Rosiglitazone in MRCP

Rosiglitazone in MRCP

Rosiglitazone is one of the popular drugs commonly asked in MRCP Part 1. It is an anti-diabetic drug and a member of thiazolidinediones group.

The mechanism of action of rosiglitazone is through activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ. Rosiglitazone is a selective ligand of PPARγ and has no PPARα-binding action.

For MRCP, side effects of Rosiglitazone is a popular topic to be asked. Just remember these side effects,

1) Higher incidence of fracture

There is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide.The information was based on data from the ADOPT trial.

2) Higher incidence of Cardiovascular event?

It was a great debate about this a few years back. I think if you are given 2 options- fracture or CVS event, choose fracture because no one will disagree with you!

3) Macular Odema

A possible side effect.

Remember, Rosiglitazone should not be used in patients with overt heart failure!

Poisoning in MRCP(IV)

Poisoning in MRCP(IV)- Methanol/ ethylene glycol

As I told you many months ago, there are many causes of metabolic acidosis you have to remember if you plan to sit for your MRCP.

When I was a medical student, my lecturer told me that when a young patient comes to hospital with shortness of breath ( air hunger) and you do an ABG showing metabolic acidosis, you must always consider 3 important diagnosis- 1) Diabetic ketoacidosis , 2) salicylates oberdose ,3 ) Ethanol/ ethylene glycol poisoning.

OK, although methanol is a component of shellacs, varnishes, paint removers and copy machine fluid, it is not uncommon to find it in some alcohol drinks produced illegally. For ethylene glycol, it is used commonly as coolant and preservative and also found in polishes and detergens.
A few important facts to remember for your MRCP Part 1 and 2,

1) Methanol can cause retina injury leading to blindness ( eye manifestations can happen as early as 15-20 hours post ingestion)

2) Ethylene glycol poisoning usually has 3 distinct clinical phases- first stage- CNS effects ( first 12 hours), second stage- cardiopulmonary effects ( CCF, ARDS etc) and third stage- renal effects- ARF.

3) Acute management include gastric lavage and correct the metabolic acidosis. Remember also that haemodialysis can be employed to fasten removal of the toxic metabolites.

4) Folinic acid can be used to protect against ocular toxicity of methanol whereas thiamine are administered to drive metabolism of ethlylene glycol to non-toxic metabolism.

Let me illustrate to you a MRCP question,
A 23-year gentleman is admitted to the A+E due to nausea and vomitting. On examination, he is dehydrated with GCS=14/15. Blood pressure on arrival= 90/60. Blood investigations sent in A+E reviews the following,

Salicylates level= normal

Na=134

K=5.1

BU=10

Creatinine= 100

ABG ( on 2L oxygen supplement)

PH=7.20

HCO3=12

PaO2=100 mmHg

PaCo2=21 mmHg

What further test you would like to order?

A) Random blood sugar B) CXR C) CT brain D) AXR E) Blood lithium level

So, do you know the answer??

Immunosuppressive Drugs (1)

Immunosuppressive Drugs- Cyclosporin





Sorry for the long absence from my blog. I just shifted to my new house and had to live without broadband for almost 3 months.


OK, today I am going to talk about cyclosporin ( prototype of calcineurin inhibitor) because this drug change the landscape we look at solid organ transplantation. It was discovered in 1971 and subsequently approved for use in 1983.


I do not think you care about the history. The more important topics you want to know are popular questions in MRCP, here are the popular questions,


1) Drug Interacations

Since cyclosporin is metabolised in the liver by cytochrome P-450, there are a lot of drug that can induce/inhibit this enzyme causing low/high cyclosporing level in the blood. Fo the mneumonics of enzyme inducers/inhibitors, you can read my previous blog. Remember that grape juice inhibit the cytochrome P-450!! ( ALL-TIME POPULAR MRCP QUESTION!!)


2) Side effects


This topic is ver popular if you get a case of kidney transplant in MRCP PACES, common side effects are,

Tremor
Hypertension
Gum hypertrophy
Electrolyte imbalance
Nephrotoxicity

I will talk more about immunosuppressive drugs in my future blogs!!

Drug in MRCP-Phenytoin

Although some of you may be not so familiar about phenytoin especially for those who are practicing medicine in developed countries. I think this is because there are so many new antiepileptic drugs available in the market now.

Actually, phenytoin is the oldest non-sedative antiepileptic drug introduced in 1938!!
I think it is not so important for you to understand how phenytoin acts because I myself never understand it when I was a medical student myself many years ago.

In MRCP examination, there are a few important facts that you must always remember.

Fact 1 : Drug metabolism/binding

Remember that phenytoin is mainly bound to protein. Therefore, when there is hypoalbuminemia, there is decreased protein binding- results in a decrease in total plasma concentration of drug but not the free concentration.

Therefore a lot of doctors tend to increase the drug dosage to maintain total drug levels in the therapeutic range- leading to toxicity.

Besides that remember that hepatic enzyme induction and inhibition also alter its drug level.

Although phenytoin is mainly metabolized in liver, its metabolites are excreted in kidney, therefore, renal failure may precipitate toxicity.

Fact 2: Side effects

As I remember as a medical student, there are two interesting side effects of phenytoin- gum hypertrophy ( Look out the photo at http://www.passpaces.com/ ) and generalized lymphadenopathy. However, remember that acute toxicity of phenytoin also leads to cerebellar signs!!

Fact 3: Cardiac complications

Since phenytoin alters Na, K and calcium conductance, it can cause cardiac arrhythmia, therefore always put patient on cardiac monitor if you suspect toxicity.

Also remember that chronic use of phenytoin can lead to Vitamin D metabolism abnormalities and osteomalacia.

New Drugs in MRCP- Rituximab

New Drugs in MRCP- Rituximab

I am going to talk about another –ximab drug today-Rituximab. If you are currently working in a haematology unit, Rituximab is not a stranger to you because I think haematologists are the ones who use this drug most.

As Infliximab, Rituximab ( Trade name: Rituxan) is also a chimeric monoclonal antibody , it was first approved in 1997 for the treatment of lymphoma and it has become a standard treatment for aggressive lymphoma. As you might remember during your medical time that CHOP is the standard treatment for lymphoma but currently the treatment of choice it is R-CHOP! (CHOP stands for Cytoxan, Hydroxyrubicin (Adriamycin), Oncovin (Vincristine), Prednisone/Prednisolone.)

Besides lymphoma, remember that Rituximab is also useful for the treatment of Rheumatoid arthritis, autoimmune haemolysis, idiopathic thrombocytopaenia purpura, Evans syndrome and SLE ( Systemic Lupus Erythematosis). Rituximab is a unique therapy that works selectively by depleting CD20+ B cells.

The side effects of Rituximab is quite similar to Infliximab.

Check out more about this drug HERE!

New Drugs in MRCP-Infliximab

Infliximab in MRCP

I learned pharmacology about 10 years ago. If you are one of few doctors that studied pharmacology many years ago, you might find some drugs that being asked in MRCP that you never come across before. I will talk about a few new drugs that are rather common and popular in MRCP that you might have not studied during your medical school.

The first drug is Infliximab ( Trade Name: Remicade) Infliximab is known as ‘ chimeric monoclonal antibody’ that blocks tumour necrosis factor alfa ( TNF alfa). You might come across the word ‘chimera’ in movies such as ‘Relic’ which means monster.



In Greek mythology, the Chimera is a monster, depicted as an animal with the head of a lion, the body of a she-goat, and the tail of a dragon (sometimes it has multiple heads).

In medicine, a chimera is an animal that has two or more different populations of genetically distinct cells that originated in different zygotes.

The first thing you need to know about Infliximab is its indications. Infliximab has been approved by the U.S. Food and Drug Administration for the treatment of psoriasis, pediatric Crohn's disease, ankylosing spondylitis, Crohn's disease, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis.

You must know that infiximab is classified as immunosuppressive drug, therefore always watch out for infections ( such as tuberculosis- always asked in MRCP. Always screen for possible latent TB before starting the drug!), blood disorders ( bone marrow suppression), cancers ( such as lymphoma) and allergic reaction.

Be careful if you want to start Infliximab in patients with heart failure and chronic viral hepatitis due to possibility of reactivation!

Poisoning in MRCP(III)

Poisoning in MRCP (III)-Tricyclic Antidepressants

The third serial of this topic- poisoning in MRCP, I am going to talk about tricyclic antidepressants. Examples of tricyclic antidepressants are amitriptyline, imipramine, doxepin etc.It is a common case scenario you would see during your internship/ housemanship. The reason is simple, doctors prescribe tricyclic antidepressants for patients with depression and these patients tend to use drugs for suicide.

As you might remember, tricyclic antidepressants help depressed patients through inhibition of reuptake of noradrenaline or serotonin in the brain, however, there are a few other effects of tricyclic antidepressants that explain its side effects,


1) it has central and peripheral anticholinergic effects
2) it causes depression of cardiac contractility
3) it slows down intraventricular and artrioventricular conduction ( cardiac conduction)
4) it causes CNS toxicity such as agitation, confusion , coma and seizures


Symptoms of Toxicity

Remember that all these symptoms are due to cardiac toxicity and anticholinergic effects of tricyclic antidepressants.

Cardiac toxicity
Cardiac arrhythmias, supraventricular or ventricular arrhythmias leading to hypotension, pulmonary oedema, therefore patients may present palpitation and breathlessness

Anticholinergic toxicity ( autonomic toxicity)
Dry mouth, urinary retention, dilated pupils, constipation and hyperreflexia

CNS toxicity
Seizures ( may cause severe metabolic acidosis), coma, confusion

Treatment

Gastric lavage
Continuous cardiac monitoring is mandatory
IV Sodium Bicarbonate may be useful to maintain arterial PH if patients develop severe metabolic acidosis
DC shock may be needed, however, anti-arrhythmias are contraindicated
Fluid resuscitation if hypotension
Haemodialysis is not useful.

Tips for MRCP
1) Remember that if you see a patient with dilated pupils, confusion and cardiac arrhythmias , always consider tricyclic antidepressants.

Poisoning in MRCP(II)

Poisoning in MRCP (II)-Salicylates

In the second serial of this topic- poisoning in MRCP, I am going to talk about salicylates poisoning. It is an important topic in MRCP Part 1 and 2 as well as in your clinical practice. The reason is simple, salicylates can be obtained easily because it can be found in aspirin .You certainly know many patients are on aspirin if you go to ward everyday and at one time, some doctors even suggested to put aspirin in our tap water!


Before we discuss common presentations of a patient with salicylates poisoning, we must know the pathophysiology of salicylates overdose. Salicylates stimulate the respiratory centre initially and cause respiratory alkalosis. However, salicylates also interfere with carbohydrate metabolism and lead to accumulation of lactic acid and lead to metabolic acidosis.

Symptoms of Toxicity ( ASPIRIM)

Acute renal failure- symptoms of acute renal failure
Salicylism- deafness, tinnitus, vomitting
Pulmonary edema or cerebral edema (confusion)
Increased temperature
Respiratory alkalosis- hyperpnoea
GI disturbances and haemorrahge
Metabolic acidosis

Signs of toxicity

Air hunger ( due to metabolic acidosis)
Hyperpnoea ( due to respiratory alkalosis)
Remember that initially, there is respiratory alkalosis but later patient will have metabolic acidosis

Interactions

Increases anticoagulation effect
Low dose of aspirin precipitates gout

Treatment

Gastric lavage
Forced alkaline diuresis
Haemodialysis is indicated in severe cases

Hope you know how to answer your MRCP questions about salicylates after this post!

Poisoning in MRCP(1)

Poisoning in MRCP(1)-Lithium

For those who recently sat for thier Part 1, good luck to all of you and hope for the best!You can do it!
" There is always hope !"

My friend sat for his MRCP Part 1 in Singapore recently. He said that questions asked in MRCP are getting more difficult to answer now. I would like to talk about poisoning today. There are a few important subtopics you must remember when learn about common drugs which are asked in MRCP.

1) Common symptoms and signs when there is poisoning.
2) Possible antidotes.
3) Drugs interactions
4) Whether the drug can be cleared by dialysis ( very important fact to remember!)

Today, I am going to talk about Lithium. If I can still remember, this drug was asked in my MRCP Part 1 in 2003.

Introduction:

Lithium is used as mood stabilizer and can be used as a treatment for acute mania/hypomania. It has a narrow therapeutic range ( <1mmol).>Symptoms for toxicity (LITHIUM!!)

- Loose motion
-Impaired vision
-Tremor
-Hypothyroidism symptoms
-Increased thirst ( polydypsia)
-Urine output increased ( polyuria)
-Muscle weakness/metallic taste

Signs for toxicity

-hyper-reflexia
- ataxia/dysarthria
-Confusion/fits

Interactions

NSAID, Thiazide, Phenothiazide, pheytoin and methyldopa increase lithium toxicity

Treatment

No specific antidotes but dialysis may be indicated!