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Block 1 Flashcards

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1
Q

What is the most common systemic inflammatory disease?

A

Rheumatoid arthritis

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2
Q

When does rheumatoid arthritis occur?

A

At any age

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3
Q

Rheumatoid arthritis occurs more frequently in (men/women)

A

Women

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4
Q

Are genetics a risk factor for rheumatoid arthritis?

A

Yes, especially rheumatoid factor as it is the most important factor

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5
Q

In RA, (osteoblasts/osteoclasts) are promoted

A

Osteoclasts; breaks down bones

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6
Q

Signs of RA

Joint involvement is (asymmetrical/symmetrical)

A

Symmetrical

whereas osteoarthritis it is asymmetrical

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7
Q

What is the most important risk factor in gout or hyperuricemia?

A

Elevated serum urate levels

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8
Q

Gout/hyperuricemia occurs more frequently in (men/women)

A

Men

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9
Q

What is hyperuricemia?

A

Accumulation of uric acid in blood (≥6.8)

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10
Q

Gout and hyperuricemia are inflammatory joint diseases due to what?

A

Deposition of monosodium urate crystals

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11
Q

Solubility limit of serum urate?

A

Anything >7 exceeds the solubility limit

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12
Q

What are some production sources of uric acid?

A

Dietary purines (beef, liver, alcohol)

Converted via 2 enzymes

De novo synthesis of purine bases

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13
Q

How is uric acid excreted?

A

Urine (66%) or GI tract

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14
Q

Which enzymes can cause a build up of uric acid?

A

PRPPase can increase the levels and a deficiency of HGPRTase can also increase it

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15
Q

Which drugs can induce hyperuricemia and gout?

A

Diuretics

Salicylates (<2g) **do not stop drug to prevent gout if they have a heart issue, risk

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16
Q

Which joint is the most commonly affect in gout?

A

Big toe

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17
Q

Do NSAIDs alter the course of RA or prevent joint destruction?

A

No, it just helps with inflammation

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18
Q

Methotrexate targets what?

A

DHFR

Inhibits PURINE synthesis

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19
Q

MTX metabolism, excretion, and AE?

A 
Metabolism = liver
Excretion = urine
AE = liver damage
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20
Q

MTX interaction?

A

PCN

Cyclosporine

NSAIDs

Probenecid

Cola

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21
Q

CI of MTX?

A

Liver disease or Immunodeficiency

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22
Q

Active form of leflunomide?

A

Teriflunomide

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23
Q

Target of leflunomide?

A

DHODH

Inhibits PYRIMIDINE synthesis

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24
Q

Leflunomide vs MTX, which one has a half life of 14-18 days?

A

Leflunomide

MTX is like 8hrs

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25
Leflunomide metabolism? AE?
Prodrug, metabolized in GI and liver AE = infection and liver toxicity
26
Interaction of leflunomide?
Live vaccines Warfarin Diabetic drugs or rosuvastatin
27
What can be used as a binding agent when used with leflunomide?
Cholestyramine; use if serious toxicities occur or if pt wishes to become pregnant
28
Metabolism and excretion of hydroxychloroquine?
Rapid GI absorption and excreted by kidney Half life = 30-50 days
29
Hydroxychloroquine AE?
Ocular toxicity
30
CI of Hydroxychloroquine?
Hypersensitive to 4-aminoquinoline or any retinal field changes
31
Rituximab MOA?
Targets CD20 protein on B cells Different from the other biological DMARDs as they are TNF alpha inhibitors
32
Which biological DMARDs contains mouse proteins?
Infliximab
33
Which biological DMARDs contains murine proteins?
Rituximab
34
TNF alpha blocker AE and interactions?
AE = inj. site reaction (etanercept only) + infections Interaction = anakira + live vaccines
35
What effect does colchicine have on serum uric acid levels?
No effect
36
Colchicine MOA?
Inhibits microtubules (for gout) Prevents activation, degranulation and migration of neutrophiles
37
Colchicine metabolism?
CYP3A4
38
Colchicine interaction?
P-gp and CYP3A4 inhibitors
39
* Enhance uric acid degradation * Increase uric acid excretion * Reduce uric acid production Pegloticase Uricosuric rx Xanthine oxidase inhibitors
Xanthine - reduce production Uricosuric - increase excretion Pegloticase - enhance degradation
40
Can you use urate-reducing drug therapy in acute gout attack?
No, may prolong it by changing equilibrium of body rate
41
What are the xanthine oxidase inhibitors?
Allopurinol + Febuxostat
42
What are the uricosuric drugs?
Probenecid (targets URAT1)
43
Pegloticase targets what?
Uric acid; converts uric acid to allantoin (more excretable metabolite) Used in refractory pts
44
Allopurinol AE? Interaction?
Allopurinol hypersensitivity syndrome DDI with azathioprine and didanosine
45
Structurally, what's different about febuxostat vs allopurinol? Interactions?
Febuxostat is NOT purine like; it's a thiazole carboxylic acid derivative. Does NOT have hypersensitivity syndrome DDI with azathioprine, mercaptopurine, theophylline
46
Probenecid AE and DDI?
GI issues, hypersensitivity DDI with ASA
47
Pegloticase AE, DDI, CI?
Chest pain, nasopharyngitis, anaphylaxis DDI - Probenecid, sulfinpyrazone, allopurinol CI - G6PD deficiency
48
Can you use NSAIDs as monotherapy for RA?
No
49
Special AE/allergy of selective COX inhibitors?
BP increases due to sodium and fluid retention Sulfa allergy
50
Can you use corticosteroids as monotherapy for RA?
No
51
To reduce systemic AE of corticosteroids, how can you give them?
Intra-articularly
52
Short and long term AE of corticosteroids?
Short term - insomnia/mood swings, BG/Wt gain, HTN Long term - Cushings, Osteoporosis, infection
53
Methotrexate dose for RA?
7.5mg ONCE WEEKLY
54
Methotrexate CI
Pregnancy, Liver issues, alcoholism Causes liver issues
55
What is the initial therapy + their considerations for RA?
Methotrexate Premedicate w/ folic acid (5mg/week) Dose adjustments for renal/hepatic impairment Use contraception for at least 3 months after d/c
56
Leflunomide dose for RA?
LD = 100mg PO daily x3days Then 20mg PO daily
57
Leflunomide considerations for RA?
Take Cholestyramine 8g TID for 11 days (overdose) Contraception is still needed for a few months after d/c Dont take live vaccine
58
Hydroxychloroquine considerations for RA?
Can be used as monotherapy for MILD disease if MTX is CI Retinal damage
59
Sulfasalazine consideration for RA?
Dont take w/ Sulfa or salicylate allergy Yellow-orange urine/skin discoloration Abx and iron can decrease absorption Affects warfarin Premedicate with antihistamine or steroids to prevent serum sickness
60
What are the JAK inhibitors?
"..inib"
61
What is the dose of Tofacitinib for RA?
5mg PO BID (IR) or 11mg QD (ER) Reduce to 5mg QD (IR) in renal or hepatic impairment
62
Tofacitinib CI and considerations?
Avoid in severe impairment, lymph count <500, ANC <1000 or hgb<9 DI w/ 3A4 inhibitors
63
Baricitinib dose for RA?
2mg PO BID Dont use if GFR<60 Used if pt failed ≥1 TNF blockers **pretty much same CI and consideration w/ Tofacitinib
64
Which JAKi can be used as monotherapy?
Upadacitinib
65
Which JAKi should be used cautiously with history of thrombosis or latent TB?
Upadacitinib + Baricitinib
66
Upadacitinib dosing for RA?
15mg PO QD
67
Which JAKi should you not take w/ biological DMARDs or strong immunosuppressants?
Upadacitinib + Baricitinib
68
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one must be taken w/ith MTX?
Infliximab + Golimumab
69
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one has a CI of sepsis?
Etanercept
70
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one is dosed at 40mg SQ q14 days?
Adalimumab
71
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one has a CI of doses >5mg/kg in CHF?
Infliximab
72
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one is dosed at 50mg SQ weekly for 25mg SQ twice weekly?
Etanercept
73
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one has murine proteins?
Infliximab
74
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one is dosed at 50mg SQ monthly?
Golimumab
75
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one is dosed as an IV infusion?
Infliximab
76
``` Adalimumab Etanercept Infliximab Golimumab Certolizumab ``` Which one is dosed at 400mg SQ at 0,2,4 weeks then 200mg q14 days?
Certolizumab
77
Abatacept (orencia) dosing?
IV based on weight <60kg - 500mg 60-100kg - 750mg >100kg - 1000mg
78
Abatacept considerations and monitoring?
Dont give w/ TNF alpha inhibitors Screen for TB and Hep B
79
Rituximab consideration and monitoring?
Give w/ MTX Premedicate w/ benadryl, steroid, APAP TB and Hep B screen
80
Tocilizumab consideration and monitoring?
Elevated lipids, transaminitis Dont give w/ combo DMARDs TB screening
81
Abatacept Rituximab Tocilizumab Humanized, inhibits IL-6
Tocilizumab
82
Abatacept Rituximab Tocilizumab Binds to CD20, depletes B cells
Rituximab
83
Abatacept Rituximab Tocilizumab Binds to CD80/86, prevents interaction of MPC and T cells
Abatacept
84
Early RA management
<6months Low activity - DMART mono then to combo Moderate/high - straight to combo No JAKi, only used in established RA
85
Established RA management
>6months Low activity - DMART mono then to combo Moderate/high - straight to combo CAN use JAKi, then start to switch to another class. Cant cure RA If in remission, consider tapering but never d/c
86
What are the killed vaccines?
Pneumococcal, IM flu, hep B, HPV
87
What is the most common symptoms of gout/uricemia?
"Joint on fire"
88
How is acute gouty arthritis classified?
Intensity ``` Mild = ≤4 Moderate = 5-6 Severe = 7-10 ``` Duration Early <12hrs Well established 12-36hrs Late >36hrs
89
What is the goal urate target?
<6
90
Which NSAIDs are approved for tx of gout? When should they be initiated?
Indomethacin, naproxen, and sulindac ASAP or within 24 hrs
91
Colchicine MOA?
Antimitotic agent Prevents migration of neutrophils No analgesic property
92
Colchicine dosing?
LD = 1.2mg PO then 0.6mg one hr later on day one, Then 0.6 1-2 times a day Max of 1.8mg in acute tx or 1.2mg in prophylaxis Beneficial to use within 36 hrs after onset of attack
93
Colchicine CI and AE?
CI = using P-gp or 3A4 inhibitors AE = diarrhea
94
Treatment guideline for gout with NSAIDs, Colchicine, or systemic corticosteroid based on mild, moderate, severe pain
Mild/moderate = monotherapy, if inadequate switch to another mono or just add another drug on top Severe = combo **Combo is NEVER NSAIDs + oral corticosteroids**
95
What are some indications for pharmacologic ULT for chronic management?
Diagnosis of gouty arthritis AND one of the following: 2+ gout attacks / year Presence of 1+ tophus Evidence of radiographic damage
96
Which ULT for chronic management should NOT be initiated during a flare up?
Probenecid, wait until its over
97
Allopurinol doisng?
100mg daily and titrate every 2-4 or 5 weeks. There is renal dosing
98
Allopurinol AE and considerations?
Dont take with HLA-B*5801 allele (asians) Maculopapular eruption DRESS, SJS, TEN
99
Febuxostat AE and consideration?
Transaminitis FDA warning for increased death in pt with CV issues Should only be prescribed if they cant take allopurinol or failed it.
100
Probenecid AE and considerations?
AE of Urolithiasis Initiate after gout attack but if attack occurs, just continue Avoid in CrCl<30
101
Lesinurad CI and AE?
CI: CrCl <30 AE: nephrolithiasis and renal failure Must take with food and water in combo with XOI
102
Pegloticase consideration?
d/c all oral urate-lowering rx prior to initiation CI in G6PD deficiency Premedication with antihistamine and corticosteroid
103
Nerve fibers in conduction A-delta vs C-polymodal
A-delta = large, myelinated, localized pain C = small, unmyelinated, poorly localized pain Both use voltage gated sodium channels
104
Acute pain lasts how long?
<30 days >30 is chronic
105
Goal of Acute vs Chronic Pain?
Acute - treat it Chronic - functionality
106
Which drug was more lipophilic and had superior CNS penetration vs morphine?
Heroin
107
Morphine derivative opioids produce their analgesic effects through which receptor?
Agonism of mu-opioid receptors
108
Oxymorphone Nalbuphine Butorphanol Buprenorphine mu (+/-) kappa (+/-(
Oxymorphone; mu + Nalbuphine and butorphanol; mu - and kappa + Buprenorphine; partial mu +
109
Pharmacophore of general morphine derivatives?
4-Phenylpiperidine; 3 rings with a nitrogen
110
Oxymorphone Nalbuphine Naloxone Naltrexone Differences in R1 group?
Oxymorphone = 1C Nalbuphine = 5C Naloxone/Naltrexone = 3-4 C
111
Morphine + Codeine Differences in R2 group?
Codeine = Methoxy group Morphine = Hydroxyl group
112
What group is associated w/ histamine release in morphine derivatives?
C6-OH
113
What must be active to contribute to analgesic activity of codeine/morphine?
Morphine-6-glucuronide + O-demethylation
114
Oral bioavailability of codeine vs morphine is enhanced due to....
methyl esters
115
Hydromorphone/oxymorphone have (more/less) DDI vs morphine/codeine
Less cause CYP450 play less of a role
116
What kind of metabolizers are a concern with codeine?
UR CYP2D6 metabolizers, especially in poor renal function
117
For naloxne and naltrexone vs mu opioid receptor agonist, what do they replace the N methyl group with?
Allyl or cyclopropylmethyl groups
118
Special info on methylnaltrexone?
AKA relistor Quaternary amine and peripherally restricted Used in opioid induced constipation
119
Special info on Buprenorphine?
Even tho it has the cyclopropylmethyl group, its NOT a mu opioid antagonist, but rather an agonist lol 25-50x more potent than morphine
120
Kappa vs Mu agonists, what are some benefits?
Kappa agonists have less respiratory depression, constipation, potential for addiction However, sedation and dysphoria are the biggies
121
Fentanyl structure?
Non-morphne derivative Has a N-phenethyl group Increased lipophilicity, fast onset, short duration
122
Which analgesic is CI w/ MAOIs?
Meperidine
123
Normeperidine AE?
Neurological issues
124
Fentanyl DI?
Interacts w/ CYP3A4 inducers/inhibitors
125
Analgesic effects of methadone are due to (R/S) enantiomer
R
126
Methadone info on metabolites?
Metabolized in liver and produces 2 metabolites that inhibit CYP2C19
127
Which analgesic carries a risk of serotonin syndrome?
Tramadol
128
Which metabolite of Tramadol exerts the analgesic effect?
Both enantiomer and its metabolite do
129
All opioid receptors (mu, delta, and kappa) are ________ receptors
G-protein coupled
130
Match plz Dynorphins Endorphins Enkephalins Delta Kappa Mu
Kappa - Dynorphins Delta - Enkephalins Mu - Endorphins
131
When a G-protein coupled receptor is activated, what happens to Calcium and Potassium channels?
Inactivates Calcium and activates Potassium Inhibits adenylyl cyclase Activates phospholipase C
132
Delta Kappa Mu Which one produces respiratory depression?
Mu + Delta
133
Delta Kappa Mu Which one produces euphoria?
Mu + Delta
134
Delta Kappa Mu Which one produces constipation?
Mu + Kappa
135
Delta Kappa Mu Which one produces dysphoria?
Kappa
136
Delta Kappa Mu Which one produces pinpoint pupils?
Mu + Kappa
137
Delta Kappa Mu Which one produces constipation?
Mu + Kappa
138
Delta Kappa Mu Which one produces psychotomimetic effects?
Kappa
139
Analgesia emerges from what steps in the message to brain/spinal cord?
Blocks ascending message Inhibits pain fibers in dorsal horn
140
Opioids increase the pain threshold at the spinal cord by....?
Inhibit release of substance P, makes it harder to get message to second order neurons
141
Pain is better controlled (before/during/after) drug effects are gone
Give drug BEFORE last dose wears off
142
(Neuropathic/Nociceptive) pain is relieved better
Nociceptive Dull > Sharp
143
Delta Kappa Mu Which one produces a sense of tranquility and rewarding properities?
Mu + Delta
144
How are opioids linked to seizures?
Mu + Delta can inhibit GABA release, hyperpolarizes cell
145
What is the primary cause of morbidity related to opioid therapy?
Respiratory depression (use cautiously in asthma, COPD, other respiratory conditions)
146
Which analgesic have antitussive properties?
Morphine + codeine (depresses cough reflex) by affected the medulla
147
If you see pupils dilating (mydriasis) in analgesic therapy, whats going on?
Onset of asphyxia
148
Opioid agonists produce N/V by affecting what?
Chemoreceptor zone in area postrema
149
Absorption and Distribution of Morphine?
Slow GI; significant first pass Enters all tissues including fetuses
150
When is fentanyl indicated?
Breakthrough pain in cancer pt who are tolerant to opioids Chronic pain in opioid tolerant pt
151
Compared to morphine, how does methadone stack up in potency, euphoria, and duration?
Equipotent Less euphoria Longer duration
152
Additional MOA of methadone?
NMDA antagonist + SNRI
153
Which analgesic is more likely to produce delirium?
Meperidine; only used for short term acute pain
154
Which analgesic can lower seizure threshold?
Tramadol
155
Compared to morphine, how does tramadol affect respiratory suppression?
Less suppression vs morphine
156
Which analgesic is used for rapid detoxification?
Naltrexone
157
If you notice a pt is using their PRN meds for pain frequently, what should you do?
Switch to scheduled
158
IV OPIOID NAIVE pt If continuous infusion is desired, when can it be set?
After 4-8hrs
159
IV OPIOID NAIVE pt How do you calculate their dose?
Add up PRN dose in 24hrs and take 50% of it. 10-15% of total infusion can be PRN q2-3hrs Example: Morphine 2mg q2h = 24*0.5 = 12mg/24hrs + 12*0.1 = 1.2 or 1mg PRN for breakthrough pain
160
What is a reasonable regimen to decrease dose when tapering opioids?
10% reduction /week or month
161
How do you go from PRN to scheduled opioid use?
Take total amount / 24 hrs period and divide by their dosing interval + PRN dose (10%) Examples: 12mg / 24hrs, they take it every 4hrs 12/6doses = 2mg q4h + 12*0.1 = 1.2mg PRN
162
How do you calculate a continuous infusion for opioid use?
Take total dose in 24hrs and divide by 50% and then by 24hrs for hourly rate + 10% for PRN 0. 5mg q2h = 12*0.5 = 6/2 = 3mg/24 = 0.125mg/hr + 3*0.1 = 0.3mg PRN 0. 125mg/hr + 0.3 PRN
163
How do you calculate opioid dose for CHRONIC pain?
Start with short-acting PRN, then add long acting opioid (50-75% of PRN) Titrate PRN to be 10% of TDD
164
What are some nonpharmacologic Tx that are considered somewhat beneficial or have limited evidence?
Somewhat - spinal cord stimulation Limited - TENS and lumbar support
165
Which Rx is the first line for osteoarthritis pain?
APAP
166
What are the first line tx for neuropathic pain?
Amitriptyline Duloxetine Pregabalin Gabapentin + Tramadol for breakthrough pain PRN
167
Naturally occuring agents Semi-synthetic agents Synthetic agents Which one has the most/least histamine release?
Most - natural (morphine, codeine) Least - synthetic
168
Which opioid should NOT be used in children or if breastfeeding?
Codeine (mothers were UR metabolizers) BBW: respiratory depression and death in children following tonsillectomy in UR metabolizers
169
Fentanyl patch info?
NEVER for acute pain, do NOT titrate up for acute pain
170
Which opioid has interactions with MAOIs?
Fentanyl + Meperidine However less blood pressure effects of fentanyl vs other opioids
171
When checking for tolerance, how much do you reduce the dose by?
25-50%
172
Risk factors for Fibromyalgia?
Females FH Physical trauma, infections, stress, cold weather
173
Clinical presentation of fibromyalgia?
Pain all over the body + fatigue
174
Drug induced fibromyalgia caused by...?
Statins or aromatase inhibitors (anastrozole, letrozole)
175
How would you diagnose fibromyalgia?
Pain present for most of the day for at least 3 months that cant be attributed to another cause
176
What are the FDA indicated drugs and what should you just avoid?
Indicated - duloxetine, milnacipran, pregabalin AVOID - opioids No cure
177
Pregabalin AE?
Somnolence, wt gain, fatigue
178
If someone has fibromyalgia and has fatigue, what do you use? No fatigue, but has depression?
Fatigue, use pregabalin Depressed, use duloxetine

IPT: MS (3 decks)

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