Diuretics in Congestive Heart Failure

Hello everyone!
I read this really cool thing I would love to share it with you guys :D

Did you know?
Before diuretics were available, rotating tourniquets were use to diminish venous return by ligating the lower extremities.
Less venous return, decreased preload. This obviously lead to pooling of blood in legs.
This procedure was effective because it diminished the intravascular volume that would otherwise accumulate in the lungs.

Amazing, ain't it?

We have diuretics now! ^__^
Diuretics decrease preload and increase ventricular efficiency by reducing circulating volume, remove peripheral edema and pulmonary congestion =D

That's all!

-IkaN

(Another blog post from me.. Yep, I survived 21st December, 2012)

Alkalinization of urine

I am sharing some of the applications since it is not put up together on the internet.. So here it goes!

How do you alkalinize urine?
The urine can be alkalinized (the pH elevated) by administering sodium bicarbonate or potassium citrate. Carbonic anhydrase inhibitiors like acetazolamide can also be used.

Cool fact:
Citrate containing fruits like lemons and limes alkalize urine.
Citric acid is not to be confused with ascorbic acid (vitamin C).
Ascorbic acid is used for acidification of urine.
Citric acid is used for alkalinization of urine.

Uses of alkalinization of urine:
• Forced alkaline diuresis has been used to increase the excretion of acidic drugs like salicylic acid and phenobarbitone (a weak acid barbiturate)
Simply because weak acids ionize at alkaline pH and will not be re-absorbed.

• To decrease risk of nephrotoxicity in methotrexate therapy.

• In dimercaprol therapy
The dimercaprol-metal complex dissociates faster in acidic urine.
The released metal can damage the kidney.
That is why, urine is alkalinized :)

• In rhabdomyolysis
Alkalinization of the urine has been postulated to minimize the breakdown of myoglobin into its nephrotoxic metabolites & to reduce crystallization of uric acid, thereby decreasing damage to tubule cells.

Uric acid, cystine, and some other weak acids are relatively insoluble in, and easily reabsorbed
from, acidic urine. Thus, it can be used to prevent crystallization of excess urate in urinary tract during probenecid treatment in chronic gout or hyperuricaemia occurring as a consequence of rapid destruction of tumor and degradation of large amounts of purines during anticancer therapy & cystinuria.

Also note that -
Calcium salts are relatively insoluble at alkaline pH, which means that the potential for renal stone formation from these salts is enhanced.
Alkalinization of the urine will decrease urinary excretion of NH4+ and may contribute to the development of hyperammonemia and hepatic encephalopathy in patients with cirrhosis.

Did you know?
Some antacids (eg, magnesium hydroxide with aluminum hydroxide) alkalize the urine somewhat, thus altering excretion of drugs sensitive to urinary pH.

That's all I have to say :)
It's amazing how pH influences drug ^__^
But there is more to it, we don't know everything about the mechanisms.
Click here to know why I say so --> http://www.ncbi.nlm.nih.gov/pubmed/15181662

Lemme know if you know of some other applications!

-IkaN
(It's 20/12/2012) :D

Related post: Acidification of urine

Cathartics

Stimulant/irritant purgatives/cathartics

How do they act?
They basically act on intestinal mucosa or nerve plexuses to

• Decrease water absorption from the bowel lumen
• Increase secretions of fluid into the bowel
• Stimulate bowel motility 

They are thought to inhibit Na+ K+ ATPase in the basolateral membrane
Secretion is enhanced by activation of cAMP in the crypt cells
& increased prostaglandin synthesis :)

They act on the colon rather than the ileum and produce evacuation within 8-10 hours after administration
This makes them particularly suitable for administration at night ^__^

Examples: Anthraquinone Derivatives, Diphenylmethane Derivatives, Castor Oil, Aloe

When are they used?
They are used to treat constipation in bed ridden patients
Also used to treat constipation due to chronic morphine administration

When are they contraindicated?
Spastic constipation (irritable bowel)
Subacute or chronic intestinal obstruction
Pregnancy (They can reflexly contract the gravid uterus)

Long term use is discouraged due to adverse effects
Larger doses may lead to excessive purgation and electrolyte imbalance (Hypokalemia may occur)
Cramps, skin rashes and fixed drug eruptions are other side effects
Colonic atony, melanosis - On prolonged use
Amount secreted in milk is sufficient to cause purgation in suckling infant

Did you know?
With use of cascara sagrada or senna a pink-red, red-violet, redbrown, yellow-brown, or black discoloration of urine may occur - But that's nothing to worry about :)

-IkaN

Stool Softeners

Stool softeners

How do they act?
They soften the stool material by permitting water and lipids to penetrate

Emollient laxatives lubricate the intestinal walls and soften the stool, thereby enhancing passage of fecal material
Some stool softeners like liquid paraffin are also known to lubricate the hard scybali by coating them

"Emollients, stool softeners, surface-acting drugs, lubricants, stool surfactant agents" are the many names used to describe these drugs @_@
According to me, there is no need to distinguish between the different terms used as most books consider them to be the same
In one of the books I read, it said that the difference between emollient laxatives and fecal softeners is that the emollient laxatives do not promote the retention of water in the stool

We'll just call them "Stool softeners" ^__^

They take 1-2 days to act
Mineral oil is preferably given on an empty stomach in the evening or bed time

Examples: Mineral oil, docusate (oral or enema), glycerin suppository, liquid paraffin

When are they used?
They are used when straining at stools is to be avoided such as hernia, cardiovascular diseases, eye surgery and perianal afflicitions (piles, fissures, anal surgery)
It is also used to prevent and treat fecal impaction in young children and debilitated adults
(May be given prior to administration of other laxatives in treating fecal impaction)

Adverse effects

Docusates by itself are relatively non toxic but when taken with other laxatives increase their absorption and may lead to liver toxicity
It disrupts the mucosal barrier and increases the absorption of many non absorbable drugs, liquid paraffin should not be combined with it

Mineral oil may impair gastrointestinal absorption of fat soluble vitamins like vitamin A, D, E and K (Avoid long term use)
Larger doses may leak out the anal sphincter and cause physical and social discomfort
Paraffin taken orally over long periods, especially at night, may be aspirated and cause chronic lipoid pneumonia
It may be carried from the intestine to the lymph nodes to produce foreign body granulomas in the intestinal mucosa, mesenteric lymph nodes, liver and spleen

Did you know?
An unusual case of lipid pneumonia resulted from attempts by a patient, an amateur singer, to lubricate his larynx with liquid paraffin

That's all for today :)
-IkaN

Bulk forming laxatives

Bulk forming laxatives

What are they?
They are hydrophilic colloids which are natural or semisynthetic polysaccharide or cellulose derivatives
Consists of unabsorbable cell wall

How do they act?
Bulk-producing laxatives are not digested by the body and therefore add bulk and water to the contents of the intestines
The added bulk stimulates peristalsis, moves the products of digestion through the intestine, and encourages evacuation of the stool.
In short, there is an increased luminal mass which stimulates peristalsis

Defecation usually occurs within 8 to 24 hours
But can take up to 3 days after the start of therapy for the stool to become soft and formed

Examples: Bran, Psyllium, Methyl cellulose

When are they used?
For the treatment of simple, functional constipation
Bulk-forming laxatives do not cause dependence
They reduce rectosigmoidal pressure and relieve symptoms of irritable bowel syndrome and colonic diverticulosis
May be used by patients with ileostomy and colostomy
Since there is a reduction in diverticulitis and constipation with no associated toxicity they are the laxative of choice for constipated patients ^__^
[Useful when straining of stools has to be avoided
Doesn't soften stools already present in colon or rectum]

Should be avoided in:
Gut ulcerations, adhesions & stenosis where faecal impaction is a possibility
Obstruction of the esophagus, stomach, small intestine, and colon has occurred when bulk-forming laxatives are administered without adequate fluid intake or in patients with intestinal stenosis
(The administration of a bulk-producing laxative is usually followed by an additional full glass of water)
The dry form can cause abdominal cramps
Dehydration may result if adequate water is not taken

Did you know?
Certain dietary fibres bind bile acids and promote their excretion in faeces
Degradation of cholestrol is enhanced  and plasma LDL is lowered <3

That's all =)

"Foods high in bad fats, sugar and chemicals are directly linked to many negative emotions, whereas whole, natural foods rich in nutrients - foods such as fruits, vegetables, grains and legumes - contribute to greater energy and positive emotions"
Quote by Marilu Henner

 -IkaN

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

Uses of alpha and beta blockers

It's tough to remember all the uses at once, since Autonomic Nervous system is a huge system!

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

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

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.

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).

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?

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