discorder

Answer 43

Buprenorphine (C-III) is a partial mu-opioid agonist. It is an agonist at low doses and an antagonist at higher doses . It is used in lower doses to treat pain and higher doses to treat addiction.
.
Naloxone is an opioid antagonist; it replaces the opioid on the mu receptor. Given by itself, naloxone (injection or nasal spray) is used for opioid overdose. Buprenorphine/naloxone combination products are used as alternatives to methadone for opioid dependence (buprenorphine suppresses withdrawal symptoms and naloxone helps prevents misuse).

Question 44

What are the roles and benefits of adjuvants in pain management, and how do they enhance the effectiveness of opioid or non-opioid analgesics in multimodal treatment?

Answer 44

Adjuvants, like muscle relaxants, antiepileptic drugs (AEDs), and antidepressants, are valuable additions to pain management, even though they aren’t considered analgesics themselves. They complement opioid or non-opioid analgesics in multimodal treatment. Commonly used in conditions like neuropathy, postherpetic neuralgia (PHN), fibromyalgia, and osteoarthritis (OA), AEDs such as pregabalin and gabapentin are particularly effective for neuropathic pain. Specific formulations, like the lidocaine 1.8% patch ZTlido, are developed and approved for certain conditions like PHN. In severe cases, opioids and other agents can also be beneficial. Tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) block norepinephrine uptake, aiding in neuropathic pain management EG: amitriptyline and duloxetine (cymbelta). Muscle relaxants have varying mechanisms of action, from CNS depression to inhibiting reflex transmission at the spinal level. Injectable adjuvants, like clonidine, can be employed by pain specialists, such as adding it to opioids in intrathecal (epidural) pain pumps for cancer patients when other treatments are inadequate. It’s crucial to use only FDA-approved analgesics for intrathecal administration.

Question 45

Oral Adjuvant for Neuropathic Pain

List the 3 Antiepileptic Drugs

Answer 45

1. Gabapentin (Neurontin)
2. Pregabalin (Lyrica) - C-V
Both of these can be used for PHN, restless leg syndrome, neuropathy. The SEs include: dizziness, somnolence, edema/ weight gain
3. Carbamazepine (Tegretol): FDA approved for trigeminal

Question 46

Oral Adjuvants for Musculoskeletal pain/ spasm

List the Antispasmodic (muscle relaxants) that exert their effects by sedation

Answer 46

1. Carisoprodol (Soma) - C-IV poor Cyp2c19 metabolizers will increase carisoprodol levels!!!
2. Methocarbamol (Robaxin): SE: sedation

Question 47

Oral Adjuvants for Musculoskeletal pain/ spasm

List the Antispasmodic (muscle relaxants) with analgesic effects: use caution with other CNS depressants

Answer 47

1. Baclofen (Lioresal)
2. Cyclobenzaprine (Amrix, Fexmid) - serotonergic! Do not combine with other serotonergic agents
3. Tizanidine (Zanaflex): SEs - hypotension, Dry mouth

Question 48

List the Topical Adjuvants and some key points

Answer 48

1. Lidocaine (patch, gel, cream): Note - approved for shingle (PHN) pain; for patches, do not apply more than 3 patches at a time.
2. Capsaicin(cream, gel, patch, stick lotion): applied 3-4x qd. Wash hands after application! Do not touch sensitive areas
3. Methyl Salicylate (Bengay, IcyHot, Salonpas, Aspercreme)

Question 49

GOUT

Question 50

Gout:What is gout, and what triggers its onset? How does uric acid accumulation lead to gout attacks, and what are the typical symptoms? How is gout diagnosed, and what diagnostic methods are utilized to confirm its presence?

Answer 50

Gout is a form of arthritis triggered by an accumulation of uric acid crystals, primarily within the joints. Uric acid is a byproduct of purine metabolism, found in many foods and constituting one of DNA’s base pairs. Normally, two-thirds of uric acid is excreted via the kidneys and one-third through the gastrointestinal tract. Normal serum uric acid levels range from 2 to 6.5 mg/dL in females and 3.5 to 7.2 mg/dL in males.

Elevated uric acid levels may not always cause symptoms; however, when uric acid crystallizes in the joints, it leads to acute gout attacks characterized by sudden onset of severe pain, burning, and swelling, often affecting one joint - the metatarsophalangeal joint (big toe). If untreated, gout attacks can recur and cause damage to joints, tendons, and surrounding tissues.

Diagnosis involves assessing uric acid levels and examining synovial fluid under a microscope to detect uric acid crystals. Imaging studies such as X-ray, ultrasound, MRI, or CT scans can also provide visualizations of affected joints.

Question 51

Gout

What are the typical treatment approaches for asymptomatic hyperuricemia and acute gout attacks? What drugs are commonly used to manage acute symptoms, and what is the goal of prophylactic drug therapy in gout management?

Answer 51

Asymptomatic hyperuricemia typically does not warrant drug treatment. However, when a gout attack occurs, anti-inflammatory drugs are utilized to address acute symptoms. These drugs target pain and inflammation and may include colchicine, NSAIDs, and steroids. Additionally, prophylactic drugs are administered to lower uric acid levels, aiming for levels below 6 mg/dL.

Question 52

General Treatment plan for Acute Gout Attack

Answer 52

Gout attacks necessitate prompt treatment due to their severe pain. Typically, a single drug is recommended initially, such as an NSAID, systemic steroid, or colchicine. In cases of more severe disease, combination therapy may involve colchicine with either an NSAID or an oral steroid. For localized attacks, intra-articular steroid injections can be beneficial. Patients experiencing acute attacks while on chronic urate-lowering therapy (ULT- such as allopurinol or febuxostat) should continue their ULT. Additionally, applying topical ice to affected joints helps alleviate pain and inflammation.

Question 53

Acute Gout Attack Therapy

Colchicine (Colcrys): tx dosing, C/I, warning, SEs, Notes

Answer 53

- TX Dosing: 1.2 mg PO (this is two 0.6 mg tablets) followed by 0.6 mg in 1 hr (do not exceed a total of 1.8 mg in 1 hr or2.4 mg/day)
- C/I: Do not use in combination with a P-gp or strong CYP3A4 inhibitor with renal / hepatic impairment
- warning: Myelosuppression, increase risk of myopathy
- SEs:Diarrhea, nausea, myelosuppression, myopathy, neuropathy (Decrease B12)
- Notes: Start within 36 hours of symptom onset, Wait 12 hours after a treatment dose before resuming prophylaxis dosing (0.6 mg qd or bid)

Question 54

Acute Gout Attack Treatment

NSAIDs! List some

Answer 54

lndomethacin (lndocin), Naproxen, Celecoxib

Question 55

Acute Gout Attack Treatment

Steroids: given PO, IM , IV, intra-articular or as ACTH (adrenocorticotropic hormone), which triggers endogenous glucocorticoid secretion … List some Steroid used…

Answer 55

- Prednisone/ Prednisolone: 0.5 mg/kg/day PO for 5-10 days (no taper) or 0.5 mg/ kg/day for 2-5 days, then taper
- Methylprednisolone (Medrol): use lntraarticular if 1-2 large joints involved

Question 56

Gout PPX Overview

Gout PPX Overview: List the Different Agents used and Caveats

Answer 56

Chronic urate-lowering therapy (ULT) is recommended for all patients with gout who have experienced a gout attack, have intermittent symptoms, or have tophi (UA crystals that form under the skin in long-term gout). When starting chronic ULT, colchicine or NSAIDs should be used as prophylaxis to reduce the risk of attacks, which can occur when UA is lowered rapidly (possibly due to mobilization of the urate crystals).

The first-line ULT is allopurinol, a xanthine oxidase inhibitor (XOI). Blocking the xanthine oxidase enzyme stops the production of UA and produces a nontoxic end product. Patients at high risk of severe allopurinol hypersensitivity reactions should be screened for the HLA-B*5801 allele prior to use. Another XOI, Febuxostat, is available as an alternative agent. XOIs are titrated up slowly to lower the UA to a target level of < 6 mg/dL. DDI: do not use XOI with mercaptopurine or azatioprine

Probenecid is a uricosuric and is a second-line treatment that can be used if XO inhibitors are contraindicated or not tolerated or can be added when the UA level is not at goal despite maximal doses of XO inhibitors. Probenecid inhibits reabsorption of UA in the proximal tubule of the nephron, which increases UA excretion. It requires adequate renal function to be effective, which many gout patients do not have.

Another option when the XO inhibitor treatment is inadequate (UA remains above 6 mg/dL) is lesinurad, a uricosuric that is taken with the XO inhibitor. Pegloticase is a recombinant uricase enzyme, which converts UA to an inactive metabolite that can be easily excreted. Pegloticase is reserved for severe, refractory disease.

Question 57

Uric Acid Production and Drug Treatment: Where the medication works

Answer 57

Question 58

Chronic Urate Lowering Therapy (ULT): Allopurinol - brands, warning, SEs, Notes

Answer 58

- Brand: Zyloprim, Aloprim
- Warning:Hypersensitivity reactions, including severe rash (SJS/TEN, DRESS); HLA-B*5801 testing
prior to use (especially for patients of Asian descent) and do not use drug if positive!!! hepatotoxicity
- SEs: Rash, acute gout attacks, nausea, increase LFT
- Notes: Due to the high rate of gout attacks when beginning ULT, use with colchicine (0.6 mg
once or twice daily) or an NSAID for the first 3-6 months

Question 59

Chronic Urate Lowering Therapy (ULT): Febuxostat - BW, warning, Notes

Answer 59

- Boxed warning: Increased risk of cardiovascular death compared to allopurinol! should be limited to those who cannot tolerate allopurinolor allopurinol is not effective
- Warning: Hepatoxicity, serious skin rxn (SJS/TEN)
- Notes: Due to the high rate of gout attacks when beginning ULT, use with colchicine (0.6 mg
once or twice daily) or an NSAID for the first 3-6 months

Question 60

Other Gout Agent

Uricosurics: MOA, drugs

Answer 60

- MOA: inhibit reabsortion of uric acid in the kidneys, which increase uric acid secretion!
- Drugs: Lesinurad (must be used with allopurinol or febuxostat), Probenecid (can be used to increase beta lactam levels!)

Question 61

Other Gout Agent

Recombinant Uricase: MOA, Drug

Answer 61

Pegloticase (IV): Anaphylactic reactions - monitor and premedicate with antihistamines and steroids!; C/I in G6PD deficiency; Do not use in combination with allopurinol, febuxostat or probenecid (can increase anaphalxis risk)
.
MOA: converts uric acid to allantoin , which is excreted

Question 62

What is TLS? and it’s treatment

Answer 62

Tumor lysis syndrome (TLS) is a severe complication of certain chemotherapy treatments, where cell breakdown releases purines into the bloodstream, leading to uric acid accumulation and potential complications like acute gout, electrolyte imbalances, and renal failure. Rasburicase (Elitek) is used to treat TLS but is contraindicated in individuals with G6PD deficiency due to the risk of hemolysis. Immediate discontinuation is required if hemolysis occurs.

Question 63

CHAP: 59 MIGRAINE

Question 64

What are the common characteristics of migraines? signs? When should individuals experiencing headaches seek immediate medical attention

Answer 64

Migraines are recurrent headaches causing intense pain lasting hours to days. Symptoms often include nausea, vomiting, and sensitivity to light and sound. Some migraines may be preceded or accompanied by sensory warning signs (auras) like flashes of light or tingling. Most migraines occur without an aura. Headaches accompanied by certain symptoms like fever, confusion, weakness, or chest pain may indicate serious cardiovascular, cerebrovascular, or infectious events, requiring immediate medical attention.

Question 65

What are the potential causes of migraines, and how can patients reduce migraine frequency by identifying triggers?

Additionally, how can menstrual-associated migraines be treated in women, and what precaution should be taken regarding estrogen-containing contraceptives in women with migraines accompanied by aura?

Answer 65

The cause of migraines is not fully understood but may involve neurotransmitter imbalances (ie. serotonin), or activation of the trigeminal nerve with release of calcitonin gene-related peptides (CGRP). Patients are advised to identify and avoid triggers to reduce migraine frequency. Menstrual-associated migraines (MAM) in women can be treated with oral contraceptives, estradiol patches, or creams to decrease their frequency. However, women with migraines accompanied by aura are at higher stroke risk and should avoid estrogen-containing contraceptives.

Question 66

COMMON MIGRAINE TRIGGERS

Answer 66

Question 67

Migraine DX Criteria

Answer 67

Migraines can be diagnosed when an adult has at least five attacks (not attributed to another disorder) fulfilling the following criteria:
1. Headaches last 4 - 72 hours and recur sporadically.
2. Headaches have 2 or more of the following characteristics:unilateral location, pulsating, moderate-severe pain and aggravated by routine physical activity.
3. One of the following occurs during the headache: nausea and/or vomiting, photophobia (sensitivity to light) and phonophobia (sensitivity to sound)

Question 68

Migraine: Acute Drug Treatment: General Overview on OTC/ RX options and what is NOT recommended?

Answer 68

• OTC options include: acetaminophen, Advil
  Migraine (which contains only ibuprofen), Excedrin Migraine (aspirin, acetaminophen and caffeine), Aleve (naproxen)
• RX: NSAIDs (at higher dose), Serotonin receptor agonist (Triptans), select CGRP Receptor Antagonists, ergotamine drugs.
  .
  Opioids, butalbital-containing products, tramadol and tapentadol are not recommended due to abuse/dependence and decreased efficacy!

Question 69

Migraine Drugs

Triptans: MOA

Answer 69

Triptans, selective agonists for the 5-HT1 receptor (1B/1D subtypes), induce vasoconstriction of cranial blood vessels, inhibit neuropeptide release, and reduce pain transmission. They are the first-line treatment for acute migraines and are most effective when taken at the onset of symptoms.

Question 70

Migraine Drugs

Triptans: List of the most common ones (brand/generic), basic dosage form/formulations

Answer 70

Drugs
- Sumatriptan: Imitrex (SC inj, tablets, nasal spray); Imitrex STAT (SC autoinj); Onzetra (nasal powder)
- Rizatriptan (Maxalt-MLT) - Tabs, ODT
- Zolmitriptan (Zomig ZMT): Tabs, ODT, nasal spray

Question 71

Migraine Drugs

Triptans: C/I, Warnings, SEs

Answer 71

Question 72

Migraine Drugs

Triptans: Drug Interactions

Answer 72

• FDA Warning: There is an FDA warning regarding the combination of triptans with serotonergic drugs like SSRIs and SNRIs. However, many patients take both safely, especially since triptans are typically taken PRN
• Contraindications: Sumatriptan, rizatriptan, and zolmitriptan are contraindicated with MAO inhibitors (selegiline, isocarboxazid, phenelzine, and tranylcypromine) or within two weeks of stopping them. Other triptans do not have this contraindication.

Question 73

Migraine Drugs

ERGOTAMINE DRUG: MOA/ Placement in therapy ?

Answer 73

Ergotamine is a nonselective agonist of serotonin receptors, which causes cerebral vasoconstriction. In patients who do not find benefit with a triptan, ergotamine is generally used next.

Question 74

Migraine Drugs

Ergotamine: List the drugs/ general dosing

Answer 74

• Dihydroergotamine (D.H.E. 45; Migranal): Injection (IM/SC/IV) , nasal spray. Injection is 1mg and spray is 1 spray
• Ergotamine + caffeine (Cafergot, Migergot): Tab (1 mg) and (1) suppository

Question 76

Migraine Drugs

Ergotamine: BW, C/I, Warning

Answer 76

Question 77

Migraine Drugs

Other Abortive Agents…

Answer 77

Rimegepant and Ubrogepant are oral CGRP receptor antagonist. CGRP contributes to vasodilation + neuro inflammation…so blocking the CGRP recptor help reduce / elimiate migraine pain. Ubrogepant is approved for treatment of acute migraine and Rimegepant is approved for PREVENTION and TREATMENT of acute migraine
.
Lasmiditan is first class serotinin agonist that’s selective for the 5-HT1F recpetor subtype. Unlike triptan a ergotamine it does not cause vasoconstriction

Question 78

Migraine PPX

PPX should be considered in patient who use acute tx 2 or more days in a week or 3 or more times per month, have migraine that decreases QoL or if acute tx is C/I…Some oral ppx optios include:… and what the injectin option?

Answer 78

• Antihypertensives: Beta-blockers (best evidence with propranolol, timolol, and metoprolol), Other options like lisinopril and verapamil have also been utilized.
• Antiepileptic drugs: Topiramate (Topamax) and valproic acid/ Divalproex are effective for migraine prevention. Topiramate is particularly popular due to its tendency to cause weight loss in many patients.
• Antidepressants: Tricyclic antidepressants, especially amitriptyline, are commonly used for migraine prophylaxis at lower doses. Venlafaxine can also be effective in some cases.
• CGRP Receptor Antagonist: more options for ppx than for acute migraine tx
• Menstrual-associated migraines (MAM): Monophasic and extended-cycle oral contraceptives can be used for if aura is absent. NSAIDs or certain triptans with longer half-lives, such as frovatriptan or naratriptan, can be initiated prior to menstruation and continued for 5 to 7 days.
• Natural products: Riboflavin, magnesium, butterbur, feverfew, peppermint
  .
  NON ORAL OPTION FOR PPX
• Bolulinum Toxin A (Botox): for chronic migraines only (> 15 HA per month)

Question 79

Migraine

Medication Overuse Headache

Answer 79

Medication overuse headaches (MOH) stem from excessive/ overuse of acute headache medications. These headaches occur more than 10 to 15 days per month.

To prevent MOH, patients should be educated to limit acute treatment medications to 2 to 3 times per week at most. The primary focus should be on discontinuing the overused medication. If the medication is an opioid or contains butalbital (e.g., Fioricet, Fiorinal), a slow tapering process is necessary.