Study group discussion: Fluoroquinolones

Review questions please!

You are asking questions?

No, I was waiting from them! :)

Haha review questions then!

Which enzyme does fluoroquinolones inhibit in gram negative and gram positive bacteria?

DNA gyrase!

Umm specific types of it in both gram negative and gram positive bacteria.

Topoisomerase 2 in gram negative and topoisomerase 4 in gram positive.

What are the side effects of quinolones?

Tendon rupture, photo toxicity!

Can cause convulsion.. Because they are also GABA inhibitory.

Somnolence. You don't prescribe them to people who drive for the same reason.

QT prolongation.

Nausea, vomiting and taste disturbance.

Tendon rupture in elderly people taking steroids.

QT prolongation only in gemifloxacin, lomefloxacin, moxifloxacin and levofloxacin.

Why don't you give it in pregnant ladies and young children?

In children, it can cause some defects in bone/cartilage formation. So it'll cause bending of long bones and stuff.

Yup. It causes defect in collagen.. Articular rupture and tendonitis!

Okie moving on.. Name the respiratory fluoroquinolones.

There are four of them. They have been termed that because they can be given to patients suffering from COPD.

Gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin.

Could you explain the concept of respiratory fluoroquinolones a lil bit more? It's a new concept to me.  sorry! Why can't you give the others to someone with COPD?

They are especially used for lower RTI and upper RTI.. Cause they inhibit anaerobic, gram positive, atypical as well as gram negative aerobes. The others do that too..but these are especially preferred for respiratory infections.

Study group experience #10

Tissues that are exclusively dependent on glucose for metabolism 

Vitamins (Antioxidants, Vitamin E and vitamins in egg) 

HNPCC (Lynch syndrome) and microsatellite instability 

Peutz Jegher's Syndrome 

Iron metabolism 

Management of Parkinson's disease (USMLE oriented case)

Gate control theory of pain 

QT prolongation 

Mechanism of pulsus paradoxus in severe acute bronchial asthma 

Sickle cell anemia

Heparin, warfarin and the anti-fibrinolytics

Aminoglycoside review questions and mnemonics 

Zidovudine 

Heparin induced thrombocytopenia and leech therapy 

Virchow's triad 

Mechanism of hypercoagulability in obesity and smoking 

Type 2 polyglandular syndrome 

Most common site of intraperitoneal abscess 

I love how when people are unable to answer questions, the person who asks gives hints, clues and mini questions to lead to the right answer. This creative thinking and understanding process is what I love most about the study group <3

How to join the study group

Study group discussion: Zidovudine

Review questions!

Full form of HAART?

Highly active anti retroviral therapy.

Which is more toxic.. Zidovudine or acyclovir? And why?

Zidovudine due to bone marrow suppression.

Yes! It causes BM suppression.

Actually, both of these drugs cause it..but zidovudine causes it at a much severe level.
Acyclovir and zidovudine have to be activated to their respective triphosphate. Zidovudine uses the host cell enzymes for this but acyclovir uses the viral enzyme FIRST and then the host cell enzyme. Hence in cases of zidovudine the toxicity is very high.

Wow what a concept!

The myelosuppression is so bad.. That you have to give blood transfusion and growth factors.

It effects the mitochondria of the cells too I guess.

AZT induces significant toxic effects in humans exposed to therapeutic doses...
Cytogenetic observations on H9-AZT cells showed an increase in chromosomal aberrations and nuclear fragmentation when compared with unexposed H9 cells...
The toxicities explored here suggest that the mechanisms of AZT induced cytotoxicity in bone marrow of the patients chronically exposed to the drug in vivo may involve both chromosomal and mitochondrial DNA damage.

Study group discussion: HNPCC (Lynch syndrome) and microsatellite instability

Just was mentioned in lecture: What is the cause of lynch syndrome (the specific cause)?

It's HNPCC. DNA mismatch repair affected.

Yes, a bit more specific! Which part of MMR?

I think it's micro satellite instability or MSH2.

Msh2 is one of them, correct!

MLH1 as well.

Mhmm. One more?

Donno any more T_T

Apparently MSH6 as well :)

Could you sum them all up? What is lynch syndrome..What are it's features?

Ovarian, Colon and Endometrial carcinoma are the features. You do the molecular talk!

Lynch syndrome (also known as HNPCC) increases the chance of colon cancer up to 80% along with increasing chances of other sorts of cancer.

It is caused by disruption of Mismatch Repair system due to mutations in 3 MMR factors : MSH2, MSH6, and MLH1

What about the microsatellite instability pathway? Which syndrome was that?

Oh I found out.. Microsatellite instability is found particularly in cells which are expressing mismatch repair defects. HNPCC is one of the of the most important syndromes where this happens. However its not an "exclusive feature" of MMR defects.

The microsatellite  instability is the evidence that the MMR isn't working properly and can't detect insertion-deletion loops that forms in the S phase. Googled and paraphrased.

Ah makes sense. Thanks!

Elaborate on the term microsatellite instability.

Umm it's kind of complex.. Usually you detect DNA by PCR, right?

Yup. You amplify the DNA!

So if while PCR, little microfragments of DNA split up which weren't there originally. They are called microsatellites. They were made during PCR. So if those are created, it means the fragment has microsatellite instability.

So these are abnormal?

They occur naturally.. But usually detected by MMR and dispatched if MMR doesn't work...
They will be present!

Yep!

Got it. Thanks!

Study group discussion: Peutz Jegher's Syndrome

What's Puetz jegher syndrome?

Hamartomatous polyp with pigmentation on lips.

Study link! http://medicowesome.blogspot.ae/2014/10/tumors-of-colon-and-of-polyposis.html

Another life problem solved! Haha thanks!

Lkb1 is involved in PJS. How?

Peutz Jegher's Syndrome mnemonic:
Remember the initial letters of the disease - PJS.
P: Pigmented oral mucosa
J: Jejunal polyps
S: STK 11 defect
Thank you  IkaN!

Oh nice. LKB1 kinase activity is lost due to somatic mutations. In Peutz Jegher's Syndrome, that is.

Study group discussion: Mechanism of pulsus paradoxus in severe acute bronchial asthma

Which one of the following does not cause pulsus paradoxus?

a. Severe aortic regurgitation
b. Cardiac tamponade
c. Constrictive pericarditis
d. Acute severe bronchial asthma

Study group discussion: Aminoglycoside adverse effects and mnemonics

1. Name the adverse effects of aminoglycosides.

Nephrotoxic
Ototoxic
Vestibulotoxic

And? (This one is most commonly forgotten)

Study group discussion: Iron metabolism

In which form is iron absorbed?

Fe2+
Ferrous!

In which form is it stored?

Ferritin!
Fe3+

Study link! http://medicowesome.blogspot.ae/2013/11/ferrous-vs-ferric-mnemonic.html

In which form does heme contain iron?
Ferrous

Remember..Heme is always in the ferrous form when free..And in the ferric form when bound. In heme..it is an exception.
Others ferritin, transferrin..it is always in ferric form

Ohh. Interesting!

Antidote for choice for acute iron overdose?

Desferoxamine?

Yup. Desferrioxamine is given IV.. It is for acute iron overload.

Which antidote is preferred for chronic iron overdose then?

Oral drug.. Deferiprone.
Desferoxamin SC.

Study group discussion: Sickle cell anemia

Name the three crisis of sickle cell anaemia.

Aplastic crisis
Vaso-occlusive crisis
Sequestration crisis

What causes aplastic crisis?
Parvovirus B19

*doubt discussion*
In sickle cell anemia what analgesic do we use? I've heard that morphine can cause vasoconstriction and that would make it worse, but I'm not sure that's true.

Yup, opiates are used.

One cause of death in sickle cell anemia is acute chest syndrome, if I give the patient morphine (that has a secondary coronary vasoconstrictor effect) that will kill the patient.

Correct.

Acute chest syndrome is due to occlusion of the pulmonary vessels.

The major issue hear is to given oxygen to the patient..Cause hypoxia aggravates the whole situation.

So I'm not supposed to worry about Myocardial Infarction?

Not that I've heard of.

Doesn't it cause CHF?

"The acute chest syndrome may mimic CHF however it is uncommon." Says the internet.

New drug for SCA. Read in Harrison. Azacytidine.

Mechanism of action of azacytidine?

Azacytidine increases HbF production and reduces anemia in sickle cell disease.

There's a drug which blocks gardos channel in RBC membrane. It's under trials too. It's the one I was talking about.

The mechanism is interesting because it prevents dehydration of the RBC.. That's the cause of sickling.

I like the sound of it - Gardos channel.

It's a potassium channel!

A greek god!

Me too.. It guards the RBC!

Gargoyle ..thats what my mind said.

Haha. They were guardians too!

Another interesting thing.. An anti fungal we use also blocks this channel in vitro!

Study group discussion: Electrolyte abnormalities that cause QT prolongation

Which electrolyte abnormalities lead to QT prolongation?

Study group discussion: Gate control theory of pain

Just had my first class of pain physiology. I loved it!

What was the most interesting thing that you learnt in class?

Melzack and Wall's theory. About the gate control of pain. I had to google the english term lol.

Aw that's so nice of you. It's an interesting concept. Why soldiers don't feel pain when they are injured in battle.. But feel it in the hospital.

What is it called in Brazilian? (I donno what language you'll speak)

Portuguese. In portuguese, it's 'teoria das comportas'

I feel better now for not recognising "Melzack and wall's theory" but I do remember learning teoria das comportas!  hahahaha I have to Google the translation all the time too.

Must be because of increase in Endorphins and adrenaline?

Not exactly. You should read more about it!

The brain determines which stimuli are profitable to ignore over time. Thus, the brain controls the perception of pain quite directly, and can be "trained" to turn off forms of pain that are not "useful". This understanding led Melzack to assert that pain is in the brain.

Awesome stuff!

Study group discussion: Type 2 polyglandular syndrome

Came across a new question today. Let me ask you guys -

So what is Type II polyglandular autoimmune syndrome?

Schmidt syndrome?

Yes, also known as Schmidt syndrome.

What are the components?

Adrenal insufficiency (Addisons)

Hypothyroidism (hashimoto)

Also gonadal insufficiency

And ?

Abs pancreatic insufficiency!

Yeah, Type 1 DM.

Good job!

Study group discussion: Vitamins (Antioxidants, Vitamin E and vitamins in egg)

Name the vitamins which are anti-oxidants?

Vitamin A, C, E.

Mnemonic: Ace the oxidants!

Which is the anti-oxidant important to prevent lipid peroxidation?

Vitamin E

Study group discussion: Tissues that are exclusively dependent on glucose for metabolism

Which things in our body are exclusively dependent in glucose for energy?

The lens.

Correct

Liver too?
Nope.
Brain?
No. It uses ketone bodies too!
Muscle?
No.

Cornea?

Cornea correct!

Heart.
Heart, no.
Interesting: Heart can use lactate.

Sperm
No. Sperm uses fructose!

It's RBC!
Oh ya. They are exclusively dependent on glucose! RBC can't metabolize anything else!

Study group discussion: Mechanism of hypercoagulability in obesity and smoking

How does smoking and obesity promote hypercoagulability?

Smoking increases reactive oxygen species. ROS reacts with LDLs causing increasing oxidized LDL, when deposited in intima becomes atherosclerotic plaques. Also ROS causes endothelial damage itself, increasing its permability to LDL.
Atherosclerotic plaques can rupture, exposing tissue factor. Or the plaque itself causes turbulent blood flow, increasing chance of thrombosis.

Nicotine causes vasculitis and thus causes turbulence of bood flow!

And obesity?

The various mechanisms by which obesity may cause thrombosis include: the actions of so-called adipocytokines from adipose tissue, e.g. leptin and adiponectin; increased activity of the coagulation cascade and decreased activity of the fibrinolytic cascade; increased inflammation; increased oxidative stress and endothelial dysfunction; and disturbances of lipids and glucose tolerance in association with the metabolic syndrome.
Source: Obesity and Thrombosis — ScienceDirect - http://www.sciencedirect.com/science/article/pii/S107858840600579X

Study group discussion: Virchow's triad

What is Virchow's triad for thrombosis? Explain please.

Virchow's triad... If there is stasis (Blood ain't flowing to wash out the collected coagulation factors), hypercoagulability (More coagulation factors) or endothelial injury (Stuff that activates coagulation factors) there'll be a predisposition to thrombosis.

In Virchow's triad 2 things are missing:
1. Role of platelets
2. Coagulation system

Study group discussion: Most common site of intraperitoneal abscess

Which is the most common site of intraperitoneal abscess?

It's pelvic.

The reason being gravity, common sites are subphrenic, paracolic, pelvic and right iliac fossa.

Pelvic is most common due to pelvic position of appendix and fallopian tubes, and due to leakages from colorectal surgeries.

I had a MCQ asking me to choose between paracolic, subphrenic and pelvic and stuff as options for the most common site.

So in that case, what would be the answer?

Pelvic would be the most common site, according to my teachers.

What is the best way to get to a pelvic abscess sample?

Through rectum? They usually burst into rectum and resolve.

In women, from the umm what do you call it..
Pouch of Douglas!

Nice Ikan :)

I tried so hard to recall the name. Almost blanked out for a moment there!

In women vaginal drainage is done.. Through posterior fornix vaginl drainage in women.

And if the abscess is pointing in rectum, rectal drainage is done.

In males, you would pass a needle through the rectum

Laparotomy is almost never necessary and rectal drainage is preferred over suprapubic which risks exposing the general peritoneal cavity to infection.

Study group discussion: Heparin induced thrombocytopenia and leech therapy

What's Heparin induced thrombocytopenia??

Antibodies are formed in the blood platelets due to heparin in certain individuals. This causes widespread petechia.

You discontinue heparin and give something else in HIT.

Lepirudin
Bivalrudin
Argatroban

And now the cool part :D
The drug Lepirudin is derived from the salivary glands of LEECH!

I know!!!

Haha ain't this cool?

Leech.. Didn't know that!

In school, they used to say if a leech bites you, you die. I never found out the truth though.

Maybe cause it releases these substances in your system..And you are not able to clot inside?

My 12th standard books also mentioned about leech having anticoagulant properties....Now I find out that it's used to prepare drugs!

HIRUDIN is the substance that is secreted by the salivary glands of leech!

I just Googled can a leech bite kill you :D
I don't think they can kill you, they don't take enough blood in a fast amount of time unless you put a few 100,000 on your body and left them there for a while.

100, 000...That's a lot of leech!

Lol I think it was a hyperbole!

I don't remember exactly....but I had heard of alopecia being treated with leech.

How? :O

The leech would suck blood... So keeping them for just the right amount of time they would increase the blood supply... I'm not sure though.

Leech therapy is known to increase blood circulation, therefore when therapy is applied to thinning or bald areas, the increase of blood circulation helps enhance the concentration and delivery of nutrients that assist in making hair follicles strong, thereby assisting in the promotion of hair growth. People suffering alopecia caused by fungal infections or dandruff can also benefit through the antibacterial component in the leeches saliva, which helps combat fungal infections.

It's also used in arthritis :O

The FDA approved the use of leeches in the USA in 2004. In October 2005 the first American hospital 'Beth Israel Medical Center New York' offered Leech Therapy to treat Osteoarthritis of the knee.

Arthritis?! Woah.

Study group discussion: Heparin, warfarin and the anti-fibrinolytics

Name the drugs which inhibit fibrinolysis.

TACA! Tranexaemic acid, amino caproic acid.

Describe the mechanism of action of heparin.

Binds to anti thrombin 3, blocks factor 10.

Which coagulation factors does warfarin affect?

Vitamin K dependent ones: 10, 9, 7, 2, protein C.

Why there is a lag of 2 - 3 days for warfarin to act?

Study group discussion: Management of Parkinson's disease

50 year old male, has no expressions, walks to your office, slowly. He complains of tremor while watching television. He says he can do tasks without the trembling his hands. His fingers keep moving as if he is rolling a pill as he is talking to you. Which drug will you prescribe to relieve his tremor?

It is Parkinson's disease. Anticholinergics will be prescribed.

Why not L-dopa? With carbidopa?

Study group experience #9

What is the kussmaul's sign? Is it seen in cardiac tamponade?

Mitral stenosis auscultatory findings

AV blocks simplified

Enzymes checked through RBCs 

G6PD deficiency and Myoglobinuria

How to study pharmacology (Most requested post ever)

Short course chemotherapy

Pharmacological management of diabetes

Mechanism of atropine induced hyperthermia 

Lepra type 1 and type 2 reaction 

Types of hypersensitivity reactions  (A simple Q&A at the end!)

Studying physiology 

Single Breath Count test in Guillain Barre syndrome

It was my birthday this week (13th February, to be precise). One of the awesomites got to know through Google plus and everyone wished me on my birthday which made it really special. Thanks everyone!

Happy belated Valentine's day everyone! May we all love what we do and do what we love.

I'm unable to access tumblr fan mails and ask messages at the moment. Sorry for the delay! I'll be back on tumblr in mid March but I'll try posting the study group experiences as and when possible!

-IkaN