FTCM Pharm 1

NSAIDs, Pain Management, Opioids, Immunopharm

NSAIDS
The following 4 patients present with moderate pain. The
doctor writes one of them a prescription for Naproxen.
Assuming he isn’t terrible at his job (a risky assumption
tbh) which patient most likely got the prescription

• A. An 8 year old girl with a sprained ankle. Mom reports she’s been taking
ibuprofen for the past few days, but is still in pain. You notice she’s
sniffling, and her mom explains there’s a cold going around at school.

• B. A 45 year old man who dislocated his hip while attempting to follow the
Kama Sutra with his new 19 year old girlfriend. He has a history of type 2
diabetes and peptic ulcer disease

• C. A 50 year old woman who threw her back out while stealing a TV from
her neighbor (they left the window unlocked, that’s on them). She has a
history of severe allergic reaction to Amoxicillin and Sulfonamides.

• D. A 30 year old man who recently had surgery to fix a torn ACL. He is
currently taking Warfarin to prevent thrombus formation and
Cephalosporin to prevent infection.
The following 4 patients present with moderate pain. The
doctor writes one of them a prescription for Naproxen.
Assuming he isn’t terrible at his job (a risky assumption
tbh) which patient most likely got the prescription
• A. An 8 year old girl with a sprained ankle. Mom reports she’s been taking ibuprofen for the past few
days, but is still in pain. You notice she’s sniffling, and her mom explains there’s a cold going around at
school: You try to avoid giving Aspirin to kids because it can trigger Reye’s Syndrome. Reye’s is most
likely if the patient has a viral illness + fever. Note this patient has symptoms of a virus, and the NSAID
she’s been taking (Ibuprofen) could be temporarily masking a fever. Although Ibuprofen is an NSAID, it’s
not associated with Reye’s and can be given. Otherwise, go with Acetominophen

• B. A 45 year old man who dislocated his hip while attempting to follow the Kama Sutra with his new 19
year old girlfriend. He has a history of type 2 diabetes and peptic ulcer disease: Naproxen, like all NSAIDs
can cause/exacerbate ulcers (due to COX-1 inhibition). It’s not the WORST (that would be Piroxicam) but
there are definitely better options. If you want to give an NSAID, Aspirin Ibuprofen or Diclofenac are all
less likely to cause GI problems. You could also give a COX-2 selective inhibitor (Celecoxib)

• C. A 50 year old woman who threw her back out while stealing a TV from her neighbor (they left the
window unlocked, that’s on them). She has a history of severe allergic reaction to Amoxicillin and
Sulfonamides: There is no reason that this patient can’t be given Naproxen. Celecoxib should be avoided
in patients with sulfa allergies.

• D. A 30 year old man who recently had surgery to fix a torn ACL. He is currently taking Warfarin to prevent
thrombus formation and Cephalosporin to prevent infection: The Cephalosporin (antibiotic) is totally
irrelevant. The Warfarin is the problem- Warfarin + NSAIDs = risk of bleeding!
 Paul got in another fight at his 5 year old’s T-Ball game.
(Dammit Paul this kind of shit is exactly why Melissa left
you). To ease his injured face and raging hangover, he
takes an Aspirin. What is true of this drug?

• A. It is safe to take Aspirin up to 72 hours prior to surgery

• B. Aspirin OD can result in both Hypo and

Hyperventilation

• C. Unlike other NSAIDs, Aspirin binds COX-1 reversibly

• D. Aspirin is contraindicated in patients with recent stroke

or Myocardial Infarction.
 Paul got in another fight at his 5 year old’s T-Ball game.
(Dammit Paul this kind of shit is exactly why Melissa left
you). To ease his injured face and raging hangover, he
takes an Aspirin. What is true of this drug?
• A. It is safe to take Aspirin up to 72 hours prior to surgery: No Aspirin
for 7-10 days prior to surgery (the life span of platelets)

• B. Aspirin OD can result in both Hypo and Hyperventilation: High doses

of Aspirin lead to over-activation of the respiratory center —>
hyperventilation. SUPER high doses shut down the respiratory center
—> Hypoventilation

• C. Unlike other NSAIDs, Aspirin binds COX-1 reversibly: Aspirin is the

only NSAID with IRREVERSIBLE binding. This contributes to it’s
cardioprotective effects

• D. Aspirin is contraindicated in patients with recent stroke or

Myocardial Infarction: Aspirin has been proven to reduce mortality post
stroke/MI. Many patients with heart problems will take
 COX 1 vs 2
COX 2: Inducible
COX 1: Constitutive
1. Inflammation
2. Reduce Platelet Aggregation
1. GI secretion (GI epithelial cells)
3. Vasodilation (PGI2)
2. Increase Platelet Aggregation
3. Vasoconstriction (TXA2)
Endothelial cells
In platelets AND endothelial cells (that’s
Makes sense! During inflammation you
why it affects both platelets AND
want vasodilation so immune cells can
vasoconstriction!)
like rush to the area and shit.
Inhibition of COX 1 will reduce clotting,
Inhibiting this will inhibit inflammation
but it can also affect GI secretion and
and the associated symptoms like
make the stomach more prone to acid
pain, fever, swelling. But the
damage
imbalance of PGI2 and TXA2 triggers
a pro-thrombotic state!
NSAIDs: What do you need
to memorize…

COX-2 selective is less likely to

affect the GI system, but more
likely to cause hyper-coagulability
—> cardiovascular risk!!
Nonselective is generally higher risk for
GI side effects. Can be managed with
misoprostol or PPIs
NSAIDs: What do you need
to memorize?

GI risk Cardiovascular Risk (Embolism,

stroke, MI
Why is Aspirin Special?
• Aspirin Binds Irreversibly!
Aspirin = Acetylsalicylic Acid
• Why does that matter?

• Platelets only have COX1, endothelial cells have both COX1 and COX2.

• Platelets don’t have a nucleus! Can’t synthesize new proteins! Once

Aspirin binds to COX1 in the platelet, that platelet is permanently
knocked out!

• The doses given for daily clot prevention is so low that it barely effects
endothelial cells at all. Lower than the anti-inflammatory dose

• When used as an anti-inflammatory the dose has to be high enough to

actually effect Prostaglandin production

FYI: Aspirin in its original form only really acts on platelets (anti-platelet effect). After its metabolized (by
the liver) to Salicylate, THAT is what acts on COX2 to reduce inflammation
 Which side effect is least likely to be
associated with high dose aspirin
administration?

• A. Hyperuricemia

• B. Respiratory Alkalosis

• C. Gout

• D. Hypercoagulability
 Which side effect is least likely to be
associated with high dose aspirin
administration?

• A. Hyperuricemia

• B. Respiratory Alkalosis

• C. Gout

• D. Hypercoagulability
 Aspirin and Uric Acid
• Aspirin competes with uric acid for transporters
Other NSAIDs

• At LOW doses: Aspirin hogs the Organic Anion (Ibuprofen,

Naproxen, etc) can
Transporter (OAT) - Prevent uric acid excretion be used to TREAT
Gout attacks

• Too much uric acid in blood (hyperuricemia) —> GOUT

• At HIGH doses: Aspirin hogs the Uric Acid Transporter

(URAT) - prevent uric acid reabsorption from urine

• Too much uric acid in urine (uricosuria) —> STONES

 A patient with chronic heart failure is being managed
with ACE inhibitors and diuretics. He has chronic pain
due to Rheumatoid Arthritis, and decides to take an over
the counter NSAID. What should his doctor advise?

• A. Switch to a COX-2 selective anti-inflammatory

• B. Regular monitoring of Creatinine

• C. Regular EKGs due to risk of long QT

• D. Monitoring of Liver aminotransferases

 A patient with chronic heart failure is being managed
with ACE inhibitors and diuretics. He has chronic pain
due to Rheumatoid Arthritis, and decides to take an over
the counter NSAID. What should his doctor advise?
• A. Switch to a COX-2 selective anti-inflammatory:
nonselective/selective NSAIDs are both associated with
potential kidney damage when combined with Diuretics/ACEis

• B. Regular monitoring of Creatinine: This drug combo is called

the triple whammy. ACEis, diuretics, and NSAIDs all have
potential to cause kidney damage. This patient is at increased
risk due to chronic heart failure. If this drug combo is being
used, kidney function must be monitored

• C. Regular EKGs due to risk of long QT

• D. Monitoring of Liver aminotransferases

 NSAIDs and Kidney Shit
• Prostaglandins dilate the afferent arterioles —> maintain RBF and GFR.

• NSAIDs reduce prostaglandins —> Reduce RBF

• Reduced RBF makes the kidney think that blood pressure must be low —>
activate RAAS system —> Hypertension

• Reduce effectiveness of ACE inhibitors!!

• People with underlying heart/kidney disease are especially sensitive to small

changes in RBF/GFR, and this can lead to acute kidney injury!

• Chronic NSAID over-use can lead to analgesic nephropathy (eg renal

papillary necrosis)
 Triple Whammy
• ACE inhibitors (or ARBs) + Diuretics + NSAIDs

• First problem: NSAIDs can reduce the effectiveness of ACE

inhibitors/diuretics

• Second problem: All of the aforementioned drugs have to potential

to cause acute kidney injury. When you combine them you
dramatically increase the chance of that happening

• Greatest risk: Elderly, diabetes, chronic kidney disease, heart

failure

• If you’re going to use this combo, monitor Creatinine and shit to

make sure you don’t kill anyone
NSAIDs: Important Clinical Shit
Problem Details

Liver damage/encephalopathy! Avoid NSAIDs in anyone under 20 w/

Reye’s Syndrome viral fever. Ibuprofen is the exception. Acetominophen is DOC for
viral fever in kids

Use NSAIDs with caution in late pregnancy. Can cause premature

Pregnancy closure of ductus arteriosus. (NSAIDs- esp Indomethacin, can be
given to treat a Patent Ductus Arteriosus in newborns)

Celecoxib is a sulfonamide —> Sulfa allergies —> rash (eg Steven’s

Hypersensitivity
Johnson)

Arachidonic acid is channeled down the LOX pathway (since it can’t

NERD (NSAID
go with COX) —> increased leukotrienes —> airway inflammation/
exacerbated respiratory
dyspnea/wheezing. Also causes vasodilation —> urticaria (hives),
disease)
hypotension, flushing, shock
 What is true regarding
Aspirin toxicity
• A. Tinnitus, headache, and confusion are early warning
signs of Aspirin toxicity

• B. Accumulation of a toxic metabolic can be treated with

Acetylcysteine

• C. Alkalosis results from a decrease in Lactic Acid

Synthesis

• D. Aspirin follows zero order kinetics in therapeutic doses,

but changes to first order at extremely high doses
 What is true regarding
Aspirin toxicity
• A. Tinnitus, headache, and confusion are early warning signs of Aspirin
toxicity

• B. Accumulation of a toxic metabolic can be treated with

Acetylcysteine: This describes Acetaminophen overdose- buildup of
NAPQI, a potentially toxic metabolite is treated with Acetylcysteine

• C. Alkalosis results from a decrease in Lactic Acid Synthesis: At high

doses, Aspirin acts as an uncoupler and inhibits the ETC - forcing the
body to rely on anaerobic metabolism. This results in Increased lactic
acid —> High anion gap metabolic acidosis. Respiratory alkalosis is
present due to hyperventilation (stimulation of respiratory center)

• D. Aspirin follows zero order kinetics in therapeutic doses, but changes

to first order at extremely high doses
 Acetominophen
• Weak COX1/2 inhibitor —> helps pain/fever

• NO anti-inflammatory properties (therefore not an NSAID)

• Also no effect on Platelets

• DOC: Viral fever in kids, osteoarthritic pain, fever/pain in pregnancy

• Toxicity: Overdose —> accumulation of N-acetyl-p-benzoquinone (NAPQI)

• NAPQI is a minor metabolite of Acetaminophen, and is usually detoxified

using the -SH group on Glutathione. If you OD on Acetaminophen (esp if
paired with alcohol), glutathione gets depleted

• Treat with Acetylcysteine (Acetadote)

Pain Management
 Your patient is a 78 year old man presenting with
Trigeminal Neuralgia. He has a history of BPH, diabetes,
and asthma. Which drug would be the *WORST* choice
to manage his pain?

• A. amitriptyline

• B. nortriptyline

• C. Venlafaxine

• D. Carbamazepine
 Your patient is a 78 year old man presenting with
Trigeminal Neuralgia. He has a history of BPH, diabetes,
and asthma. Which drug would be the *WORST* choice
to manage his pain?

• A. amitriptyline: Tricyclic antidepressants should be used with caution in patients

with BPH. In elderly patients, we are especially worried about the potential for
central anti-cholinergic effects- sedation, confusion, etc. Amitriptyline is a
tertiary amine, and is more prone to entering the CNS and causing these effects

• B. nortriptyline: Not a great choice- Tricyclic antidepressants should be used

with caution in patients with BPH. But nortriptyline is a secondary amine, and is
thus less likely to have CNS anti-cholinergic effects

• C. Venlafaxine: Venlafaxine is an SNRI (Serotonin and norepinephrine reuptake

inhibitor. Although its not the DOC for trigeminal neuralgia, it’s generally useful
for nerve pain.

• D. Carbamazepine: This is definitely the BEST choice! Carbamazepine (an

anticonvulsant) is the DOC for Trigeminal neuropathy. Related drug,
Oxcarbazepine is also very effective and may be better tolerated.
 John visits his grandma in the nursing home, and decides to
make a few bucks by rigging the morning Bingo game.
Unfortunately for him, Herman notices, and uses his cane to
shatter John’s kneecaps. John comes to your office seeking
pain relief. You recommend a good therapist, and a drug with
no analgesic ceiling. That drug is most likely…

• A. Buprenorphine

• B. Ketorolac

• C. Diclofenac

• D. Fentanyl
 John visits his grandma in the nursing home, and decides to
make a few bucks by rigging the morning Bingo game.
Unfortunately for him, Herman notices, and uses his cane to
shatter John’s kneecaps. John comes to your office seeking
pain relief. You recommend a good therapist, and a drug with
no analgesic ceiling. That drug is most likely…

• A. Buprenorphine: Mixed Opioid Agonist

• B. Ketorolac: NSAID

• C. Diclofenac: NSAID

• D. Fentanyl: Most drugs have a Analgesic ceiling (at a certain

point, increasing the dose will not help pain, it’ll just increase
side effects). The exception is pure Opioid agonists like
Fentanyl
A patient is starting on Opioids and is concerned
about side effects. Which side effect is LEAST
likely to go away on it’s own after a few days?

• A. Sedation

• B. Nausea

• C. Diarrhea

• D. Itching
A patient is starting on Opioids and is concerned
about side effects. Which side effect is LEAST
likely to go away on it’s own after a few days?

• A. Sedation

• B. Nausea

• C. Constipation: There are the 4 main side effects of

opioids. (Respiratory depression can also occur at high
doses). The effect most likely to occur and least likely to
resolve on it’s own is constipation

• D. Itching
 Non-NSAID/Opioid Pain
TCAs
Relief Anticonvulsants

Ca Channel Blockers
2º- better for elderly (prevent release of Glu,
1. Despiramine Substance P)
2. Nortriptyline SNRIs 1. Pregabalin
1. Duloxetine 2. Gabapentin
2. Venlafaxine
3º Na Channel blockers
1. amitriptyline 1. Carbamazepine
2. Imipramine 2. Oxcarbazepine
Glucocorticoids:
advances illness/nerve
Some Risk: compression
-Closed angle
Glaucoma, BPH, Urinary 1. Dexamethasone Bisphosphonates:
retention, constipation (DOC) Bone Pain
2. Prednisone
1. zoledronate
AVOID 2. pamidronate
-heart block/arrythmia,
long QT, recent MI
 Topical Pain Relief

• 1. Lidocaine- Localized neuropathic pain (esp post-

herpetic neuralgia)

• 2. Capsaicin- Deplete substance P (also used for post-

herpetic neuralgia)

• 3. Clonidine: Topical, oral, or intraspinal

Opioids
 Pain Mechanisms
• 1. Ascending/Spinal - Signal coming from body, being sent up to brain

• Receptors: NMDA, AMPA

• Ascending fibers: Dorsal horn

• When neurons are depolarized, Ca channels open. This allows exocytosis of the
pain neurotransmitters like Glutamate and Substance P

• Mu Opioid Rec: Prevent opening of Ca channel on presynaptic neuron, open

K channel on postsynaptic neuron (hyperpolarization)

• 2. Descending/SupraSpinal - Signal from brain to body

• Serotonin/Norepinephrine prevent release of pain neurotransmitters

• Opioids increase release of Serotonin and Norepinephrine

 Absence of Opioids:
Inhibitory neurons
secrete GABA. This
stops other neurons
from releasing NTs like
dopamine, serotonin,
and norepinephrine

Presence of Opioids:
Opioids INHIBIT
Inhibitory neurons and
prevent GABA
secretion. This allows
other neurons to
secrete their NTs, and
activate nearby
neurons
(Basically you inhibit
the inhibitor)
Opioids increase release of Serotonin,
Norepinephrine, and Dopamine

• Release of Serotonin/Norepinephrine: Reduce pain

sensation.

• Thalamus, Brainstem, Spinal Cord

• Release of Dopamine: Reward pathway!

• Nucleus Accumbens, prefrontal cortex, VTA

• This is why Opioids are so addictive

Opioid Receptor Types

• Analgesia (ascending/descending) - mu, kappa, and delta

• Sedation: mu and kappa

• Psychotomimetic: Kappa only

• Resp depression + Decreased GI motility: mu only

 Pure Opioid Agonists
Drug Receptor Affinity Key points
High: mu DOC for severe pain. One metabolite (normorphine)
Morphine
Low: Kapp/delta can cross BBB
Heroin —> MAM —> Morphine
Heroin *MAM is super liposoluble and can get through the
BBB really easily. This means it hits the brain FAST
Short term use only! Toxic metabolite
Meperidine Mu only
(normeperidine) has a super long half life.
Antimuscarinic effects + seizures/hallucinations
Rapid onset —> Treat severe acute pain +
Fentanyl Mu only
breakthrough pain
Mu agonist, NMDA antagonist, Longer duration/less euphoria —> treat opioid
Methadone inhibit serotonin/norepi reuptake withdrawal
Mu/kappa/delta agonist, NMDA
Levorphanol antagonist, inhibit serotonin/ Less likely to cause nausea/vomiting
norepi reuptake
Lower affinity (partial Mild-moderate pain. Not given to kids (metabolized
Codeine
agonist) too rapidly- CYP2D6)
Oxy/ Stronger version of codeine, moderate —> severe
hydrocodon pain
e
Opioid Mixed Agonist/
Antagonist
Drug Receptor Key Points

Pentazocine
Rarely used- Kappa
affinity causes
psychomimetic effects.
Mu antagonist, kappa
Nalbuphine Analgesic ceiling
agonist
(increasing dose further
won’t help pain, just
make psychosis worse)
Butorphenol

Mu agonist, kappa Management of opioid

Buprenorphine
antagonist addiction
A 14 year old suburban teen wants to treat
his mild cough and get high before Algebra
class. What drug will he most likely take?

• A. Loperamide

• B. Pentazocine

• C. Diphenoxylate

• D. Dextromethorphan
A 14 year old suburban teen wants to treat
his mild cough and get high before Algebra
class. What drug will he most likely take?

• A. Loperamide: antidiarrheal, no CNS penetration —> less

risk of abuse

• B. Pentazocine- Mixed agonist/antagonist

• C. Diphenoxylate: Antidiarrheal- paired with Atropine to

prevent abuse

• D. Dextromethorphan: Cough syrup- potential for abuse

 Random Opioids
Use Key Points

chronic neuropathic pain

Tramadol (weak mu agonist, inhibit Seizure risk, not for kids
serotonin/norepi reuptake)

Dextromethorphan Cough med Lower than analgesic dose

Can penetrate CNS, so

Diphenoxylate Anti-Diarrhea combined with Atropine to
prevent abuse

Can’t penetrate CNS, low

Loperimide Anti-Diarrhea
abuse potential
 A 12 yearl old girl is being treated for acute pain post
surgery. He is currently being treated for major
depressive disorder. What drug would most likely be
given?

• A. Codeine

• B. Fentanyl

• C. Levorphanol

• D. Morphine
 A 12 yearl old girl is being treated for acute pain post
surgery. He is currently being treated for major
depressive disorder. What drug would most likely be
given?

• A. Codeine: Not given to kids

• B. Fentanyl: Potential for serotonin syndrome if mixed

with SSRIs (most likely tx for MDD)

• C. Levorphanol: Potential for serotonin syndrome if mixed

with SSRIs (most likely tx for MDD)

• D. Morphine
 Serotonin Syndrome
• Basically a serotonin overdose. May occur when certain opioids are mixed
with MAOis, TCAs, or SSRIs

• Symptoms: Delirium, hallucinations, seizures, hyperthermia, coma

• Opioids Associated (inhibitors of serotonin reuptake)

• Levorphanol

• Methadone

• Meperidine

• Tramadol

• Fentanyl
 Opioid Antagonists

• Anatagonists at mu, kappa, and delta

• Naloxone (Narcan) - Short acting, treat acute overdose

• Naltrexone- long acting, management of opioid/alcohol

addiction

• Reduce cravings/reward
Immunopharmocology
Immunosuppressants treat autoimmune
disease and prevent transplant rejection.
I’m too lazy to write that on every slide.
It’s easier to specify the exceptions.
 Glucocorticoids
• Example: Dexamethasone

• Mechanism: Reduce Transcription of pro-inflammatory genes (eg COX-2)

• Also inhibit activity of inflammatory enzymes (eg PLA2)

• PLA2 (Phospholipase A2) is what releases arachidonic acid from

the cell membrane! Arachidonic acid is what COX acts on to make
prostaglandins

• Uses: Autoimmune disease, pain, nausea/fatigue (palliative)

• Adverse Effects: Hypertension/Hyperglycemia (short term), Cushing’s

Syndrome/Osteoperosis (long term)
 Calcineurin Inhibitors
• Calcineurin activates the transcription factor NFAT

• NFAT promotes transcription of cytokines, especially IL2

• IL2 stimulates T-Cell proliferation! If we stop IL2, we turn down the T-

cells

• 1. Cyclosporin: Form complex with Cyclophilin —> complex inhibits

calcineurin

• AE: Gum hyperplasia, hirsutism, Nephrotoxicity

• 2. Tacrolimus: Form complex with FKBP —> Complex inhibits calcineurin

• Unique Use: Topical Formulation for dermatitis/psoriasis

Calcineurin Inhibitors
This complex could either be Tacrolimus +
FKBP sitting on Calcineuron, or Cyclosporin +
Cyclophilin doing the exact same thing!
 Proliferation Signal Inhibitor:
Sirolimus
• Remember how IL-2 stimulates T-Cell proliferation, and we want to
stop it?

• Sirolimus waits until after IL-2 has been transcribed, but then
blocks it from stimulating T-Cells

• Sirolimus forms complex with FKBP

• Complex inhibits mTOR —> Blocks IL-2 driver T-Cell proliferation

• Use: Kidney transplant, coronary stent

• AE: myelosuppression, hepatotoxicity

 Tacrolimus

Tacrolimus
vs Sirolimus

Sirolimus
 Angiogenesis Inhibitor:
Thalidomide

• MOA: Inhibit TNF-a —> Inhibit angiogenesis

• Use: erythema nodosum leprosum and multiple

myeloma

• AE: Teratogen
 Cytotoxic Agents:
Antimetabolites
Drugs MOA Use AE Notes

Metabolized by
Azothiprine (6- Inhibit purine transplant, Bone marrow Xanthine Oxidase.
mercaptopurine) synthesis severe RA suppression Reduce dose if patient
is on Allopurinol

Inhibit AICAR transformylase RA, psoriasis, nausea,

metabolism, no conversion Contraindicated in
of AMP to IMP (last step of SLE, psoriatic ulcers,
pregnancy. Side
Methotrexate purine metabolism). AMP arthritis, leukopenia,
builds up and is released/ effects reduced by
converted to Adenine. Ankylosing anemia,
Adenine = anti-inflammatory Leukovorin + Folate
spondylitis hepatotoxicity

Inhibit IMP Nausea, vomiting,

Mycophenolate
Dehydrogenase —> transplant, SLE headache, HTN,
Mofetil No GTP synthesis myelosuppression

Inhibit Dihydroorotate Diarrhea, Monitor CBC and

Dehydrogenase. RA, SLE,
alopecia, rash, liver function.
Leflunomide Decrease UMP —> myasthenia
No pyrimidine myelosuppres Carcinogenic and
Gravis
synthesis sion Teratogenic
 Cytotoxic Agents:
Antimetabolites
The
Drugs Cytotoxic MOA Antimetabolites Use are basically
AE chemo
Notes
drugs. They prevent proliferation of rapidly dividing Metabolized by
cells. In(6-this Inhibit
Azothiprine case insteadtransplant,
purine of preventing proliferation
Bone marrow of
Xanthine Oxidase.
mercaptopurine) synthesis severe RA suppression Reduce dose if patient
cancer cells, you’re preventing proliferation ofis on immune
Allopurinol

cells, but Inhibit

itmetabolism,
works pretty
AICAR transformylase
no conversion
RA,much
psoriasis,the same
nausea, way! You get
Contraindicated in
SLE, psoriatic ulcers,
a lot
Methotrexate
of the same side effects
of AMP to IMP (last step of
purine metabolism). AMP arthritis,
asleukopenia,
chemo- nausea, pregnancy. Side
effects reduced by
ulcers, anemia, converted toand
Adenine. myelosuppression. anemia, B and T cells
builds up and is released/
Ankylosing
Adenine = anti-inflammatory Leukovorin + Folate
spondylitis hepatotoxicity
are EXTRA affected because these drugs inhibit De
Novo nucleotide
Mycophenolate synthesis.
Inhibit IMP
B and T cells can’t use the
Nausea, vomiting,
Dehydrogenase —> transplant, SLE headache, HTN,
Mofetil
salvageNo GTP pathway,
synthesis so they are extra fucked
myelosuppression

Inhibit Dihydroorotate Diarrhea, Monitor CBC and

Dehydrogenase. RA, SLE,
alopecia, rash, liver function.
Leflunomide Decrease UMP —> myasthenia
No pyrimidine myelosuppres Carcinogenic and
Gravis
synthesis sion Teratogenic
 Cytotoxic Alkylating Agent:
Cyclophosphamide
• Great immunosuppressant… because it destroys your
entire fucking body!

• Destroy proliferating lymph cells, alkylate DNA + proteins

• Use: Autoimmune (eg SLE)

• AEs: infertility, bone marrow suppression, hemorrhagic

cystitis (due to acrolein (metabolite)

• Long term: Infection + Cancer

Drugs where we don’t really
know how they work…
• Hydroxychloroquine

• Anti-inflammatory (somehow)

• Use: Kinda effective for RA and SLE? Eventually… (3-6 months)

• AEs (rare)- Hemolysis in G6PD deficiency, retinal damage

• Sulfasalazine: 5-ASA connected to Sulfapyridine (by diazo bond)

• MOA: Bacteria in colon break the diazo bond, release the pieces

• 5-ASA: Treat ulcerative Colitis

• Sulfapyridine: Treat RA

• AE: Neutropenia, hemolysis in G6PD, drug induced lupus (rare)

 Polyclonal Antibodies
• Anti-Lymphocyte Globulin (ALG) / Anti-Thymocyte
Globulin (ATG)

• Used for stem cell/organ transplant

• Rh D Immune Globulin

• Bind IgG antibodies against Rh+ RBCs

• Prevent hemolytic disease of the newborn

 Polyclonal Antibodies
• Anti-Lymphocyte Globulin (ALG) / Anti-Thymocyte
Antibody Meds: Antibodies are built to bind to their target
Globulin (ATG)
antigen. Great inhibitors! Prevent the normal function of
whatever they are bound to.
• Used for stem cell/organ transplant
Polyclonal: Antibodies are from different B cell lineages-
• soDthey
Rh look aGlobulin
Immune little different and bind to different parts of
the antigen
• Bind IgG antibodies against Rh+ RBCs
Monoclonal: All from identical B Cells- genetically
identical, bind to the same exact epitope
• Prevent hemolytic disease of the newborn
 A Ulcerative Colitis patient is being treated with a
chimeric monoclonal antibody. Which drug are they
receiving and what warning should they be given?

• A. Adalimumab - Take supplemental Folate to reduce side

effects

• B. Adalimumab - Get tested for HIV/TB prior to starting

treatment

• C. Infliximab - Do not get the MMR and VZV vaccines

• D. Etanercept - Avoid crystal meth

 A Ulcerative Colitis patient is being treated with a
chimeric monoclonal antibody. Which drug are they
receiving and what warning should they be given?

• A. Adalimumab - Take supplemental Folate to reduce side effects. Adalimumab is a

fully human (NOT chimeric) antibody. Folate (along with leukovorin) can reduce the
side effects from methotrexate (a cytotoxic antimetabolite)

• B. Adalimumab - Get tested for HIV/TB prior to starting treatment: Although patients
should get tested to make sure they are HIV/TB negative before beginning
Adalimumab (or any other TNFa inhibitor), Adalimumab is a fully human (NOT
chimeric) antibody

• C. Infliximab - Do not get the MMR and VZV vaccines: Infliximab is chimeric (2
special fused together), Fc portion of the antibody is human, variable region is rodent
or something. Patient should NOT be given live attenuated vaccines with taking
Infliximab (or any TNFa inhibitor)

• D. Etanercept - Avoid crystal meth: While avoidance of meth is always great advice
for your patients (we all need a reminder now and then), Etanercept is not a chimeric
antibody (not actually an antibody at all). It’s a TNFa receptor fused to an antibody
 Monoclonal Antibodies:
TNF alpha inhibitors
• Adalimumab: Fully human IgG antibody

• Infliximab: Chimeric antibody (half human/half rodent)

• Etanercept: Not actually an antibody, just a human

TNFa receptor fused to the Fc portion of an IgG
antibody

• All: Do NOT give to patients with TB, HIV, or active

infection

• Do NOT give live attenuated vaccines!

• AEs: Cancer, GI ulcer/perforation, exacerbate heart

failure. Formation of antibodies AGAINST the antibodies
 You prescribe a monoclonal antibody
treatment for Chronic Lymphocytic
Leukemia. Which of the following is true?

• A. This drug acts as an IL-2 antagonist

• B. This drug binds CD20

• C. This drug binds IgE

• D. Monoclonal antibodies are not indicated for treatment

of CLL, way to go, you killed Jerry.
 You prescribe a monoclonal antibody
treatment for Chronic Lymphocytic
Leukemia. Which of the following is true?
• A. This drug acts as an IL-2 antagonist: This describes
Basalixumab. Only indicated to prevent rejection of kidney
transplant (as far as we know)

• B. This drug binds CD20: This is Rituximab! Binds CD20 on B

Cells—> B cell depletion. Treats Non-Hodgekins Lymphoma and
CLL

• C. This drug binds IgE: This describes Omalizumab. Binds IgE

and prevents mast cell activation- good for treatment of asthma/
hives

• D. Monoclonal antibodies are not indicated for treatment of CLL,

way to go, you killed Jerry.
 Other monoclonal
antibodies
• 1. Omalizumab- Antibody against IgE. Prevent IgE mediated mast
cell activation, prevent allergic reaction

• Use: Treat asthma + urticaria

• 2. Basalixumab- chimeric IgG and IL-2 antagonist

• Use: Kidney transplant

• 3. Rituximab- Chimeric antibody, binds CD20 on B cells and

leads to B-cell depletion

• Treat non-Hodgkins lymphoma + Chronic lymphocytic leukemia

 Other biological
immunosuppressants

• Biological immunosuppressants: Slightly modified

versions of immunosuppressants our body naturally
makes

• Both treat moderate-severe RA

• 1. Anakinra: Recombinant IL1 antagonist

• 2. Abatacept: Fusion protein, prevent T-Cell activation

 Immunosuppressants-
Overview
Polyclonal Antibodies
Calcineuron Inhibitors: Cytotoxic: Antimetabolites 1. ALG/ATG: Transplant
Prevent IL2 Transcription (prevent DNA synthesis) 2. Rh D Immune Globulin:
1. Cyclosporin 1. Aziothiprine hemolytic disease of newborn
2. Tacrolimus 2. Methotrexate
3. Mycophenolate Mofetil
4. Luflunomide

Sacrolimus Cytotoxic: Alkylating Monoclonal Abs: TNFa

inhibit mTOR to Prevent Kill all the cells! inhibitors
IL2 function 1. Cyclophosphamide 1. Adalimumab
2. Infliximab
3. Etanercept

Monoclonal Abs: Misc

Random Synthetic
Random Biological 1. Omalizumab
1. Thalidomide
1. Anakinra 2. Basalixumab
2. Hydroxychloroquine
2. Abatacept 3. Rituximab
3. Sulfasalazine
 ImmunoSTIMULANTS!
• 1. Aldesleukin: Recombinant IL2- treat melanoma + renal cell carcinoma

• 2. Interferon (IFN)

• alpha: Cancer (hairy cell, CML, melanoma, Kaposi’s) and Hep B/C

• beta: Relapsing MS

• gamma: Chronic Granulomatous Disease

• 3. BCG (Bacillus Calmette Guerin: attenuated mycobacterium bovis bacteria

• Prophylaxis/treatment of bladder carcinoma

• AEs: Hypersensitivity, shock, fever, etc