Pharmacology

Question 1

Describe the mechanisms of action of monoclonal antibodies, fusion proteins and kinase inhibitors

Answer 1

Mab: monoclonal Ab- can bind a target ligand (TNF-alpha), or receptor

• cept: fusion protein- Acts as a decoy receptor for a particular ligand (neutralize it)
• nib: kinase inhibitor- binds to a kinase receptor and acts as an antagonist.

Question 2

Explain the mechanisms of action of methotrexate

Answer 2

Methotrexate acts as a folic acid antagonist (similar structure) by inhibiting dihydrofolate reductase which reduces dihydrofolate to tetrahydrofolate. Inhibiting this reaction decreases tetrahydofolate concentrations thus inhibiting DNA and RNA synthesis.

Folic acid supplementation can out-compete this mechanism. THIS IS NOT THE MECHANISM RELATED TO RA.

It also promotes the release of adenosine (high adenosine levels), an endogenous anti-inflammatory mediator!****Main mechanism RA

Side effect-GI upset, Bone marrow suppression, and cirrhosis

Question 3

Explain the mechanisms of action of the DMARD le-flu-nomide

Answer 3

Leflunomide is a prodrug its active, metabolite,
(teri-flunomide)

It decreases lymphocyte proliferation

Teratogentic for up to two yrs after stopping medication;-drug elimination procedure.

Elimination procedure is cholestyramine which is a non-absorbed bile acid binding drug used to treat cholesterol levels.

Question 4

What is the role of TNF-alpha in joint inflammation?

Answer 4

Activates leukocytes, endothelial cells, and synovial fibroblasts-inducing production of cytokines, chemokines, adhesion molecules; suppresses Treg and activates osteoclasts.

Question 5

Explain the treatment of RA?

Answer 5

Goal is remission- treat with DMARDs, corticosteroids, and NSAIDs (not disease modifying).

Remember that corticosteroids can induce cushings syndrome.

Question 6

What are some things to know about cephlosporins structure that is important in regard to hypersensitivity reactions and drug options?

Answer 6

It is a beta-lactam antibiotic just like penicillin, but has a different R group.

This drug can have potential cross-sensitivity reactions in persons that are allergic to beta lactam drugs.

Question 7

A friend of yours tells you there is a 5th generation cephalosporin drug called _______that is the only one effective against Staph epidermidis as well as what other elusive bacteria? Why is this so unique?

Answer 7

Ceftaroline is effective against S. Epi and MRSA.

It is the only beta lactam antimicrobial that has activity against MRSA because it binds to the unique PBP of MRSA.

Question 8

The cephalosporins are universally useless against which unique bacteria species?

Answer 8

E.coli and Klebs sp. ESBL+ and KPS+

Question 9

Which drugs from the cephalosporin family can have an effect against P. aeruginosa?

Answer 9

Cefepime and ceftazidime

oral cephalosporins are not active against P. seruginosa or B. frag.

Question 10

Cefoxitin has good activity against what anaerobic bacteria?

Answer 10

Bacterodies fragilis

Question 11

Cefazolin has 100% activity against which G+ bacterium?

Answer 11

MSSA

Question 12

Ceftriaxone kills what bacteria very well?

Answer 12

Lyme disease, Neisseria (both types)

Question 13

While obtaining a patient history you find that your new patient has had an allergic reaction to penicillin in the past. Upon further inquiry you find that the reaction was a rash that occurred two days after they received the antibiotic, and was widespread throughout their body. They require another antibiotic for a new G + infection, how should you proceed?

A) Use penicillin again but a lower dose
B) Avoid beta lactam drugs
C) Use another beta lactam drug but with a different side chain
D) Use a broad spectrum Mab

Answer 13

A) Hell no. Lets not kill them with a more robust adaptive response
B) Not necessarily, you have other options. This is meant to make you feel safe and confident and is correct if the patient had an immediate reaction to the drug.
C) Correct- this lecture outlines the fact that because the R-groups of cephalosporins are different than other beta lactam drugs (like penicillin) they can be used in the case where someone has NOT had an IMMEDIATE hypersensitity reaction (morbilliform reaction).
D) come on, I hope you didn’t pick this

Question 14

Daptomycin is lethal to bacteria via what mechanism of action? What is its antibacterial spectrum? What is an important contraindication for it’s use?

Answer 14

Alters cell membrane permeability causing rapid depolarization and death.

Gram + only

Pneumonia-binds to surfactant and will not work

Question 15

Daptomycin should not be taken if your patient is using which other drug? What needs to be closely monitored when taking daptomycin?

Answer 15

Statins

Monitor creatine phosphokinase (CPK) for myopathy

Question 16

How does Linezolid work? What does it’s spectrum of activity include? What is important about its ADME? What is a major risk that’s associated with this drug that’s related to an important neurotransmitter?

Answer 16

Inhibits protein synthesis

Includes G + bacteria

ADME- IV and oral use deliver same serum levels so de-escalation is important (switch to oral use)

SSRI - serotonin syndrome re-uptake inhibitor: drugs should be avoided: these drugs increase the amount of serotonin in the synapse and can lead to a fatal hyperpyrexia.

Question 17

Neurons that use serotonin as their neurotransmitter AKA __________ are targets of SSRI. These drugs are used to treat what?

Answer 17

5-Hydroxytriptamine or 5-HT

Used to treat depression by increasing serotonin levels

Question 18

Clindamycin MOA is what? Antibacterial spectrum? Commonly recommended to treat what soft tissue infection? When would you recommend against using this drug?

Answer 18

Inhibits protein synthesis
Gram +
Necrotizing Fasciitis
Anerobic/aerobic mixed infections due to its low efficacy

Question 19

Gout is managed in 3 stages, but has 4 stages. What type of drugs are used for each stage and which recommend no pharmacologic intervention?

Answer 19

1) Asymptomatic hyperuricemia > 6 mg/dL (NO DRUGS)
2) Acute gout Typically big toe, lots of pain- treat NSAIDs, Colchicine, and Glucocorticoids.
3) Intercritical phase. Had gout attack once, asymptomatic hyperuricemia (10% never have it again) NO DRUGS
4) Chronic gout: Hyperuricemia, tophi, recurrent attacks of acute gout- Treat: Allopurinol, Febuxostat (xanthine oxidase inhibitors), Probenecid (uricosuric), Pegloticase and if necissary Rasburicase (uricases).

Allopurinol is cheaper than febuxostat and should be used first

Question 20

You have a patient presenting with acute gout that has comorbidities limiting your ability to treat them with NSAIDs or colchicine. The gout attack is in the MTP joint of the first metatarsal and is easily accessible. How should you treat them?

Answer 20

Depo shot with steroid- use when comorbidities limit use of NSAIDs and colchicine and the joint is easily accessible.

Question 21

You determine that your patient has Chronic gout and you want to put them on Allopurinol a urate-lowering therapy. What’s the best way to prevent an acute gout flare while beginning this new medication?

Answer 21

Prophylacticly treat with an anti-inflammatory a few weeks before starting them on the allopurinol, and continue this LOW dose anti-inflammatory with allopurinol for 6 months, or until tophi resolve.

Only treat acute flares with HIGH dose anti-inflammatory medication.

Question 22

What is colchicines mechanism of action and side effects?

Answer 22

Mitotic spindle poison which inhibits cell division by interfering with microtubules

Side effects include the prevention of neutrophil activation, degranulation, and migration (which can help with gout symptoms)

IV administration can be FATAL use orally

Question 23

How do uricosuric drugs and uricases work to lower uric acid levels?

Answer 23

Uricosuric drugs-Increase uric acid excretion by inhibiting kidney re-absorption.

Uricases further oxidize uric acid into allantoin (a-lan-toy-n) which is more soluble in urine.

Question 24

How does allopurinol and febuxostat work to decrease uric acid? What drug interaction do you need to know about that can be very serious?

Answer 24

Both are xanthine oxidase inhibitors. Thus inhibiting the enzyme that converts Hypoxanthine to xanthine and xanthine to uric acid. Although this same enzyme converts allopurinol to OXYpurinol there is still sufficent enzyme to make this active metabolite.

Both of these drugs can prolong the half-lives of azathioprine and its metabolite 6-mercaptopurine (by inhibitng xanthine oxidase which inactivates 6-mercaptopurine). These are immunosuppressants and this interaction increases the patients risk of bone marrow depression.

Question 25

Which two uricases should you know, and how are they different?

Answer 25

Pegloticase for adults with chronic gout

Rasburicase for patients with leukemia, lymphoma receving anti-cancer therapy, b/c it results in tumor lysis and elevation of uric acid, due to the liberation of free purines= tumor lysis syndrome.

Rasburicase has a potential for allergic reaction and is a last line therapy. Allopurinol should be used to treat TLS preferentially.