Download Drugs for RA

Class of Drugs
Penicillin
Drug Names
- Narrow Spectrum
- Antistaphyloccocal
- Extended Spectrum
Specific For
- Narrow Spectrum:
Gm (+) Cocci,
spirochetes
- Antistaphyloccocal:
Staph
- Extended Spectrum:
Gm (-) bacilli
Cephalosporin
1st Gen:
- Cefazolin: IV
- Cephalexin: Oral
2nd Gen
- Cefurozime sodium: IV
- Cefuroxime axetil: oral
3rd Gen:
- Ceftazidime: against P.
aeruginosa
- Ceftriaxone: against
Gonorrhea
th
4 Gen:
- Cefepime: P. aeruginosa
1st Gen: Gm (+)  4th
Gen: Gm (-)
Imipenam – cilastatin
Ertapenem
Doripenem
Meropenem
Broad Spectrum: Gm
(+/-) and anaerobes
Carbapenems
(DIME)
Special Things
Adverse Effects
Degraded to penicilloic acid
which binds to antigens and
forms an immune response
- Hypersensitivy: urticaria
or anaphylactic shock
- serum sickness
- interstitial nephritis
- Non-allergic amoxicillin
rash
Platelet dysfunction and
bleeding w/ cefotetan
5% Cross-sensitivity with
penicillin
- seizures w/ renal
insufficiency
- cross-sensitivity w/ pcns
- Dose adjustments
needed with renal
insufficiency
Monobactam
Aztreonam
Vancomycin –
Glycopeptide
antibiotic
Gm (-) aerobes
When there are
multo-drug resistant
strains of:
Enterobacter,
Citrobacter,
Klebsiella, P.
aeruginosa (PECK)
Gm (+) Cocci and
MRSA
- hypersensitivity reactions
Oral – Don’t use for
systemic infections
Beginning to
experience VRE
Concentration
Dependent Killing
Lipoglycopeptides –
Dalbavancin
interfere with bacterial Oritavancin
Telavancin
cell wall synthesis
MRSA
(DOT)
Bacitracin – messes
with
dephosphorylation;
inhibits transfer of
peptidoglycan subunits
Staph, Strep
- Red Man Syndrome:
hypotension, erythematous
rash on face  caused if
infused too quickly
- Oto and Nephrotoxicity
- Fevers, chills, flushing
and phlebitis
- Dalbavancin – Red man
Syndrome
- Oritavancin – Itching and
flushing
- Telavancin – Red man
Syndrome & CI for
pregnant women
(nephrotoxicity)
- Nephrotxicity if not used
topically
Fosfomycin – stops
formation of Nacetylmuramic acid
-Aminoglycosides (30S) Amikacin
Gentamicin
Neomycin
Streptomycin
Tobramycin
Tetracycline (30S)
(GNATS)
Doxycyline
Minocycline
Tetracycline
Tigecycline
Gram (+/-), UTI in
Women
Aerobic Gm (-) bacilli
Bacteriocidal
Nephro and Ototoxicity
Aerobic Gram (+/-),
rickettsia,
mycoplasma,
chlamydia, CA-MRSA
Bacteriostatic
Gm (+/-) bacteria
Bacteriostatic
- Bind to divalent cations,
so [ ] goes down with milk
and yogurt
- Discoloration of teeth –
avoid in pregnancy and
children < 8
- Photosensitization
- Esophageal ulcers (so
swallow with a full glass of
water)
- Diarrhea
- Cholestatic hepatits
- Azithromycin &
telithromycin: QT interval
prolongation
- CYP3A4 inhibitor (except
for azithro)
- Teli – contraindicated w/
myasthenia gravis (resp.
(DOMInaTE TI)
Macrolides (50S)
Erythromycin
Azithromycin
Clarithromycin
Telithromycin
Gm (+) Cocci,
Anaerobes, MRSA
Gm (+) Cocci,
meningococci, H.
Influenza
Static or cidal
depending on [ ]
Quinupristin
Dalfopristin
30:70 mixture (Syndercid)
Gm (+), VRE
Static alone
Linezolid
Tedizolid
Gm (+), MRSA VRE
Clindamycin (50S)
Chloramphenicol (50S)
Streptogramins (50S)
Oxazolidones (50S)
Cidal in combination
Static against
enterococci & staph
Cidal against strept
Sulfonamides – inhibit
ability to make folic
acid
Sulfamethoxide
Trimethoprim
Together: (TMP-SMX)
Gm (-), MRSA
Static separately
Cidal – TMP-SMX
failure)
- Diarrhea
- C. dif.
- “Gray baby” syndrome:
weakness, resp. depression,
hypotension, shock & ashen
gray cyanosis
- Aplastic anemia
- Arthralgia
- Myalgia
- Diarrhea
- Nausea
- Linezolid:
thrombocytopenia
- Serotonin syndrome:
severe diarrhea, mental
status changes,
hyperthermia – common
with other drugs that
increase serotonin
Warfarin: Serious bleeds
Phenytoin:
- Crystalluria
- Kernicterus
- Hyperkalemia (increase in
potassium)
- Hemolytic anemia with
G6PD deficiency
- Stevens-Johnson
Fluoroquinolones –
Inhibit 2 bacterial DNA
topoisomerases
Type II (DNA Gyrase)
Type II – Gm (-)
Type IV
Ciprofloxacin
Levofloxacin
Moxifloxacin
Ofloxacin
Norfloxacin
Type IV – Gm (+)
Concentration
dependent killing
Cidal against Gm (+/-)
Long PAE
COLuMN
Metronidazole &
Tinidazole – creates
reactive reduction
products (nitroradicals), which has
antimicrobial effects
Nitrofurantoin –
causes DNA damage
Anaerobes:
bacteroides,
C. dif,
H. Pylori,
E. Histolytica,
Giardia,
Trichomonas
vaginalis
GET BitCH
E. Coli,
E. faecalis,
K. Pneumonia,
S. Saprophyticus
USE WITH UTI’s
Syndrome (Skin
hypersensitivity)
- Tendonitis & rupture
- CI in pregnancy &
pediatrics – Cartilage
damage
- hypo/hyperglycemia
- phototoxicity
- peripheral neuropathy
- QT prolongation
- Binds with Caffeine
(CYP1A2 inhibitor)
- Bind to divalent cations,
so [ ] goes down with milk
and yogurt
- Anorexia
- Metallic taste – so take
w/ food
- Disulfarim-like reaction
w/ EtOH: nausea, vomiting,
sweating, flushing,
palpations, dyspnea
- Nausea
- Diarrhea,
- Hemolytic anemia w/
G6PD deficiency
- pulmonary fibrosis w/
prolonged use
- CI: CrCL < 60ml/min =
possible accumulation of
toxic metabolites
- CrCL < 40 mL/min =
ineffective
Daptomycin – Inserts a
MRSA, VRE, VR S.
aureus (VRSA)…
lipophilic tail into the
bacterial cell
membrane  messes
with cell membrane
causes K efflux 
leads to nucleic acid
and protein synthesis
arrest  cell death
1. Against MRSA
a. Inhibit Cell Wall Synthesis:
i. Vancomycin
ii. Lipoglycopeptides
b. 30S inhibitor
i. Tetracycline
c. 50S inhibitor
i. Clindamycin
ii. Oxazolidones
d. Folic Acid synthesis inhibitor
i. Sulfonamides
e. Nucleic and amino acid synthesis arrest by lipophilic tail insertion
i. Daptomycin
myopathy
2. Against VRE
a. 50S inhibitor
i. Streptogramins
ii. Oxizoladones
b. Nucleic and amino acid synthesis arrest
i. Daptomycin
3. Leave Quin alone to ride his bicycle
a. Tetracycline and Fluorquinalones bind to di and tri-valent cations like milk and yogurt
4. Nitro and his furious sulfur causes you to bleed
a. Nitrofurantoin and Sulfonamides: Hemolytic anemia with G6PD deficiency
5. When Quin and Mac’s heart races when they do down the slide.
a. Macrolides (Azithromycin and Telithromycin) and fluoroquinalones cause QT prolongation
6. Quin likes coffee and Mac likes drugs
a. Fluoroquinalones inhibit 1A2
b. Macrolides (except azithromycin) inhibit 3A4
Systemic AntiFungal Drugs
Drug
Amphotericin B
Mode of Action
Clinical Uses
Binds ergosterol and forms leaky Candida,
pores on cell membranes
C. neoformans,
B. dermatitidis
H. capsulatum
S. shenkii
C. immitis
Paracoccidioides
braziliensis
Aspergillus
Penicillium marneffei
Mucormyces
Adverse Effects
Systemic AntiFungal Drugs
Flucytosine
Systemic AntiFungal Drugs
Azoles –
Imidazoles
 Ketoconazole
 Miconazole
 Clotrimazole
Systemic AntiFungal Drugs
MiCKey
Azoles –
Triazoles
 Itraconazole
 Fluconazole
 Voriconazole
FIVe
Forms the active metabolite 5fluorodeoxyuridine
monophosphate (inhibits DNA
synthesis)
&
Forms fluorouridine
triphosphate (inhibits RNA
synthesis)
Inhibit fungal cytochrome p450
and reduce ergosterol synthesis
- C. neoformans
- Some Candida
- Some dermatiaceous
molds that cause
chromoblastomycosis
Inhibit fungal cytochrome p450
and reduce ergosterol synthesis
Fluconazole:
- Used to treat
mucocutaneous
candidiasis
More selective for fungal p450
than imidazoles
Fluconazole:
- Water soluble and good
body fluid distribution (CSF)
- High bioavailability and has
least effects
- Best cytotoxicity to fungals
Voriconazole:
- Good absorption, high
Intestinal flora converts
drug to fluorouracil (an
anti-neoplastic drug) 
gives:
- bone marrow toxicity
- anemia
- leukopenia
- thrombocytopenia
Systemic Anti-Fungal Drugs
Echinocandins
 Caspofungin
 Micafungin
 Anidulafungin
MAC is a fun-gi-n
bioavailability and less
plasma protein binding than
Itraconazole
- Oral and I.V. forms available
- Undergoes hepatic
metabolism, less human
P450 induction
Destroys fungal cell wall by
inhibiting Beta-glycan synthesis
Caspofungin:
- mucocutaneous
candida infections
- antifungal during
febrile neutropenia
- For aspergillosis as a
back up when
amphotericin B fails.
Micafungin:
- mucocutaneous
candidiasis
- Prophylaxis of
candida in bone
marrow transplant
Anidulafungin:
- esophageal
candidiasis
- invasive candidiasis
septicemia
Oral Drug for
Mucocutaneous
Infection
Griseofulvin
Binds to microtubules and
disrupts mitosis.
Systemic treatment of
dermatophytosis ONLY
USE TOPICALL
It also binds to keratin in the
skin and protects form new
fungal infections
Oral Drug for
Mucocutaneous
Infection
Terbinafine
Viral Nucleic acid
Synthesis inhibitor
- They are
nucleosides that are
phosphorylated to
their nucleotide
analog and then act
as a substrate for
viral enzyme
Interferes with ergosterol
biosynthesis (like azoles)
Dermatophytes –
especially Onchomycosis
No action on P-450
Inhibits fungal squalene
epoxidase  accumulation of
sterol squalene which is toxic to
fungi
Drug
Mechanism of Action
Acyclovir (AntiPhosphorylated by viral
herpetic)
thymidine kinase (TK) –
this increases it’s
selectivity
Clinical Uses
HSV
EBV
VZV
Adverse Effects
Resistance to acyclovir
can develop in HSV or
VZV due to alteration in
either viral TK or viral
polymerase
Viral Nucleic acid
Synthesis inhibitor
Famciclovir (Antiherpetic)
Undergoes first-pass
metabolism to
penciclovir (PCV) after
oral administration –
happens in intestinal
wall and liver
For management of
acute herpes zoster
For suppression of
recurrent genital
herpes
Reaches maximum
serum levels in less than
an hour if taken while
fasting
Viral Nucleic acid
Synthesis inhibitor
Ganciclovir (AntiCMV)
Guanine
Viral Nucleic acid
Synthesis inhibitor
Cytosine
Cidofovir (Anti-CMV)
MOA similar to Acyclovir
Guanosine analog that’s Inhibits DNA
phosphorylated by virus polymerase of CMV
protein kinase UL97 and
then by cellular kinases
Cytosine analog that’s
Broad Spectrum  in
activated by intracellular vitro activity of:
enzymes to form an
- CMV
inhibitor of DNA
- HSV-1
polymerases
- HSV-3
- VZV
1000-fold more effective - EBV
against DNA
- HHV-6
polymerases of viruses
- Adenovirus
instead of DNA
- HPV
polymerases of host cell
- Approved for
treatment of CMV
retinitis in AIDS
patients
Viral Nucleic acid
Synthesis inhibitor
Foscarnet (AntiCMV)
Inorganic
pyrophosphate
compound
Inhibits viral DNA
polymerase, RNA
polymerase, HIV RT, and
DOES NOT require
activation of
phosphorylation
Topical for
mucocutaneous herpes
infections
HSV
VZV
CMV
EBV
HHV-6
HBV
HIV
Parathyroid and Osteoporosis
Type
Osteoporosis
Drug
Teriparatide
MOA
PTH analog
Clinical Use
-Increase bone mass in men
with primary or hypogonadal
osteoporosis
-
Use for postmenopausal
osteoporosis
AE
Oral Phosphate
Binder
Oral Phosphate
Binder
Vitamin D
Analogue
Calcimimetic
Calcium
carbonate
Calcium acetate
Sevelamer
Calcitriol
Paricalcitol
Cincalcet
Bisphosphonates Pamidronate
Alendronate
Drugs for
Risedronate
osteoporosis
Ibandronate
&
Zolendronate
Paget Disease
Etidronate
Binds to dietary phosphates and
inhibits their absorption
A non-absorbable cationic ion
exchange resin that binds intestinal
phosphates
Calcitriol – D3 analogue
Paricalcitol – D2 analogue
Binds to the transmembrane portion
of the calcium-sensing receptor in
the parathyroid and increases
sensitivity to calcium
So, the parathyroid thinks it’s seeing
more calcium than is really present,
and then it won’t release PTH
Substitute for pyrophosphate
Hyperphosphatemia in chronic
kidney disease - also 2ndary
hyperparathyroidism
Hyperphosphatemia in chronic
kidney disease - also 2ndary
hyperparathyroidism
Low vitamin-D due to 2ndary
hyperparathyroidism
Don’t use Calcitriol until
hyperphosphatemia is
controlled – because it will
increase calcium, but it will
just bind to the excess
phosphates
2ndary hyperparathyroidism
Hypercalcemia associated with
parathyroid carcinoma
USED FOR OSTEOPOROSIS
Induce apoptosis of osteoclasts
Results:
- Increases BMD
- Decreases vertebral
fractures
Alendronate & Risedronate –
prevent treatment of
Poor GI absorption
Long half-lives
CI: Pregnancy
Esophageal ulcers
Esophageal stricture
Dyspepsia
Dysphagia
Acid regurgitation
postmenopausal and
glucocorticoid-induced
osteoporosis
Ibandronate – treatment and
prevention of postmenopausal
osteoporosis
- Can be used prophylactically
Drug for Paget
Disease
Drug for
Osteoporosis
Calcitonin
Estrogen
- Raloxifene
Physiologic antagonist of PTH
Inhibits osteoclast action
Increases BMD and decreases
vertebral fracture
- Stabilizes bone remodeling
- Increases GI calcium absorption
- Promotes Calcitonin synthesis
- Increases the # of Vit. D receptors
on osteoblasts
- Increases BMD and decreases
fractures
- Increases HDL and triglycerides
Abdominal pain
Nausea
Diarrhea
MSK Pain
Osteomalacia with long-term
use of etidronate
For Paget Disease
Can use for osteoporosis in
women who are at > 5 years
postmenopausal
Administration:
SC or IM of 50-100
Used to treat osteoporosis in
post-menopausal women
Raloxifene – DOES NOT
stimulate endometrium, so
decreased risk of endometrial
cancer
Increased risk of breast
cancer and endometrial
cancer
- Weight gain, fluid retention
- Vaginal bleeding and
spotting
- Increased risk of thrombosis
Breast enlargement and
tenderness
NSAIDS
Type
Acetylsalicylic
Acid
Drug
Aspirin
-
Non-Selective,
Irreversible COX
Inhibitor
MOA
Anti-inflammatory – Decreases
prostaglandins
Analgesic – decreases PGE2
Antipyretic – decreases PGE2
Blood thinner (anti-platelet)
Clinical Use
60-80 mg/d - Antithrombotic effect
(Prophylaxis for MI &
stroke)
AE
3-4 g – Salicylism – tinnitus,
hearing loss, dizziness, confusion,
headache
CI: Children with a viral infection =
Reye’s Syndrome – hepatitis &
cerebral edema which is fatal
Zero-order kinetics @ high doses
-
Propionic Acid
Derivatives
Non-selective,
reversible COX
Ibuprofen**
Naproxen**
Ketoprofen
Flurbiprofen
Oxaprozin
Use for
pain/inflammation
caused by:
- Trauma
- Infection
GI – Epigastric distress,
ulceration, hemorrhage (Due to
decreased prostaglandins)
Platelets – inhibits COX-1 
inhibits TxA2  results in
decreased platelet aggregation
Kidneys – Inhibits COX 
decreases PGE2 & PGI2 which
inhibits renal function, thus
increasing salt/water retention
GI disturbances, peptic ulcers,
liver/kidney injury
inhibitor
Acetic Acid
Derivatives
Non-selective,
reversible
COX inhibitor
Oxicam
Derivatives
Selective COX-2
Inhibitor
Ketones
Selective COX-2
Inhibitor
- Autoimmunity
- Neoplasms
- Joint degeneration
- arthritis
Use for severe acute
inflammatory
conditions
Indomethacin**
Sulindac
Etodolac
Diclofenac
Ketorolac**
Piroxicam
Meloxicam**a
Indomethacin – one of the most
potent inhibitors of COX
- Strong GI and CNS AE’s
Treatment for patients
with patent ductus
arteriosus in infants
Meloxicam - Highest selectivity for COX-2
Lower GI risk
Piroxicam – long half-life – so just need a
single daily dose
Nabumetone
Celecoxib
Anti-inflammatory
Antipyretic
Analgesic
-
No anti-platelet action – so chance of GI
bleeding is only 20%
-
RA
OA
Acute pain in
adults
Dysmenorrhea
- Renal effects
**Cardiovascular risk** - PGI2
provides cardiovascular protection.
Prolonged decrease in PGI2
produces these adverse
cardiovascular effects
DI: CYP2C9 inhibition, so you don’t
metabolize fluconazole (A trizole)
and fluvastatin
GENERAL
NSAIDS
Gastroprotective Drugs
to take with
NSAIDs
Gastroprotective Drugs
to take with
NSAIDs
1. Use COX-1 over COX-2 when trying
to avoid cardiovascular risk
2. Consider Tylenol for pain first
3. Try Naproxen first since it has the
lowest cardiovascular risk
4. If taking aspirin in combination with
other NSAIDs, take first so it can do
it’s blood thinning effect
Misoprostol
- reduces risk of gastric problems by 40%
Proton pump
inhibitors
- decreases risk of NSAID-related bleeding
(NNT-11)
Fever
Mild/moderate pain
from:
- Headache
- Sports injury
- Dysmenorrhea
- OA
- RA
- Bone Cancer
1. GI bleed risk with all NSAIDs
increases 4x
2. Major Risk Factors - males,
history of peptic ulcers,
dyspepsia, CV disease, age >
60
3. Risk increases when taking
NSAIDs with aspirin,
corticosteroids, or
anticoagulants like warfarin
4. NSAIDS decrease risk of
diuretics
5. NSAIDs decrease
elimination of lithium and
methotrexate = toxicity
6. Taking with warfarin =
bleeding a lot
- Diarrhea and cramping
Topical NSAID
Diclofenac
Local inhibition of COX-2
Use when first-line
agents fail
Pruritus, burning, pain, rash
ACETAMINOPHEN
Type
Drug
Acetaminophen
MOA
Inhibits
prostaglandin
synthesis in the CNS
by blocking central
COX
Clinical Use
Fever, pain from OA
F = 60-98%
Biotransformation
via conjugation w/
sulfate or
glucuronide – Nhydroxylation via a
CYP
So NSAIDs block COX
after it’s been made
Acetaminophen
blocks the production
of COX altogether
Metabolites are
renally excreted
AE
Hepatotoxicity
- Don’t take more
than 4 g/day
- Chronic use
- Taking with EtOH
- Taking with
Isoniazid
DI
- Increases action of
warfarin
- Izoniazid =
heptatotoxicity
Topical Analgesic
Type
created from hot
peppers
Drug
Capsaicin
MOA
Depletes substance P
from nociceptor nerve
fibers
Clinical Use
MSK pain
AE
Burning, stinging,
erythema
WASH HANDS AFTER
USE
Glucocorticoids
Type
Endogenous
Glucocorticoids
Drug
Cortisol
Corticosterone
Cortisone
MOA
Asthma – inflammatory
response is mediated by
thromboxanes, prostaglandins,
and leukotrienes --> increased
platelet aggregation, vascular
permeability, and
vasoconstriction
- GC’s block this process
Clinical Use
- Addison’s
- RA, Asthma
- Depress
Immune
response – for
cancer or
transplantation
AE
Long-term GC’s inhibit ACTH
from pituitary – so taper drug as
removing to avoid adrenal
insufficiency
- Iatrogenic Cushing’s syndrome
caused by prolonged use of
synthetic glucocorticoids
- Osteoporosis occurs due to GCs
inhibiting vitamin-D mediated
calcium absorption so that
secondary hyperparathyroidism
develops. GCs also inhibit
osteoblast function.
- Impaired wound healing
Peptic ulcers, psycosis (with large
doses), salt retention and its
complications(cortisone,
hydrocortisone)
Multiple disorders for energy
storage and possible development
of type II diabetes mellitus; als
redistribution of fat from
periphery to trunk
Protein break down  free aa. 
glucogenesis. This results in
weight gain, visceral fat deposit,
myopathy and muscle waisting
Adrenal suppression may occur if
glucocorticoids are administered
for more than two weeks
Exogenous
Glucocorticoids
Fludrocortisone
Dexamethasone
Betamethasone
Glucocorticoid
Hydrocortisone
Dexamethasone – Binds to
glucocorticoid receptors in the
anterior pituitary which
supplies a negative feedback
mechanism to lower the
release of ACTH.
-
Adrenoinsu
ffiiciency:
Addison’s
Acute
Adrenoinsu
ffiiciency
Addison’s Supplement
with an
aldosterone
analogue to
account for salt
loss – Like
fludrocortisone
Acute – large
does initially,
then taper does
down before
adding an
aldosterone
analogue
Glucocorticoid
Inhibitors
Mineralocorticoid
Mitotane
Metyrapone
Ketoconazole
Mifepristone (RU-586)
Fludrocortisone
Deoxycorticosterone
Aldosterone
Top 3 = Enzyme inhibitors
Mifepristone – Blocks GC
intracellular receptor
Aldosterone –
Excessive Aldosterone causes
hypokalemia, metabolic
alkalosis, and increase plasma
Fludrocortisone – Most
common salt-retaining
hormone prescribed – It has
glucocorticoid and
mineralocorticoid activity.
- Undergoes first-pass
metabolism much slower
than aldosterone does.
- Be sure to monitor blood
pressure and serum
potassium
Deoxycorticosterone –
endogenous precursor of
aldosterone – controlled only
by ACTH (unline aldosterone)
Mineralocorticoid
Spironolactone
Aldosterone –
mineralcorticoid – regulated by
ACTH and renin-angiotensin
pathways
Activation of aldosterone
receptor cause increase
expression of the Na+/K+ ATPase
and the epithelial sodium
channel (ENaC)
Mineralocorticoid receptor
Aldosteronism
antagonist
Inhibits androgen and
volume - hypertension
progesterone receptors so that
it can cause gynecomastia in
men
Mineralocorticoid
Eplerenome
More selective
mineralocorticoid receptor
antagonist
Heart failure
Be sure to monitor blood
potassium levels
Treating Gout and Osteoarthritis
Type/Purpose
Osteoarthritis
Drug
Acetaminophen
MOA
Inhibits prostaglandin
synthesis in the CNS by
blocking central COX
Clinical Use
Knee and hip OA
AE / Dosing regimen
2.6 – 4 g/day = Ibuprofen 1.2 – 2.4
g/day = naproxen 0.75 g/day
Take Acetaminophen every 6-8 hours
Osteoarthritis
Topical
Analgesic
Osteoarthritis
Topical NSAIDs
Osteoarthritis
Capsaicin -
Depletes substance P from
nociceptor nerve fibers
Hand OA
Burning, stinging, erythema
Diclofenac
Local inhibition of COX-2
Knee OA if Acetaminophen
fails
Pruritus, burning, pain, rash
Glucosamine
Chondroitin
Stimulate proteoglycan
synthesis from cartilage
Ameliorative effect in patients
with OA of the knee, but NIH
couldn’t prove that
Gas, bloating, cramps
WASH HANDS AFTER USE
DI: Increases bleeding when taken
Osteoarthritis
Osteoarthritis
Corticosteroid
Injection
Hyaluronic Acid
Synovial Fluid
constituent
Reconstitutes synovial fluid
& decreases symptoms
Knee/Hip pain relief (4-8
weeks)
Decrease OA
Evidence of this is poopy
with warfarin
Osteonecrosis, tendon rupture, skin
atrophy
Acute joint swelling
Effusion
Stiffness
Rash
Ecchymoses
Pruritus
ALSO VERY EXPENSIVE
Acute Gout
Acute Gout
Acute Gout
NSAIDs Indomethacin
Corticosteroids –
equivalent to
NSAIDs
Prednisone
Colchecine
Use when NSAIDs are
contraindicated (like renal
insufficicency)
Antimitotic agent – disrupts
microtubules and inhibits
leukocyte migration and
phagocytosis
Pharmacokinetics – Rapidly
absorbed
Partly metabolized in the
liver
Excreted via bile and urine
Prednisone PO 30-60 mg 3-5 days –
taper over 10-14 days in 5 mg
increments
Avoid with renal insufficiency
Has the lowest benefit to toxicity ratio
- Diarrhea
- Bone marrow suppression –
agranulocytosis & aplastic anemia w/
long-term or high dose use
DI – P-glycoproteins and CYP3A4
inhibitors – they decrease biliary
excretion of colchecine
Prophylaxis of
Gout
Allopurinol
Lowers serum urate levels in
a dose-dependent manner
Works for overproducers and
underexcreters
Xanthine
Oxidase
Inhibitors
- Skin rash
- Leukopenia
- Headache
- Hypersensitivity Syndrome – severe
rash, hepatitis, interstitial nephritis,
and eosinophilia
- Reduce dose for renal insufficiency
- Start with low does and titrate up
DI – metabolized to oxypurinol in the
liver
Inhibits metabolism of warfarin
Prophylaxis of
Gout
Febuxostat
-
Xanthine
Oxidase
Inhibitor
-
Nausea
Arthralgias
Increases risk of
thromboembolism
EXPENSIVE
No dose reduction for ClCr > 30
mL/min
DI – metabolized in inactive
metabolites
Prophylaxis of
Gout
Uricosuric
Agents
Probenecid
Increase uric acid excretion
Only works for
underexcreters
CI – azathioprine and mercaptopurine
GI irritation
Rash
Aplastic anemia
CI – CrCl < 50 mL/min
DI – prolongs duration of many
medications, so you can use with
penicillin to prolong effects
Gout
Gout
Gout
Fenofribate
Losartan
Pegloticase
Increase clearance of
ypoxanthine and xanthine
Management of
hypertriglyceride
Decreases serum urate by
20-30%
Angiotensin receptor-II
antagonist for HTN and HF
Hypertension and heart
failure
Inhibits tubular reabsorption
of uric acid & increases
urinary excretion
IV recombinant uricase –
Chronic gout in adults
catalyzes the oxidation of
uric acid to allantoin, thereby Used as a uric acid “debulker”
lowerin serum uric acid
Anaphylaxis and infusion reactions –
so premedicate with antihistamines
and corticosteroids
Gout flares
CI – G6PD deficiency – run the risk of
hemolysis and methmoglobinemia
Drugs for RA
Type
Drug
RA drug – most
Methotrexate
famous because it has
the greatest positive
to negative side effect
ratio
RA Drug
Luflunomide
Immunosuppressant
drug (Also anticancer)
Abatacept
Non-TNF-directed
mab
MOA
Low doses – Inhibits
AICAR transofrmylase
and thymidylate
synthetase – thus it
inhibits immune cell
proliferation and
stimulates apoptosis
- Inhibits
proinflammatory
cytokines
Active metabolite –
A77-1726 – inhibits
dihydroorotate
dehydrogenase 
arrests cells in G1
phase and inhibits cell
proliferation and B cell
antibodies
Binds to CD80/86 on
APC
Clinical Use
-RA
- Juvenile chronic arthritis
- psoriasis
- Ankylosing spondylitis
- polymyositis
- Systemic lupus
- erythematous
Vasculitis
AE
Always give a large 100 mg
Loading dose for 3 days
then drop to 20 mg/day
after that - IV
Diarrhea (25%)
Elevated liver enzymes (ALT
and AST)
Weight gain
Increased blood pressure
Immunosuppressant
drug (Also anticancer)
Rituximab
Targets CD20 on B
lymphocytes
Use with Methotrexate
Non-TNF-directed
mab
Immunosuppressant
drug (Also anticancer)
Non-TNF-directed
mab
TNF-Directed
TNF-Directed
TNF-directed
RA that is refractory to antiTNF agents
Alefacept
LFA-3 which binds to
CD2 on T-Cells
Adalimumab
Complexes with TNF-a
itself, preventing
macrophage activation
and interrupting T-cell
function
Infliximab
Etanercept
Decreases the rate of
formation of new
lesions
Complex with TNF-a
Complexes with TNF-a
Give in 2 IV infusions 2
weeks apart
Plaque psoriasis
RA
AS
Psoriatic arthritis
Works like Adalimumab
Use for Crohn’s Disease
Works better combined
with methotrexate
Juvenile chronic arthritis
Psoriasis
Reduces T cells in plaques –
so monitor T cell levels.
STOP if CD24 drops below
250 cells/microliter
Apremilast
Glucocorticoids
Selective
phosphodiesterase
Type 4 inhibitor
(PDE4)
It’s expressed in
immune cells and it’s
involved in breaking
down cAMP
Resolve RA promptly
and dramatically
Inhibit phospholipase
A2  so no
arachidonic acid
Inhibits COX2
Suicidal ideation and
behavior found in psoriatic
arthritis
Prednisone – Don’t exceed
7.5 mg/day
Insomnia
Hypomania
Peptic ulcers
Adrenal suppression with
longterm use