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