Term
|
Definition
| Ketorolac, Diclofenac, Ibuprofen, Indomethacin, Nabumetone, Aspirin, Naproxen |
|
|
Term
|
Definition
|
|
Term
| NSAID toxicities based on body system |
|
Definition
-Central Nervous System
• Headaches
• Tinnitus
• Dizziness
-Cardiovascular
• Fluid retention, edema
• Hypertension
• Myocardial infarction (rare)
• Congestive heart failure (rare)
-Gastrointestinal
• Abdominal pain
• Dysplasia
• Nausea/vomiting
• Ulcers and/or bleeding
-Hematologic (rare)
• Thrombocytopenia
• Neutropenia
• Aplastic anemia
-Hepatic
• Abnormal liver function tests
• Liver failure (rare)
-Pulmonary
• Asthma
-Skin
• Rashes (all types)
• Pruritis
-Renal
• Renal insufficiency
• Renal failure
• Hyperkalemia
• Proteinuria |
|
|
Term
|
Definition
-Risk reduction of:
• Transient ischemic attacks
• Unstable angina
• Myocardial infarction
• Thrombosis post CABG (coronary artery bypass graft) and stent placement |
|
|
Term
|
Definition
• Osteoarthritis, rheumatoid arthritis
• Ankylosing spondylitis
• Migraine
• Analgesia |
|
|
Term
| has toxicities of • Liver function test abnormalities |
|
Definition
|
|
Term
|
Definition
• Osteoarthritis, rheumatoid arthritis
• Analgesia
• Pericarditis |
|
|
Term
Has toxicities of:
• Rare
• Aseptic meningitis
• Agranulocytosis
• Aplastic anemia |
|
Definition
|
|
Term
|
Definition
• Potential inhibition of:
• Phospholipase A/C
• Decreased neutrophil migration
• Decreased T/B cell proliferation |
|
|
Term
|
Definition
• Inflammatory/rheumatoid disorders
• Closure of patent ductus arteriosus • Acute gouty arthritis
• Many off-label trials |
|
|
Term
Has toxicities:
• Pancreatitis
• Headache (15–25%)
• Dizziness, confusion, depression
• Renal papillary necrosis |
|
Definition
|
|
Term
|
Definition
|
|
Term
Has toxicities:
• Headache
• Injection site pain
• GI bleeding (>5 days of therapy)
• Renal function abnormality
-maximum duration in therapy is 5 days |
|
Definition
|
|
Term
|
Definition
|
|
Term
Has Toxicities:
rare:
• Pseudoporphyria
• Photosensitivity |
|
Definition
|
|
Term
|
Definition
• Osteoarthritis, rheumatoid arthritis
• Analgesia
• Acute gouty flare
• Migraine
• Ankylosing spondylitis |
|
|
Term
Has toxicities:
• Upper GI bleeding
- Rare:
• Allergic pneumonitis
• Leukocytoclastic vasculitis
• Pseudoporphyria |
|
Definition
|
|
Term
|
Definition
• Osteoarthritis
• Rheumatoid arthritis
• Acute pain
• Ankylosing spondylitis |
|
|
Term
has side effects/toxicities:
• Associated with fewer ulcers
• Does not inhibit platelet aggregation
• Toxicities - Rash |
|
Definition
| Celecoxib (COX-2 selective) |
|
|
Term
| Indications for Meloxicam |
|
Definition
Osteoarthritis, rheumatoid arthritis
• Note: preferential selection for COX-2 vs. COX-1 |
|
|
Term
|
Definition
• Weak COX-1 and COX-2 inhibitors
• Block prostaglandin synthesis in the CNS
• No significant anti-inflammatory effects
• Major metabolites
- Nontoxic sulfate and glucoronide
- Reactive: N-acetyl-p-benzoquinone |
|
|
Term
Has Toxicities:
Therapeutic doses
• Mild hepatic enzyme elevations
Larger doses
• Dizziness
• Excitement
• Disorientation
>15grams
• Severe hepatotoxicity
• Acute renal tubular necrosis
• Death |
|
Definition
|
|
Term
| APAP/Acetaminophen: Toxicity Timeline |
|
Definition
Stage 1 (Days 0–1)
N/V
Abdominal pain
Sweating
General discomfort
Pale color
Stage 2 (Days 1– 3)
Liver injury develops
Upper right quadrant pain
Rise in LFTs
Stage 3 (Days 3– 5)
Hepatotoxicity peak
Rapid/severe liver failure
Glucose, lactate, phosphate abnormalities
Coma and death |
|
|
Term
| Considerations for choosing an NSAID |
|
Definition
• Similar efficacy
• Key considerations
• Toxicities
- Indomethacin, ketorolac, diclofenac
- Celecoxib, meloxicam
• Cost-effectiveness |
|
|
Term
|
Definition
• Progressive immunologic disease
• Outcomes
-Systemic effects (joint)
- Shortens lifespan
- Reduces mobility and quality of life |
|
|
Term
| Treatment for Rheumatoid arthritis |
|
Definition
|
|
Term
| Rheumatoid arthritis MOA diagram |
|
Definition
[image]
In rheumatoid arthritis, we have a pretty complicated system occurring. So first, we have some type of antigen, hypothesized, maybe a microbe. It's going to be going and attaching to the CD4 T cell. That CD4 T cell will go on to have B cell activation, macrophage activation, as well as activation of the endothelial lining. Ultimately, a series of cascading events will occur with cytokine activation, formation of auto-antibodies. Ultimately, bottom line, we're going to have pannus formation in the joints. We're going to have destruction of the bone occurring at that joint, as well as cartilage, fibrosis, as well as ankylosis occurring.
We want to prevent that from occurring. This is where our DMARDs come in, the first being methotrexate. By far, it's probably the first agent that will be prescribed by rheumatologists for the management of rheumatoid arthritis. |
|
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Term
|
Definition
AICAR inhibits intracellular AMP deaminase ->
Increased AMP levels ->
AMP exits cell -> adenosine ->
Adenosine = inhibits inflammation
• Secondary effects on PMN chemotaxis
• Immune-inflammatory cells
- Inhibitory effects on proliferation - Increased apoptosis
• Inhibits proinflammatory cytokines |
|
|
Term
| Methotrexate: Indications |
|
Definition
• Rheumatoid arthritis
• Juvenile chronic arthritis • Psoriasis
• PA
• AS
• Polymyositis
• SLE |
|
|
Term
Has toxicities:
- Hematologic
• Anemia • Leukopenia
- Gastrointestinal
• Nausea • Mucosal ulcers • GI ulcerations • Stomatitis
- Hepatic
• Elevated liver function tests • Cirrhosis (rare)
- Pulmonary
• Hypersensitivity-like reaction |
|
Definition
|
|
Term
|
Definition
| Methotrexate, Azathioprine (a wrath of pine), Cyclosporine, Leflunomide (Left in time), Sulfasalazine, Tofacitinib (Total kit of bibs) |
|
|
Term
|
Definition
• Major metabolite = 6-thioguanine
• 6-thioguanine suppresses:
- Inosinic acid synthesis
- B-/T-cell function
- Immunoglobulin production
-IL-2 secretion |
|
|
Term
| Azathioprine: Indications |
|
Definition
• Rheumatoid arthritis
• Prevention of organ transplant rejection
• PA
• Reactive arthritis
• Polymyositis
• SLE |
|
|
Term
Has toxicities:
- Bone marrow suppression
- GI disturbances
- Rare
• Acute allergic reactions with: • Fever • Rash • Hepatoxicity |
|
Definition
|
|
Term
|
Definition
• Inhibits IL-1 and IL-2 receptor production
• Secondarily inhibits:
- Macrophage-T-cell interaction - T-cell responsiveness
• Impairs T-cell-dependent B-cell function |
|
|
Term
| Cyclosporine: Indications |
|
Definition
• Rheumatoid arthritis
• SLE
• Polymyositis
• Juvenile chronic arthritis • Solid organ transplant |
|
|
Term
Has Toxicities:
• Hematologic
- Leukopenia - Thrombocytopenia - Anemia
• Cardiotoxic
• Infertility |
|
Definition
|
|
Term
|
Definition
• Active metabolite: A77-1726
• Inhibits: dihydroorotate dehydrogenase •-Decreased ribonucleotide synthesis - Arrests cell growth in stimulated cells
• Inhibits T-cell proliferation
• Decreases production of autoantibodies by B-cells
- Secondary effects:
• Increases in IL-10 receptor mRNA
• Decreased IL-8 receptor type A mRNA
• Decreased TNF-alpha dependent nuclear factor kappa B activation |
|
|
Term
|
Definition
|
|
Term
Has Toxicities:
• Diarrhea
• Elevated LFTs
• Mild alopecia
• Weight gain
• Increased blood pressure
• Leukopenia, thrombocytopenia
• Contraindications: pregnancy |
|
Definition
|
|
Term
|
Definition
• Active agent: sulfapyridine
• Suppresses T-cell response to concanavalin
• In-vitro studies show inhibition of:
- B-cell proliferation
- Inflammatory cytokine release from monocytes and macrophages |
|
|
Term
| Sulfasalazine: Indications |
|
Definition
• Rheumatoid arthritis
• Juvenile chronic arthritis
• Psoriatic arthritis
• IBD |
|
|
Term
Has Toxicities:
• Nausea/vomiting • Headache
• Rash
• Rare
- Hemolytic anema
- Methemoglobinemia
- Neutropenia
- Thrombocytopenia |
|
Definition
|
|
Term
|
Definition
Inhibits Janus kinase (JAK) enzymes
- JAK stimulates: • Hematopoiesis • Immune cell function
- Reduced cytokine or growth factor mediated gene expression
- Reduced intracellular immune cell activity
• Includes: CD15/56+, NK cells, serum IgG, IgM, IgA, CRP |
|
|
Term
|
Definition
• Rheumatoid arthritis
• IBD
• Spondyloarthritis • Psoriasis
• Dry eyes |
|
|
Term
Has toxicities:
• Increased infection risk
• Malignancy
- Lymphoma, lung, breast cancer
• Lipid panel changes
• Neutropenia, anemia |
|
Definition
|
|
Term
|
Definition
T-cell modulation, B-cell cytotoxic, Anti-IL-6 Receptor Antibody, IL-1 Inhibition, TNF-a Blockade
Generally, there's five different categories of biologic DMARDs. And what are biologic DMARDs compared to non-biologic? Well, generally, these medications are large protein molecules that are often produced by recombinant DNA technology. |
|
|
Term
|
Definition
[image]
T-cell modulator
The first medication class is the T-cell modulators. Here the medication is Abatacept. It's a pretty unique mechanism of action. So here we have an antigen presenting cell in the bottom left-hand corner.
It has a major histocompatibility receptor in its cell surface, as well as CD80/86 receptor. In the upper right-hand corner, we have the T-cell. It has a T-cell receptor as well as a CD28 receptor.
When these two cells combine, well, the overall result is activation, proliferation, and production of inflammatory mediators. We do not want this to occur in our rheumatoid arthritis patients. So this is where Abatacept comes in.
Abatacept will bind with CD80/86 receptor. What happens here is blockade of this activation, proliferation, and production of inflammatory mediators, just exactly what we wanted. We don't want that T-cell to be activated. |
|
|
Term
|
Definition
• Rheumatoid arthritis
• PJIA
• Psoriatic arthritis |
|
|
Term
|
Definition
• Increased risk of infection
• Infusion related reactions
• Hypersensitivity reactions
• Increased lymphoma risk |
|
|
Term
|
Definition
B-cell cytotoxic
Targets CD20 B lymphocytes ->
1. Cell-mediated/complement mediated cytoxicity
2. Stimulation of cell apoptosis ->
Reduced inflammation |
|
|
Term
|
Definition
• Rheumatoid arthritis (moderate-severe)
• Granulomatosis with polyangitis
• Vasculitis |
|
|
Term
|
Definition
• Rash
• Increased risk of infection
• Hepatitis B reactivation
• Hematologic - Cytopenias |
|
|
Term
|
Definition
Anti-IL-6 Receptor Antibody
• Binds to soluble/membrane bound IL-6 receptors
• IL-6 = proinflammatory cytokine
- Physiologic processes: • T-cell activation • Hepatic acute-phase protein synthesis • Stimulation of inflammatory processes |
|
|
Term
|
Definition
• Rheumatoid arthritis
• SJIA (Systemic juvenile idiopathic arthritis)
• PJIA (Polyarticular juvenile idiopathic arthritis ) |
|
|
Term
Has Toxicities:
• Increased risk of serious infections
• Hematologic - Neutropenia, thrombocytopenia
• Lipid panel abnormalities
• Common - Headache - Hypertension - Elevated LFTs |
|
Definition
|
|
Term
| Interleukin-1 Inhibition Biologic DMARDs |
|
Definition
| Interleukin-1 is very interesting. So it was one of the first biologic DMARDs. However, it really doesn't have a clinical role anymore in the management of rheumatoid arthritis. But historically, I felt it was necessary to include in our talk of biologic DMARDs. |
|
|
Term
|
Definition
TNF-a Blockade (biggest group)
• Fully humanized IgG anti-TNF monoclonal antibody
- Prevents TNF interaction with p55 and p75 cell receptors
• End Result
- Downregulation of macrophage and T-cell
function |
|
|
Term
|
Definition
• Rheumatoid arthritis
• Plaque psoriasis
• Ulcerative colitis
• Crohn disease
• Ankylosing spondylitis |
|
|
Term
|
Definition
TNF-a Blockade (biggest group)
• Recombinant fusion protein comprised of:
- Two soluble TNF p75 receptor moieties
- Fc portion of human IgG
• Binds to TNF-α and inhibits lymphotoxin α |
|
|
Term
|
Definition
• Rheumatoid arthritis
• Plaque psoriasis
• Ankylosing spondylitis
• Psoriatic arthritis |
|
|
Term
|
Definition
TNF-a Blockade (biggest group)
• Chimeric IgG1 monoclonal antibody:
- Binds with high affinity to TNF-α
- Prevents TNF interaction with p55 and p75 cell receptors |
|
|
Term
|
Definition
• Rheumatoid arthritis
• Crohn disease
• Plaque psoriasis
• Psoriatic arthritis
• Ulcerative colitis |
|
|
Term
Has Toxicities:
• Bacterial infections
• Activation of latent TB
• Reactivation of HBV
• Increased risk of skin cancer • SLE
• Antidrug antibodies
• Injection site reactions
• GI ulcers, bowel perforation |
|
Definition
| TNF-α Blockers (Adalimumab- a day of mobs, Etanercept- etan intercept, Infliximab- inflict a mob) |
|
|
Term
|
Definition
• Metabolic disease characterized by:
- Acute arthritis in joints and cartilage • Due to monosodium urate deposits
• Usually associated with ↑ serum uric acid levels |
|
|
Term
|
Definition
[image]
Taking a closer look at the pathophysiology of gout, you'll see that we have the synovial site. It's absorbing those urate crystals. This is going to result in an inflammatory response where we'll have prostaglandin release, and it will affect our neutrophil cells.
Then we'll also have formation of interleukin-1. And you'll see the MNP cell at the bottom. That's a macrophage. That's going to become activated. It's going to result in inflammation and pain at that specific affected joint.
So looking here at this diagram, you can see there's potentially areas where we can have interventions to reduce that inflammation. We could use colchicine to block neutrophils. We can potentially use indomethacin, which is a nonselective NSAID, to also reduce that inflammation as well, to provide some acute pain relief in our patients that are suffering with gout. |
|
|
Term
|
Definition
1. Treat the acute gout attack
2. Prevent future attacks
3. Hypouricemic therapy |
|
|
Term
|
Definition
Binds to intracellular tubulin in neutrophils ->
Prevents polymerization into microtubules ->
Inhibits activation, degranulation, migration, and phagocytosis ->
Reduced inflammation |
|
|
Term
|
Definition
• Gout
• Flare treatment: 1.2 mg once followed by 0.6 mg one hour later
• Prophylaxis: 0.6 mg daily, twice daily • Maximum 1.2 mg/day
• Familial Mediterranean fever(FMF)
• Pericarditis(off-label)
• Postpericariotomy syndrome(off-label) |
|
|
Term
Has Toxicities:
- Gastrointestinal
• Diarrhea, nausea, vomiting, abdominal pain
- Rare
• Hematologic
• Hepatic necrosis
• Acute renal failure • Peripheral neuritis • Myopathy |
|
Definition
|
|
Term
|
Definition
• Inhibits reabsorption of uric acid in the proximal renal tubule
• Increased excretion of uric acid
• Reduced urate pool
- Reabsorption of tophaceous deposits |
|
|
Term
|
Definition
• Gout (under excretion of uric acid)
• Prolong penicillin serum levels |
|
|
Term
Has Toxicities:
• Acute gouty flare
• GI irritation
• Hematologic - Anemias - Leukopenia
• Rash
• Nephrotic syndrome • Hepatic necrosis |
|
Definition
|
|
Term
|
Definition
[image]
Allopurinol is a very popular option in the management of gout. So first off, we have allopurinol being metabolized by xanthine oxidase into alloxanthine. Then further below you'll see hypoxanthine being converted by xanthine oxidase to xanthine, which then gets further metabolized into uric acid. Well, allopurinol will come in and will block this final step of xanthine oxidase converting xanthine into uric acid. And again, alloxanthine, that's going to be the metabolite of allopurinol and the active agent that's ultimately blocking that uric acid formation. |
|
|
Term
|
Definition
• Chronic gout
• Cancer-induced hyperuricemia |
|
|
Term
Has Toxicities:
• Acute gouty flare
• GI intolerance
• Hypersensitivity reaction -Drug rash
• Hepatic toxicity
• Interstitial nephritis |
|
Definition
|
|
Term
|
Definition
• Inhibits prostaglandin synthase
• Inhibits urate crystal phagocytosis |
|
|
Term
| Indomethacin: Indications |
|
Definition
• Gout
• Inflammatory/rheumatoid disorders
• Bursitis/tendonitis of the shoulder
• Acute pain |
|
|
Term
Has Toxicities:
• Standard NSAIDs toxicities
• Pancreatitis
• Headache (15–25%)
• Dizziness, confusion, depression
• Renal papillary necrosis |
|
Definition
|
|
