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431 Cards in this Set

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Drug class: lispro
ultra-short acting insulin
Drug class: aspart
ultra short acting insulin
Drug class: regular
short acting insulin
Drug class: lente
delayed onset, extended duration insulin
Drug class: NPH
delayed onset, extended duration insulin
Drug class: ultralente
delayed onset, extended duration insulin
Drug class: glargine
delayed onset, extended duration insulin
Drug class: Exubera
inhaled insulin
Drug class: glyburide
Insulin secretagogue (sulfonylurea)
Drug class: Glipizide
Insulin secretagogue (sulfonylurea)
Drug class: Glimepiride
Insulin secretagogue (sulfonylurea)
Drug class: repaglinide
Insulin secretagogue (meglitinide)
Drug class: netaglinide
D-phenylalanine (insulin secretagogue)
Drug class: metformin
Drug class: rosiglitazone
Drug class: Pioglitazone
Drug class: Acarbose
alpha-glucosidase inhibitor
Drug class: miglitol
alpha glucosidase inhibitor
MOA sulfonylureas
increases insulin secretion
decreases glucagon in circulation
MOA meglitinides
(which type of hyperglycemia does it affect)
increased insulin secretion
fast/brief onset and duration
Reduces **post-prandial** hyperglycemia (NOT fasting)
MOA thiazolidinedione
decrease insulin resistnace, increase insulin uptake and use in muscle, adipose, and liver
No insulin resistance
Decreaesd visceral fat deposits, but can cause modest weight gain, fluid retention, and anemia
MOA exenatide
stimulates insulin secretion
decreaes glucagon
slows gastric emptying
increases satiety and suppresses post-prandial plasma gluccagon and hepatic glucose output
MOA pramlintide
--> weight loss
slows gastric emptying
2nd line agent
Chemical constituents of echinacea
lipophilic constituents (alkamides, polyacetylenes)
water soluble polysaccharides
water soluble caffeoyl conjugates (echiacoside, chicoric acid, caffeic acid)
What are the uses of echninacea
immune stimulation
wound healing
respiratory infections
anti-oxidation effects
Effects of echinacea on the immune system?
increased phagocytosis, but not immunostimulation
increased production of IL-1, 6, 10, and TNF-alpha
Enhanced NK cell activity and AB dependent cellulary toxicity
Cytokine activation
Effects of echinacea on anti-inflammation
COX inhibition
5-lipoxygenase might be involved
reduced edema in animal s
Too few clinical trials to warrant wound healing in animals
Results of clinical trials of echinacea
favorable results in reducing cold and flu symptoms if agent is given in first 24 hrs of a cold
Decreased sx and duration by 25-30%
No prophylactic effect in preventing upper respiratory infection
Ineffective in treating recurrent genital herpes
Drug interactions reported with echinacea
NONE, although preps with high alcohol content should not be used with meds that cause disulfiram like reaction
Active constituents of feverfew
parthenolide, but amount varies depending on growing conditions, manufacturing process, duration of storage
Common uses for feverfew
menstrual irregularities
general stimulant
Pharm effects of feverfew
proph for migraines, related to 5HT hypothesis
What is the active compound in garlic?
allicin (gives garlic its smell)
what are the common uses for garlic
preventing vascular dz, lowering BP and cholesterol, treating colds, flu, and sinus infection
low blood sugar
What are the pharmacologic effects of garlic on CV system?
in vitro, inhibits HMG-CoA reductase
anti-platelet effects and mixed effects on fibrinolysis
antioxidant efefcts
may effect BV elasticity and BP by opening K channels in vascular smooth muscle, NOS stimulation, and ACE inhibition
What effects does garlic have on endocrine system?
Some constituents of garlic have hypoglycemic effects in nondiabetic animal models, but does nothing for human diabetics
What are the antimicrobial effects of garlic?
in vitro: activity against gram + and gram -, protozoa and fungi.
Inhibits thiol containing enzymes needed by microbes
Not tested in clinically
What are the antineoplastic effects of garlic
in clincal trials, certain populations with high dietary garlic consumption have a reduced incidence in stomach cancer
What drugs does garlic interact with? (caused by?)
anti-clotting medications (from the diallylsulfides that inhibit thromboxane formation and platelet aggregation)
Or: through stimulation of NO synthesis

Enhanced therapeutic effect of HMG-CoA reductase inhibitors

Enhanced hypoglycemic agents

Can reduce the bioavailability of anti-retroviral agents (saquinavir, but not ritonavir)
Chemical constituents of ginko?
Flavone glycosides and terpenoids
Common uses for gingko?
Memory loss
Peripheral vascular dz
CV effects of gingko?
Increases blood flow and decreases viscosity
Enhancement of endogenous NO
Can relieve claudication
Metabolic effects of gingko?
Antioxidant and radical scavenging properties
CNS effects of gingko?
Increased densities for muscarinic, alpha-2, 5HT1a receptors and decreasd B-adrenceptors
Incresad ACh and NorE
Enhanced synaptosomal reuptake of serotonin Reduced corticosterone synth
Enhanced GABA
Treatse AD
Possible AD proph
Drug interactions with gingko?
Increased therapeutic effect of anticoags
If with trazadone, enhanced sedative effects
Increased effect of MAOI
Gingko seeds are epileptogenic and can decrease effectiveness of pts taking carbamazepine or valproic acid
Uses for ginseng
increase resistance to phsyical, chem, biological stresses
Treat fatiuge
Stimulates immune system
Can enhance mood
Improves mental and physical performance
Clinical trials of ginseng
improvement in mental fxn and physical performance, or no effect
American ginseng lowers postprandial glucose
Inconclusive evidence
Drug interactions with ginseng
If taken with psych drugs --> sleeplessness and mia
Don't take with warfarin
Cytokine stimulation occurs so be cautious in immunocompromised patients
LT use --> HTN
what part of the plant do the extracts from kava come from? what are the active constituents called?
kavalactones or kavapyrones
lawain, methysticin, yangonin
Possible MOA of kava
GABA receptors likely involved
kavalactones bind to GABA-A receptors, but don't compete with BZ binding sites
Might inhibit norE uptake, reversible MAO-B inhibition or DA antagonism
Possible COX inhibition activity
Results of clinical trials of kava
improvements in anxiety in pts wiht moderate to severe anxiety
Similar anxiolytic effects when compared with oxazepam, with fewer side effects
Drug interactions seen with kava
potentiates effects of other CNS depressants, impaired cognitive performance
Chemical constituents of St. John's Wort
Common uses for St. John's Wort
natural source of food flavoring
depression, nervousness, anxiety
fibrositis, sciatica
muscle soreness and burns
Pharmaceological effects of St. John's Wort
Hyperforin inihitits 5HT, norE, DA reuptake in vitro
Downregulates expression of cortical B-adrenoceptors and upregulates the expression of 5HT receptors in rodents
MOA St. John's Wort
NOT a competitive antagonist at tramitter binding sites to decrease uptake
It actually attenuates Na gradient to alter NT transport
Drug interactions of St. John's Wort
drugs with similar MOA should be avoided b/c --> serotonin syndrome or MAO crisis
May induce CYP enzymes and glycoprotein drug transporter --> low levels of digoxin, OC, cyclosporin, HIV meds, warfarin, irinotecan, theophylline, and anti-convulsants
Uses for saw palmetto
Clinical studies of saw palmetto
not as effective as a1-antagonists
Common uses of DHEA
slow/reverse aging changes
promote weight loss
increase strenght and energy
improves memory, prevents heart dz and SLE
Clinical trials of DHEA (weight loss, CVD, AD, SLE, DM)
Don't use DHEA for weight loss
high and low levels fo DHEA associated with CV dz
To treat AD, use still contraversial
Most ppl using it for SLE discontinued use
To treat DM: unknown
Common uses for melatonin
jet lag
immune enhancement
Clinical trials for melatonin in jet lag
Reduced daytime fatigue, improved mood, quicker recovery time, but studies were inconsistent in dosing, duration of therapy, etc
Clinical trials for melatonin in insomnia
improves sleep onset, duration and quality when given to healthy volunteers
increased REM
Clinical trials for melatonin in female reproductive function
melatonin receptors ID in granulosa cell membranes and follicular fluid
it suppresses midcycle LH surge and secretion --> partial inhibition of ovulation
If given with progestin on days 1-21, lower LH levels
Dont' use melatonin if pregnant or attempting to conceive, or who are nursing (also decreases PRL levels)
Clinical trials for melatonin in male reproductive funcion
decreaes sperm quality, maybe through aromatase inhibition
Drug interactions in melatonin
possiby alters [] of NSAIDS, antideressants, b-agonists/antagonists, scopolamie, and Na valproate
But none have been formally studied
What should every patient with altered mental status receive?
what if respiratory depression is present?
naloxone .4-2 mg to reverse respiratory depression if caused by opioids
What is flumazenil?
What effects does it specifically have?
it's a BZ antagonist, but does nothing for blocking barbiturates, opioids, etc
reverses sedation from BZ, effects on resp depression less clear
When should flumazenil NOT be given
should ID toxin first, since it can cause convulsions in pts with TCA
don't give to pts with h/o seizures
What does a toxicologic exam include
vital signs
nervous system
What effect do salicylates have on respiration?
increases it
Which drugs will cause a horizontal nystagmus?
Which drugs will cause a vertical nystagmus?
phencyclidine (angel dust)
What drugs cause icterus?
mushroom poisoning
Which drugs can cause seizures?
diphenyhdramine (in sleep preparations)
Which drugs can cause muscle rigidity?
Which drugs can cause a combo of nystagmus, dysarthria, and ataxia?
What makes up the difference in the anion gap?
What is a normal anion gap?
What are the general causes of metabolic acidosis from toxins?
Organic acid metabolites from the toxin (MeOH --> foramte, ethylene glycol --> glyoxylate and oxalate)
Toxin is an organic acid (salicylate acid)
Toxin produces ischemia --> lactic acidosis (CO, ibuprofin, valproate)
HOw do you calculate osmolar gap?
What is the noraml value?
How can it be measured (w/o calculating it)?
2x Na + (glucose/18) + BUN/3
280-290 mosm
Measure the degree to which freezing point is depressed, whci can be used to estimate the BAC
What does an elevated osmolar gap represent?
Some sort of alcohol intoxication (EtOh, MeOH, ethylene glycol, isopropanol)
What is the main value in toxicology screening tests?
confirming or r/o a suspected intoxication
What EKG changes are seen in TCA OD?
Widened QRS
Prolonged QT interval (also seen in SSRI and anti-psychotics)
What are the ways to decontaminate GI tract? Which is the most effective method?
gastric lavage
**activated charcoal and bowel irrigation**
What can be used to cause emesis?
syrup of ipecac
must be done within 1-2 hrs of ingestion or else the toxin will be into intestines
When should ipecac NOT be used?
if toxicant is a corrosive agent, a petroleum distillate, or rapidly acting CNS stimulant
What are the 2 types of lavage, and which is the preferred method?
Orogastric** (better b/c cna use a wider diamter tube)
How does activated charcoal work to empty the stomach?
What can activated charcoal be combined with to enhance the effects?
sorbitol, to draw water into the GI tract and cause diarrhea containing charcoal and the adsorbed drug (most effective in slow-release or enteric drug formulation since the drug will still be in the intestines hours after ingestion)
What type of compounds can be filtered out in dialysis?
most effectively removed if drug has low Vd, b/c if the toxins or drugs are bound, then they will be too large to fit through the porous filter
Dialysis also effectively restores plasma electrolyte levels and pH
What is sorbent hemoperfusion used for?
What is the main problem associated with this?
hydrophobic toxins
most highly lipid soluble molecules have large Vd so only a smal fraction can be cleared
Which drugs specifically are most effectively removed from the body using sorben hemoperfusion?
What is one of the main complications of sorben hemoperfusion?
Blood comes incontact with activated charcoal surface adn the platelets adhere very strongly and cause severe thrombocytopenia and bleeding
Which drug class has the highest number of deaths attributed to its use?
What is the classic presentation of opiate OD?
respiratory depression
pinpoint pupils
needle tracks on antecubital fossa
Treatment for opiate OD?

they reverse toxindrome within seconds to minutes
What is the difference between naloxone and nalmefene?
both are identical pharmacologically, except that nalmefene has a longer duration
What things are necessary to have a successful transdermal patch?
highly lipid soluble
very potent drug
Which drugs are in transdermal patches?
scopolamine (for motion sickness)
What can make patches extremely toxic?
if sucked on they deliver huge dosages compared to the standard therapeutic dosages
What precautions should be taken with patches?
Wash hands thoroughly after placing or removing a patch
throw them out in a place where children can't get to them
What causes liver damage in acetominophen?
highly toxic free radical metabolite is produced in liver and detoxified by glutathione
Toxicity appears when glutathione is depleted
What is the antedote to acetaminophen toxicity?
how soon must it be given?
acetylcysteine, which acts as a glutathione substitute
within 8-10 hours
Which of the BZ are most fatal?
--> coma and respiratory arrest
What is the treatment for BZ OD?
What if this drug is given to patients who have taken antidepressants or barbiturates?
Can cause status epilepticus
Which are the antidepressants that are associated with fatal intoxications?
SSRI (since most widely prescribed)
amitriptyline (TCA)
How do TCAs cause fatalities?
profound hypotension
centrally mediated agitation
tonic-clonic seizures
depress cardiac contractility --> ventricular conduction block and v-fib
Treatment for OD of antidepressants
IV fluids and catecholamines for hypotension
antiarrythmics (sodium bicarbonate)
What is contraindicated in antidepressant OD? Why?
Aggravates deression of cardiac conduction and exacerbates seizures
What is the most common cause of death from EtOH?
hypothermia (falling asleep outside when it's cold) and increseased vasodilation --> heat loss
respiratory arrest
What is the metabolism of EtOH?
Acetaldehyde by alcohol dehydrogenase using NAD --> NADH
Acetaldehyde is oxidized by aldehyde dehydrogenase to form acetate (NAD --> NADH again)
Acetate --> Acetyl CoA (enters TCA cycle) --> CO2
How is ethylene glycol metabolized?
Forms glycoxylic acid and dicarboxylic acid oxalate (both of which --> metabolic acidosis)
What is the toxidrome of ethylene glycol?
metabolic acidosis
respiratory depression
urinary oxalate (is an anion, so it draws the K into the urine)
What is the treatment for ethylene glycol OD?
Fomepizole (inhibits alcohol dehydrogenase and diminishes the formation of the metabolic acids)... oxalate crystals in the urine --> acute renal failure
What extra precaution must be taken with ethylene glycol OD treatment?
it binds Ca, so if muscle spasms develop administer Ca
What is the metabolism of methanol?
forms formaldehyde and formic acid (--> blindness)
What is the toxidrome of methanol toxicity?
metabolic acidosis
respiratory arrest
vision changes
NO oxalate in urine
What is the treatment for methanol toxicity?
fomepizole to prevent the formation of formic acid
MOA of disulfiram?
inhibits aldehyde dehydrogenase so acetaldehyde accumulates --> flushing, severe vasodilation, N/V
Lasts for 48 hrs
How can disulfiram be fatal?
if it taken after EtOH consumption --> accumulations of acetaldehyde
MOA of cocaine?
blocks the reuptake of DA, NorE, 5HT
--> profound euphoria
--> incrases BP, HR (w/ arrhythmias, increses work load and O2 requirements of heart)
--> lowers seizure threshold
Treatment for cocaine OD?
Diazepam for seizures
beta-blockesr and Ca channel blockers for arrhythmias
nitro for HTN
What are the lethal effects experienced from ca channel blockers?
dramatically reduces CO and BP
How is OD from CCB treated?
give whole bowel irrigation adn oral activated charcoal... these drugs are given in extended release forms and they persist in GI tract following OD
There is NO antidote!!!
What is the major side effect of CCB?
constipation (Ca enntry through channels drives peristalsis --> paralytic ileus and gastroparesis
charcoal and irrigation must be administered before bowel motility is lost
Is the Vd high or low in CCB?
What is the most important maintenance strategy while treating someone on CCB?
maintenace of CO (pacing and placing an intraaortic balloon counterpulsation and maintenance of BP using catceholamines
give Ca IV since entry is driven by Ca concentration gradient and increasing the extracellular Ca drives mroe Ca in
What happens to beta selectivity in beta blockers at high doses?
the selectivity is lost
what are the most common manifestations of beta blocker OD?
bradycardia with AV block and hypotension
what is the treatment for beta blocker OD?
Glucagon works on cardiac myocytes through elevating cAMP but through a different receptor, acts as a positive inotropic and chronotropic agent to restore CO, BP, and liver perfusion
What causes death from CO?
hypoxia d/t formation of carboxyhemoglobin adn a decreased O2 carrying capacity in blood
Treatment for CO poisoning
transfer pt to fresh air
give 100% pure O2 ASAP with mechanical assist if necessary
monitr CV status
how long does it take to treat CO poisoning
320 minutes if pt is in room air
80 mins if pts are in 100% O2
Under hyperbaric conditions, can be <25 mins
What is the advantage to hyperbaric chambers when treating ppl with CO poisoning
recovery rate is father, but survival rate is still the same
What are the different forms of lead
inorganic lead salts
organic lead (in gasoline)
lead oxide in dust (most common)
How does lead spread throughout body?
taken up by RBC, distributed to soft tissues, then to sub-periosteal surfaces of bone and to bone matrix
What type of anemia is caused by lead poisoning
mycrocytic hypochromic (blocks incorporation of Pb into protoporphyrin IX to form heme) also blocks other enzymes in heme synth pathway
What are the major signs of inorganic lead poisoning?
hemolytic anemia
treatment for inorganic lead poisoning?
Use of chelators
How is lead poisoning diagnosed?
atomic absorption spectrophotometry
How can lead poisoning treatment be monitored?
urinary measruement of lead loss
declining plasma concentrations
Where is arsenic exposure commonly from
cotton desiccants
nonferrous alloys
vet drugs
how is arsenic excreted?
undergoes methylation in the liver and subsequent urinary excretion
how does arsenic exert its effects
binds sulfhydryl groups of proteins, interfering with their catalytic and structural competencies
which form of arsenic is more toxic?
trivalent (10x more toxic)
the other form is a pentavalent
presentation of acute arsenic poisoning
abrupt gastroenteritis
metabolic acidosis
treatment for acute inorganic arsenic poisoning
gut decontamination
intensive supportive care
prompt chelation
arsine gas poisoning presentation
massive hemolysis
treatment for arsine gas poisoning
exchange transfusion
mannitol infusion (to protect from porphyrin induced acute renal failure)
chelators don't help
what is the primary source of Hg exposure
inhalation, it then gets concentrated in the kidneys
what effects does Hg have on the body?
interacts with sulfhydryl groups in protins... it inhibits enzymes
presentation of acute Hg intoxication
pulmonary edema
acute gingivostomatitis
neurological sx
What is seen with acute ingestion of inorganic mercury salts
corrosive hemorrhagic gastroenteritis --> ATN and oliguric renal failure
What is dimercaprol?
classic chelator used to treat acute poisoning wiht
severe Pb poisoning (when combined wiht EDTA)
Advantage of dimercaprol
readily x cellular membranes and can remove intracellular and extracellular deposits of toxic metal
the complex of metal and dimercaprol is lost in the urine
Adverse effects of dimercaprol
pain at injection site
What is succimer?
water analog if dimercaprol
approved for Pb poisoning and has supplanted EDTA in outpatient tx
also used to treat arsenic and Hg poisoning
Adverse reactioins to succimer?
GI dz
rashes and neutropenia can occur
strong chlator
how is EDTA administered?
IV infusion
excreted by glomerular filtration, bringinng lead into teh urine from plasma and exchanged from soft tissue
Unithiol-DMPS uses
binds and increases excretion of Hg, arsenic, and Pb
Effectiveness of Unithiol-DMPS
more effective than succimer and dimercaprol for inorganic Hg or arsenic
Adverse effects of Unithiol-DMPS
Stevens-Johnson syndroem
Cu chelator (treats Wilson's dz and copper poisoning )
Also used to treat severe RA
Adverse effects of penicillamine
50% experience
hypersensitivity rxn
binds Fe avidly
removes Fe from hemosiderina dn ferritin, but not from heme iron proteins
Deferoxamine treats?
ironing poisonings (from treating Fe-deficiency anemia
Administration of deferoxamine
parenterally (poorly absorbed orally)
Excreted in urine (turns urine orange-red)
Adverse effecs from deferoxamine
esp if infusions last more than 24 hrs
Examples of SERMS
Examples of anti-estrogen drugs
exampes of anti-progestins
mifepristone (RU-486)
examples of androgen drugs
testosterone cypionate
testosterone enanthate
examples of anabolic steroids
examples of anti-androgens
GnRH analogs
DA agonist
pituitary hormone
urofollitropin (FSH)
examples of aromatase inibitors
examples of 5-a reductase inhibitors
What is the most potent estrogen? next most potent? last?
E2 (17-beta-estradiol)
E1 (estrone)
E3 (estriol)
What is the principle structural feature of the estrogens?
phenolic A ring
What is DES?
nonsteroidal compound similar to estradiol, but has a longer t1/2
What is ethinyl
it is a substitution on the D ring of estrogens that increases oral potency by inhibiting first pass hepatic metabolism
What do gonadotropins do?
Increase the activity of aromatase and cholesterol side chain cleavage enzymes and facilitates the transport of cholesterol and steroid biosynthesis
In post-menopausal women, what is the source of estrogen?
adipose stroma (estrogen is made from DHEA secreted by the adrenals)
Where is estrogen produced in men?
also, extragonadal production by aromatiziation of C19 steroids (accounts for most)
What is the link between esetrogen production and breast CA?
mammary tumors contain aromatase and hydrolytic enzymes
Where does estrogen come from in the fetus?
fetal DHEA forms E1 and E3
What does estrogen do for girls?
responsible for pubertal changes and secondary sex characteristics
Molds body contours
Shapes skeleton
Causes pubertal growth spurt of long bones and epiphyseal closure
growth of axillary and pubic hair
What does estrogen do to pregnant women?
pigments genital region
pigmentations of nipples and areoae after 1st trimester
What role do estrogens play in males?
If deficient --> diminished pubertal growth spurt and delays in skeletal maturation
delays in epiphyseal closure
increased gonadotropins
increased testosterone macroorchidism
can affect lipid and carb metabolism
affects fertility
What does FSH do in women?
growth and maturation of graafian follicle in ovary
ovarian production of estrogen and progesterone
How does estrogen interact with FSH/LH?
decreases amount of LH and FSH released during most of hte cycle, but triggers a surge of LH release during midcycle (after the estrogens get above a certain threshold)
How is FSH controlled, other than with estrogens?
What do follicles produce?
What happens when FSH levels drop?
all the smaller follicles not chosen to mature, regress
What does the FSH/LH surge do?
Causes follicular rupture and ovulation within 1-2 days
What happens to the ruptured follicle?
develops into corpus luteum, which produces large amounts of progesterone and a little bit of estrogen
What enzyme does aspirin inhibit?
postaglandin synthase (aka COX)
Adverse effects of NSAIDS
GI disturbances
inhibit platelet aggregation
inhibit uterine motility
inhibit PG mediated renal fxn
what are general therapeutic actions of NSAIDS
relieve pain
reduce fever
reduce inflammation (all except acetaminophen)
Sites of acetaminophen action
may have better COX inhibition in nervous system
why is acetaminophen not effective in inflammation
COX inhibition is low int eh presence of high [peroxide] found in inflammatory lesions
does not inhibit neutrophil activation (other NSAIDS do)
Adverse rxns to acetaminophen
NO respiratory or cardiovascular systems
NO acid-base probs
NO GI disturbances
NO changes in bleeding time
6% cross-reactivity with aspirin --> AIS
Therapeutic uses of acetaminophen
good substitute when aspirin is contraindicated
NOT an anti-inflammatory, but can be a useful adjunct for pain
Acetaminophen toxicity causes?
fatal hepatic necrosis
Treatment of acetaminophen toxicity
emesis or gastric lavage with activated charcoal
N-accetylcysteine to replenish glutathione in liver
What does acetaminophen get broken down to?
sulfate derivative
glucuronide derivative
toxic intermediates (via p450)
What combines with toxic intermediates of acetaminophen?
glutathione --> mercapturic acid
nucleophilic macromolecules -->damaged macromolecules --> cell death
What does COX do?
converts arachidonic acid --> PGG2 (short lived) --> PGH2 by peroxidase
What does PGH2 form?
What enzyme do NSAIDS inhibit?
Is this reversible?
All except aspirin inhibit reversibly
Aspirin inhibits irreversibly through acetylation
What effects does aspirin have on platelets?
depletion of COX for the lifetime of the platelet
What effects do other NSAIDS (opther than aspirin) have on COX?
COX inhibition is related to the turnover rate of COX in each tissue
Structure of COX-1?
Homodimeric membrane protein
4 alpha helices with exposed hydrophobic surfaces rests within the lipid bilayer
Helices form an entrance to COX channel and arachidonic can enter through the channel
What exactly does acetylation by aspirin do to the COX channel?
blocks the access to the channel, so arachidonic acid can't enter
How do non-aspirin NSAIDS affect the COX channel?
it competitively excludes arachidoniate from the channel
What is COX2?
What is difference btwn that and COX 1?
induced during inflammation in response to cytokines, endotoxins
COX 1 is ubiqitously expressed in GI, kidney, and platelets
What is the anti-inflammatory activity of NSAIDS?
inhibits chemotaxis
down-regulates IL-1
Decreased production of free radicals and superoxide
Interferes with Ca-mediated cellular events
Decreased sensitivy of vessels to bradykinin and histamine
affects lymphokine production from T cells
reverses vasodilation
Effects of highly selective COX2 inhibitors
Most important route of elimination for NSAIDS
How long does it take for salicylates to enter bloodstream
15-30 mins
What effects do aspirin and other salicylates have on respiration?
respiratory stim (stimulates medullary center, and increases O2 consumption/CO2 production in skeletal muscles by uncoupling ox-phos)
also respiratory depression at toxic doses (central resp paralysis, circulatory collapse, and renal failure)
What is the relationship between aspirin and ibuprofen?
If using both, ibuprofen inhibits aspirin's cardioprotenctive effects (competes for access t o acetylation site on platelet COX)
But, if you take aspirin 2 hrs prior to ibuprofien, then negative effect gone
IF ibuprofen taken regularly, then antiplatelet benefit of aspirin is lsost
Which drugs don't interfere with aspirin
Mechanism behind unwanted GI effects from NSAIDS?
local irritation
decreased PGE2 and PGI2 production (all except acetaminophen and salicylate) --> loss of cytoprotection
What do NSAIDS do to platelet fxn? What do COX2 inhibitors do to platelets?
decrease TXA2 production and increase bleeding time (ESP ASPIRIN, NOT ACETAMINOPHEN OR SALICYLATE)
TXA2 is COX-1 mediated, so not really a problem with COX-2 inhibitors
What effect does NSAIDS have on gestation?
decreases production of PGE2 and PGF2 which are usually increased prior to partiution
it prolongs gestation
How do NSAIDS affecct renal fxn
decrease PGE2 (made in kidneys) for vasodilation
decreases RBF
Can lead to fluid retention and may cause renal failure or HTN
Both only occur if the patient is at risk
Who is at risk for renal side effects from NSAIDS?
renal insufficiency
volume depletion
those on diuretics
What are some effects of NSAIDS on pregnant mother?
prolongation of gestation (decreased PGE2 and PGF2)
during late pregnancy, chronic use --> pulmonary HTN in fetus from pulm smooth muscle proliferation fro DA closure
Advantageous for smal preterm infants with PDA and respiratory distress syndrome
What is aspirin intolerance syndrome?
vasomotor rhinitis
angioneurotic edema
bronchial asthma
who is at risk for AIS?
middle aged adults with asthma, chronic urticaria or nasal polyps
mechanism for AIS?
shunting of arachidonic acid towards 5-lipoxygenase (for increased LT production)
Features of salicylism
CNS depression
GI probs
treatment for salicylism
cut back on dose
Features of severe salicylate poisoning
hyperventilation and respiratory alkalosis
CNS and GI probs
marked alterations in acid-base status and electrolyte composition
Treatment for severe salicylate poisoning
emesis or gastric lavage with charcoal
sponging with tepid water, alcohol or fluids
Vitamin K or transfusion
dialysis or exchange transfusion
How do salicylates affect acid-base status
increase rate and depth of ventilation --> primary respiratory alkalosis --> eventual renal compensation
Metabolic acidosis occurs b/c ox-phos gets decoupled --> decreased ATP --> increased glycolysis
What role do salicylates play in clotting
inhibit vitamin K dependent synthesis off prothrombin and other clotting factors --> prolonged PT
Which NSAID is contraindicated in Children? Why?
aspirin --> Reye syndrome
Which NSAID is specficially for children?
Whcih NSAID is useful for a very high fever
Ibuprofen (can give with acetaminophen)
Which drugs are indicated for antipyresis?
Which is indicated for children? Which is indicated for very high fever?
acetaminophen (children)
ibuprofen (high fever, can be given with acetominophen)
Why would someone use salicylates over aspirin for pain relief?
More favorable toxicity profile, though onset of analgeisa is slower
difference in effectiveness is not clear
What is ketorolac?
only injecctable NSAID available in US
for post-op use
superior to aspirin for treatment of chronic pain states
What are the limitations on ketorolac?
should not be used for more than 5 days
--> peptic ulcers and renal problems
it's a great analgesic, but only moderately effective as an anti-inflammatory
What drugs can be used to treat IBD?
How is mesalamine given?
poorly absorbed when given orally, so administer rectally or give formulation in pH sensitive polymer coating
How is olsalazine metabolized?
hydrolyzed in lower intestine to mesalamine
How is sulfasalazine metabolized?
poorly absorbed orally
cleaved into its 2 constituents by bacteria in colon, both portions are anti-inflammatory
What is the utility of sulfasalazine in IBD and RA?
good for sulfasalazine
it is partially effective for RA??
Which drugs are indicated for dysmenorrhea?
fenamic acids
mefenamic acid
MOA of fenamic acids
COX inhibition
phospholipase A2 inhibition
adverse effects of meclofenamate
diarrhea and abdominal pain
enhances effects of oral anticoagulents
contraindicated in pregnancy
NOT for children
adverse effects of mefenamic acid
more toxic than aspirin
NOT for children
only use for 1 week
How is choice made in general for pain relief in rheumatalogic dzs?
choice is empirical
What drugs are children restricted to in rheumatic dzs?
what drugs can be given to treat rheumatologic dzs in pregnancy?
low doses of aspirin are ok, but discontinue prior to partuition
What is dilfunisal?
derivative of salicylic acid, though not converted to salicylic acid in vivo (so salicylism not observed)
what is dilfunisal used for?
analgesic for OA, musculoskeletal strains, sprains, RA
NOT good antipyretic (poor CNS penetration)
What is indomethacin?
first NSAID developed
COX1 inhibitor
poorly tolerated (35-50% of pts have averse rxns)
adverse reactions from indomethacin?
salt and water retention (antagonizes diuretic effects of drugs)
GI pros
hematopoietic rxns
AIS (100% cross-reactivity with aspirin)
Contraindications for indomethacin?
nursing mothers
psych d/o
uses for indomethacin
acute tx for Bartter syndrome
PDA closure in premature infants
acute gouty arthritis
RA (efficacy ~ aspirin)
refractory fever of Hodgkin's dz
don't use reoutinely for analgesic or antipyretic
What does sulindac treat?
akylsing spondylitis
Adverse reactions to sulindac
mild GI effects
CNS effects (drowsiness, HA, nervousness)
skin rxns (rash, pruritis)
uses for etodolac
post-op anagesia
adverse rxns to etodolac
GI irritation and ulceration
what is a benefit of etodolac
arge difference btwn doses that --> anti-inflamatory effects and those that cause gastric irritation
what is diclofenac?
more potent COX inhibitor than indomethacin
decreases intracelular [] free arachidonate in WBC
adverse rxns to diclofenac?
reversible increase in hepatic aminotransferases
uses of diclofenac
long-term RA, OA, ank spond tx
short-term acute musculoskeletal injury
post-op ophthalmic inflammation
How can GI toxicity be reduced in diclofenac?
add PGE1 analog (misoprostol)
What is nabumetone
weak COX inhibitor
active anti-inflammatory with analgesic and antipyretic activities
adverse reactions to nabumetone
lower bowel complains
skin rash
doesn't interfere with platelet aggregation
decreaesd GI ulceration
uses of nabumetone
short-term soft tissue injuries
General info with regard to proprionic acid derivatives
COX inhibition
anti-inflammatory, analgesic, and anipyretic activity
prolong bleeding time
high degree of binding to albumin
adverse rxns of proprionic acid derivatives
GI (less severely than aspirin)
some CNS effects
uses for propionic acid derivatives
ankylosing spondylitis
acute gouty arthritis
analgesics for acute probs (incl primary dysmenorrhea)
which propionic acid derivative has been shown to be safe and effective in children
which propionic acid derivative has the longest half life?
Which propionic acid derivative is associated iwth interstitial nephritis
Which propionic acid derivative is available in topical formuation? What is it used for?
prevents miosis during ophthalmic surgery
Which propionic acid derivative is preferred for analgesia and relieve of morning stifffness?
what are the propinoic acid derivatives
what are the enolic acid derivatives?
How long does it take for maximal therapeutic response to occur in piroxicam?
2 weeks
adverse rxns ot piroxicam?
GI effects
peptic ulcers
therapeutic uses for piroxicam
akylosing spondyltisi
acute musculoskel d/o
post-op pain
acute gout
adverse rxns to meloxicam
COX2 selective inhibition
adverse rxn to meloxicam?
increase aminotransferases
serious GI disturbances (but less than piroxicam)
What is the main advantage to COX 2 inhibitors compared to non-selective COX inhibiton?
they are NOT any more effective, they just have decreased side effects (esp GI toxicity!!)
Increased risk of CV events
What are the disadvantaes of COX 2 inhibitors?
inbalance of prostanoids in kidneys --> salt and water retention
this interferes with ovulation, bone remodeling, healing of gastric ulcers, PROTHROMBIC effects
COX2 KO mice have histologically deranged kidneys
COX 2 inhibitors and pregnancy?
should not be given in 3rd trimester or pregnancy
they have decreased fetal survival in pregnant animals
mechanism behind the COX inhibitors and CVD risk
COX1 mediates platelet TXA2 production in platelets (--> decreased aggregation, reduced platelet proliferation, and vasodilation)
PGI2 is mediated by COX1 and COX2, so there is decreased PGI2 and TXA2 is unaffected
In non-selective COX inhibition, both TXA2 and PGI2 are reduced equally
What does PGI2 do?
inhibits platelet aggregation
What does TXA2 do?
promotes platelet aggregation
uses of celecoxib
moderate to severe pain
dental pain
what is the initially favored treatment for RA
methotrexate (esp if severe) b/c of relatively rapid response, hihg repsonse rate, and longest sustained efficacy
can also be used for mild-moderate dz
what DMARD drug is sometimes preferred for mild dz
folate antagonist
supplement with folate
adverse rxn to MTX
mucosal ulcers
hepatotoxicity with LE changes, cirrhosis rare (toxicity reduced by giving leucovorin 24hrs after MTX)
contraindication of MTX
pregnancy (teratogenic)
decreased fertility in men and women
uses of MTX
juvenile chronic arthritis
psoriatic arthritis
giant cell arteritis
features of hydroxychloroquine
may decrease RF
may not slow progression of erosive bone lesions
3-6 months to work
adverse rxn to hydorxychloroquine
CNS and GI disturbances
skin rxns
peripheral neuropathies
retinal damage
use of sulfasalazine in RA
IgA and IgM RF production decreased
adverse rxns to sulfasalazine
MOA leflunomide
inhibits pyrimidine synthesis
critical step for rUMP production
induces cell cycle arrest of activated autoimmune lymphocytes
adverse rxns leflunomide
elevated LE
weight gain
increased BP
teratogenic and carcinogenic
what class of drug is leflunomide
use of glucocorticoids in RA
used orally when pts are waiting for onset of DMARD action or during brief flares of multiple joints
examples of gold compounds
gold sodium thiomalate
adverse rxns to gold compounds
1/3 of pts suffer
skin and mucous membranes
severe blood dyscriasis (incl aplastic anemia)
choestatic jaundice
perpheral neuropathies
pulmonary infiltrates
therapeutic uses of gold compounds
RA if early and active (nto for mild dz)
usually of little behefit if dz is advanced
contraindications of gold compounds
renal dz
hepatic dysfxn
hematological d/o
recent radiation tx
condomitant use of anti-malarials, immunosupressant s
What do TNF-alpha and IL-1 do?
stimulate PGE and collagenase production
stim cartilage resorption
inhibits proteoglycan synth
--> inflamm cell recruitment, neoangiogen, and joint damage
where are TNF-alpha and IL-1 found
what are they derived from
rheumatoid synovial fluid and tissues
macrophages and fibroblasts
which drugs are the TNF inhibitors
what is etanercept
recombinant fusion protein made of 2 soluble TNF receptor moieties linked to Fc portion
it binds TNF-alpha wiht high affinity and neutralizes it's bio activity
what does etanercept treat?
juvenile chornic arthritis
psoriatic arthritis
ank spond
what is infiximab?
MAB to TNF-alpha
Fc region of human IgG and Fab sequences
reduces TNF-alpha level
may dislodge TNF-alpha bound to cells
What does infliximab treat?
What is adalimumab?
recombinent human MAB to TNF-alpha
complexes with soluble TNF-alpha and prevents interaction with p55 and p75
what does adalimumab treat?
adverse effects common to TNF inhibitors?
risk of macrophage-dependent infection increaes
must monitor for lymphoma
newly formed dsDNA AB and ANA documented, but does not contradict use if clinical lupus symptoms don't occur
what is anakinra?
recombinant non-glycosylated IL-1Ra for moderate to severe active RA pts who have failed 1 or more DMARD
Might be less effective than anti-TNF agents
administration of anakinra?
daily subQ injection
what is abatacept?
fusion protein of cytotoxic T lymphocyte associated Ag 4, linke to IgG1
inhibits binding of ligants to CD28, which prevents Tcell activation and lowering serum concentrations of inflammatory markers, cytokines, and RF
what does abatacept treat?
moderate to severe RA pts who haven't responded to 1+ DMARD
what is rituximab
anti-CD20 MAB
selectively depletes CD20+ B cells, which play a role n autoimmune response and in chronic syndovitis seen in RA
uses for rituximab
B-cell non-hodgkin's lymphoma
can be used with MTX to treat mod-severe RA in pts who haven't responded to TNF inhibitors
what is gout?
syndrome caused by an inflammatory response to the formation of monosodium urate monohydrate crystals that develop 2/2 hyperuricemia (either environmental or genetic)
what can cause increaed uric acid in body?
under-elimination of uric acids by kidneys (impaiared fxn or EtOH interference)
increased intake of foods with purines (meats, seafood, dried peas and beans)
are men or women more likely to get gout?
what are some of the associated risk factorS for gout?
Dx for gout?
needle aspiration --> uric acid crystal in the joint fluid during an acute attack
what % of ppl with hyperuricemia develop gout?
How is acute gout treated?
disabling leukocyte migration and phagocytosis (colchicine)
COX inhibition (indomethacin and oxaprozin)
long-term management of gout?
increase uric acid excretion with uricosuric agents (probenecid adn sulfinpyrazone)
reducing uric acid synth (allopurinol)
pharmacodynamics of colchicine
ibnds tubulin and prevents tubulin polymerization
inhibits WBC migration and phagocytosis
inhibits formation of LT B4
relieves pain and inflammation w/i 24 hrs
indications for colchicine
alleviates inflammation of acute gouty arthritis
proph for recurrent episodes of gouty arthritis and Med fever
adverse effects of colchicine
diarrhea and N/V
abdominal pain
what is the dosing for colchicine
.5-1 mg
8mg in 24 hrs = lethal
Which NSAIDS are not used to treat gout?
what is the mechanism of NSAIDS in gout
inhibits COX and urate crystal phagocytosis
When should indomethacin be used to treat gout?
can be used initially or as a 2nd choice if colchicine is unsuccessful
how does exaprozin treat gout?
lowers serum uric acid by increasing excretion
not to be used in pts iwht uric acid stones
whihc drugs are the uricosuric agents?
use of the uricosuric drugs?
for pts with the tophaceous gout or in those wiht increasingly frequent attacks
use when plasma tissue levels are high
start tx 2-3 weeks after acute attack
who should not use the uricosuric agents?
those that excrete large amounts of uric acidin order to avoid uric acid calculi
MOA of uricosuric acids?
act at anionic transport sites of the renal tubule
metabolism of probenecid
completely resorbed by the renal tubules
metabolized very slowly
metabolism of sulfinpyrazone
rapidly excreted by the kidneys
pharmacodynamics of uricosuric drugs?
affect active transport sites in middle segments of prox tubules to net resoprtion of uric acid is decreased
what role does aspirin play in the treatment of gout?
should not be used in small doses b/c it encourages the retention of uric acid by the kidneys

it's ok in large doses
how can formation of renal uric acid stones be avoided in treatment of gout
maintain high urine output
keep urine pH >6 esp early in treatment
adverse effects of uricosuric drugs
GI irritation (esp sulfinpyrazone)
allergic dermatitis (probenecid)
rash (both)
nephrotic syndrome (probenecid)
aplastic anemia (rare, both)
how should uricosuric drugs be administered?
in beginning give with colchicine or NSAIDS to avoid precipitating acute gouty attack
How is uric acid formed?
How does allopurinol work?
hypoxanthine --> xanthine (via xanthane oxidase) --> uric acid (xanthine oxidase)

allopurinol --> alloxanthine (whcih inhibits xanthine oxidase)
dosing of allopurinol?
long duration of action
dose once a day
80% absorbed orally
indications for allopurinol?
chronic tophaceous gout
in pts with gout whose 24 hr urine on purine-free diet exceeds 1.1 g
when uricosuric drugs can't be used b/c of adverse rxns
for recurrent renal stones
pts with fxnal renal impairment
gross elevations of serum urate levels
adverse effects of allopurinol?
acute attacks of gouty arthritis occur early with allopurinol when urate crystals are being removed and plasma urate levels are below normal
(administer with colchicine and/or indomethacin)
GI intolerance
peripheral neuritis and necrotizing vasculitis
depression of BM elements
aplastic anemia
hepatic toxicity
interstitial nephritis
allergic skin rxn
exfoliative dermatitis
drug interactions iwth allopurinol
mercaptopurine and azathioprine doses should be reduced ot 25%during CA chemo
increased risk fo BM suppression
inhibits metabolism of prbenecid and oral anticoags
increases hepatic ion []
safety not est in children and pregnancy
what is pseudogout?
Ca pyrophosphate deposition in joints
what is familial mediterranean fever?
how is it treated?
recurrent episodes of unprovoked episodes in joints, peritoneal cavity, and skin
innate immunity
NK cells
mast cells
adaptive immunity
AB from B cells
T cells (helper, regulatory, cytotoxic
uses of immunosuppressants
preventing graft rejection
treatment of autoimmune dzs
is monotherapy or combination therapy more effective when treating transplant rejection
purpose of biological induction therapy
delays the use of nephrotoxic calcineurin inhibitors or to intensify initial immunosuppressive tx in pts of high risk rejection
who is at high risk for transplant rejection
repeat transplant
african american s
what are the 2 types of drugs for biologic induction therapy
depleting agents
immune modulators
what comprises the depleting agents
antithymocyte globuliesn
muromonab CD3 MAB
what drugs are immune modulators
anti-IL-2R MAB blocsk IL-2 mediated T cell activation
which drugs are included in maintenance immunotherapy?
calcineurin inhibitor
mycophenolate mofetil
Which drugs are used for maintenance in transplants?
mycophenolate mofetil
monoclonal and polyclonal AB
what tx is there for established rejection?
use of agents against activated T cells (GC in high doses)
polyclonal antilymphocytes or muromonab CD-3 MAB
classes of immunosuppressant drugs
depletion of lymphocytes (AB, cytotoxic drugs)
Ag recognition by Ag presenting cells (MAB)
Production of pro-inflammatory cytokines (GCs)
T cell activation and IL-2 production (AB and calcineurin inhibitors)
Proliferation and differentiation of T and B cells (ABs, cytotoxic drugs, GCs and mTOR inhibitors)
Which drugs are calcineurin inhibitors?
what is calcineurin?
Readily diffuse into cytoplasm of target T cells and inhibit T cell receptor activated signal transduction pathway
T cell receptor activation --> increase in intracellular Ca --> calcineurin, which dephosphoyrlates NF-AT that increases the transcription of IL2 and other lymphkines
MOA of calcineurin inhibitors
they complexes with their cytoplasmic receptors and bind calcineurin and inhibits calcineurin activiyt n T cells
NFAP translocation is blocked --> interleukin production inhibition and T cell proliferation
pharmacokinetics of cyclosporine
given Iv or PO
metabolized by p450
Pharmakinetics of tacrolimus
IV or oral admin
met by p450
receptor for cyclosporine? tacrolimus?
Uses of cyclosporine and tacrolimus?
kidney, heart, liver, BM, lung and pacreas trasplant
treats psoirasis, RA, Crohn's dz
which calcineurin inhibitor is more potent?
tacrolimus (by 100x)
toxicity of calcineurin inhibitors?
nephrotoxicity in 70%
altered mental status
increased risk of malignancy and opportunistic infectinos
drugs that are mTOR inhibitors
what is sirolimus?
what is everolimus
macrolide AB
derivative from sirolimus
MOA of sirolimus
inhibits IL-2 induced T and B cell expansion
Forms a complex with FKBP12 that inhibits mTOR activity
what is mTOR
protein kinase that plays a central role in the growth and expansion of T and B cells
pharmacokinetics of sirolimus
given orally
hihg fat diet decreases absorption
CYP3A4 metabolism
transported by p-glycoprotein
difference between sirolimus and everolimus in terms of pharmacokinetics?
shorter half life in everolimus
therapeutic uses for sirolimus and everelimus
organ transplant
can be used alone or in combo with other immunosuppressants
some dermatologic d/o
uveoretinitis (in combo with cyclosporine)
when is the use of sirolimus recommended?
if pt has calcineurin inhibitor associated nephrotoxicity, can be used with GC and mycophenylate mofetil
it will avoid permanent renal damage
toxicity of mTOR inhibitors
dose dependent cholesterol and TG increases
lymphocele can develop (complication from renal transplant)
anemia, leukopenia
GI effects
delayed wound healing
opportunistic infections
drug interactions with sirolimus
interacts with cyclosporine --> renal toxicitym, hyperlipidemia, and myelosuppression
Interacts with other drugs metabolized by CYP3A4 and transported by glycoprotein
what is azathioprine?
purine anti-metabolite
preodrug of mercaptopurine but is mroe potent than it for immunosuppression
MOA of azathioprine
cleave to mercaptopurine and gets converted to thio-GTP, which gets incorporated in DNA, inhibiting cell prolif --> cell death
how is azathioprine metabolized?
excreted by urine
therrapeutic uses of azathioprine
prevents transplant rejection
used in pts who don't respond ot cyclosporine or glucocorticoids
can treat RA, CD, and MS
toxicity of azathioprine
affects rapidly growing cells in BM adn GI
--> leukopenia and thrombocytopenia
mutagenic and carcinogenic
drug interactions with azathioprine
metabolized by xanthine oxidase, so administration with allopurinol --> toxicity
What is structure of mycophenolate mofetil
2 morpholinoethyl ester of mycophenolic acid (MPA)
MOA of mycophenolate mofetil
inhibits inosine monophosphate dehydrogenase
B and T cells depend on this enzyme for cell prolif
MPA suppresses lymphocyte prolif and fxns (including migration, adhesion, and AB production)
Pharmacokinetics of mycophenolate mofetil
rapidly absorbed orally
therapeutic usees of mycophenolate mofetil
following renal transplant
used in combo with calcineurin inhibitor and GCs
lupus nephritis
some dermatologic d/o
toxicity of mycophenolate mofetil
increased incidence of infection
drug interactions with mycophenolate mofetil
antacids with Al or MgOH --> decreased absorption
don't give wiht cholestyramine or drugs that affect enterohepatic circulation b/c they decreae MPA conecntrations by binding free MPA in intestines
how are poly and MAB used in preventing transplant rejection
ABs abainst lymphocyte cell-surface Ags are effective in interfering with activation and fxn of lymphocytes
examples of ABs used to prevent organ rejection
antithymocyte globulins
anti-CD3 monoclonal ABs
Anti-CD25 MAB
anti-TNF-alphha agents
MOA of antithymomcyte globulins
deplete thymocytes by cytotoxicity and by blocking lymphocyte fxns by binding to cell surface molecules
side effects of antithymocyte globulins and how can these side effects be prevented
fever, chills, hypotension (from giving a foreign protein)
leukopenia and thrombocytopenia
these rxns can be minimized by giving slow infusion or pretreatement with corticosteroids, acetaminophen and/or anti-histamines
what is muromonab and how does it work?
mouse monoclonal AB against CD3 receptor complex on T cell surface
Causes depletion of mosmt T cells from blood and peripheral lymphoid organs
AB reduces fxn of remaining T cells
uses of muromab
prevents acute rejection of heart kidney, and liver transplants
depletes donor bone marrow prior to BM transplant
adverse rxns to muromonab
allergenicity to foreign mouse AB
toxicity associated with immunosuppression
repeated treatment is contraindicated
cytokine release syndroem from increase in cytokines, manifests as fever, chills, HA, tremor, N/V, diarrhea, abdominal pain, malaise, myalgias, arthralgias, and generalized weakness
which drug is used mroe frequently: muromonab or antithymocyte globulins
muromonab is obsolete b/c of toxicity and availability of antithymocyte globulins
What is daclizumab
MAB against CD25 of IL-2 receptor, specific to acivated but not resting T cells
competitive antagonism of IL2 induced T cell prolif
uses for daclizumab
proph for acute organ rejection in adults
better than mouse ABs b/c of improved effector function, low potential for immunogenicity and long elimination half life
can be used for maintenance triple therapy regimen
what are the drugs included in the maintenance triple therapy given with daclizumab
cyclosporine or tacrolimus steroids
mycophenolate mofetil (MMF)
toxicity associated with daclizumab
rare, except those associated with immunosuppression
what is basiliximab
CD25 MAB, combo murine-human
what is infliximab
anti-tnf-alpha agent
humanized anti-TNF alpha MAB
binds to TNF alpha and prevents it from binding to its receptosr
uses for infliximab
adverse rxns to infliximab
all within 1-2 hrs
MOA of GCs
exACT MOA unknown
may inhibit T cell prolif
T cell dependent imunity and expression of cytokines
advantages of GCs over other immunosuppressants
no BM suppression or GI toxicity