Non-Opioid Analgesics + Rheumatoid Arthritis and Gout Flashcards
1
Q
Non-Pharmacological Treatments for Gout + RA
A
Dietary Modifications
- reduce purine rich foods (deer meat)
- weight management
PT
Compresses
2
Q
What does the inflammatory process start with?
A
Soluble and Surface Active Mediators
(Prostaglandins + Leukotrienes)
3
Q
A fatty acid located in cell membrane phospholipids
A
Arachidonic Acid
4
Q
Arachidonic Acid is released when the cell is activated or damaged via what enzyme?
A
Phospholipase A2
5
Q
What is derived from Arachidonic Acid?
A
Prostaglandins + Leukotrienes
6
Q
From lipoxygenase pathway
Active in Monocytes, Mast Cells, and Granulocytes
Involved in Allergic Reactions + Asthma
A
Leukotrienes
7
Q
From cyclooxygenase pathway
TXA₂ is released from platelets with injury
PGI₂ is produced by endothelial Tissue
Net effect depends on the balance of TXA₂ and PGI₂
A
Prostanoids
8
Q
Regulates normal cellular processes.
- Gastric Mucus Production
- Vascular Homestasis
- Platelet Aggregation
- Reproduction
- Kidney Function
A
COX-1 Enzyme
9
Q
Present in the brain, kidney, and bone.
Induced at site of chronic disease and inflammation.
A
COX-2 Enzyme
10
Q
Work by inhibiting cyclooxygenase (COX) enzymes (COX-1 + COX-2), which are involved in the production of prostaglandins that mediate pain and inflammation.
A
NSAIDs
11
Q
Name some Non-Selective NSAIDs
A
Aspirin
Bismuth-Subsalicylate (Pepto-Bismol)
Salicylic Acid
12
Q
Name a COX-2 Selective NSAID
A
Celecoxib (Celebrex)
13
Q
What are some other NSAIDs that we discussed?
A
Ibuprofen (Advil or Motrin)
Naproxen (Aleve)
Diclofenac (Voltaren)
Indomethacin
Meloxicam (Mobic)
Ketorolac (Toridol)
14
Q
Name two Non-selective NSAIDs that are PROPIONIC ACID derivates and are OTC.
A
Ibuprofen
Naproxen
15
Q
Name two Non-selective NSAIDs that are PROPIONIC ACID derivatives and require a prescription.
A
Ketoprofen
Oxaprozin
(Long-half life, once daily dosing)
16
Q
Which NSAID is used to close a PDA?
A
Ibuprofen
Indomethacin
17
Q
What is Indomethacin derived from?
A
Acetic Acid
18
Q
What is the first line medication for an Acute Gout flare?
A
Indomethacin
19
Q
What are the adverse effects of Indomethacin?
A
Highly Toxic
- (adverse effects in 1/3 of patients)
Pancreatitis
Headache
Dizziness
Confusion
Hallucinations
20
Q
What medication preferentially inhibits COX-2 but is not as selective as Celecoxib.
It also has less GI effects than Piroxicam at low doses
A
Meloxicam
- long half life, once daily
21
Q
What are the two strongest NSAIDs that have a comparable potency to opioids?
Derived from Heteroaryl Acetic Acids.
A
Diclofenac
Ketorolac
22
Q
What NSAID is great for Kidney Stones?
A
Ketorolac
- up to 5 days PO outpatient
23
Q
What is the Onset and Duration of Ketorolac?
A
Onset → 10 - 30 minutes
Duration → 6 - 8 hours
24
Q
Ketorolac (PO) Outpatient for 5 days has what adverse risks?
A
Nephrotoxicity
GI Bleed
PUD
25
Before prescribing Ketorolac or Diclofenac, what should you obtain?
Baseline Creatinine
- monitor with severe renal disease
26
What might Diclofenac increase?
LFTs
- check at baseline and monitor
27
Selective and Reversible inhibition of COX-2
Celecoxib (Celebrex)
28
What is Celecoxib good for?
Trauma
- doesn't affect platelets
Long-term treatment of RA + OA
29
Adverse Drug Reactions of Celecoxib
Same black box warning as NSAIDs
Increased risk of MI + Stroke
May interfere with Aspirin's anti-platelet effects
Pregnancy Category C → 1st and 2nd Trimester
Pregnancy Category D → 3rd Trimester
30
What toxicities can be caused by NSAIDs?
GI
- Good Absorption → CYP2C9
- Protect with PPI or H2 Blockers
Renal
- Dose adjustments needed
- AKI
- Nephrotic Syndrome (Proteinuria)
- Hyperkalemia
Cardiovascular
Hepatic
31
Non-Selective
Irreversible inhibition of COX
→ COX 1 > COX-2
Aspirin
- Acetylsalicylic Acid
32
What are the primary clinical uses of Aspirin?
Anti-platelet
- irreversibly binds TXA₂
- effects last 8 days
- reduces risk of Stroke and TIA
Myocardial Infarction
33
What GI symptoms might Aspirin cause?
Discomfort
Bleeding
PUD
Take with Food or use Enteric Coated
34
What medication may still be used to treat GI symptoms caused by Aspirin?
A prostaglandin that inhibits gastric acid secretion.
Cytotec (Misoprostol)
- Pregnancy Category X
- Used for Medical Abortions
35
How soon before surgery should you advise a patient to stop Aspirin?
1 Week
36
5-10% of patients with what pathology develop an Aspirin sensitivity?
Asthmatics
37
Hepatitis with cerebral edema that is often fatal.
Increased incidence when given Aspirin during a viral illness to people less than 16 years old.
Reye's Syndrome
38
What 3 medications can Aspirin displace?
Warfarin
Phenytoin
Valproic Acid
39
How can Aspirin increase symptoms of Gout?
ASA decreases renal uric acid clearance
40
What Pregnancy Category does ASA fall under?
1st and 2nd Trimester → C
3rd Trimester → D
41
What are the signs and symptoms of mild salicylism (ASA toxicity)?
How do you treat it?
Nausea
Vomiting
Tinnitus
Activated Charcoal within 1 hour
Hospitalization + Supportive Care
42
What are the signs and symptoms of moderate to severe ASA overdose?
How do you treat it?
Metabolic Acidosis
Respiratory Alkalosis
Activated Charcoal + Sodium Bicarb
- possible emergency dialysis
ICU + Supportive Care
43
Anti-inflammatory + Antacid
Used for:
- Nausea
- Heartburn
- Indigestion
- Upset Stomach
Part of H. Pylori quadruple therapy
Bismuth-Subsalicylate (Pepto-Bismol)
44
Common side effect of Pepsi-Bismol
Dark Stools
45
What Cardiovascular side effect may occur due to the use of NSAIDs?
Hypertension
- due to fluid retention
46
Most NSAIDs are what Pregnancy Category during the 1st and 2nd Trimesters?
C
47
Most NSAIDs are what Pregnancy Category during the 3rd Trimester?
D
- overall recommended to avoid
48
Which NSAID is least likely to cause GI Symptoms?
Ibuprofen
49
Which NSAID is most likely to cause GI Symptoms?
Ketorolac
50
Which NSAID is most likely to cause Cardiovascular Risks?
Naproxen
51
Which NSAIDs are least likely to cause Cardiovascular Risks?
COX-2 Selective NSAIDs
- Celecoxib
- Meloxicam
- Diclofenac
52
Inhibits COX enzymes in the brain, reducing prostaglandin production.
Acetaminophen
53
Effects of Tylenol
Analgesic
Antipyretic
No Anti-Inflammatory
No Anti-platelet
54
Where is Acetaminophen Metabolized and Excreted?
Metabolized → Liver
Excreted → Kidney
55
Which medication is the drug of choice for children with a viral illness?
Tylenol
56
What is an advantage of Tylenol over NSAIDs?
Less GI irritation
57
What is a disadvantage of Tylenol?
Liver Toxicity (NAPQI)
(N-acetyl-p-benzoquinone imine)
58
What converts Tylenol into the NAPQI in the liver?
CYP2E1
59
What is the daily max dose of Tylenol?
4 grams per day
60
How do you treat a Tylenol (NAPQI) Overdose?
N-acetylcysteine (NAC) or Mucomist
- replenishes Glutathione
- neutralizes NAPQI
61
DMARDs for RA
Methotrexate
Sulfasalazine
Leflunomide
Hydroxychloroquine
62
Biologic Agents for RA
TNF-Alpha Inhibitors
- Etanercept
- Infliximab
- Adalimumab
T-Cell Activation Inhibitor
- Abatacept
63
Glucocorticoids for RA
Prednisolone
Prednisone
Methylprednisolone
Dexamethasone
64
NSAIDs for RA
Ibuprofen
Naproxen
Ketoprofen
Piroxicam
Diclofenac
65
Medications that prevent and slow disease progression of Rheumatoid Arthritis and subsequent joint destruction + loss of function.
DMARDs
66
How long does the Therapeutic Effect of DMARDs take?
2 week - 6 months
67
What Rheumatoid Arthritis medication is considered safest in pregnancy?
CORTICOSTEROIDS
Sulfasalazine + Hydroxychloriquine are sometimes used.
68
Folic acid antagonist that is the primary drug of choice for RA
Methotrexate
69
How is Methotrexate dosed?
NEVER DOSED DAILY
Weekly dose
- 7.5 to 22.5mg
70
Adverse Drug Reactions of Methotrexate
Teratogenicity
- Men + Women must wait 3 months after to conceive or donate blood
Pregnancy Category X
71
What types of tests should be performed on patients before starting Methotrexate?
Hepatitis B + C
- Hepatotoxic
72
Other Adverse Effects of Methotrexate
Bone Marrow Suppression
Immunosuppression
- cannot give live vaccines
Interstitial Pneumonitis or Pulmonary Fibrosis
73
What labs should be regularly monitored while on Methotrexate?
LFTs
CBC
Renal Function
Folinic Acid
- may need supplementation
74
Aminosalicylate anti-inflammatory COX inhibitor - contains 5-aminosalicylic acid (5-ASA)
1st line for mild, moderate, and severe RA
Sulfasalazine
- 1 to 3 months for therapeutic effect
75
Adverse Drug Reactions of Sulfasalazine
Skin Rash
Arthralgia + Myalgia
Bone Marrow Suppression
76
Who is Sulfasalazine contraindicated for?
ASA + Sulfa Allergies
Pregnancy Category B
- use only if benefit outweighs risk
77
Sulfasalazine interferes with the absorption of what?
Folate
- can supplement with daily folic acid
78
Medication that inhibits pyrimidine synthesis.
Also inhabits T-Cell proliferation and B-Cell production of antibodies.
1st line for mild, moderate, and severe RA
Leflunomide
- Therapeutic effects in 4-6 weeks
79
Adverse Drug Reactions of Leflunomide
Nausea + Diarrhea
Headache
Alopecia
HTN
Hepatotoxicity
- get Hep. B + C test prior
80
What pregnancy category is Leflunomide?
Category X
MUST have (-) pregnancy test before starting AND use 2 forms of birth control while taking
Must have undetectable drug levels on two separate occasions >14 days apart to advise getting pregnant
81
What medication can be used to enhance rapid drug elimination of Leflunomide?
Cholestyramine
82
Secondary RA medication. Used for Mild cases.
May inhibit lymphocyte function and neutrophil involvement (chemotaxis)
Hydroxychloroquine
- Therapeutic in 3 to 6 months
83
Adverse Drug Reactions of Hydroxychloroquine
Ocular Toxicity
Steven Johnson Syndrome
Pregnancy Category C
- use only if risk outweigh benefits
84
RA medications that can be given as an adjunct to Methotrexate if the disease is severe with poor prognostic factors.
Biologic Agents
- Etanercept
- Infliximab
- Adalimumab
85
Adverse Drug Reactions of Biologic Agents
SERIOUS INFECTION + MALIGNANCY
Immunosuppression
- cannot administer live vaccines
Tuberculosis
- evaluate risk and test for disease annually
86
Other Adverse Reactions of Biologic Agents
Infusion Reaction
Heart Failure
Hepatoxicity
87
What should be monitored when using Methotrexate (Starred Slide)
LFTs
CBC
Serum Creatinine
88
What should be monitored when taking Biologics (Starred Slide)
Infections
CBC
LFTs
Renal Function
89
What should be monitored when taking Hydroxychloroquine (Starred Slide)
Ocular Toxicity
- eye exams
90
Adverse Drug Reactions of Methotrexate (Starred Slide)
Liver Toxicity
Bone Marrow Suppression
91
Adverse Drug Reactions of Biologics (Starred Slide)
Infections + Malignancy
92
Adverse Drug Reactions of Hydroxychloroquine (Starred Slide)
Ocular Toxicity
93
Disorder of uric acid metabolism that can lead to monosodium urate crystal deposition in soft tissue
Gout
94
What joint is most commonly involved with Gout?
MTP Joint of 1st Toe
- Podagra
95
Risk Factors for Gout
Genetic
Dietary
- High purine + alcohol
Medications
- thiazides, ASA, Niacin
96
How do you treat an Acute Gout Attack?
Indomethacin
Colchicine
Corticosteroids
97
What medications are used to manage Chronic Gout?
Allopurinol
Febuxostat
Probenecid
98
What is the drug of choice for Acute Gout?
Indomethacin
99
What NSAID should not be used to treat Gout?
ASA
- decreases uric acid excretion
100
Gout medication.
Inhibits leukocyte migration and phagocytosis
Blocks their ability to inflame the joint and RELIEVES PAIN + INFLAMMATION
No direct analgesic effects
Colchicine
101
What is Colchicine a Substrate of?
CYP3A4 + PGP
- strong inhibitors can lead to Colchicine toxicity
- Amiodarone + Clarithromycin
- reduce the dose of Colchicine if used in combo
102
What are the indications for Colchicine?
Used if NSAIDs are Contraindicated
2ⁿᵈ line due to narrow Therapeutic Index
103
What is the dose for Colchicine?
Initial = 1.2mg + 0.6mg after 1 hr
104
Adverse Drug Reactions of Colchicine
Nausea + Vomiting + Diarrhea
- precedes pain relief
Caution in Hepatic and Renal Impairment
105
What is a rare side effect of Colchicine?
Blood Dyscrasias
106
How do you diagnose Gout?
Joint Aspiration
- Monosodium Urate Crystals
107
3rd Line Agent for Acute Gout
- used if NSAIDs and Colchicine are contraindicated
Corticosteroids
108
When should you avoid Corticosteroids?
If you haven't ruled out Septic Joint
109
Gout medication that inhibits xanthine oxidase and reduces uric acid production
Allopurinol
110
Gout medication that is a non-purine xanthine inhibitor
Febuxostat
111
Gout medication that increases renal excretion of uric acid
Probenecid
112
When do you start Allopurinol?
2 - 3 or more attacks per year with continued elevated uric acid levels
Not anti-inflammatory
Not effective in acute attacks
113
Adverse Drug Reactions of Allopurinol
GOUT FLARE RISK
Cataracts
114
Which Chronic Gout medication can be administered to patients with renal insufficiency without dose adjustments.
Febuxostat
115
Chronic Gout medication that decreases uric acid reabsorption
Probenecid
116
Probenecid predisposes patients to what?
Kidney Stones
(Also inhibits excretion of Penicillins)
117
What medication can decrease the effectiveness of Probenecid?
Aspirin
118
Adverse Drug Reactions of Probenecid?
Gout Flare
Nephrolithiasis
- must drink 2L of fluid per day
119
Pregnancy Category for:
- NSAIDs
- Acetaminophen
- Methotrexate
- Colchicine
- Biologics
NSAIDs
- Category B (1st and 2nd Trimester)
- Category C (Celebrex)
Acetaminophen
- Category B
Methotrexate
- Category X
Colchicine
- Category C
Biologics
- Category B or C
