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WorksheetsPharmacotherapeutics Exam 5 Part 1 OA/RA
Total questions: 83
Worksheet time: 42mins
NSAIDs affect 3 stages of disease. What are they?
Pain
Inflammation
Fever
What is the max dose of NSAIDs daily?
3200mg/day
4500mg/day
NSAID example medications?
Aspirin, Celecoxib
Diclofenac, Indomethacin
Ketorolac, Piroxicam
Meloxicam
NSAID Mechanism of action?
Inhibit Cyclooxygenase Enzyme
Degranulation of mast cells
Drug specific to COX-2 receptor?
Celecoxib (Celebrex)
Pregabalin (Lyrica)
COX-1 is mostly found ___ and COX-2 is found in ____.
GI mucosa and other tissues ; Injury site
Injury site ; GI mucosa and other tissues
NSAID absorption, metabolism and excretion?
Absorbed rapidly from GIT
90% bound and carried to inflammation site by albumin
Metabolized by liver
99% excreted in urine
Adverse drug reactions of NSAIDs?
Fluid retention = (remember the afferent arteriole is constricted)
Abd pain/Cramps (decreased prostaglandin synthesis leads to risk of injury)
NSAIDs block?
COX-1 and COX-2
COX-1 Only
COX-2 Only
Half life of NSAIDs?
2-4 hours, but variable
88 hours exactly
NSAID drug interactions?
Antihypertensives (inhibited by NSAIDs, we'll review this when we do clin med Nephro)
Decreased Platelet aggregation occurs with anticoagulants leading to increased risk of GI bleed
Aminoglycoside drug interaction with NSAIDs?
Decreased renal clearance (why?)
Increased renal clearance
Corticosteroid use with NSAID drug interaction?
Increased risk of GI bleed
Decreased risk of GI Bleed
Contraindications to NSAID?
Peptic Ulcer Disease (PUD)
Chronic GI Inflammation
Aspirin is considered? (2 are right, Possesses analgesic, antipyretic, and antiplatelet properties)
Prototype drug for Non-Narcotic Analgesics
Considered an NSAID
Considered an antcoagulant
Aspirin mechanism of action? (2 are right)
Inhibits prostaglandin and thromboxane synthesis, providing its NSAID and Antiplatelet effect
Acetylates Serine at platelet Cyclooxygenase preventing Thromboxane A and decreasing platelet Aggregation
Destroys platelets
Aspirin inhibiting effect lasts?
Until new platelets are formed (8 days)
Until Plasmapheresis is done
Until new WBC are formed
Aspirin absorption, metabolism and excretion?
Salicylates (Aspirin) is rapidly absorbed with 1-2 hour peak
Metabolized by liver
Excreted in urine
3-6 hours half life of small doses // high doses is 15-30 hours
Aspirin adverse effects?
GI intolerance due to decreased prostaglandin synthesis = decreased
Hematology: Antiplatelet effect
Metabolism: Acid-Base Imbalance
Neuro: Toxic doses may cause convulsions and depression
Renal ADR of ASA?
low doses such as 2 grams or less decrease urate excretion which is needed for uric acid excretion
low doses such as 2 grams or less Increase urate excretion which is needed for uric acid excretion leading to more uric acid pumped out
Acetaminophen DOES NOT have what compared to ASA?
Gastritis, Ulceration
Inhibition of platelets effect caused by ASA effect
Aspirin drug interactions? (discuss why! Important for nephro)
ACEi
Beta Blockers
Loop Diuretic
Thiazide Diuretic
APAP acute overdose may cause?
Hepatic Necrosis
Creudzfeldt Jakob Disease
APAP max dose?
4 grams (4000 mg)
6000mg
APAP clinical uses?
Analgesic
Antipyretic
MILD forms of arthritis
APAP Mechanism of action?
Raise pain threshold by inhibiting nitric oxide pathway that would act on substance P and NMDA receptors
Narrow pain threshold by inhibiting nitric oxide pathway that would act on substance P and NMDA receptors
Blocks production of prostaglandin release into CNS = no effect on anterior hypothalamus = prevents increase in body heat and preventing retention of heat
Why would you choose APAP vs NSAIDs?
Patient on anticoagulation
Allergy to ASA
Children preferred because it is not associated with Reye Syndrome
Absorption, metabolism, half life and excretion of APAP?
85-98 % absorbed
Does not enter fat tissue and metabolized by liver
Excreted in urine
Half life of 1-4 hours
What can alter absorption of APAP?
Diseased states or meds that delay gastric emptying
xx
GU/GI APAP adverse effects?
Hepatic Failure with high doses
Renal Failure with high doses
APAP drug interactions?
Warfarin effect increased with 2 grams or more
Alcohol increases hepatic toxicity
Carbamazepine, Isoniazid and Rifampin decrease APAP effect
Cholestyramine decrease absorption of APAP
Is APAP safe in pregnancy?
Yes, it also crosses placenta and little bits into breast milk
xx
Contraindications to APAP?
Liver disease
Restless leg syndrome
Synthetic prostaglandin analogue can be used for? What is the name of the drug?
Prevention of gastric mucosa damage by NSAIDs
Misoprostol
Carbamazepine
Phenytoin
MOA for Misoprostol and ADR of Misoprostol?
Affect basal and nocturnal acid secretion to prevent ulceration
Miscarriage and menstrual disorder
Increase gastric acid secretion
Increases T3 and T4
Misoprostol Drug Interactions?
Increased toxicity of methotrexate, digoxin, cyclosporine and lithium
Hyperkalemia with K+ sparing diuretics
Ibuprofen MOA and when does it have an antiplatelet effect?
Only when in the blood
Inhibits COX, blocking prostaglandin synthesis
Proton Pump Inhibitor
In the urine
Ibuprofen absorption, metabolism, excretion and half life? ADR?
Absorbed rapidly and readily in GIT, bound to albumin
Hepatic Metabolism, Renal Excretion, Half Life of 2-4 hours
Prolonged bleeding time and thrombocytopenia, GI Bleed and Drowsiness
Ibuprofen drug interactions? Ibuprofen increases the risk of bleeding with which drugs?
Limits cardioprotective effect of ASA
Increased Hypoglycemia effect and increased effect with NSAID, ASA, and Corticosteroid
Cefotetan, Valproate and Anticoags increase bleeding risk
CI to ibuprofen + Chewable ibuprofen is contraindicated in ___ because ____.
CI to Ibuprofen are Cardiovascular Dz, Hepatic Dz
Pheynketonuria ; it contains Aspartame
Meloxicam Clinical Use and MOA?
OA, RA, Juvenile Arthritis
Increased inhibition of COX, leading to decreased prostaglandin synthesis
Decreased inhibition of COX, leading to decreased prostaglandin synthesis
Meloxicam absorption, metabolism, and excretion? ADR?
Levels Prak in 4-5 hours; Metabolized by liver; Excreted in urine; Halflife of 15-20 hours
ADR: SJS, TEN, Abnormal LFT's, Anemia, Leukopenia and Thrombocytopenia
ADR: Priapism
Nephrotoxicity by COX2 inhibitors is worse why? Meloxicam drug interactions?
Nephrotoxicity because: Kidney expresses COX2
Decreases antihypertensive effect of ACEi
Reduce diuretic effect of thiazides and loop diuretics
Example of a COX-2 inhibitor? Clinical use of COX-2 inhibitor?
Celecoxib
RA, OA, Dysmenorrhea
Malaria
Aspirin
MOA for COX-2 inhibitors? COX-2 absorption, metabolism, excretion and half life?
Inhibits prostaglandin synthesis by blocking COX-2 with little to no effect on COX-1 and no antiplatelet activity
Well absorbed orally, Metabolized by liver, Excreted in urine and feces, Half life of 11 hours
Enhances prostaglandin synthesis by blocking COX-2 with little to no effect on COX-1 and no antiplatelet activity
COX-2 inhibitors ADR? Drug interactions?
Increased risk of MI/CVA, Swelling of extremities, Black tarry stools, Vomit, Wt gain
Renal Toxicity, Tiredness and Flulike symptoms
Increases effect of Warfarin
Other drugs that have bad interactions are Diazepam, Glyburide, Estradiol, Omeprazole and ASA
Contraindication to Celecoxib? Step up therapy for Hip OA?
Renal failure and CVD are contraindications
Step up therapy: Lifestyle Mod, APAP, NSAID, Glucosamine/Chondroitin, Opiod, CCS, Hyaluronic Acid, Hip Arthroplasty
Drugs such as methotrexate produce only 18-20% reduction in symptoms after? AND Methotrexate is issued as a?
1 year
3 years
Administered as a weekly schedule
Administered as a yearly schedule
Examples of DMARDs? (Disease Modifying Anti Rheumatic Disease) (Enbrels Ritual to Orencia was HUM, RAP and REM)
Enbrel, Humira
Orencia, Raptiva
Remicade, Rituxan
Methotrexate is a ____. What drug can be used to reduce methotrexate toxicity?
Methotrexate is : Antimetabolite, antineoplastic, and immunosuppressant and a DMARD
Leucovorin can be used to decrease toxicity but reduces effect and does not reverse neurotoxin
Methotrexate is : An antacid
Methotrexate clinical use? Methotrexate MOA?
Can be used for: Psoriasis, SLE, Sarcoidosis, Rheumatoid Arthrits
Can be used for: Antifolate property for lung, head/neck, breast cancer and leukemia
MOA: Folate Antimetabolite that inhibits DNA Synthesis, Unknown Mech in Arthritis but thought to work by Cel ANTIPROLIFERATION
Methotrexate absorption, metabolism, excretion and half life?
Absorbed readily in GIT in small doses, large doses incompletely absorbed
Slow delivery to tissues, Hepatic Enzymes convert to inactive metabolite, 90% unchanged dose and metabolite is excreted in URINE
Methotrexate ADR? Hematologic Toxicity when taking methotrexate is increased when? READ WELL!!!
ADR: Transient blindness, Mucosal Ulcer, Hep Toxicity, Anorexia, Infertility
ADR: Blood Problems, Nephropathy, Soft Tissue Necrosis, Pulm Fibrosis
Hema Tox Worse When: given with high dose ASA, NSAID, Oral Hypoglycemics, Tetracyclines and Sulfonamides
Any drug that competes with methotrexate for excretion can lead to? AND What stimulant will lower effect of methotrexate?
Kidney/Liver Disease can result
Caffeine will lower the effect
Water will lower the effect
Tourette can result
What herbs can interfere with immune suppression effect of methotrexate? Methotrexate is CI in? (3 are right)
Herbs: Echinacea, Melatonin
Herbs: Albaca, Romero
CI: Women AND MEN attempting pregnancy
Men should wait 3 months before attempting because of teratogenic effects
Leflunamide is an immunomodulator and what should you check when using this drug? Leflunomide MOA? (READ CAREFULLY)
MOA PART 1: Ibhibits de novo ribonucleotide synthesis, arrests cell in G1 Phase= inhibition of Enzyme Required for Pyrimidine Synthesis
MOA PART 2: Alleviates pain and inflammation = slow progression of dz and improves joint function
Check ROM, Swelling and Pain
Check Bilirubin and Alk Phosphate
Leflunomide absorption, distribution, and excretion? Drug Interactions? (half life is 4-18 days)
80% absorbed, rapidly converted to active metabolite
99% Protein Bound, Half Excreted in feces and Half in urine
Interactions: Any hepatotoxic drugs
Interactions Water
Adverese effects of leflunomide? Leflunomide Contraindications?
ADR: Alopecia, Rhinitis, Cell turnover of B&T cells is increased leading to increased bilirubin, Abn LFTs, Synovitis
Contraindiated in Pregnancy and Liver Disease
Hydroxychloroquine requires frequent eye exams because?
Causes irreversible retinopathy leading to blindness
It causes Drussen spots to appear
Hydroxychloroquine is a ___ drug, and is used for?
Last resort ; Antirheumatic, SLE, Suppress Malaria
1st line ; Antirheumatic, SLE, Suppress Malaria
Last resort ; Antiarrhythmic
MOA for Hydroxychloroquine and ADR?
MOA: suppress T cell response to mitogens to treat RA
ADR: Bleaching of hair, Ototoxicity, Cramps, Agranulocytosis, Psychosis
MOA: Increase T cell response to mitogens to treat RA
ADR: Priapism
Hydroxychloroquine absorption, distribution, metabolism, excretion and half life? CI to Hydroxychloroquine?
Safer Orally and rapidly aborbed from GIT, Slow distribution, Metabolized by liver, Excreted by urine, Half life 30-60 days
Contraindications: Liver Disease, Renal Disease, Alcohol Use
Hydroxychloroquine drug interactions?
Drugs requiring biliary excretion result in increased hepatotoxicty
Drugs requiring biliary excretion result in decreased hepatotoxicty
Penicillamine chelates Copper, Iron, Mercury, and lead to form complexes to excrete?? Indication?
to excrete Copper and also helps with chelating Cysine Complexes to decrease Cystine Stones
Indicated for: RA Juvenile Arthritis
Indicated for Restless leg syndrome
to excrete water
Penicillamine absorption, metabolism, excretion and half life? Penicillamine MOA?
Only 50% absorbed, liver metabolism, found in urine and feces unchanged or as metabolite, 1.7-3.2 hours is the half life
MOA: Decrease cell mediated immune response, inhibits collagen formaation= anti inflammatory
MOA: Increase cell mediated immune response, inhibits collagen formaation= anti inflammatory
Penicillamine ADR? Drug Interactions? Contraindications?
ADR: Leukopenia, White Papules on Venipuncture, Hot flashes
Drug Interactions: Cross reactivity with PCN, Mg and Aluminum hydroxide Antacid block absorption
Contraindicated in pregnancy, aplastic anemia, and renal failure
Gold Compounds are used to treat inflammation, drawbacks? And Myochrysine is used to treat?
Drawback: Very short acting and toxic, LAST RESORT as well.
Myochrysine is used to treat Juvenile arthritis
Myochrysine is used to treat HIV-1
Any minor reaction to a gold compound warrants? Gold copound drug drug interaction?
Discontinuation of gold compound is warranted with any reaction
No drug-drug interactions are noted
Water interaction
Examples of Gold Compound? (RSM)
Ridaura (Auranofin)
Solganal (Aurothioglucose)
Myochrysine (Gold Sodium Thiomalate)
Figure it out LOL
Ridaura Solganal some Myochrysine
Gold compounds mechanism of action? ADR? Contraindications?
Interferes with IL-1 and TNF, inhibit phagocyte function and decrease their antiinflammatory mediators. IM Gold salts are used to treat synovitis but not curative
ADR: Oral ulceration, altered taste is SUPER COMMON, Nephritic Syndrome, Blood Dyscrasias
CI: Hx of Blood disorders, CHF, Dermatitis
Examples of TNFinhibitors
Etanercept (Enbrel)
Infliximab (Remicade)
Anakinra (Kineret)
(AEI = Ana Etane and Inflix)
Patients on TNFi require that they be monitored for? Indicated for?
Monitor for: Latent or active TB
Indicated for: Moderate to severe Rheumatoid Arthritis
MIld RA
What drug may be used concurrently with TNFi? What GI disease that is a moderate to severe can be treated with TNFi?
Concurrently with: Methotrexate
Other GI Dz: Crohn's
Other GI Dz: Hirschsprung's
Etanercept/Infliximab can be used for?
Moderate to severe RA or inadequate response after DMARD
Mild RA
Etanercept MOA? Choose both
Protein that acts as a TNFi, developed by recombinant DNA synthesis
Interfere with inflammation cascade initiated by TNF= Lowering Cytokines, by inactivating them and unable to drive inflammation response of cell surface receptors found in synovial fluid in those with RA
Infliximab MOA?
Chimeric monoclonal AB
Neutralizes and prevents TNF-alpha = anti-inflammatory and anti-proliferative activity
Anakinra Mechanism of action?
Blocks action of IL-1 and is an immunomodulator
Increases action of IL-1 and is an immunomodulator
Absorption of Anakinra? Etanercept? Infliximab?
Anakinra is not stored or accumulated in tissue after daily SC doses
Etanercept is well absorbed post SC dose
infliximab is well absorbed due to IV administration
Excretion of TNFi?
Anakinra excreted in urine
Others are unknown
Distribution and metabolism of of TNFi?
Unknown
Liver
Lung
Half Lives of TNFi?
Infliximab has longest
Anakinra is lowest half life
Etanercept is in between the others
ADR of TNFi? Drug Interactions?
ADR: Oral and Tooth Pain, Involuntary muscle spasm, Increased URI
Drug Interactions: None
Drug interactions: Metformin
ADR: Priapism
CI to TNFi?
Patients with serious infections
People with infectious TB or latent TB
People with leg pain
People with finger pain
