NSAID/ DMARD _Mayanil pt 2 e3

What is the mechanism of action for a NSAIDS

Competitive inhibition of Cox enzymes
Inhibition of PG synthesis

True or false: NSAIDS work on the receptor

False NSAIDS Target an enzyme

What are the downstream effects of the use ofNSAIDS

Inhibits release of PG
Inhibits expression or activity of CAM (cell adhesion molecules)
Inhibits activation and function of leukocytes
Free radicals scavenger

Describe the action of NSAIDs On the vascular system, what is the result of this, what are the cautions

Reverse vasodilation of inflammation, in his platelet aggregation
Irritate G.I., Nephrotic and Hepato toxic

True or false: NSAIDS Are highly protein-bound and highly metabolized in the liver via CYP3A, CYP2C

True �> renal excretion depending on enterohepatic circulation

What are the therapeutic actionsNSAIDS

Antipyretic, Analgesic, anti-inflammatory,

NSAIDS have Also been used for a classic conditions like

Closure of ductus arteriosus, relieve dysmenorrhea, relieve niacin induce flushing

What are the common shared adverse effects of nonsteroidal anti-inflammatory drugs

CNS: headache, tinnitus, Dizziness
CV: fluid retention, Adema, hypertension, rarely heart failure
G.I.: abdominal pain, NV, Ulcers, bleeding
Hematologic: thrombocytopenia, Neutropenia, aplastic anemia,
Hepatic: rarely liver failure
Pulmonary: asthma
Skin:

Between Cox one Cox two in nonsteroidal anti-inflammatory drugs, which has the highest level of G.I. ulcers and Bleeding risk

NSAIDS: Inhibits production of G.I. protective PG

What are the wrist factors of G.I. Ulcers with pharmacological use of NSAIDS

Higher doses
Long treatment
History of ulcer or G.I. complications
Increasing age
Contaminant anticoagulant or corticosteroid use this includes Aspirin

It is common to give a G.I. protective agent like what with long-term treatment of NSAID

Misoprostal or PPI

Regarding altered platelet functions, which Cox receptor Is the only iso form expressing platelets, what is the result

TXA2, Stimulates platelet aggregation, consider to be prothrombic (COX1)

Regarding alter platelet function, which Cox receptor is predominantly the ice form in the endothelial, what is the result

COX2, PGI2 Inhibits platelet activation, considered anti-thrombic
Different from Cox to selective inhibitor: this inhibits PGI I2 Synthesis potentially making pro thrombic

Traditional nonsteroidal anti-inflammatory drugs inhibit the production of both ___ and ____ ,This keeps the balance of platelet function

TXA2 and PGI2

With altered renal function, result in decreased renal blood flow and GFR in patients with renal injury. NSAID can make this worse, reducing the effectiveness of anti-hypertensive agents because....

It promotes salt and water retention, Adema, In further because Reno injury

____ Ardmore peripheral acting, whereas ____ Is more central acting

NSAID - Peripheral
Opioids - Central

Opioids and nonsteroidal anti-inflammatory drugs target different receptors , what are they

Opioids target GPCr and NSAID target Cox

What does aspirin irreversibly inhibit, how does it do this, What is its affect

Irreversibly inhibits Cox enzymes, covalently acetylatesenzymes
If sexless for life with patient, increases bleeding time

Why should Aspirin be used with caution with children?

REYE Syndrome. Associated with viral infection in children with the use of a essay
Symptoms include mental status changes increase liver enzymes in hypoglycemia

True or false: when taking low-dose aspirin, the aceytlation and platelets occurs before first pass metabolism Causing a cumulative affect on platelets

True, complete inhibition platelet TXA2 Production, has increased risk of bleeding

What is the most selective inhibitor of Cox2, Has less G.I. effects, use for patients allergic to celecoxib and or sulfonamides

Etodolac

Drug: potent analgesic used for a cute parenteral used as opioid alternatives

KetoRolac

Diclofenac can be used in combination with which to Agents, however may have a greater CV risk

Misoprostal (PGE1)
Omeprazole (PPI)

What drug is considered a selective Cox2 Inhibitor, with fewer G.I. adverse reactions than traditional nonselective agents.
This drug has no effect on platelets

Celecoxib

How is celecoxib metabolized

CYP2C9
Caution_ sulfonamide group watch out for allergy

What agent is not considered a nonsteroidal anti-inflammatory drug, however has a Analgesic and Antipyretic activity.

Acetaminophen, paracetamol, Tylenol

Mechanism of action: weak inhibitior of COX inflammation
Inhibition of COS in CNS for antipyretic effect
Some central serotonin analgesic pathways

Acetaminophen

Which agent has no effect on CV, respiratory, acid base, G.I. irritation, platelets or bleeding, or neutrophil activation

Acetaminophen

What are the adverse effects of acetaminophen

Skin rash fever , mucosal lesion

Acetaminophen has a Black Box Warning of what, what can increased risk?
Who should be cautious when taking acetaminophen

Black Box Warning of fetal hepatic necrosis
Risk increases with alcohol consumption
Caution with use of acetaminophen in severe renal impairment

What is the difference in indication of NSAIDs and dMARDS

NSAID provide symptomatic relief, whereas DMARD slows progression

What is considered the corner stone treatment for rheumatoid arthritis

DMARDS

MOA: anti-metabolite, that inhibits the enzyme dihydrofolate reductase, Which inhibits the synthesis of Pearians and pyrimidines that are necessary for a nucleaic acid synthesis

Methotrexate

Which three enzymes does methotrexate inhibit

Dihydrofolate reducatse
Thymidylate synthase
AICAR transformylase
Overall increases the level of adenosine which is considered anti-inflammatory

What are the adverse reactions of methotrexate

Most common stomatitis, N/V/D
Do use of fully may decrease adverse reactions

Describe toxicity in methotrexate usage

Hepatic, pulmonary,Hematologic
Pregnancy category X

Agent: endogenous. Nucleoside involved in extracellular local signaling
Generated at sites subject to stressful conditionsAnd released after metabolic stress. This provides a protective role, Imbalances the over active immune response __> Considered anti-

Adenosine

MOA: inhibits diHydrorotate Dehydrogenase, which is a rate limiting step in pyrimidines synthesis.
Results in anti-proliferative effects on an inflammatory cells

Leflunomide

What are the black box warning's for leflunomide

Eternal toxicity and fetal Toxicity, pregnancy category X

MOA: metabolized by gut bacteria to five amino salicylic acid and sulfapyridine

Sulfasalazine

What are drug interactions with sulfasalazine

Antibiotics, it kills bacteria that generate an active drugs

What agent may only provide symptomatic treatment, often used in combination with the MARD or Biologics

Hydroxycloroquine

Hydroxychloroquine has white adverse reaction with log treatment in high doses

RETINAL TOX, some hepatotoxicity, fluid retention and UTI

Recombinant proteins use for biological DMARDS are used to target itself And later fuse with Fc Portion on what

IgG: This portion recognizes the antigen if the body thinks there is too much auto immune attack may occur

What are the cons for using biological MARDS

Expensive, increased risk of systemic infections

What are the agents that inhibit tumor necrosis factor alpha

Etanercept
Infliximab
Adalimamab
Golimumab

What are the Black Box Warning's of biological DMARDS

Severe infections
Lymphoma is another cancers
Activation of latent TB or new risk of TV infection

Which biological DMARDS should not be used in combination with Anti-TNF alpha agents

Anakinra and abatacept

Which biological DMARDS has over four black box warning's, questioning the safety

RITUXIMAB

Which biological DMARD, should not be given with other biologicals?

TOCILIZUMAB, has a Black Box Warning of serious infections

TNF-a is also known as,?
Role of TNF -a

CACHECTIN
This induces pro inflammatory cytokines, which simulate expression of adhesion molecules, which induces tissue degrading enzymes that break down proteins and carbs. With elevated levels in synovial fluid, pain and joint destruction may occur

Turn: characterized by reoccurrence episodes of acute arthritis due to deposit of mono sodium urate in joints and Cartlidge

Get out

Main end point of purine Metabolism, this is poorly soluable, this stimulates the release of inflammatory mediators

Uric acid

What are the goals of treating acute gout attacks

Relieve symptoms of pain using nonsteroidal anti-inflammatory drugs or COLCHICINE

What is the goal of the use of gout prophylaxis

Prevent reoccurring attacks and keep uric acid levels low, prevent urate lithiasis using XO inhibitiors and uricosuric agents

Where is uric acid reabsorbed in the body

Reno proximal tubule

MOA: Decreases in that reabsorption of uric acid by affecting specific transporter. This increases excretion of uric acid, reabsorption of Gouty deposits

URICOSURIC agents

MOA: increases excretion of uric acid by inhibiting renal organic acid transporter
This maintains fluid intake to decrease risk of renal stones

Probenecid

What are the adverse reactions of probenecid

Allergic dermatitis
Precipitate acute gout
Uricosuric stone formation
GI irritation
Caution with use of impaired renal function or stones

When should you use FEBUXOSTAT

Only use if allopurinol is not working

MOA: decrease production of uric acid by Inhibiting' xanthine oxidase
�> purine metabolism

Allopurinol

What are the adverse reactions for allopurinol

Diarrhea nausea skin rash elevated liver enzymes
Does a Jasmine every anal impairment
Precipitate acute gout

When can precipitation of acute acute gout attack happen

May occur with uricosuric agents, and XO inhibitiors
Initial treatment
When urate deposits are mobile

What can you do to decrease the risk of acute gout attacks

Cole administeringNSAID and colchicine for initial weeks of therapy

MOA: binds to in interferes with tubulin, this decreases polymerization In microtubules
This decreases infiltration and phagocytic actions of inflammatory cells

COLCHICINE

What are the adverse events of COLCHICINE

Diarrhea
N/V and abdominal pain