Sunday, December 16, 2012

ACE inhibitors, prostaglandins and the renin angiotensin system

Greetings everyone!

What are ACE inhibitors?
They inhibit angiotensin converting enzyme which converts angiotensin 1 to angiotensin 2

ACE inhibitors
Normally, the amount of renin in plasma acts as a limiting factor for angiotensin 2 generation
[Renin? Renin converts angiotensinogen to angiotensin 1]

This is why, ACE inhibitors enhance renin release
Changes that lower blood pressure or volume of decrease Na+ content release renin by three pathways-
The intrarenal baroreceptor pathway: The decreased tension in the afferent glomerular arterioles is sensed and is possibly increasing the local production of prostaglandins
The macula densa pathway: Low Na+ concentration in the tubular fluid is sensed by the macula densa cells
This induces the synthesis of COX 2 and neural nitric oxide synthase which is causes release of PGE2 and PGI2
Released prostaglandins act on the juxtaglomerular cells to promote renin secretion
Beta adrenoceptor pathway: Baroreceptor and other reflexes increase sympathetic impulses to the JG [Juxtaglomerular] cells activated through the beta1 receptors

So, beta blockers and other sympatholytics will decrease renin release
NSAIDs decrease renin release by inhibiting prostaglandin production

ACE inhibitors also inhibit an enzyme (kininase) responsible for the degradation of bradykinin
Prostaglandin synthesis is enhanced by kinins
This maybe responsible for cough and angioedema in susceptible individuals

So that is why, for the treatment of ACE inhibitor associated cough, which is prostaglandin mediated, indomethacin and other NSAIDs can be used
Another cool fact I found out is that you can use nifedipine, a calcium channel blocker, for the same :O
Usually, ACE inhibitors are substituted with angiotensin antagonists like Losartan since they do not interfere with the degradation of bradykinin and adverse effects like cough are not encountered

That's all!
I always have a tough time recalling role of prostaglandins when in comes to the renin angiotensin pathway..
So I blogged whatever I knew =D

Random cool fact:
Rennin is a milk-coagulating enzyme
found in the gastric juice of the fourth stomach of young ruminants, used in making cheese. It is also known as chymosin
This is why, some cheese packets have the non vegetarian label
It's because of the enzyme used in the production of cheese obtained from animals
Note the difference in the spellings :)

-IkaN

Tuesday, December 11, 2012

Friday, December 7, 2012

Mechanism of action of anticholinesterase enzyme

We are going to cover an exhausting topic today
Let's get started!

What is acetyl choline esterase?
It is an enzyme which catalyzes the hydrolysis of acetyl choline to acetate and choline

The active region of acetylcholine esterase contains an aromatic anionic site [near tryptophan 86] and an esteratic site formed by serine 203, glutamate 334 and histidine 447

Mnemonic:
aromaTic has T, so does Tryptophan
eSteratic site has S, so does Serine
[That's how I remember :D ]

I know it's a very complex molecule
Stay with me on this one.. It gets better when you visualize it
This is how I imagine it to look like ^_^


Acetyl choline esterase



How does acetyl choline react with acetyl choline esterase?
Hydrolysis of acetyl choline involves electrostatic attraction between the positive N+ of acetyl choline to the aromatic pocket and nucleophilic attack of serine-OH leading to acetylation of serine

Acetyl choline & acetyl choline esterase

Updated on 20th Oct, 2016 -  Image correction: It is acetylcholine* and not acetylcholine enzyme. 

Acetyl choline & acetyl choline esterase
The acetylated enzyme reacts with water to produce acetic acid and choline :)


How do Organophoshates react with acetyl choline esterase?
Organophosphates attach to the esteratic site
The anionic site is free

Organophoshates & acetyl choline esterase


If the organophosphate molecule loses it's alkyl group, it becomes resistant to hydrolysis
This process is called aging

So if you have to rescue your acetyl choline enzyme from the evil force of Organophosphorous compounds, you'll have to do it before aging (6-8 hours) :P
How do you do it? Use cholinesterase reactivators!

What are choline esterase reactivators?
They are used to restore neuromuscular transmission in cases of Organophosphate poisoning
You basically give more reactive OH groups.. Since the phosphorylated enzyme reacts very slowly or not at all with water
In the presence of Oximes, [Generic formula R-CH=N-OH], reactivation occurs much faster

Example of an Oxime is Pralidoxime
Let's see how they work!

Pralidoxime, organophosphate and acetyl choline esterase
Pralidoxime has a quarternary nitrogen which attaches to the anionic site
It's oxime end reacts with the phosphorous atom attached to the esteratic site
The oximephosphonate so formed diffuses away leaving the reactivated cholinesetrase :)

 That's all for today ^_^
*phew* That was a lot!
Lemme know if I have made any mistakes in the explanation or in the diagram, I'll correct it.

Have an awesome day!

-IkaN
Related post: Treatment of organophosphorus poisoning mnemonic

Tuesday, December 4, 2012

Dermatophytes

What are Dermatophytes?
They are a group of filamentous fungi that infect only the superficial keratinized tissues
They are classified into three genera: Trichophyton, Microsporum & Epidermophyton
I had a tough time learning them at first so I made a mnemonic ^_^"
I have put it up in the image itself

Trichophyton mnemonic
Microsporum mnemonic

Epidermophyton mnemonic


Did you know?
Fungal Wet Mount is used for direct detection of fungal forms in patient specimens
KOH lyses host cells and keratin and makes fungal elements more easily detected by elimination of host materials
Calcofluor white, a fluorogenic dye, binds to specific polysaccharide bonds found in the chitin-rich fungal cell walls and can be used for detection of fungi too ^_^

That's all =D

-IkaN

Monday, December 3, 2012

Difference between Blood agar and Chocolate agar

Hi everyone!

To understand what is the difference between Blood agar and Chocolate agar, we'll need to know about nutrient agar first.

Nutrient agar: It is a simple basal medium used for growth of common pathogens. It constitutes peptone water, meat extract and agar.

So now, let's see how blood agar and chocolate agar is made, and the difference between the two -

How is Blood agar made?
Nutrient agar is sterilized by autoclave, cooled to 50°C and sterile sheep blood (5-10%) is added gradually and poured into plates.

How is Chocolate agar made?
Nutrient agar is sterilized by autoclave, cooled to 75-80°C and sterile sheep blood (5-10%) is added gradually and poured into plates.


Difference between Blood Agar and Chocolate Agar
What is the similarity between Blood agar and Chocolate agar?
- Blood agar and Chocolate agar are enriched media.
- They are used for the growth of Gram positive cocci and Gram negative fastidious organisms (see below) like Neisseria and Haemophilus species.
- They can be used to indicate hemolysis.

(If you can't remember the organisms that grow on chocolate agar, here's a mnemonic:
“Nice Homes have Chocolate” - Neisseria and Haemophilus grow on Chocolate agar)

What are fastidious organisms?
Fastidious organisms require specialized environments due to their complex nutritional requirement.

How is the difference in temperature used in the manufacturing of blood agar and chocolate agar significant?

Certain organisms such as Haemophilus species require V factor for growth (complex nutritional requirement). Factor V is present in blood but it is present inside the red blood cells (RBC).

These organisms can not utilize V factor which is trapped inside the RBC's in Blood agar.
When Blood agar is heated to 80-90°C for a few minutes (boiled blood agar), the V factor is released from within the erythrocytes and made available to the organism for utilization.

Some strains of Neisseriae and Diphtheroids require V factor too. That is why, these media are superior to plain Blood agar for growing organisms requiring V factor.

What is V fatcor?
V fatcor is a coenzyme, Nicotinamide Adenine Dinucleotide (NAD) or Nicotinamide Adenine Dinucleotide Phosphate (NADP) which acts as a hydrogen acceptor in the metabolism of cell.

Conclusion:
Chocolate agar is a type of Blood agar in which the blood cells have been lysed by heating for growing fastidious organisms.

Did you know?
Modified Thayer Martin is a type of chocolate agar which contains antibiotics (Vancomycin, Nystatin and Colistin) to suppress growth of other bacteria and promote growth of  N gonorrhoeae.

*phew* That's all for today!

The image is my first Photoshop work on the site, hope you like it =D
Just to remind you guys, Chocolate agar contains no chocolate, they simply named it after the yummy color :P

-IkaN

Questions asked by readers:
Which blood is used for the production of blood agar?
The blood of any animal can be used.
For example - Rabbit blood, sheep blood, ox blood or human blood.

Wait, you can use even human blood? (No, nothing creepy! :P)
Human blood is usually the one which is unused in blood banks for a long period of time and can no longer be used for transfusions.



Friday, October 5, 2012

Methemoglobin

What is Methemoglobin?

Methemoglobin is a form of hemoglobin in which the iron in the heme group is in the Fe3+ (ferric) state.
Normally, it is in the Fe2+ (ferrous) state. So it is an oxidized form of Hb (hemoglobin).

Monday, October 1, 2012

Mechanism of action of antibiotics (Protein synthesis inhibitors) mnemonic

A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins.

How do you remember them?

Wednesday, August 15, 2012

Alpha blockade

Whenever we use a non selective alpha blocker, a reflex tachycardia is prominent.

Why?
Alpha2 receptors are present prejunctionally on nerve endings which inhibit transmitter release

If you block these receptors, there is an increased release in NA from sympathetic nerves
which causes the tachycardia

What happens if you use a selective alpha1 blocker?

There is a block in sympathetically mediated vasoconstriction and produces a fall in BP which is attended by mild tachycardia; NA release is not increased due to absence of alpha2 blockade


-IkaN

Friday, July 20, 2012

Oral Rehydration Therapy

Hello everyone! :D
Indian Academy of Pediatrics is celebrating the ORS week where we create awareness about Oral Rehydration Therapy :)

Oral Rehydration Therapy (ORT) is a treatment for dehydration associated with diarrhea.

ORS saves millions of children a year from death due to diarrhea.
But sadly, even today children die due to diarrhea in some developing countries.
Sometimes people don't understand that praying is not enough, treatment should also be given. They should not be negligent when it comes to health.
We have a quotation, "Dawa and Dua" are essential to save a person's life.
Dawa means medicine & Dua means Prayer.
So I give equal importance to both the factors in our lives, faith and medicine, and this was the basis of my poster for the ORS awareness week :)

Francis Bacon said, ''Hope is a good breakfast, but it is a bad supper."

ORS awareness poster


So lemme tell you about ORS ^_^
You see, normally our body pumps out fluid in the intestine during digestion
This fluid has a high concentration of sodium
Nearly all of this fluid is reabsorbed by the intestine, in an healthy individual, to maintain a balanced sodium level in the body.

During diarrhea, liquid secreted in the intestinal lumen passes the gut so quickly that very little sodium and water is absorbed. This is why, heavy continuous diarrhea can be a very dangerous and potentially life-threatening condition within hours.
This is the reason why you need sodium and water replenishment via ORT

Why is glucose needed?
The co-transport of sodium into the epithelial cells via the SGLT1 protein requires glucose or galactose. Without glucose or galactose present, intestinal sodium will not be absorbed.

Remember: Glucose is never more than 110mMol/lit to avoid the risk of osmotic diarrhea.

Why is sodium citrate or sodium lactate or NaHCO3 used?
The alkali loss due to diarrhea causes acidosis. It is corrected :)

I also wrote a poem as a part of this program, even though I'm VERY bad at rhymes :D

The ORS says :
"I'm oral rehydrating solution,
I help balance water distrubution.


Whatever the cause maybe,
Whether it's rotavirus or cholera,
and it's causing vomitting or diarrhoea,
utilize me properly in this era.

I'm a medicine that barely costs,
So when water from the body is lost,
Don't hesitate to use sugar and salt,
& put dehydration to a halt.


I've saved millions of lives,
But still some don't survive.
So please create awareness about me,
& let people use me wonderfully.
"

Please create awareness.. If you know a mother with a child, educate her about diarrhea. Let people know. You never know, you could save a life. :)

-IkaN

Update: I won the first prize for this poster in National ORS week conducted by Indian Pediatric Association ^__^

Thursday, July 5, 2012

Stockholm syndrome

Recently, this word has been haunting me.. So.. Let's see what's it about!

Stockholm syndrome is a psychological response sometimes seen in an abducted hostage, in which the hostage shows signs of loyalty to the hostage-taker, regardless of the danger (or at least risk) in which the hostage has been placed.

Stockholm syndrome

A song by Muse from the album Absolution is of the same name
It has always got me wondering.. Is the song about memories holding you captive?
Even when those memories have the capacity of hurting you, you still don't let go and set yourself free.. You still don't forget.. Even when you want you.. But you just can't..
The verse however let's you decide what perspective you choose to have.. The abusers or the victims.. But the chorus expresses the syndrome well..

I heard it on the television series, White Collar too..
Neal Caffrey: No. There are things about this life I'm not ready to give up.
Mozzie: Do you even know what this life is anymore? I mean, you're... on a leash. You're still in prison. You have Stockholm syndrome.
Let's analyze Mozzie's view.. Giving up THE final score for what? Stockholm syndrome it is!
I feel Caffrey's pain throughout the series though.. Because the hardest part isn’t choosing, it’s learning to live with the choices you make T_T

I also know someone whose WhatsApp status is Stockholm syndrome.. Professional secrecy shall prevent me from commenting any further.. :D
[And damn, he is good at using these laws against you!]

In psychology, Stockholm syndrome is a psychological phenomenon in which hostages express empathy and have positive feelings towards their captors, sometimes to the point of defending them.
This sounds like some milder form of sadism..
You know you've got the Stockholm syndrome when you hear yourself saying, “I know what he’s done to me, but I still love him” ;)

Did you know?
The syndrome is named after the Norrmalmstorg robbery of Kreditbanken at Norrmalmstorg, Stockholm, Sweden, in which the bank robbers held bank employees hostage and the victims became emotionally attached to their victimisers, and even defended their captors after they were freed from their six-day ordeal.. This is the art of brainwashing! :O

This blog post doesn’t reflect the thoughts or opinions of either myself, my family, my friends, or my dragon :P
Blogging about psychology does get you all serious.. Lighten up and stay awesome! :)

-IkaN

Friday, June 29, 2012

Awesome Twosome Drugs

So today I was asked two fixed dose combinations of drugs which antagonize each others side effects..
Lemme tell you about the combinations I thought of! :D

First.. *drum roll*
Aluminum hydroxide & Magnesium Trisilicate!
These two are antacids ie neutralize gastric acids

Magnesium salts act fast & Aluminum salts are slow acting
Magnesium salts act as laxatives & Aluminum salts are constipating
Magnesium salts hasten gastric emptying & Aluminum salts delay it

So.. What do you get when you mix em together? Dose reduction & minimization of systemic toxicity! ^_^

They are indicated in hyperacidity gastritis, reflux  esophagitis, dyspepsia

Second combination is seen in OCPs [Oral Contraceptive Pills]
Levonorgesterol & Ethinyl estradiol

Progesterone inhibits the frequency of LH secretory pulses & estrogen inhibits FSH secretion
So estrogen and progesterone synergise to inhibit ovulation
Estrogens increase the risk of endometrial carcinoma while progestin given concurrently blocks the risk..

So use em together!

Side effects of medicines combined (:


Each coin has two sides.. The trick is to use both sides to your benefit.. Team up!

Lemme know if know of any other such combinations.. Where the evils come together for the good without creating a dilemma..
Please do comment or email me and let me know.. :)

"I make bad look so good" -Megamind ;)
Have a nice day lol

-IkaN

Friday, June 22, 2012

Neuromuscular (myoneural) junction


Neuromuscular junction labelled

 Hello, lovely folks!

Lets learn something about the neuromuscular junction!
Refer the diagram as you read.. Otherwise it might not make sense to you..

1 As the nerve suppplying skeletal muscle reaches its termination it divides into a number of terminal buttons or end feet

2 The endfeet contains many small clear vesicles that contain acetyl choline, the transmitter at these junctions!

3 The endings fit into depressions in the motor plate - the thickened portion of the membrane at the junction

4 Underneath the nerve ending, the muscle membrane of the end plate is thrown into a number of folds called the junctional folds

5 The space between the nerves and the thickened membrane is comparable to a synapse! (Remember, this is a chemical synapse and there shall be delay.. In chemical synapses there is no delay)

 6 Ach muscle type nicotinic receptors are concentrated at the tops of the junctional folds of membrane of motor end plate

7 Only one nerve fibre ends on each end plate, with no convergence of multiple units

THIS, my dear friends, is known as the neuromuscular junction or myoneural junction

That's all! ^_^
You can use this as a ready made short note :P

Oh.. One more thing, in one of my first year vivas, I was asked what are the two types of Acetylcholine receptors..
The answer is nicotinic and muscarinic receptors.. There is an interesting story about how they were named!
Muscarinic receptors were named as such because they are more sensitive to muscarine.. isolated from a mushroom! :O
Nicotinic receptors could be opened by nicotine and hence the name!
Imagine someone naming you dust because you are sensitive to it! [That was a lame attempt to crack a joke on hypersensitivity reactions.. I should stop typing now :D ]

-IkaN

PS: I apologize for the awful diagram.. It's from one of my old notes, when I had no intentions of blogging :D
If time permits I'll update the diagram.. Till that you may rely on Google :)

If you do not heal yourself, you die

In some cases of myocardial infarction, the clot spontaneously resolves itself, this is the healing process.

But at the same time the atheroma can worsen, there maybe haemorrhage & disruption exposing the thrombogenic components causing expansion of the atheroma.

So do you get what I'm talking about? In life too we can either choose to heal or worsen our condition, it's your decision really.. To feel better or worse about the smallest thing or the biggest problem you think you have..

Do you choose to heal?

-IkaN