Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
219 Cards in this Set
- Front
- Back
- 3rd side (hint)
What is MSM similar to?
|
DSMO
|
|
|
What class are glucosamine and chondroitin sulfate in?
|
Nutraceuticals
|
|
|
What does glucosamine inhibit? Increase?
|
Inhibit: MMP, NO production, and stops IL-1's from inducing aggrecanase activity
|
Increase: GAGs, PG's, Hyaluronic acid, and aggrecan synthesis
|
|
Chondrotin sulfate inhibits translocation of ____ into chondrocytes.
|
NFkB
|
|
|
Name 4 areas that are hindered in patients taking Nutraceuticals for Inflammation (OA).
|
1. NO
2. Proteases 3. IL-1 4. TNF |
|
|
What does chondroitin sulfate do to NFkB?
|
inhibits its translocation of NFkB into chondrocytes and synovial membrane
|
|
|
Do glucocorticoids have mineralcorticoidal activity? How or how not?
|
Yes, bc affect Na and K+
|
|
|
What is the flow of the HPA axis?
|
Ceberal cortex stimulated (via stress) --> triggers hypothalamus --> releases CRH ---> anterior pituitary lobe --> releases ACTH --> adrenal gland --> steroids are made (cortisol)
|
|
|
What is CRH?
|
Corticotropin releasing hormone
|
|
|
What are the 2 negative feedback mechanisms of the HPA axis?
|
Coritsol (long ) and ACTH (short)
too much of either will stop the production of CRH |
|
|
What receptor does ACTH act on in the adrenal glands?
|
Melanocortin-2 receptor
|
|
|
How many weeks does it take to get suppression/atrophy of the HPA axis? How long to recover?
|
2 weeks;
|
9-12 months
|
|
What is the normal release of cortisol? Under stress?
|
10-25 mg/day
|
300mg/day
|
|
The genomic theory of steroids is that it enters the ____ of the cell and either synthesizes ___ or interferes with ____.
|
cytoplasm/nucleus; proteins; transcription
|
|
|
How do steroids stop NFkB activation?
|
By surrounding the complex with IkB's so IKK cannot remove the one for activation
|
|
|
What two items are transported from the periphery to the liver as a result of steroids?
|
amino acids and glucose
|
|
|
In regards to metabolism, Steriods promote ___ and ___ ____.
|
gluconegenesis
|
lipid breakdown
|
|
What disease can be induced by steriods? How?
|
Diabetes (How...)
|
Liver increases gluconeogenesis; increases blood glucose and glycogen storage (deposition)
|
|
Steroids promote lipid breakdown increasing FFA. They also decrease insulin sensitivity except what two areas of the body? What does this cause?
|
Face and shoulders
|
lipid deposition --> moon face and buffalo hump
|
|
Concerning electrolytes, while on steroids you get ___ reabsorption and ___ loss.
|
Na
|
K
|
|
While on steroids, what is one cell that is increased in the plasma but the function is not?
|
neutrophils
|
|
|
With steroids many blood cells are decreased. What can this cause an increase in?
|
infections
|
|
|
Why are steroids so good of a drug?
|
Bc they are anti-inflammatory and immunomodulators (which is vital with chronic inflammation)
|
|
|
What happens to fibroblasts while on steroids?
|
dec synthesis of cytokines and MMP
|
|
|
What happens to cartilage while on steroids?
|
inc glycosaminoglycan synthesis
|
|
|
What happens to bone while on steroids?
|
Inhibits bone formation; increase osteoCLAST activity by inc RANK/RANKLY and dec OPG
|
|
|
What happens to endothelial cells while on steroids?
|
inhibits expression of adhesion molecules, NO, PG's, complement, and angiogenesis
|
|
|
Which type of immunity is most affected by steroids?
|
cellular
|
|
|
What two key mechanisms are blocked with steroids in SLE?
|
1. cytokines
2. antigen processing (SLE = Type III - so immune cells are also not working as well) |
|
|
Can you get HTN while on steroids?
|
Yes
HOW? |
Bc of Na+ retention
|
|
While on steroids, what happens to protein synthesis? What conditions can occur
|
It is decreased
|
Myopathy, skin thinning, delayed wound healing, fetal growth retardation, negative Ca2+ balance, osteoporosis, fractures and GI ulcers
|
|
What is the main possible MOA of colchicine in acute attack of GOUT?
|
irreversible binding to tubulin protein within the PMN....what does this cause?
|
the lysosomes cannot get to the crystals bc the tubulin is what guides them
|
|
What is the dose for colchicine for an acute attack of gout? the max dose?
|
0.6mg PO q1-2 hrs
|
6 mg
|
|
How long does it take to see colchicine working in Gout? Faster or slower than NSAIDs?
|
12-24 hrs (24 hrs = 90% pain free)
|
slower
|
|
What is the major SE of colchicine?
|
Hyperperistalsis
(also abdominal pain, N&V) |
|
|
What is the prophylactic dose of colchicine with Gout?
|
0.6mg QOD or once/twice daily
|
|
|
Where is the site of action of Probenecid? How does it work?
|
renal tubules (most be secreted in)
|
blocking the reabsorption of UA, increasing the amount of urate excreted from the body
|
|
Does Probenecid have bad AE's? What stones could be formed?
|
No
|
uric acid stones; so decrease amount of acidic drinks/foods
|
|
What interactions occur with Probenecid: + Penicillin; + APAP; + Indocin; + MTX
|
increase penicillin levels (benefit?!?)
increase t1/2 of APAP and indocin increase blood levels of MTX (toxic!!!) *these occur bc probenecid competes for secretion into renal tubule |
|
|
What happens with low levels of ASA taken with Probenecid?
|
Low ASA levels block secretion so Probenecid won't be able to get it and do it's job; inc levels of UA
|
|
|
Besides block xanthine oxidase, how else are these drugs working?
|
By inhibiting the AMP/GMP feedback mech; these drugs with inc AMP and GMP and if they didn't block the FB mechanism then PRPP would increase to get rid of the levels of AMP/GMP (bad thing with gout)
|
|
|
Allopurinol is good for those patients that are overproduces with ___. And the drug of choice for those with gout and ___ ___ disease.
|
tophi; chronic kidney
|
|
|
What is allopurinol an analog of? What is it a competitive antagonist of?
|
hypoxanthine
|
xanthine oxidase
|
|
Allopurinol + xanthine oxidase = ?
|
Alloxathnie (Oxipurinol)
Competitive or non? |
Non-competitive with XO (unlike parent Allopurinol)
|
|
What syndrome can be fatal as a result of taking allopurinol?
|
Allopurinol hypersensitivity syndrome (rash)
|
|
|
Why not give Probenecid with Allopurinol?
|
Bc allopurinol is excreted along with UA; so it wouldn't be able to have an effect due to probenecid
|
|
|
Is Uloric similar to Allopurinol structurally? Benefit?
|
NO; it's a non-purine
|
No interaction with Probenecid and those with decreased renal funt can take as well
|
|
Patients with CKD can take Uloric. WHy?
|
BC metabolized by liver (not kidneys like allopurinol)
|
|
|
Which is less toxic Uloric or Zyloprim
|
Uloric
|
|
|
How does steroids affect Ca2+ balance?
|
Negatively; dec GI absorption and renal reabsorption
|
|
|
What do steroids do to osteoBLASTs? To collagen?
|
decrease its activity
|
increases breakdown
|
|
What does steroids to do RANKL? To OPG?
|
increase
|
decrease
|
|
What do PG's do to renal blood flow and GFR?
|
decreases them
|
|
|
What causes Arachondic acid formation?
|
a stimulus
|
|
|
What Pg does COX go to first?
|
PgG2
|
|
|
What three things does steroids block?
|
PLA2, PLC, and COX
|
|
|
What 2 key features that AAcid have that COX-I's mimic?
|
acid center; double bonds (e- rich area)
|
|
|
COX adds ___ at Carbon #___. This causes a ____ group to form.
|
O2 at C11
|
cyclic
|
|
Which amino acid forms an ion bond with _COOH of AAcid?
|
Arg120
|
|
|
What does amino acid Tyr385 contribute to AAcid binding?
|
being an aromatic amino acid it offers e- density (pi-pi stacking)
|
|
|
Which two C's are oxidized in AAcid rxn?
|
C9 and C11
|
|
|
How does ASA uniquely modify COX?
|
by acetylating the Ser530 amino acid --> irreversible bond
|
|
|
ASA acts on Arg120 thru it's _____. What does this cause?
|
byproduct breakdown
|
blockage of COX competitively
|
|
Do salicylates modify COX like ASA? Why or why not?
|
No
|
Bc salicylates are the by-products of ASA, so only works on Arg120 and not Ser530
|
|
What is one way to know your ASA is no longer good? What caused this?
|
a vinegar smell
|
by moisture cleaving off the acetyl group now leaving only salicylic acid (can't modify COX)
|
|
At what form is ASA in to become trapped in the mucous buffer lining of the stomach?
|
ionized (ASA = weak acid)
|
|
|
If you sub out the hydroxyl group on ASA with an amide (--NH2) what will happen?
|
increase toxicity bc -NH2 would increase the compounds liphilicity (get into stomach cells easier and thus cause greater damage)
|
|
|
Why is Dolobid reversible?
|
bc's it only blocks COX, does not modify it
|
|
|
How many rings does Dolobid have? Why is this impt?
|
2
|
bc it's more like AAcid with increased e- density
|
|
What do added fluro groups do?
|
increase lipophlicity
|
yields greater analgesic properties in Sulindac than Indocin
|
|
What is Salsalate?
|
2 salicylic acids bound together
Where is it cleaved? |
in the intestines
|
|
Why is Salsalate better for ASA intolerable people?
|
bc it's insoluble in stomach; gets cleaved in the intestines
|
|
|
Which carbon is affected when going from PgG2 to PgH2?
|
C15 gets oxidized
|
|
|
What amino acid blocks the pocket in COX-1? Why does it block it?
|
Ile523
|
bc of the ethyl group is too bulky
|
|
What amino acid is at the pocket in COX-2? Why does it allow binding in the pocket?
|
Val353
|
bc only a methyl group
|
|
What amino acid is inside the pocket of COX?
|
Arg513
|
|
|
In general how many C's is the acid group away from the ring system in NSAIDs (arylalkanoic acids) SAR?
|
1 carbon away; if increase the length what happens?
|
decease in activity of the NSAIDs
|
|
Adding a methyl group separating the acid center from the ring system in NSAIDs does what? What is the name classifies those that have that?
|
increases activity
|
profens
|
|
What is Indocin an analog of?
|
serotonin
|
|
|
In Indocin, is substitution prefered? If so where and what?
|
yes
|
5-position of the indole ring; --OCH3 or F
|
|
Is the N necessary for activity for Indocin?
|
no
|
|
|
The parent of Sulindac is a weak or strong COX-I?
|
weak
|
|
|
When is the metabolite of Sulindac activated? Why is this beneficial?
|
once gets thru stomach to liver
|
Bc less local COX-1 inhib in the stomach
|
|
What in Sulindac structure have poor water solubility?
|
the p-suloxide group (vs the p-Cl group that Indocin has)
|
|
|
Replacing the 5-methyl group (on Indocin) with 5-flouro group (on Sulidac) yields what?
|
greater analgesic properties
|
|
|
What isomer form is a more potent anti-inflam drug for Sulindac?
|
Z-isomer (Z same side --> F and sulfide)
|
|
|
Parent drug Sulindac has a t1/2 of ___. And the metabolite has a t1/2 of ___.
|
8 hours
|
16 hours
|
|
What planar effect is preferred for COX. Which isomer has that in Sulindac?
|
antiplanar
|
the Z isomer does
|
|
Why is DMSO so good at suspending drugs?
|
bc very lipohilic
|
|
|
What drug is DMSO reduced like? What's a result of this?
|
Sulindac
|
it inhibits/interferes with the metabolism of Sulindac
|
|
Tolmentin has strictly _____ properties.
|
anti-inflammatory
|
|
|
Ketorolac primarily has ____ properties
|
analgesic
|
|
|
Ketorolac's structure is the fused structure of what drug? What does this fusion do?
|
Tolmentin
|
prevents rotation of the compound; so ring is sticking out
|
|
What big side effect is increased with Ketorolac?
|
GI bleeding and post operative bleeding
|
|
|
The pleuotrophic effects of Diclofenac makes it a more potent ____ agent.
|
anti-inflammatory
|
|
|
What two compounds does Diclofenac inhibit (pleuotrophic effects)?
|
lipoxygenase synthesis and AAcid release
|
|
|
What is significant about misoprostol in Arthrotec?
|
it's a synthetic PgE1 --> reduces GI ulcers and erosion
|
|
|
What does the --OOCH3 addition (from --COOH) do to Misoprostol?
|
Increases the potency and duration of action bc it gets cleaved to the acid
|
|
|
What does the movement of the hydroxyl group from C15 to C16 (farther from the ring) do to Misoprostol?
|
Allows oral dosage (only 1 in US) and increases the duration of action
|
|
|
How does Etodolac increase some selectivity from COX2?
|
By decreasing COX 1 selectivity by increasing the number of C's btwn the ring and the acid
|
|
|
Is Etodolac less GI toxic? Which form only has AI activity?
|
Yes
|
S+
|
|
Where is Nabumetone absorbed? What is special about this drug?
|
Duodenum
|
non-acidic prodrug
|
|
What is Nabumetone bioactivated into?
|
6MNA
|
|
|
T/F The higher the irritancy # = the better
|
True; the lower = more GI problems (Nabumetone is 21.25 and Diclofenac is 0.72)
|
|
|
What chemistry happens to get to 6MNA from Nabumetone?
|
hepatic oxidation reaction removes 2 C's and adds active carboxy group
|
|
|
Which form of Ibuprofen becomes active in vivo?
|
R- (it turns into S+ so both become active)
|
|
|
Is extensive ionization good for Ibuprofen?
|
NO - increases excretion
|
|
|
Is Fenoprofen as good an AI as other drugs? What form is active in mixture?
|
No
|
S+
|
|
How is Ketoprofen unique in activity?
|
It stabilizes lysosomal membranes during inflammation; less GI toxicity
|
|
|
Ansaid has enhanced acidity because of these 2 added structure.
|
F and Ring (added to Ibuprofen back bone)
|
|
|
Anaprox is what from of Naproxen? When is it activated?
|
R-
|
In vivo
|
|
Naprosyn is what from of Naproxen? When is it activitated?
|
S+
|
In vitro
|
|
Is Naproxen better at COX-I than Indocin?
|
NO!!! 300x less COX inhib
|
|
|
6MNA is structurally similar to drug ____ without the ___ group.
|
Naproxen
|
methyl (--CH3) --> adds potency to Naproxen
|
|
Pirioxicam inhibits COX ___ as Indocin with a ___ half life.
|
equally
|
longer
|
|
Meloxicam and Piroxicam are interestingly not ___.
|
acids
|
3-carboxymide
|
|
In Oxicam's SAR what stucture is required for AI properties?
|
3-carboxymide
|
|
|
For Oxicams, what causes acidity?
|
resonance and de-localization
|
|
|
What makes Mobic preferential COX2-I?
|
the methyl-thiazolyl group (ring)
|
|
|
With Mobic what does increased acidity do?
|
Increase AI properties
|
|
|
What structurally group gives COX2-I selectivity?
|
p-sulfonamide
|
|
|
Is Celecoxib an acid?
|
no, non-acid
|
|
|
Celecoxib is metabolized primarily by ___ and inhibits ___ (CYPs)
|
CYP 2C9
|
CYP2D6 (inhibits)
|
|
What happens if patient is on Celebrex and Fluconazole?
|
Build up of Celebrex (cannot metabolize)
|
|
|
At high doses what channel did Vioxx bind to in the heart?
|
K+ channel (HERGG)
|
|
|
COX2 has been shown to be upregulated in what two incidences?
|
Alzheimer plaque and polyps in the colon
|
|
|
Is APAP more or less acidic?
|
Less ; basic drug with pKa of 9.5
|
|
|
What does acute alcoholic intake do to APAP metabolism in the liver?
|
dec the CYP450 enzyme so decreases active metabolite
|
|
|
What does chronic alcoholic intake do to APAP metabolism in the liver?
|
Upregulates CYP450 oxidases so more good and BAD metabolite being made --> inc risk of toxicity
|
|
|
Decrease in pH (like inflamed tissue) causes a(n) ___ in urate solubility and thus a(n) ___ in crystal formations
|
decrease
|
increase
|
|
What is Allopurinol a isomer of?
|
Hypoxanthine
|
|
|
Is Allopurinol competitive or non to Xanthine Oxidase? Is it reversible or not?
|
Competitive
|
Reversible
|
|
Why is Hypoxanthine and Xanthine ok to have in excess due to Allopurinol?
|
bc more water soluble that UA, easier to excrete
|
|
|
What contributes to Allopurinol's effect?
|
It's long active metabolite, Oxypurinol (non-competitive of XO)
|
|
|
What labs should be done with Gout? (5)
|
CBC, ESR, AST/ALT, Serum urate, and a urinalysis
|
|
|
What 3 medical conditions should be controlled when treating Gout?
|
HTN, DM, and Hyperlipidemia
|
|
|
Are NSAIDs good for treating geriatric patients with an acute attack of Gout?
|
no, even in short term use there is increased AE's
|
|
|
Can ppl with recent MI or CABG surgery take NSAIDs?
|
no
|
|
|
Dose for Indocin when treating Gout?
|
25-50 mg po qid x 3 days; then taper to 25-50 mg bid x 4-7 days
|
|
|
Dose for Naproxyn when treating Gout?
|
500 mg po bid x3 days; then 250-500mg qd x4-7 days
|
|
|
Dose for Sulindac when treating Gout?
|
200 mg po bid x7-10 days
|
|
|
What's the 1st line for Gout (when not CI)? How long should they be used for on average?
|
NSAIDs
|
8-10 days
|
|
What should be monitored when taking Colchicine long-term?
|
GI side effects, WBC/RBC count (checked every 6-12), SCr/BUN, Muscle weakness (neuromyopathy)
|
|
|
What are CI for NSAIDs? (4)
|
severe uncontrolled CHF; severe renal impairment; Active PUD; allergy to ASA (or another NSAID)
|
|
|
How long should Colchicine be used in conjunction with an urate lowering drug
|
3-6 months
|
|
|
Can Colchicine be used for preventative therapy?
|
Yes; what's the dose?
|
0.6 mg QOD to QD
|
|
How should Colchicine be taken if pt is also on Verapamil? Why?
|
two tabs for acute attck (1 then 1 hour later)
|
bc Verapamil is a moderate inhibitor of CYP3A4 (enzyme Colchicine is metabolized by)
|
|
How should Colchicine be taken if pt is also on Clarithromycin? Why?
|
1 tab followed by a 1/2 tablet 1 hour later
|
bc Clarithromycin is a strong inhibitor of CYP3A4 (enzyme Colchicine is metabolized by)
|
|
What is the current FDA regimen for Colchicine when treating acute attack of Gout?
|
two 0.6 mg tablets po followed by 1 tab one hour later
|
|
|
Do you get WBC increase with Colchicine?
|
NO!!! WBC decreases
|
|
|
Name some Colchicine CI's?
|
Serious renal disease, Serious GI disorder, Serious hepatic disorder, Serious cardiac disorder, and blood disorders
|
|
|
When should Colchicine be D/C when taking for an acute attack?
|
as soon as pain resolves
|
|
|
What is the Gout regimen for oral prednisone? How should it be tapered?
|
20-60 mg daily for 3-5 days
|
taper in 5 mg decrements each day over 7-14 days until discontinuation
|
|
What is Intra-articular trimacinolone acetaninde dose in Gout for large joint(s)? Small joint(s)?
|
large: 10-40 mg
|
small: 5-20 mg
|
|
usual dose for Allopurinol?
|
300 mg po qd
|
|
|
Name some SE's of Allopurinol.
|
Skin rash, GI upset, Musculoskeletal complaints, Leukopenia, liver toxicity, and severe hypersensitivity rxn
|
|
|
When should Allopurinol be initiated?
|
AT LEAST 1 month after acute attack; pt must be completely back to normalcy
|
|
|
Allopurinol and Amoxicillin increases what SE?
|
rash
|
|
|
Hypersensitivity risk increases when take Allopurinol plus ____ and ____.
|
ACE-I's and Thiazide diuretics
|
|
|
What labs should be monitiored while on Allopurinol? (5) When should they periodically be checked?
|
BUN, basic metabolic panel, AST/ALT, SCr, and CBC
|
6th and 12th months
|
|
Where is 90% of Uloric metabolized?
|
liver
|
|
|
What is the initial dose of Uloric? After 2 weeks and UA >6?
|
40 mg daily
|
80 mg daily
|
|
Does Uloric require use of a NSAID or Colchicine at initiation?
|
yes; just like Allopurinol
|
|
|
Is dose modification required on Uloric if there is mild/moderate renal insufficiency?
|
NO (unlike Allopurinol)
|
|
|
Can Uloric cause Cardiovascular SE's?
|
Yes...what 3 specifically?
|
MI, CHF, and thromboembolism (these should be monitored while taking med)
|
|
Initial dose of Probenecid? What's the max dose?
|
250 mg BID x 1-2 weeks; increase gradually to 500-2000mg/day
|
2 g
|
|
Probenecid is ineffective in CrCl that is ______.
|
less than 50 mL/min
|
|
|
T/F. Probenecid is CI if had a history of urolithiasis?
|
True
|
|
|
To prevent Kidney stones in GOUT what should protein intake be limited to?
|
<90 g/day
|
|
|
To increase urine pH what two drugs can be used?
|
Potassium bicarbonate (citrate) and acetylzolamide
|
|
|
Do OA patients typically have a fever?
|
No!
|
|
|
Acupuncture had a ___% decrease in pain and improvement in knee functions in OA patients.
|
40
|
|
|
Whats a good APAP starting dose in treating OA?
|
500 mg QID -- scheduled
|
|
|
Can APAP be taken along with tramadol or opoids in severe pain in OA?
|
yes, also with capsaicin and glucosamine (COMBO = Better)
|
|
|
What's the dosage of Tylenol XR or Tylenol Athritis?
|
650 mg XR; 1-2 tabs TID (no more that 5-6 tabs)
|
|
|
What's Salsalate's OA dosage?
|
500-1000 mg BID-TID
|
3g
|
|
What's Nabumetone's OA dosage? Max dose?
|
500 mg qd-bid
|
2g/day
|
|
What's Etodolac's OA dosage? Max dose?
|
300-500 mg bid
|
max: 1200 mg/day
|
|
What's dicolfenac's OA dosage? Max dose?
|
75 mg bid; XR 100 mg qd
|
200 mg/day
|
|
What's Piroxicam's OA dosage? Max dose?
|
10-20 mg qd
|
20mg/day
|
|
What's Meloxicam's OA dosage? Max dose?
|
7.5 mg qd
|
15mg/day
|
|
What's Ibuprofen's OA dosage? Max dose?
|
1200-3200 mg qd in 3-4 divided doses
|
3200 mg/day
|
|
What's Naproxen Sodium's OA dosage? Max dose?
|
275-550 mg bid
|
1375mg/day
|
|
What's Oxaprozin's OA dosage? Max dose?
|
600-1200 mg qd
|
1800mg/day
|
|
What's Celebrex's OA dosage? Max dose?
|
100mg bid or 200 mg qd
|
200 mg
|
|
How much should Celebrex's dose be reduced in an OA patient with hepatic impairment?
|
dec by 50%
|
|
|
What initial labs should be down before starting NSAIDs?
|
SCr, BUN, K+, CBC, AST/ALT, weight (bc of edema) and vital signs (like BP)
|
|
|
Can diabetes and pre-exisiting HTN/CVD increase risk of renal impairment with NSAIDs?
|
yes
|
|
|
What are some S/S of renal AE?
|
increased BP, SCr, Serum K+, BUN, Edema and weight gain
|
|
|
What two NSAIDs have a relatively higher risk of renal toxicity?
|
Indocin and Piroxicam
|
|
|
What oral agents are preferred in OA patients with CV disease or ischemic heart disease?
|
APAP, ASA, tramadol, opoids, and non-acetylated salicylates
|
|
|
How often should Capsaicin be used? How long before see full effects?
|
qid (or tid if after several weeks)
|
1-2 weeks
|
|
Where are topical salicylates used for OA?
|
the knee
|
|
|
What is Flector indicated for?
|
minor sprains, strains and bruises
|
|
|
Where is significant improvement seen when Volteran Gel is applied?
|
hands, knees
|
|
|
How often should Voltaren gel be applied daily? How many grams?
|
qid
|
upper = 2 grams (max 8g)
lower = 4 grams (max 16 g) TOTAL MAX: 32 g |
|
What is Pennsaid indicated for?
|
OA of the knee
|
|
|
How many times a year can injectable glucocorticoid be used? When will you see the peak pain relief and how long does it last?
|
3-4 times a year
|
peaks in 7-10 days; last 4-8 weeks
|
|
Glucosamine dose for OA? Which form is best?
|
at least 500 mg tid (with food)
|
sulfate over HCL salt form
|
|
Can people with shellfish allergy take Glucosamine or Chondroitin?
|
no
|
|
|
Chondroitin dose of OA?
|
at least 1200 mg daily with food
|
|
|
Tramadol dose for OA? Max dose?
|
50 mg q4-6 hours
|
200 mg/day
|
|
At what age and CrCl should Tramadol's dose be decreased?
|
75
|
<30mL/min
|
|
Name some SE's of Tramadol.
|
Sweating, constipation, nausea, dec seizure threshold (bad with SSRI's)
|
|
|
What 3 metabolisms does Glucocorticoids regulate?
|
carbohydrate, lipid and protein
|
|
|
T/F. Mineralocorticoids have AI effects
|
False
|
|
|
In 3-D space Alpha is ____ and Beta is ___.
|
coming out (towards you)
|
going into page (away from you)
|
|
Name some consequences of GR activation (AI effects)
|
Regression of:
BK B1 and B2 receptors; COX-2; IL-4R, IL-1beta, IL-6, IL-8. IL-11, iNOS; PLA |
|
|
Steroid biosynthesis leads to formation of _____, which serves as the precursor of all adrenocorticoids.
|
pregnenolone
|
|
|
Cortisone is converted to ____ in vivo.
|
Cortisol (hydrocortisone)
|
|
|
Which one has better oral bioavailability -- Cortisol or Cortisone?
|
Cortisol (95%)
|
|
|
Cortisone ____ly goes to MR's.
|
weak-ly
|
|
|
Cortisone has what unique structure that's converted in vivo?
|
ketone --> goes to alcohol (-OH) at C-11
|
|
|
What disease is Fludrocortisone used for? Why?
|
Addison's disease
|
bc in Addison's there's severe adrenocortical insufficiency and Fludrocortisone is very potent for GR and MR!
|
|
In steroids, what structure is required for GR activity? For MR?
|
11beta-OH group or 11-ketone group on ring C
|
C21-OH group on ring D
|
|
In steroids, why does adding C=C bond at C1-C2 greater for GR activity?
|
bc of changes in the structure's confirmation; chair --> half-chair --> FLAT-BOAT (which fits better at GR than MR pocket)
|
|
|
The 6alpha-methyl group does what for Methylprednisolone?
|
decreases affinity for MR and increases GR activity slightly
|
|
|
Why does the 16alpha-methyl group in Dexamethasone increase GR activity?
|
adds lipophilicity
|
|
|
Is Betamethasone more active than Dexamethasone? Is more toxic than other corticosteroids?
|
yes
|
no; less toxic SE's
|