Immunopharm - Eicosanoids/Inflammation/RA Flashcards
1
Q
Eicosanoids:
This is a family of _____ C20 ___ ___ that are metabolites of 5, 8, 11, and 14 eicosatetraenoic acid (_____ acid)
A
Eicosanoids:
This is a family of oxygenated C20 fatty acids that are metabolites of 5, 8, 11, and 14 eicosatetraenoic acid (arachadonic acid)
2
Q
Eicosanoids:
What are the four major groups and their products?
A
Eicosanoids:
a. Cyclooxygenases: PGs, TX, and prostacyclin (PGI2)
b. Lipoxygenases: LTs, HPETEs, HETEs, and lipoxins
c. P450: HETEs, diHETEs, and EETs
d. Endocannabinoids
3
Q
Steps in eicosanoid biosynthesis:
- What is the precursor? How is the precursor derived?
- What stimulates the formation of the precursor?
A
Steps in eicosanoid biosynthesis:
- Precuror is arachidonic acid generated from phospholipids by PLPA2
- PLPA2 is stimulated by mechanical trauma, cytokines, or growth factors
4
Q
Cyclooxygenases:
- Where are the membrane proteins?
- What are the 3 isomers?
- Aspirin irreversibly inhibits by ___ of ___
A
Cyclooxygenases:
- Membrane proteins are in the ER
- 3 isomers: COX-1. COX-2, and COX-3
- Aspirin irreversibly inhibits by o-acetylation of Ser
5
Q
Lipoxygenases:
- Where is 12 lipoxygenase found?
- What two have a lot of sequence homology?
- What do they require?
A
Lipoxygenases:
- 12 lipoxygenase: CNS
- Sequence homology: 5 and 15 lipoxygenases
- They all require Ca++, ATP, and hydroperoxy acid
6
Q
- Eicosanoids are paracrine or ___ hormones that are not stored but?
- They act largely as ____ hormones though the activation of?
A
- Eicosanoids are paracrine or autocrine hormones that are not stored but synthesized on demand
- They act largely as local hormones through the activation of G-protein coupled receptors
7
Q
Pharmacology of Prostaglandins:
Cardiovascular:
- Blood pressure: What causes it to increase? Decrease?
- What dilates coronary vessels?
- What constricts coronary vessels?
A
Pharmacology of Prostaglandins:
Cardiovascular:
- BP: increased by TXA2; decreased by PGE and PGI2
- Dilation: PGE and PGI2
- Constriction: TXA2
8
Q
Pharmacology of Prostaglandins:
Cardiovascular:
- What stimulates platlet aggregation?
- What inhibits platlet aggregation?
A
Pharmacology of Prostaglandins:
Cardiovascular:
- Stimulates: TXA2
- Inhibits: PGI2
9
Q
Pharmacology of Prostaglandins:
Cardiovascular:
- What can maintain the patency of the ductus arteriosus?
- Clinical function of Alprostadil? What is it?
A
Pharmacology of Prostaglandins:
Cardiovascular:
- Patency of ductus arteriosus: PGE2 and PGI2
- Alprostadil (PGE1) maintains maternal/fetal blood flow
10
Q
Pharmacology of Prostaglandins:
Kidney:
Role of PGE and PGI2?
A
Pharmacology of Prostaglandins:
Kidney:
PGE and PGI2 cause vasodilation, natriuresis, diuresis, and renin release
11
Q
Pharmacology of Prostaglandins:
Respiratory:
- What dilates bronchioles?
- What constricts bronchioles?
A
Pharmacology of Prostaglandins:
Respiratory:
- Dilation of bronchioles: PGE and PGI2
- Constriction of bronchioles: TXA2 and PGF2alpha
12
Q
Pharmacology of Prostaglandins:
Respiratory:
- ___ can be used as aerosol in bronchial asthma
A
Pharmacology of Prostaglandins:
Respiratory:
- _PGE2 _can be used as aerosol in bronchial asthma
13
Q
Pharmacology of Prostaglandins:
GI:
- Roles of PGE2 and PGI2?
- Misoprostrol: analog of? use?
A
Pharmacology of Prostaglandins:
GI:
- PGE2/I2: inhibit gastric acid/pepsin secretion and increase mucous secretions
- Misoprostrol: PGE1 analog to promote ulcer healing
14
Q
Pharmacology of Prostaglandins:
Reproductive system:
- Role of PGE2?
- Role of PGF2alpha?
- PGE2alpha and PGF2alpha are used for?
A
Pharmacology of Prostaglandins:
Reproductive system:
- PGE2: relaxes non-pregnant but contracts pregnant uterus
- PGF2alpha: contracts both nonpregnant and pregnant uterus
- PGE2alpha/F2alph: used as contraceptive, to induce abortion and to control postpardum hemorrhage
15
Q
Pharmacology of Prostaglandins:
Reproductive system:
- Drugs for parturition? Their analogs?
- What is alprostadil used for?
- What prostaglandin is responsible for facilitating labor? How?
A
Pharmacology of Prostaglandins:
Reproductive system:
- Carboprost tromethamine (PGF2alpha) and Dinoprostone (synthetic PGE2)
- Alprostadil - used for impotency
- PGE2 facilitates labor through dilation of the cervix
16
Q
Pharmacology of Prostaglandins:
Pain and inflammation:
PGs produce ___ or ____ (increased sensitivity to painful stimuli)
Fever: central administration of PGs - especially into the ____ produces fever
A
Pharmacology of Prostaglandins:
Pain and inflammation:
PGs produce pain or hyperalgesia (increased sensitivity)
Fever: central admin, especially into the hypothalamus produces fever
17
Q
Lipoxygenase Products:
Hydroperoxy-eicosatetraenoic acids (HPETE):
Role in:
- Blood vessels?
- Platelets?
- Inhibit ____ synthetase
A
Lipoxygenase Products:
Hydroperoxy-eicosatetraenoic acids (HPETE):
Role in:
- Contract blood vessels
- Promote platelet aggregation
- Inhibit prostacyclin synthetase
18
Q
Lipoxygenase Products:
Hydroperoxy-eicosatetraenoic acids (HPETE):
- Cause ____
- Role in pain?
- May be __ ___ in cells
A
Lipoxygenase Products:
Hydroperoxy-eicosatetraenoic acids (HPETE):
- Cause chemotaxis
- May cause pain or hyperalgesia
- May be second messengers
19
Q
Lipoxygenase Products:
Leukotrienes:
- Synthesized from ____ in ___ cells and ___.
- What is the predominant mediator of inflammation?
- What causes bronchoconstriction? Through activation of?
A
Lipoxygenase Products:
Leukotrienes:
- Synthesized from 5-HPETE in mast cells and neutrophils
- Predominant mediator of inflammation = LTB4
- Bronchoconstriction: LTC4 and LTD4 by activation of the cys-LT1 receptor
20
Q
Lipoxygenase Products:
Leukotrienes:
- LTC4 and LTD4 are the slow reacting substance of ____
- Actions of LTC4/D4/#4 at cys-LT1 receptor are blocked by what two antagonists? What are these used in
A
Lipoxygenase Products:
Leukotrienes:
- LTC4 and LTD4 are the slow reacting substances of anaphylaxis
- cys-LT1 receptor is blocked by zafirlukast and montelukast in the treatment of asthma
21
Q
NSAIDs:
- Inhibit the formation of ___ by blocking the actions of ______.
- Reduce symptoms associated with inflammatory disease but?
- NO _____ development
A
NSAIDs:
- Inhibit the formation of PGs by blocking the actions of cyclooxygenases
- Do not affect the underlying disease
- NO tolerance development
22
Q
NSAIDs:
- Main therapeutic actions?
- Acetaminophen does not have one of the main actions: which?
- Aspirin is the only prophylactic drug to reduce risk of ____: why?
A
NSAIDs:
- Analgesic, Antipyretic, and anti-inflammatory
- Acetaminophen - is NOT anti-inflammatory
- Aspirin is the only prophylactic drug to reduce the risk of MI because it is the only drug that irreversibly blocks the pathway
23
Q
NSAIDs:
Untoward effects:
- Stomach?
- Respiration?
- Coagulation?
- Gestation?
- Potential ___ damage and disturbance in ___/___ balance
A
NSAIDs:
Untoward effects:
- Gastric irritation
- Altered respiration
- Increased bleeding
- Increased gestation time
- Potential renal damage and disturbance in acid/base balance
24
Q
Salicylates:
- Drug?
- Therapeutic action?
- Role of aspiring in MI? and other cardiac conditions?
- Topical for?
A
Salicylates:
- Acetylsalicylic acid
- Analgesia, antipyresis, anti-inflammatory
- Aspirin: reduces incidence of acute MI and death in patients with unstable angina and reduces frequency of ischemic attacks in patients with atherosclerosis
- Topical for keratolytic action (warts)
25
Salicylates:
Primary effects:
1. CNS?
2. GI?
3. Respiration?
4. \_\_\_\_thermia and \_\_\_\_\_
Salicylates:
Primary effects:
1. CNS - tinnitis, confusion, decreased hearing
2. GI - N/V
3. Stimulates respiratory center
4. **_hyper_**thermia and _dehydration_
26
Salicylates:
Primary effects:
1. Uncoupling of ____ \_\_\_
2. Inhibits ____ cycle
3. Lipid metabolism?
Salicylates:
Primary effects:
1. Uncoupling of _oxidative phosphorylation_
2. Inhibits _TCA_ cycle
3. Stimulates lipid metabolism
27
Salicylates:
Therapeutic doses:
1. ____ respiration secondary to ___ oxygen consumption and ____ CO2 production.
2. Also directly ____ respiration
3. Results in respiratory ____ (\_\_ CO2 expelled due to ___ breathing) and increased renal excretion of ___ to compensate and return pH to normal
Salicylates:
Therapeutic doses:
1. _Stimulates_ respiration secondary to _increased_ oxygen consumption and _decreased_ CO2 production
2. Also directly _stimulates_ respiration
3. Results in respiratory _alkalosis_ (_decreased_ CO2 expelled due to _increased_ breathing) and increased renal excretion of _HCO3-_ to compensate and return pH to normal
28
Salicylates:
Toxic doses:
1. Respiration?
2. Metabolic \_\_\_\_. Displacement of \_\_\_\_. Decreased renal excretion of organic \_\_\_. Increased ___ \_\_ production secondary to increased carbohydrate metabolism
Salicylates:
Toxic doses:
1. Decreased respiration --\> increased CO2 (shifts towards H+ then)
2. Metabolic _acidosis_. Displacement of _HCO3-_. Decreased renal excretion of organic _acids_. Increased _lactic acid_ production secondary to increased carbohydrate metabolism
29
Salicylates:
Toxicity:
1. Effects on GI?
2. Effects on blood?
3. Liver?
Salicylates:
Toxicity:
1. GI: epigastric distress, N/V, _gastric ulceration_, hemorrhage, exacerbation of ulcers
2. Blood: inhibit platelet aggregation and _prolong bleeding_
3. Potential _hepatotoxicity_
30
Salicylates:
Toxicity:
1. Acute ___ insufficiency in patients with underlying disease. What kind of patients would this be?
2. ___ acid excretion. Low doses can worsen \_\_\_.
3. And \_\_/\_\_ balance issues.
Salicylates:
Toxicity:
1. Acute _renal_ insufficiency; liver disease with ascites, CHF, or renal disease
2. _Uric_ acid excretion. Low doses can worsen _gout_
3. _Acid/base_ balance issues
31
Salicylates:
Toxicity:
Can lead to Reye's syndrome: what are the symptoms?
What is prognosis linked to?
Salicylates:
Toxicity:
Reyes: persistant/recurrent vomitting, listlessness, irritability, combativeness, disorientation or confusion, delirium, convulsions, and loss of consciousness
Prognosis is linked to the severity of brain swelling
32
Salicylates:
Toxicity:
How do you treat poisoning?
Salicylates:
Toxicity:
Poisoning: charcoal, laxative, lavage (up to 1 hour after), IV fluids, alkaline diuresis, and/or hemodialysis
33
Salicylates:
Contraindications:
Thinking of the side effects of toxicity and the things they cause, what kind of patients should not take salicylates?
Salicylates:
Contraindications:
a. Patients with ulcers or clotting disorders
b. Patients allergic to aspirin
c. Pregnant women
d. Gout (but only in high doses)
e. Viral infections in kids (increased risk of Reyes)
34
Salicylic acid derivatives:
1. Mesalamine = amino salicylate: treats?
2. Sodium salicylate: function
Salicylic acid derivatives:
1. Mesalamine: treats/prevents _ulcerative colitis_ and mild to moderate _chrons_
2. Sodium salicylate: replacement for those with salicylate sensitivity
35
Acetaminophen:
In contrast to salicylates:
1. Not a useful ______ agent with weak effects on \_\_\_.
2. No alterations in ___ balance and thus no ____ effects.
3. Minimal effects on?
Acetaminophen:
In contrast to salicylates:
1. Not a useful _anti-inflammatory_ agent with weak effects on _platelets_
2. No alterations in _pH_ balance and thus no _uricosic_ effects
3. Minimal effects on GI
36
Acetaminophen:
In contrast to salicylates:
Because its weak on platelets, no pH alteration, minimal GI effects, no uricosuric effects its advantageous in:
1. Patients with ___ \_\_\_ disease
2. People who are ___ intolerant
3. Patients on oral ____ or have ___ disorders
4. Patients with ___ or infections suceptible to \_\_\_
Acetaminophen:
In contrast to salicylates:
Because its weak on platelets, no pH alteration, minimal GI effects, no uricosuric effects its advantageous in:
1. Patients with _peptic ulcer_ disease
2. Patients who are _aspirin_ intolerant
3. Patients on oral _anticoagulants_ or _coagulation_ disorders
4. Patients with _gout_ or suceptibility to _Reyes_
37
Acetaminophen:
Therapeutic uses?
Acetaminophen
Analgeia and antipyresis
38
Acetaminophen:
Toxicity:
1. Most serious potential problem?
Course: initially ___ symptoms followed by a period of recovery and then appearance of \_\_\_\_\_\_. A metabolite has been formed to exceed the availability of ___ to inactivate it before it causes cell ___ and necrosis. _NAPQI_ - irreversibly conjugated with \_\_\_\_.
Acetaminophen:
Toxicity:
1. Most serious: _fatal hepatic necrosis with acute od_
Course: initially _GI_ symptoms followed by a period of recovery and then appearance of _jaundice_. A metabolite has been formed to exceed the availability of _glutathione_ to inactivate it before it causes cell _death_ and necrosis. _NAPQI_ - irreversibly conjugated with _glutathione_
39
Acetaminophen:
Toxicity:
2 treatment for poisons? Administration?
Acetaminophen:
Toxicity:
Poison: methionine (oral) and N-acytylcystine (NAC: precursor for glutathione: IV or Oral)
40
Acetaminophen:
1. Side effects?
2. Rare but serious/fatal side effects?
Acetaminophen:
1. SE: rash, mucosal lesions, and leukopenia
2. Rare: steven johnson's, toxic epidermal necrosis, or acute generalized exanthematous pustulosis
41
Other NSAIDs:
1. Indomethacin - why no longer first choice?
2. Sulindac - prodrug used in what patients? Where does inactivation occur?
3. Ibuprofen: lowest incidence of?
Other NSAIDs:
1. Indomethacin - High GI toxicity
2. Sulindac - prodrug used in _patients with impaired renal function_. Inactivation occurs in the kidney
3. Ibuprofen: lowest incidence of GI side effects of all NSAIDs
42
Other NSAIDs:
1. Naproxin - lowest incidence risk of?
2. Diclofenac - better \_\_\_\_
3. Piroxicam is ____ acting
Other NSAIDs:
1. Naproxin - lowest CV risk of all NSAIDs
2. Diclofenac - better _tolerated_
3. Piroxicam is _long_ acting
43
Other NSAIDs:
Name the other NSAID categories and the drug(s) associated.
Other NSAIDs:
a. Indole/Indene Acetic Acids - indomethacin and sulindac
b. Heteroaryl Acetic Acids - Ketorolac
c. Arylpropionic Acids - ibuprofen and neproxin
d. Phenyl Acetic Acid - Diclofenac
e. Enolic Acids - Piroxicam
44
COX-2 inhibitors:
1. Drug?
2. Less ___ \_\_\_ compared to those that inhibit both COX-1 and COX-2.
3. Contraindications?
4. ___ onset of analgesia and thus not used for __ pain
COX-2 inhibitors:
1. Celecoxib
2. Less _side effects_
3. Celecoxib - contra w. sulfa sensitivity
4. _Slow_ onset of analgesia and thus not used for _acute_ pain
45
COX-2 inhibitors:
1. Some reports of?
Warnings:
1. NEVER EVER?
2. ___ plasma protein binding of NSAIDs and _____ (anti-diabetics)
3. Increased risk of bleeds with NSAIDS + \_\_\_
COX-2 inhibitors:
1. Some reports of GI bleeding/ulceration
Warnings:
1. NEVER EVER use 2 NSAIDs concurrently
2. _High_ plasma protein binding of NSAIDs and _sulfonylureas_
3. Increased risk of bleeds with NSAIDs + _Warfarin_
46
Rheumatoid arthritis:
1. Symptoms?
2. Diagnosis?
3. Key cytokine?
Rheumatoid Arthritis:
1. Symptoms: swollen glands, morning stiffness, joint pain, swollen joints, decreased appetite and can have pleurisy, nodules under skin, and numbness/tingling/burning in hands or feet
2. Diagnosis: anti-CCP antibody test, X-ray, MRI, ultrasound
3. Key cytokine = TNF
47
Rheumatoid Arthritis:
1. These are all DMARDs: what does this stand for?
2. What are the antineoplastic drugs and when are they used?
3. Side effects of antineoplastic drugs?
Rheumatoid Arthritis:
1. Disease Modifying Anti-Rheumatic Drugs
2. Antineoplastic drugs: azathioprine, leflunomide, methotrexate, and penicillamine; used only in severe RA
3. SE: fever, chillse, anorexia, N/V, hepatotoxicity, agranulocytosis, leukopenia, anemia, and thrombocytopenia
48
Rheumatoid Arthritis:
Methotrexate:
1. Uses?
2. Analog of?
3. Inhibits metabolism of ___ acid by inhibiting _____ \_\_\_.
Rheumatoid Arthritis:
Methotrexate:
1. One of the most effective drugs for RA, also good for neoplasms, GVHD, and autoimmune disorders
2. Analog of _folic acid_
3. Inhibits metabolism of _folic_ acid by inhibiting _dihydrofolate reductase_
49
Rheumatoid Arthritis:
Methotrexate:
1. Has \_\_\_ and anti-inflammatory activity.
2. SE?
Rheumatoid Arthritis:
Methotrexate:
1. Has _cytotoxic_ activity
2. SE: dyspnea, diarrhea, vomitting, blood in stool/urine, fever, chills, aches, and teratogenic
50
Rheumatoid Arthritis:
Methotrexate:
MOA:
_RA_: inhibition of enzymes involved in ____ \_\_\_\_ --\> accumulation of ___ or inhibition of __ cell activation
_Cancer_: competitive inhibition of ____ for _____ synthesis needed to make ___ --\> this inhibits synthesis of?
Rheumatoid Arthritis:
Methotrexate:
MOA:
_RA:_ inhibition of enzymes involved in _purine metabolism_ --\> accumulation of _adenosine_ or inhibition of _T_ cell activation
_Cancer_:competitive inhibition of _DHFR_ for _tetrahydrofolate_ synthesis needed to make _thymidine_ --\> inhibits synthesis of DNA, RNA, thymidylates, and proteins
51
Rheumatoid Arthritis:
Methotrexate:
1. The one main drug interaction?
Rheumatoid Arthritis:
Methotrexate:
1. Penecillin: causes decreased elimination of methionine and thus increases the risk of toxicity
52
Rheumatoid Arthritis:
1. Etanercept: moa?
2. Infliximab and Adalimumab: MOA?
3. Anakinra: MOA?
Rheumatoid Arthritis:
1. Etanercept: acts as a decoy and binds to TNFalpha receptor
2. Infliximab and Adalimumab: antibodies to TNFalpha
3. Anakinra: IL-1beta receptor antagonist
53
Rheumatoid Arthritis:
Etanercept, Infliximab, Adalimumab, and Anakinra:
1. Major side effects secondary to injection for Etanercept?
2. Infusion reaction between ____ and anakinra: causes?
3. Major SE of concern?
Rheumatoid Arthritis:
Etanercept, Infliximab, Adalimumab, and Anakinra:
1. SE secondary to injection: pain, swelling, redness, and itch
2. Infusion reaction between _infliximab_ and anakinra: causes fever, chills, rash, and itch
3. Major SE of concern is infection
54
Rheumatoid Arthritis:
Etanercept, Infliximab, Adalimumab, and Anakinra:
1. Other SE?
2. Rarely, infliximab can cause?
3. These are contraindicated in?
Rheumatoid Arthritis:
Etanercept, Infliximab, Adalimumab, and Anakinra:
1. SE: nausea, HA, abdominal pain, and vomitting
2. Infliximab: anaphylaxis, hypotension, or lupus-like syndrome
3. Contraindicated in _sepsis_
55
Rheumatoid Arthritis:
Abetacept:
MOA?
Function?
Rheumatoid Arthritis:
Abetacept:
MOA: Binds to _B7_ on APC and prevents delivery of costimulatory signal to T cells
Function: to render T cells inactive
56
Traditional DMARDS:
Hydroxychloroquine:
1. Type of drug? For?
2. MOA? Result?
Traditional DMARDS:
Hydroxychloroquine:
1. Antimalarial also for arthritis and lupus
2. MOA: blocks TLR on dendritic cells --\> _decreases activation of dendritic cells and inflammatory processes_
57
Traditional DMARDS:
Leflunomide:
1. Activities?
2. MOA?
3. T1/2?
Traditional DMARDS:
Leflunomide:
1. Immunomodulator and anti-inflammatory
2. MOA: inhibition of mitochondrial DHODH for pyrimadine ribonucleotide uridine monophosphate (rUMP); _pyrimidine synthesis inhibitor_
3. Very long
58
Gold compounds:
1. Name 3 drugs?
2. Uses?
3. Can relieve ___ and ___ and for some may ___ progression but DO NOT ___ \_\_\_ that has already occured
Gold compounds:
1. Auranofin, Aurothioglucose, and Gold sodium thiomalate
2. Management of progressive RA that is unresponsive to traditional therapies
3. Can relieve _pain_ and _symptoms_ and for some may _arrest_ progression but DO NOT _reverse damage_ that has already occured
59
Gold compounds:
Side effects?
Gold compounds:
SE: metallic taste, stomatitis, diarrhea, cramping. Some develop a rash, dermatitis, thrombocytopenia, aplastic anemia, agranulocytosis, and acute tubular necrosis
60
Rituximab:
1. What is this? MOA?
2. SE?
3. Major SE?
4. Contraindications?
Rituximab:
1. Monoclonal Ab to _CD20_ on B cells - allowing a new population of healthy B cells to develop from lymphoid stem cells
2. SE: pain/swelling/itching/fever/chills/rash, N/V, HA
3. Major: infection
4. Contraindication: sepsis
61
Gout:
Acute gout:
1. Where does this occur?
2. Symptoms?
3. Duration?
Gout:
Acute gout:
1. It is **_mono_**articular in the first metatarsophalangeal joint
2. Symptoms: severe pain (allodynia), inflammation, limited range of motion
3. Can resolve in a week or more even with no treatment
62
Gout:
Chronic gout:
1. Where?
2. Associated with what in the elderly?
3. Contains Tophi - what is this? Where?
4. What can Tophi cause?
Gout:
Chronic gout:
1. **_Poly_**articular in joints in upper extremities
2. Associated with diuretic use or renal insufficiency in old
3. Tophi = deposit of monosodium urate crystals; in joins, cartilage, and bones
4. Can cause deformities, tissue damage, and joint destruction
63
Causes of Hyperuricemia: name 2?
Causes of hyperuricemia:
a. increased uric acid production or
b. decreased uric acid excretion
64
Hyperuricemia:
Increased Uric acid production associated with:
1. High ___ intake
2. ___ disorders such as myeloproliferation or?
3. Medications such as?
Hyperuricemia:
Increased Uric acid production associated with:
1. High _purine_ intake
2. _Hematologic_ disorders such as myeloproliferation or sickle cell anemia
3. Cytotoxic medications
65
Hyperuricemia:
Increased Uric acid production associated with:
1. Genetic factors resulting in altered ____ metabolism
2. What 4 other things?
Hyperuricemia:
Increased Uric acid production associated with:
1. Genetic factors resulting in altered _hypoxanthine_ metabolism
2. diabetes, obesity, alcohol consumption, and excessive exercise
66
Hyperuricemia:
Decreased uric acid excretion associated with:
1. Use of what med?
2. Disease factors affecting ___ function (hypertension)
3. Genetic factors resulting in ___ \_\_\_ or excretion of urate
4. What 2 other things?
Hyperuricemia:
Decreased uric acid excretion associated with:
1. Use of diuretics
2. Disease factors affecting _renal_ function
3. Genetic factors resulting in _reduced clearance_ of urate
4. Obesity and toxemia/pre-eclampsia in pregnancy
67
4 ways to diagnose gout?
Gout diagnosis:
a. Synovial fluid analysis
b. Joint x-ray (may be normal)
c. Synovial biopsy
d. Uric acid in blood or urine
68
Drug treatment of Gout:
Name 8 drugs or classes?
Drugs:
a. NSAIDs
b. Glucocorticoids
c. Cochicine
d. Probenecid and Sulfinpyrazone
e. Allopurinol and Febuxostat
f. Rasburicase
69
Treatment of gout:
Cochicine:
1. Use?
2. Not \_\_\_\_\_
3. Inhibits migration of ___ to inflammed area.
4. SE? Long term?
Treatment of gout:
Cochicine:
1. _Acute_ attacks and prophylactic for actue attacts
2. _Not ucosuric_
3. Inhibits migration of _granulocytes_ to inflamed area
4. SE: _GI distress_, N/V, diarrhea, abdominal pain; _Long term_: blood dyscrasias
70
Treatment of gout:
Probenecid and Sulfinpyrazone:
1. Prevention of ____ by increasing renal clearance of ___ \_\_ by ____ reabsorption
2. Probenecid: no longer for elderly - why?
3. Patient should dring lots of water and ___ the urine to prevent?
Treatment of gout:
Probenecid and Sulfinpyrazone:
1. Prevention of _hyperuricemia_ by increasing clearance of _uric acid_ by _decreasing_ reabsorption
2. Probenecid: no longer for elderly due to decreased renal function
3. Water and _alkalanize_ to prevent precipitation of uric acid in renal tubules
71
Treatment of gout:
Probenecid and Sulfinpyrazone:
1. MOA: Prevent uric acid ___ in tubules by interfering with ___ \_\_\_ ___ which reclaims uric acid from ___ and returns it to \_\_\_
2. SE?
3. Caution in what patients? WHy?
Treatment of gout:
Probenecid and Sulfinpyrazone:
1. MOA: Prevent uric acid _crystals_ in tubules by interfering with _organic anion transporter_ which reclaims uric acid from _urine_ and returns it to _plasma_
2. SE: rash and hypersensitivity
3. Caution in patients with peptic ulcers bc it can cause GI irritation
72
Treatment of gout:
Allopurinol and Febuxostat:
1. Allopurinol is?
2. Febuxostat is?
3. How does it prevent hyperuricemia?
Treatment of gout:
Allopurinol and Febuxostat:
1. Allopurinol is a purine analog
2. Febuxostat is a non-purine inhibitor
3. Prevents hyperuricemia by decreasing uric acid production
73
Treatment of gout:
Allopurinol and Febuxostat:
1. MOA: inibition of ___ \_\_\_ which is responsible for?
2. SE?
Treatment of gout:
Allopurinol and Febuxostat:
1. MOA: inhibition of _xanthine oxidase_ which is responsible for the succesive oxidation of hypoxanthine and xanthine --\> resulting in production of uric acid
2. SE: rash and hypersensitivity; also maybe fever, malaise, muscle aches, and rarely leukopenia
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Treatment of gout:
Rasburicase:
1. How does it prevent hyperuricemia?
2. Recombinant version of?
3. MOA: catalyzes the conversion of?
Treatment of gout:
Rasburicase:
1. Prevents hyperuricemia by decreasing uric acid production
2. Recombinant version of urate oxidase
3. MOA: catalyzes the _conversion of uric acid to allantoin_ which is an inactive metabolite of purine metabolism (renal excretion is then more effective)
