Official Step 1 High Yield Concepts Thread

[Transposony]

Let's discuss our doubts/offer clarifications about mechanisms/concepts for Step 1

ASK ANY QUESTIONS here.

To kick start the thread here is something I didn't know:

1. Penicillin-binding proteins (PBPs) are actually enzymes (transpeptidases & carboxypeptidases) which cross-link peptidoglycan. Penicillins binds to these enzymes and inactivating them thereby preventing cross-linkiing of peptidoglycan.

2. Periplasmic space (Gram -ve) contain proteins which functions in cellular processes (transport, degradation, and motility). One of the enzyme is β-lactamase which degrades penicillins before they get into the cell cytoplasm.
It is also the place where toxins harmful to bacteria e.g. antibiotics are processed, before being pumped out of cells by efflux transporters (mechanism of resistance).

There are three excellent threads which you may find useful:

List of Stereotypes

Complicated Concepts Thread

USMLE images

---

Members don't see this ad.

 

[Focused1]

O and Z are known treatments for existing disease (decrease prevalence). And they also prevent viral spread (decrease incidence). They do both.

That's a good one...
never thought about it that way !

 

[Keto]

Opioid-induced hypoventilation = really high-yield to know that's a normal A-a gradient.

Other causes of normal A-a gradient hypoxemia:

• Hypoventilation due to (neuro)muscular conditions
• obesity
• high altitude.

High A-a gradient is seen with most lung diseases:

• Pneumonia
• edema
• fibrosis, ...

Underlying mechanism for a high A-a gradient are:

• V/Q mismatch
• shunting
• fibrosis

How do you calculate the A-a gradient?

• pressure O2 in alveoli minus pressure O2 in arteries
  =Alveolar O2 [mmHg] - arterial O2 [mmHg]
  • arterial O2 from arterial blood gas [mmHg]
  • Alveolar O2 from gas equation because the inspired O2 is of course not the same as the alveolar O2 due to alveolar oxygen mixing with CO2 (you need arterial CO2 pressure from your arterial blood gas analysis to calculate that)
    • (FiO2) * (Atmospheric Pressure - H2O Pressure) - (PaCO2/0.8)
    • 150 - arterial CO2 / 0.8

How do you calculate the alveolar-arterial gradient on room air without a calculator?
Modified:

• (150 - 1.25 x PaCo2) - PaO2

What is an normal A-a gradient?

• 9-15 mmHg
  
• Can be estimated with: (Age/4) + 4

 

[Transposony]

O and Z are known treatments for existing disease (decrease prevalence). And they also prevent viral spread (decrease incidence). They do both.

So, for infectious diseases, reducing the pool of people with the disease (prevalence) will, over time, reduce new cases (incidence).
But this is not a direct effect, rather an effect of decreased prevalence on future incidence(s) of an infectious disease.
Am I understanding it correctly?

 

[aspiringmd1015]

yeah i think the key distinction, is the fact that in communicable diseases, giving a certain RX like pholston had mentioned can decrease incdedene too, i believe Kaplan qbank had an explanation on it, not sure UW did or didnt.

 

[aspiringmd1015]

does anyone have a link to a good blood smear image of malaria, showing the different types of stages, ie trophozoite ring, schizont w/merozoites, and shuffner bodies?

 

[aspiringmd1015]

out of the intestinal nematodes, only the pinworm isnt a/c with eosinophilia?

 

[aspiringmd1015]

also do the hyperphsophorylated tau proteins have anything to do with Beta cleavage of the APP protein in alzheimers? or is it just an incedental finding that we dont knwo why it happens in alzheimers

 

[aspiringmd1015]

..ok. another ?, any other vaccine that we can give in pregnancy/immunocompromised states besides MMR?

 

[addidas]

also do the hyperphsophorylated tau proteins have anything to do with Beta cleavage of the APP protein in alzheimers? or is it just an incedental finding that we dont knwo why it happens in alzheimers

From a nature article:

Mutations in the tau gene could cause autosomal dominant frontotemporal lobe dementia, chromosome 17-type. The tau pathology in this disease is similar to the tau pathology seen in AD, but without the appearance of amyloid beta plaques. Thus, tau pathology itself can cause neuronal loss. This observation places tau pathology downstream of amyloid-beta pathology.

Also a reduction in endogenous levels of tau can ameliorate some of the behavioural and other deficits that are mediated by amyloid-beta again placing tau downstream of amyloid beta.

Ultimately, the precise temporal and mechanistic relationships between amyloid-beta deposition and tau pathology remain to be resolved.

Was doing Alzheimer's and remembered someone had asked a question about Tau.

 

[aspiringmd1015]

thanks for the reply, love it when these forums are actually put to use, you know, w/answering peoples questions!

 

[aspiringmd1015]

why would giving estrogen in andorgen dependent prostate cancer be beneficial?

 

[faisal 2000]

which drugs and diseases can cause flu-like symptoms ??

 

[aspiringmd1015]

if testo levels are unaffected by temperature, why in B/L cyptorchidism is it decreased?

 

[AZ7]

if testo levels are unaffected by temperature, why in B/L cyptorchidism is it decreased?

Sertoli cells normally secrete inhibin. As they are temperature sensitive, in bilateral cryptorchidism - Inhibin levels go down, FSH levels go up = Increased aromatase activity and conversion of testosterone to estrogen. Therefore decreased testo levels.

 

[Dr joji]

Thank you

 

[aspiringmd1015]

leydig cells are unaffected by temp, and fsh levels correlate w/aromatase?

 

[AZ7]

leydig cells are unaffected by temp, and fsh levels correlate w/aromatase?

Yes and yes.
factors known to increase aromatase activity include : age, obesity, gonadotropins, alcohol. ( source - wikipedia )

 

[AZ7]

why would giving estrogen in andorgen dependent prostate cancer be beneficial?

Beneficial? I was under the impression that it also contributes to the carcinogenesis

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3134227/

 

[aspiringmd1015]

so decrease in testoterone levels isnt due to decreased production, its due to increased aromatization. FSH increases ovarian aromatoase, but also the aromatase in your adipose?
and yes, its in FA in the repro pharm section.

 

[aspiringmd1015]

what is responsible for flexion of your fingers? the lumbricals? or the flex digitorum profundus?

 

[ATypicalLymphocyte]

what is responsible for flexion of your fingers? the lumbricals? or the flex digitorum profundus?

The lumbricals 1) flex the MCP joint + 2) extend the IP joints = L-shaped hand.
As for flexion, sure, FLEXOR DIGITORUM (profundus, as well as superficialis) both produce flexion of the digits. Other muscles do as well (e.g., flexor pollicis longus, flexor pollicis brevis, flexor digiti minimi).

 

[RLSGrasshopper]

Bump

 

[faisal 2000]

which drugs and diseases can cause flu-like symptoms ??

 

[Focused1]

Interferons for sure...and probably a bunch of other stuff... flu like symptoms is a pretty vague descriptor and I would be comfortable picking an answer if presented with options rather than drawing up a list..

 

[W19]

Nice thread

 

[sepsis 3050]

Hi guys
What causes tendonitis and tendon rupture in pxt > 60yrs, steroid, renal failure on quinolones

 

[faisal 2000]

Hi

Most common causes of polyneuropathy are diabetes mellitus, alcohol abuse and HIV. But of course you have to watch out for drug induced neuropathy.

Other etiologies of peripheral neuropathy can be broken down in nutritional (B6, B12), hereditary (Friedreich's ataxia, Charcot-Marie-Tooth), Infections (HIV, Lyme disease), and others. I will focus here on some classical examples of drug induced peripheral neuropathy.


HIV Drugs

• Nucleoside analogues (esp. Didanosine, Stavudine)

A challenge would be here to differentiate between HIV neuropathy and drug-induced neuropathy. Watch out for the classic NRTIs that cause neuropathy or a patient, that is not on triple therapy.

Chemotherapy-induced peripheral neuropathy (CIPN)

• Vincristine
• Cisplatin
• Taxanes (Paclitaxel)

Classic Example: A patient, that is on chemotherapy for weeks and develops now "stocking glove neuropathy". They will ask you is this because of the drug or because of cord compression of a metastasis? A Cord compression would give you also back pain, upper motor symptoms, prominent motor deficits.

Antimicrobial Drugs

• Isoniazid (prevent with B6)
• Linezolid

Immunosuppressive Drugs / Inflammatory drugs

• Colchicine
• Cyclosporine

Toxins

• Arsenic poisoning (chronic)

Classic Example: Wood preservatives, weed killers, pesticides.


As an interesting side note:

• Watch out for a patient with Diabetes, who is taking Metformin and develops polyneuropathy after years of treatment. Metformin interferes with the absorption of folate and B12, and the question is now: Is the neuropathy due to diabetes or B12-deficiency? (Get CBC with MCV and look for your macrocytic anemia with hypersegmented neutrophils. Measure B12 levels.

Metronidazole, diphtheria, vit E dificiency, and Pyridoxine (vit B6) toxicity cause peripheral neuropathy

 

[faisal 2000]

flu like symptoms:Fever, headache, Fatigue, Stuffy nose, cough, Sore throat.
flu like symptoms occur in tremendous diseases and drugs but here which always confused me
Giant Cell arteritis: flu-like symptoms, headache, jaw claudication, and visual problem
side effects of Statins: flu-like symptoms, headache, stomach pain, fatigue, and myalgia (without changes in creatine kinase)

 

[faisal 2000]

how can we differentiate between acute lead poisoning and iron poising based on symptoms ?

 

[faisal 2000]

what type of cardiomyopathy will occur in Pompe's disease ( alfa 1,4 glucosidase deficiency) ?? restrictive cardiomyopathy or hypertrophic cardiomyopathy ???

 

[faisal 2000]

how can we differentiate between acute lead poisoning and iron poising based on symptoms ?

acute lead poisoning : nausea, vomiting, severe GI distress and pain, paresthesis, tinnitus, and tremors
treatment : dimercaprol, EDTA, succimer for children. (we can use penicillamine if unable to use dimercaprol, EDTA, or succimer).

iron poisoning : severe GI distress --> necrotizing gastroenteritis with hematemesis and bloody diarrhea, dyspnea, shock, coma, and normal anion gap acidosis.
treatment : deferoxamine IV

 

[aspiringmd1015]

a stone in the cystic duct: can cause jaundice or no? and if you have an isolated stone in the common hepatic duct, can that produce jaundice?

 

[Phloston]

Of RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) for the management of tuberculosis:

Step 1 level:

1) Which are notably hepatotoxic?
2) Which are known to cause gout?
3) Which causes innocuous orange secretions/urine?
4) What are the MOAs of all four drugs?
5) Which one is toxic to the visual system? What signs/symptoms are seen?
6) Which one causes a vitamin deficiency? What is the vitamin? And what are the symptoms/signs of the deficiency?
7) Why does the drug in #6 cause this vitamin deficiency?
8) Why does that vitamin deficiency cause those symptoms/signs?
9) Which drug works best against TB that's already been phagocytosed? And why?
10) What type of hypersensitivity is the PPD test?
11) Which drug upregulates P-450; which inhibits it?

-------

Step 2CK level (19 and 21 overlap with Step 1):

12) When do you give prophylaxis versus full-on Tx? And what are the durations of drug therapy?
13) Which is the preferred monoprophylaxis? How long do you give it for?
14) If you get a + PPD test, what's the next thing you do?
15) If you get a - PPD test, what's the next thing you do?
16) When is a PPD test considered positive?
17) What's the TB vaccine called and when is it given?
18) If a person previously vaccinated against TB has a + PPD later on, what do you do?
19) Which pneumoconiosis notably increases the risk of TB?
20) How many people in the world have been exposed to TB?
21) There are certain drugs that can increase the risk of TB - which class notably?

 

[Transposony]

a stone in the cystic duct: can cause jaundice or no? and if you have an isolated stone in the common hepatic duct, can that produce jaundice?

A stone in the cystic duct usually will not cause jaundice unless it's large enough to compress the CBD (extrinsic compression- Mirizzi's syndrome) but stone in the common hepatic duct can cause jaundice +/- cholangitis.
However, it's very unlikely to have a stone in the common hepatic duct (unless associated with stricture) due to bile flow and the fact that stones usually lodge at the narrowed areas of a tube.

 

[Focused1]

Responded in the RIPE format

Step 1 level:

1) Which are notably hepatotoxic?
All except E

2) Which are known to cause gout?
P

3) Which causes innocuous orange secretions/urine?
R

4) What are the MOAs of all four drugs?
R -> RNA poly inh
I -> inhibits mycolic acid synthesis
P -> err..unknown maybe..or well atleast unknown to me :-/
E -> arabinosyl synthesis inhibitor..something about the carb content of the wall

5) Which one is toxic to the visual system? What signs/symptoms are seen?
E -> R/G color change, optic neuritis

6) Which one causes a vitamin deficiency? What is the vitamin? And what are the symptoms/signs of the deficiency?
I, B6, Periph Neuropathy

7) Why does the drug in #6 cause this vitamin deficiency?
I combines with the active form of B6 Pyridoxal phosphate and makes a complex INH-Pyridoxal Phosphate and decreaeses availability

8) Why does that vitamin deficiency cause those symptoms/signs?
B6 is involved in a reaction as a cofactor...forgot the reaction..can't recollect spontaneously but maybe able to recall from a line-up of options

9) Which drug works best against TB that's already been phagocytosed? And why?
Pyrazinamide works in phagolysosomes and is converted into active for pyrazinoic acid or something. That works inside the cell and mediated intra-cellular bactericidal activity

10) What type of hypersensitivity is the PPD test?
Type 4 Delayed

11) Which drug upregulates P-450; which inhibits it?
R

-------

Step 2CK level :
I knew a few and hence answered em..

17) What's the TB vaccine called and when is it given?
BCG...

19) Which pneumoconiosis notably increases the risk of TB?
Silicosis
21) There are certain drugs that can increase the risk of TB - which class notably?
Anti - TNF ones.. Etenercept Infliximab Golimumab Adalimumab



Thanks for the questions !!
Awaiting answers..
Please do post more...much appreciated !

 

[faisal 2000]

Responded in the RIPE format


6) Which one causes a vitamin deficiency? What is the vitamin? And what are the symptoms/signs of the deficiency?
I, B6, Periph Neuropathy

vit B6 def causes sideroblastic anemia, cheilosis or stomatitis, and convulsion.

 

[faisal 2000]

what type of cardiomyopathy will occur in Pompe's disease ( alfa 1,4 glucosidase deficiency) ?? restrictive cardiomyopathy or hypertrophic cardiomyopathy ???

pompes disease causes restrictive cardiomyopathy initially, but eventually it can become dilated cardiomyopathy (i am not sure)

anyone have idea about it
@Transposony @Phloston

 

[Transposony]

pompes disease causes restrictive cardiomyopathy initially is Restrictive, but eventually it can become dilated cardiomyopathy (i am not sure)

It's hypertrophic cardiomyopathy (with left ventricular outflow obstruction) leading to congestive heart failure usually within 2 yrs.

 

[Dr.serotonin]

a 22 year old female during interview said she has never been sexually abused. but her records show that she was treated for STD during the age of 9 to 11. the defence mechanism used here is?

A. Denail
B. regression
C. supresson
D. reaction formation
E. projection

 

[faisal 2000]

Of RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) for the management of tuberculosis:


4) What are the MOAs of all four drugs?

_ isoniazid inhibits synthesis of mycolic acids which are essential components of mycobacterial cell walls
_ rifampin inhibits RNA synthesis in bacteria
_ ethambutol inhibits Arabinoglycan which are essential component of mycobacterial cell wall.
_ Pyrazinamide is a prodrug which is converted to the active form “pyrazinoic acid” by the enzyme pyrazinamidase that is found in mycobacterium tuberculosis. pyrazinoic acid lowers intracellular pH that destroys the bacterium. Pyrazinamide causes Hyperuricemia due to inhibition of renal tubular secretion of uric acid by the drug metabolite pyrazinoic acid, so gout occur .

Of RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) for the management of tuberculosis:


11) Which drug upregulates P-450; which inhibits it?

rifampin upregulates P-450
isoniazid inhibits P-450

 

[aspiringmd1015]

A stone in the cystic duct usually will not cause jaundice unless it's large enough to compress the CBD (extrinsic compression- Mirizzi's syndrome) but stone in the common hepatic duct can cause jaundice +/- cholangitis.
However, it's very unlikely to have a stone in the common hepatic duct (unless associated with stricture) due to bile flow and the fact that stones usually lodge at the narrowed areas of a tube.

nice thanks. and why is it that a stone in the hepatic duct will cause it? bc bile is still being sent to the GB?

 

[Phloston]

a 22 year old female during interview said she has never been sexually abused. but her records show that she was treated for STD during the age of 9 to 11. the defence mechanism used here is?

A. Denail
B. regression
C. supresson
D. reaction formation
E. projection

None. I'd say repression. And if this is a real question somewhere then that's unfortunate for me isn't it.

 

[faisal 2000]

conditions mimic schizophrenia ?
MOA of Memantine ?

 

[Dr.serotonin]

None. I'd say repression. And if this is a real question somewhere then that's unfortunate for me isn't it.

actually I forgot to add repression in the options, which in fact is the best distractor. here the answer is Denail. bcuz memory is not mentioned in the stem. she was abused but she is not accepting it. she has not said she can't remember that.

repression : you forget a memory and then you forget that you forgot it.
Denail : is simply not accepting the reality / not allowing to penetrate the reality

 

[Keto]

Hi,

what are your thoughts on the following defense mechanism question:

A nurse, working in a hospice, has been ignoring an elderly patient who has a terminal condition. When asked why, he has been ignoring the patient, the nurse replies "he wants to be left alone." Which of the following defense mechanisms best explains her response?

A Denial
B Isolation of affect
C Intellectualization
D Projection
E Rationalization​

Keep up the good work!

 

[Keto]

MOA of Memantine ?

Simplified approach to treatment of dementia:

1. Mild/moderate dementia:
   Treatment trial with cholinesterase inhibitors (Donepezil, Rivastigmine, Galantamine)
2. Moderate + Advanced dementia:
   Add Memantine
3. Severe Dementia:
   Stop cholinesterase inhibitors, continue memantine.
   Restart cholinesterase inhibitors, if patient worsens without medication.

• Role of Vitamin E (believed to protect against oxidation) not entirely clear. Also watch out for Vitamin E toxicity (in very high doses it acts as a Vitamin K).

(modified from uptodate)


Memantine

• Non-competitive NMDA (glutamate receptor) blocker (the only drug that is FDA-approved with a different pharmacological approach)
• In brain ischemia, excessive glutamate leads to excitotoxicity, suggesting that agents that block pathologic stimulation of NMDA receptors may protect against further damage in patients with vascular dementia.
• Also it appears that Aβ might interact with NMDA receptors (showed in vitro).
• Memantine has fewer side effects than the cholinergic agents.
• SE: Dizziness, confusion, hallucinations.

Donepezil, Rivastigmine, Galantamine

• AChE inhibitors; SE: Dizziness, insomnia, nausea.

 

[Dr.serotonin]

Hi,

what are your thoughts on the following defense mechanism question:

A nurse, working in a hospice, has been ignoring an elderly patient who has a terminal condition. When asked why, he has been ignoring the patient, the nurse replies "he wants to be left alone." Which of the following defense mechanisms best explains her response?

A Denial
B Isolation of affect
C Intellectualization
D Projection
E Rationalization​

Keep up the good work!

that will be Projection.

 

[Focused1]

Of RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) for the management of tuberculosis:

Step 1 level:

1) Which are notably hepatotoxic?
2) Which are known to cause gout?
3) Which causes innocuous orange secretions/urine?
4) What are the MOAs of all four drugs?
5) Which one is toxic to the visual system? What signs/symptoms are seen?
6) Which one causes a vitamin deficiency? What is the vitamin? And what are the symptoms/signs of the deficiency?
7) Why does the drug in #6 cause this vitamin deficiency?
8) Why does that vitamin deficiency cause those symptoms/signs?
9) Which drug works best against TB that's already been phagocytosed? And why?
10) What type of hypersensitivity is the PPD test?
11) Which drug upregulates P-450; which inhibits it?

-------

Step 2CK level (19 and 21 overlap with Step 1):

12) When do you give prophylaxis versus full-on Tx? And what are the durations of drug therapy?
13) Which is the preferred monoprophylaxis? How long do you give it for?
14) If you get a + PPD test, what's the next thing you do?
15) If you get a - PPD test, what's the next thing you do?
16) When is a PPD test considered positive?
17) What's the TB vaccine called and when is it given?
18) If a person previously vaccinated against TB has a + PPD later on, what do you do?
19) Which pneumoconiosis notably increases the risk of TB?
20) How many people in the world have been exposed to TB?
21) There are certain drugs that can increase the risk of TB - which class notably?

Responded in the RIPE format

Step 1 level:

1) Which are notably hepatotoxic?
All except E

2) Which are known to cause gout?
P

3) Which causes innocuous orange secretions/urine?
R

4) What are the MOAs of all four drugs?
R -> RNA poly inh
I -> inhibits mycolic acid synthesis
P -> err..unknown maybe..or well atleast unknown to me :-/
E -> arabinosyl synthesis inhibitor..something about the carb content of the wall

5) Which one is toxic to the visual system? What signs/symptoms are seen?
E -> R/G color change, optic neuritis

6) Which one causes a vitamin deficiency? What is the vitamin? And what are the symptoms/signs of the deficiency?
I, B6, Periph Neuropathy

7) Why does the drug in #6 cause this vitamin deficiency?
I combines with the active form of B6 Pyridoxal phosphate and makes a complex INH-Pyridoxal Phosphate and decreaeses availability

8) Why does that vitamin deficiency cause those symptoms/signs?
B6 is involved in a reaction as a cofactor...forgot the reaction..can't recollect spontaneously but maybe able to recall from a line-up of options

9) Which drug works best against TB that's already been phagocytosed? And why?
Pyrazinamide works in phagolysosomes and is converted into active for pyrazinoic acid or something. That works inside the cell and mediated intra-cellular bactericidal activity

10) What type of hypersensitivity is the PPD test?
Type 4 Delayed

11) Which drug upregulates P-450; which inhibits it?
R

-------

Step 2CK level :
I knew a few and hence answered em..

17) What's the TB vaccine called and when is it given?
BCG...

19) Which pneumoconiosis notably increases the risk of TB?
Silicosis
21) There are certain drugs that can increase the risk of TB - which class notably?
Anti - TNF ones.. Etenercept Infliximab Golimumab Adalimumab



Thanks for the questions !!
Awaiting answers..
Please do post more...much appreciated !

@Phloston could you please let us know the correct answers to these ?
Thanks..

 

[Phloston]

Where do you gather from any of this that she has accepted this as reality? I've interacted with patients who had been abused for years with essentially minimal recollection. It's quite remarkable. Total repression. It's a complete and genuine omission of detail from memory as an ultimate form of self-preservation. It has nothing to do with denial. And until you encounter this in real life you probably have very little appreciation for it.

Denial is better illustrated as someone refusing to acknowledge a death, serious illness or other major loss. Denial implies a reactionary process, one that is likely to evolve into acceptance. Denial is essentially an immature form of suppression. Repression doesn't evolve into acceptance.

Same goes for children who have experienced their parents go through a tough divorce. Some of them have zero recollection of events or even having gone to counselling. Repression there too.

I'm not here to argue with you, but those are my two cents.

 

[Dr.serotonin]

Where do you gather from any of this that she has accepted this as reality? I've interacted with patients who had been abused for years with essentially minimal recollection. It's quite remarkable. Total repression. It's a complete and genuine omission of detail from memory as an ultimate form of self-preservation. It has nothing to do with denial. And until you encounter this in real life you probably have very little appreciation for it.

Denial is better illustrated as someone refusing to acknowledge a death, serious illness or other major loss. Denial implies a reactionary process, one that is likely to evolve into acceptance. Denial is essentially an immature form of suppression. Repression doesn't evolve into acceptance.

Same goes for children who have experienced their parents go through a tough divorce. Some of them have zero recollection of events or even having gone to counselling. Repression there too.

I'm not here to argue with you, but those are my two cents.

I respect your explanations. no doubt you have more experience / knowledge then me. I'll try to learn from all of you.
thanx