Pharm and Physiology

Question 0

How does S. aureus become resistant to most penicillins? How does MRSA become resistant to penicillinase-resistant pencillins?

Answer 0

Most penicillins - S. aureus produces beta-lactamase which cleaves the beta-lactam ring

Nafcillin/methicillin/oxacillin - alterations in penicillin-binding protein (PBP) structure with greatly reduced affinity for all beta-lactam antimicrobials

both reduce cell wall synthesis by interfering with PBP crosslinking of peptidoglycans

Question 1

Which penicillins are penicillinase-stable (resistance to beta-lactamase cleavage)?

Answer 1

Oxacillin, nafcillin, and methicillin

Question 2

What is the drug suffix for receptor molecules? monoclonal antibodies? kinase inhibitors?

Answer 2

receptor molecules: “-cept”
monoclonal antibodies: “-mab”
kinase inhibitors: “-nib”

Question 3

What is etanercept and what does it do?

Answer 3

TNFalpha inhibitor, acts as a decoy receptor

fusion protein linking a soluble TNFa receptor to the Fc component of human immunoglobulin G1 (IgG1)

Question 4

Pt recently diagnosed with psychiatric disorder - head now tilted to one side and cannot straighten without considerable pain?

Answer 4

typical antipsychotics are D2 receptor blockers
(Haloperidol + “-azines”, trifluoperazie, fluphenazine, thioridazine, chlorpromazine)

extrapyramidal symptoms with typical antipsychotic use due to resulting cholinergic excess in the striatum when D2 blocked!

Question 5

Pt back from vacation with white spots all over otherwise tanned body - what fungus? Identification? Treatment?

Answer 5

Malassezia furfur causing pityriasis versicolor / tinea versicolor

KOH preparation of skin scrapings show “spaghetti and meatballs”

Tx: topical miconazole, selenium sulfide

Question 6

Most common cause of hematogenous osteomyelitis? Most common age group, mechanism, and location?

Answer 6

S. aureus
predominantly disease of children
affects the long bones most frequently
usually secondary to a bacteremic event

Strep. pyogenes (group A strep) second most common cause

Question 7

What organism is responsible for gas gangrene? What other affliction does it cause?

Answer 7

Clostridium perfringens

also causes late-onset, toxin-mediated food poisoning, characterized by a transient watery diarrhea

Question 8

What is the main toxin of C. perfringens and what does it do?

Answer 8

Lecithinase (also known as alpha toxin)
catalyzes the splitting of phospholipid molecules (hydrolyzes lecithin-containing lipoprotein complexes in the PM)

degrades lecithin, a component of cellular phospholipid membranes, leading to membrane destruction, cell death, and widespread necrosis and hemolysis

Question 9

Pt with fracture and osteoporosis - past medical history of HTN and CHF - what drug could’ve been used to help prevent?

Answer 9

Hydrochlorothiazide
increases absorption of Ca2+ from DCT
(ideal agent for treatment of HTN/CHF in women at risk for osteoporosis)

Question 10

Diuretics that have an effect on calcium homeostasis? Ideal pts to be used for?

Answer 10

Hydrochlorothiazide - increases absorption and decreases excretion at DCT

Furosemide - loop diuretic that increases excretion (Loops Lose calcium)

HCT ideal for pts with osteoporosis or pts with renal stones
Furosemide ideal for pts with hypercalcemia

Question 11

Ecthyma grangrenosum?

Answer 11

Pseudomonas aeruginosa
associated with bacteremia or septicemia, typically in immunocompromised pts

rapidly progressive, necrotic cutaneous lesions due to perivascular invasion and release of exotoxins to cause edema and necrosis

Question 12

Pt with diffuse pruritic papulopustular rash, friend also had it. Pustular fluid = oxidase+, gram negative rods with pigment on culture epithelium? Source?

Answer 12

Pseudomonas aeruginosa - “hot tub folliculitis”
water source, blue-green pigment

motile, non-lactose fermenting, and grape-like odor

Question 13

Treatment of acute gout? Side effects?

Answer 13

NSAIDs, glucocorticoids, colchicine

Colchicine side effects: GI - nausea and diarrhea

Question 14

What is the mechanism of S. aureus’s virulence factor?

Answer 14

Protein A
binds the Fc portion of IgG at the complement-binding
prevents the activation of complement, resulting in decreased C3b production and thus impaired opsonization

Question 15

Sickle cell pt with osteomyelitis?

Answer 15

Salmonella most common, followed by E. coli (then by S. aureus)

Question 16

What are the encapsulated bacteria? What vaccinations are available for asplenic pts?

Answer 16

SHiNE SKiS
Strep.pneumo, H.influenza, Neisseria meningitidis, E.coli
Salmonella, Klebsiella, group B Strep.

Question 17

Pyrrolidonyl arylamidase (PYR)-positive organism? Bacitracin sensitivity?

Answer 17

Group A Strep
Strep. pyogenes

Bacitracin sensitive

Question 18

Which organisms use an adenylate cyclase toxin?

Answer 18

Bacillus anthracis (Edema factor)
Bordetella pertussis (Adenylate cyclase toxin)

Both increase cAMP production to cause edema and phagocyte dysfunction

Question 19

What preventative drugs are used in chronic gout? Mechanism? Name them.

Answer 19

Xanthine oxidase inhibitors (Allopurinol, Febuxostat)
inhibits conversion of xanthine to uric acid

Uricosuric drugs (Probenecid)
inhibits reabsorption of uric acid in the PCT

Question 20

Pt treated for acute gout with diarrhea and nausea?

Answer 20

Colchicine - MT inhibitor

Question 21

What are the toxicities of hydrochlorothiazide?

Answer 21

Hypokalemic metabolic alkalosis (manifests as muscle weakness and cramping)
Hyponatremia (manifests with neurological symptoms like altered mental status, seizures, etc.)

"HyperGLUC"
HyperGlycemia
HyperLipidemia
HyperUricemia
HyperCalcemia

Question 22

What is succinylcholine and what is it used for?

Answer 22

depolarizing NMJ blocking drug
strong ACh receptor agonist that produces sustained depolarization and prevents muscle contraction

used for muscle paralysis in surgery or mechanical ventilation

Question 23

How can succinylcholine NMJ blockade be reversed?

Answer 23

administration of a cholinesterase inhibitor (e.g., neostigmine) during PHASE 2

Phase I (prolonged depolarization) - neostigmine augments block and prolongs paralysis
Phase II (repolarized but blocked, so ACh receptors available but desensitized) - neostigmine reverses the block

Question 24

26yo athlete with comedonal and inflammatory nodular eruption on face, chest, back? What drugs cause this?

Answer 24

Acne at later age, suspect:
anabolic steroids (e.g. methyltestosterone) which are androgens –
after conversion to DHT, promote both follicular epidermal hyperproliferation and excessive sebum production (two of the major elements of acne pathophysiology)

also EGFR inhibitors and lithium

Question 25

What is piperacillin-tazobactam and what is it used for?

Answer 25

antipseudomonal with a beta-lactamase inhibitor

used for Pseudomonas and gram-negative rods (including anaerobes like Bacteroides fragilis)

Question 26

56yo female with joint pain and swelling gets treatment - weeks later presents with hemoptysis and acid-fast bacilli?

Answer 26

Treated for RA with TNFalpha inhibitor most likely
decreases macrophage function and may cause Tb reactivation

PPD should be performed to screen for latent Tb before starting therapy

Question 27

What are bisphosphonates analogs of? Side effects?

Answer 27

Pyrophosphate analogs
bind hydroxyapatite in bone (major component, makes it more insoluble), inhibiting osteoclast activity

• corrosive esophagitis
  (caustic and poor GI absorption – drink plenty of water while fasting, sit up for 30min after to prevent reflux)
• osteonecrosis of the jaw

Question 28

Treatment for pt with joint pain and history of facial palsy?

Answer 28

Lyme disease - easily treated with doxycycline or penicillin-type antibiotics (e.g. ceftriaxone)

Question 29

Pt with low bone density and family history of breast cancer - treatment?

Answer 29

Raloxifene - selective estrogen receptor modulator
agonist at bone
antagonist at breast and uterus

Question 30

First-line therapy for acute gouty arthritis? Can drugs used to treat chronic gout be used?

Answer 30

1) NSAIDs (COX inhibitors) are first-line for most pts, but avoided in pts with renal and hepatic dysfunction, elderly
2) Colchicine considered second-line due to GI side effects
3) Glucocorticoids indicated in pts with contraindication for both NSAIDs and colchicine (e.g. renal failure)

Xanthine oxidase inhibitors (allopurinol and febuxostat) and uricosuric agents (probenecid) are contraindicated in acute gout – they can exacerbate acute arthritis.

Question 31

45yo pt treated for severe joint pain and swelling develops mouth ulcers and nausea with elevated AST&ALT? How to reverse?

Answer 31

Methotrexate - preferred disease-modifying treatment for moderate to severe rheumatoid arthritis

May cause stomatitis (painful mouth ulcers) and LFT abnormalities, myelosuppression

Supplementation of folic acid reduces occurrence (MTX inhibits dihydrofolate reductase)

Question 32

Drug-induced SLE - what are the common drugs? How are they metabolized and what pts are at most risk? Classic serum finding?

Answer 32

Hydralazine and procainamide
both metabolized via phase II N-acetylation in the liver

Genetic predisposition determines acetylator phenotype
Pts that are slow acetylators are at greater risk for developing drug-induced SLE.

Anti-histone antibodies found! (vs. anti-nuclear antibodies in SLE)

Question 33

Child with malar rash and headache/stuffy nose for past 3 days?

Answer 33

Erythema infectiosum ("fifth disease")
caused by Parvovirus B19

causes slapped-cheek appearance
as facial rash fades, erythematous rash in reticular/lace-like pattern appears on trunk and extremities

Most commonly transmitted via respiratory route

Question 34

How do corticosteroids exert their antiinflammatory effects?

Answer 34

inhibit phospholipase A2 activity, which decreases prostaglandin and leukotriene synthesis
also depress immune response by reducing macrophage phagocytosis and IL-1 secretion

Question 35

32yo pt with right knee pain and swelling - WBC count of 100,000/mm3 in synovial fluid? Best initial treatment?

Answer 35

Septic arthritis, usually due to gonococcus, is the most common cause of acute monoarticular arthritis in this age group

Gout and pseudogout usually has WBC count LESS THAN 20,000/mm3

High synovial fluid WBC count and absent crystals suggest bacterial joint infection - treat with ceftriaxone

Question 36

Pt about to go on etanercept - pre-test for what?

Answer 36

PPD for Tb

make sure won’t reactivate latent infection with etanercept

Question 37

Quadriplegic man about to be intubated - skeletal muscle relaxant administered and goes into cardiac arrest. High K+ levels drawn - what drug used?

Answer 37

Succinylcholine
depolarizing NMJ-blocking agent

PHASE I
- attaches to nicotinic ACh receptor and depolarizes NM end plate
- not degraded by ACh-esterase so continuously stimulates the endplate
sodium channels surrounding endplate are inactivated and cannot reopen until repolarization

PHASE II
- eventually, continuous depolarization of endplate gives way to gradual repolarization as receptors become desensitized to succinylcholine

nACh receptor is nonselective cation channel so increased K release leading to potential arrhythmias in pts with crush/burn injuries, denervating injuries/diseases (quadriplegia or Gullain-Barre), and myopathies
These states cause up-regulation of muscle nAChRs and/or rhabdomyolysis which can result in large amts of K+ release with succinylcholine administration – NONDEPOLARIZING agents preferred in these pts!