Friday, July 23, 2010

I'm not dead, and I haven't forgotten about you all

Just updating to say I intend on continuing this blog with the coming semester. However I left my pencil case in Geelong and my three year old sister (according to my mother) is having a lovely time with it. I'll go buy some more textas soon and try to get this week's lectures summarised. (I may ignore Melvin's lectures, because he annoys me, but if I can manage to find the time I'll do his.)

Here is a Cthulhu joke that I can't take credit for coming up with.

For those of you who don't know the Cthulhu Mythos, just trust me, it's hilarious.

Saturday, July 3, 2010

I'm on a zole!

Today we start on antimicrobials, beginning with antifungals.
The basic function of of azoles is to stop the conversion of lanosterol into ergosterol, which interferes with the membrane and prevents reproduction making it fungistatic.
Four main azoles: ketoconazole, not used all that much any more since it can be quite toxic, fluconazole, used for CNS infections such as meningitis as it enters the cerebrospinal fluid, itraconazle, usually used for dermatophytes, and miconazole, usually for GIT infections.
Aphoterecin puts holes in the membrane and lets all the potassium leak out, but can cause renal impairment. Nystatin is much the same but is not absorbed from the GIT.
Griseofulvin cleaves microtubules and echinocandins render ergosterol ineffective and lyse the cell walls.
Flucytosine (I know runny nose is a symptom of rhinovirus not influenza but shhhh, it helps me remember) is taken up by both human and fungal cells, but only fungal cells convert it into a toxin, although resistance develops quite quickly so it is usually used in concert with other antifungals.
Turbinafine is a drug absorbed with great affinity for keratin and adipose tissue, it fills the cell wall with squaline and destroys it. In 10% of patients it has side effects.

I'm leaving for QC in a matter of hours, I'll probably have internet while I'm away but I doubt I'll be doing much for this, I rather hope I won't have time. When I get back we'll cover the rest of the antimicrobials.

Friday, July 2, 2010

Turning the Yellow Tide

The week we studied kidneys was the same week that my glandular fever decided to make its final stand to see just how much it could mess up my life. I therefore missed the introduction to the kidneys, and subsequently didn't understand a damn thing for the next few weeks. It is human nature to fear that which we do not understand, fear leads to anger, and anger leads to hate. God I hated the kidneys for the longest time. Then I jumped on this "studying" band wagon. They're like the coolest things ever, you just have to look a little deeper.
The majority of this section is about diuretics, you know, being the kidneys and all. I've divided them up according to which section of the nephron they act upon. There are few drugs that act upon the Proximal Convoluted Tubule, the main one is acetazolamide, causing excretion of bicarbonate and along with it more water.
Loop diuretics act upon the thick ascending limb and are the most powerful diuretics. They inhibit absorbtion of Na+ and Cl- and secretion of Mg2+ and Ca2+ resulting in what can be described as a "torrential flow" of urine which can cause a number of problems if not monitored. The most common loop diuretic is Fureosemide and is commmonly marketed under the name Lasix. They have a degree of vasodilation as well.
Thiazide diuretics act upon the Distal Convoluted tubule in a similar manner to loop diuretics (inhibiting Na+ and Cl- absortion), they are commonly used as anti-hypertensives.
Spironolactone and Eplerenone are potassium sparing diuretics and are often used alongside non-potassium sparing diuretics as they are quite weak in isolation. They act as aldosterone antagonists, inhibiting water and potassium absorbtion.
Amiloride and triamterene act on the collecting duct and are also potassium sparing diuretics.
There is only one common osmotic diuretic and that is mannitol. It is filtered by the glomerulus but is not absorbed, thus is raises the osmotic pressure within the nephron causing more water to be excreted.
Moving on from the diuretics we come to drugs used to alter urine pH. Why? Apparently carbonic anhydrase inhibitors and citrate will raise the pH and this reduces incidence of kidney stones. Ammonium chloride will lower the pH but no-one uses it any more.
Finally there are drugs to alter excretion of uric acid. The two main drugs that do this are probenecid, which stops reabsorbtion and allopurinol, which stops synthesis. These are important in relation to gout.

Leaving for QC tomorrow, and so far I've packed... A jacket. Yep, that's really it. Although I did have to go out and buy a case to pack it in. You'd think that's something I also would have considered earlier. Anyway....

Thursday, July 1, 2010

Pharmacology makes me fit with rage

*sigh* Antiepileptics represent the reason I have always hated pharmacology. Rang & Dale cover fourteen antiepileptics, each of them different enough from each other that you have to learn them separately. They don't lend themselves at all to summarisation and several of them don't even have understood mechanisms of action. So instead of making fourteen rather repetitive pictures I've drawn a reference table. If you want to learn these drugs get Rang and Dale, this is just a memory tool (which most of this blog is supposed to be, but these especially) for revision. There are three major methods of action of antiepileptics, Na+ channel blockers, Ca2+ channel blockers and GABA agonists. They treat three types of seizures, partial seizures, generalised seizures (tonic-clonic) and generalised (absent).
Phenytoin - Sodium channel blocker - All but absent
Carbamazepine - Sodium channel blocker - All but absent
Valproate - Weak calcium channel blocker and is possibly a GABA agonist - All types
Levetiracetam - Mechanism unknown - Partial seizures
Phenobarbital - GABA agonist and possibly a sodium channel blocker - All except absent seizures
Benzodiazepines - Strong GABA agonist - All seizures but is usually only used in status epilepticus
Vigabatam - GABA transaminase inhibitor - All seizures, even when there are drug resistances
Lamotrigine - Sodium channel and possibly and calcium channel blocker - All types
Gabapentin - Not actually a GABA agonist, but may be a Ca2+ channel blocker - Partial seizures
Felbamate - NMDA antagonist and possibly a Calcium channel blocker -
Tiagabine - GABA agonist and inhibits GABA reuptake - Partial seizures
Topiramate - Unknown mechanism - All except absent
Ethosuxamide - Strong Calcium channel blocker - Absent seizures, exaggerates tonic-clonic seizures
Zonisamide - Sodium channel blocker - Partial seizures

Tomorrow I'll put up the kidney drugs. They're much more fun. :D

Wednesday, June 30, 2010

Rang and Dale just love them some asthma

Heya, short post today as I've been having a social life and all that jazz you do on holidays. This is the respiratory section of Rang & Dale. And by respiratory I really just mean asthma.

So the first 80% of Rang & Dale is just the pathogenesis of Asthma. In short, when susceptible people are exposed to allergens, CD4 gets upset, it produces Th0, which produces Th2, which attracts granulocytes which inflame the bronchi.
Bronchodilators: B2 receptor agonists, muscularinic receptor antagonists, xanthines and cysteinyl leukotriene receptor antagonists. All are smooth muscle relaxants.
Even Rang and Dale couldn't be bothered explaining the immunosuppressant mechanisms of glucocorticoids. Just know that they quash basically all immune response and cause Cushings Syndrome.
Rang and Dale saw fit to cover a brief section on other resp conditions. Treat allergic emergencies with adrenaline, COPDh as little pharmaco management and is largely irreversible, surfactant is important in babies breathing and cough medications are largely useless.

Told you it was short, I don't even have a humourous unrelated drawing to mitigate it. So instead here is a picture of a cat with a top hat and bowtie.
I hope this is in some way pleasing to you.

Tuesday, June 29, 2010

FYI Heparin doesn't really go in your face

This is where it all started, I was locked outside Friend's house waiting for her to return for our group study session for which I was the only one remotely on time. I decided I'd start studying anyway, despite the fact it was cold like the grave. As you've probably quickly noticed, I enjoy playing with words and anti-thrombin III just rearranged itself in my head into Aunty From Bin III, and by the time Friend arrived and let me in I was madly scribbling pictures as fast as I could.
Anti-thrombin III is the main agent against clotting.
Heparin interacts with Anti-thrombin III and inhibits factors 9-12a and thrombin II
Thrombin II cleaves fibrinogen into fibrins and also aggregates platelets, stimulates cell proliferation and modulates smooth muscle contraction
Vitamin K makes factors 2,7,9 and 10. The common F2A channels in Australia.
Heparin -IV, fast, short term. Warfarin - Oral, slower, longer term
Heparin can cause haemorrhage, thrombosis (oddly), hypoaldosteronism and osteoporosis
Heparin IV onset is almost immediate, with s/c it takes about an hour, and it takes 40-90 minutes to wear off. Low Molecular Weight heparin takes longer.
Warfarin is a Vitamin K antagonist
Warfarin is absorbed by the gut, and therefore administered orally, is teratogenic, can occasionally be hepatotoxic, can cause haemorrhage and have a narrow therapeutic window.
I don't really understand this, but those are the basic principles.

Asprin inhibits production of TXA2 which promotes aggregation and promotes production of PCI2 which inhibits platelet aggregation.
Dipyridamole is a phosphodiesterase inhibitor, but just remember it's an anti-platelet drug.
Thienopyridine derivatives (Ticlopidine and clopidogrel) inhibit ADP-dependent aggregation
Seriously. Abciximab? Who the hell came up with that name? Were they trying to summon Cthulhu?
But ridiculous name aside, abciximab, along with tirofiban and eptifibatide, are often given as adjuncts to heparin and aspirin, to reduce restenosis. All of these are glycoprotein IIB/IIIA receptor antagonists.
The fibrinolytic system is activated at the same time as the coagulation system, and plasminogen is deposited on fibrin strands.
Streptinokinase, alteplase, duteplase and reteplase are fibrinolytic drugs with slightly different mechanisms, but in practise they have all been shown to have equal long term outcomes.

Monday, June 28, 2010

It's a total eclipse of the voltage gated calcium channel

This is a short one, most the the drugs that you would think act on the heart are covered under other categories.
Anti-Arrhythmics are broken down into four classes. Class I drugs act by blocking sodium channels, and are divided into three sub classes. Ia (Quinidine, Disopyramide and Procainamide), Ib (Lignocaine (also an anaesthetic) and Phenytoin) and Ic (Flecainide and Encainide). Ib drugs associate and disassociate rapidly, Ic drugs more slowly, and Ia have properties in between. Class II are the beta blockers, and they all end in -olol. Amidarone and Sotalol are Class III and they extend action potential of the heart through unclear mechanisms that somehow affect K channels. Finally Verapamil and Diltiazem are Class IV which block calcium channels and slow conduction of the SA and AV nodes.
Digoxin is a cardiac glycoside derived from foxglove (digitalis), it blocks Na/K channels, which slows down AV conduction. This causes the heart to fill more with each contraction, causing it to contract harder and resulting in a greater ejection fraction. It is used in heart failure and as an antiarrythmic, but it is not a particularly pleasant drug.Nitrates are the most common anti anginal drug. They're a smooth muscle relaxant which allows greater cardiac perfusion. They do however have side effects such a postural hypertension and development of tolerance.
And finally calcium channel blockers (antagonists) as oral antihypertensives. These are grouped under the heart because they have a greater effect on the heart that other smooth muscle relaxants do. As described before they are Class IV anti-arrhythmics, but they also cause the arteries to dilate, with little effect on the veins.

That's it for heart pharmacology, for those of you wondering how the magic of Manic Grandiosity happens below is a portrait of my sister and I 'working together' to construct this blog.

Scanners are the bane of my existence

I was trying to get this done last night, but I ended up being ridiculously late and I gave up. Why was I up so late? Is it because I stayed up to watch the soccer? Nope. Is it because I wasted ages on Facebook? Well, yes, a little bit. But mainly it's because scanners hate me. Like it's not annoying enough having to lift the lid remove the old sheet, place new one in, adjust its position, close the lid, tell the computer to start scanning, and then have a concentration span long enough not to get distracted while the page scans, scanners seem to enjoy being 'helpful' and cropping the pictures down to what it deems as the necessary sections of the picture. It is always wrong in its judgement.
Of course drawing this picture made it take longer and I had to scan it, but I don't pretend for a second to be a rational person.

Anyway this is a little different to what I planned on doing (apparently all my posts come with disclaimers about how not to expect more posts like them :P) this is how I explained the kidney to my friends, but in that case the diagrams were only an aid, rather than the focus, and most of it was me talking. What this verbose vichyssoise ironically attempts to convey is that reducing verbiage is the aim of this project and so I have attempted to remove as much of the associated chatter as possible. We'll start with the gross anatomy.
Put simply, the kidney is divided into a number of lobes, each with a renal pyramid (the medulla) and its associated cortex. Each of the renal pyramids (the peak of which is called a papilla) drains into a minor calyx (calyx meaning cup) which drains into a major calyx, which drains into the renal pelvis and drains into the ureter.
Seriously, the circulation of the kidney makes sense. It's a nice change. The artery that goes to the kidney is called the renal artery. It divides into segments called segmental arteries. Between each lobe there is an interlobar artery. These split at a 90 degree arc into the arcuate arteries. They then shoot off interlobular arteries. That's the only bit that's slightly confusing. And the veins all have the same names. Isn't it nice when the people naming things are being logical instead of artistic or egotistic?
The functional unit of the kidney is the nephron, that's what it looks like . Note that the afferent arteriole is bigger than the efferent arteriole, it's important for maintaining a pressure gradient.
The high hydrostatic pressure of the blood in the glomerulus pushes the blood out into the glomerular capsule. It has to be filtered through the fenestrations in the leaky blood vessels of the glomerulus, which stops large particles including red blood cells. The basement membrane is a gel that acts like a negatively charged sponge, small particles (like water) come through it fine, but large particles (like sand in our sponge metaphor) are filtered, though a few may make it through, it's negativity also keeps out small negatively charged particles like albumin. The final barrier is the podocytes, whose legs wrap around glomeruli and interdigitations (laced fingers) form slits that keep out large particles.

The regulation of filtration rate is quite important. And there are three main regulatory methods. The first is the myogenic reflex, when the arterioles are stretched by a high blood pressure they respond by constricting, which lessens the blood flow into the glomerulus keeping the filtration rate steady. The second is tubular feedback, the mechanisms of which aren't entirely clear, but when the PCT detects a lower or higher flow the juxtaglomerular cells constrict or relax the arterioles to change the blood flow. The final method is the renin-angiotensin cycle, the kidney secretes renin, which converts angiotensin to angiotensin I, which is converted by ACE into angiotensin II. Which acts on the brain, vessels, adrenal glands and kidneys, stimulating thirst, raising blood pressure secreting aldosterone and increasing NaCl and H2O retention respectively.
Proximal Convoluted Tubular re-absorption is driven by sodium. The cells which line the tubule constantly pump out Na+ keeping the concentration low, causing Na+ to diffuse across the membrane. Glucose is bound to Na+ by transport proteins, causing it to follow along, along with negatively charged molecules such as chlorine . As the osmolarity changes water also diffuses out. Bicarbonate is unable to be absorbed, but none is usually found in the urine, so within the cell water and CO2 combine to form bicarbonate and H+. The H+ moves into the tube and breaks the bicarbonate into water and CO2, which can diffuse out.

This is possibly one of the coolest things ever. No really, I know it's nerdy. But seriously, the thin part of the nephron loop is permeable only to water, so when it dips into the salty medulla the water leaves the tube and the osmolarity increases. When it reaches the thick part which is non-permeable to water the concentration of sodium has increased, and so as it leaves the medulla the sodium bails as well, preserving the sodium gradient.
Now think about this, what would happen if the vessels went straight through the medulla? The salt would go in and the water would go out. Very very bad. Hence the vasa recta, they go enter and leave the medulla next to each other and thus as the gradient increases the salt enters and the water leaves, but as the vasa recta returns more or less on its original path the reverse occurs, meaning the osmolarity and concentration is essentially unchanged.
Finally we reach the Distal Collecting Tubule and Collecting Duct, these remove the last of the water and the salt, and are modulated by aldosterone, anti-natriuretic peptide, antidiuretic hormone and parathyroid hormone depending on whether or not the body needs to conserve or excrete water. The method of the collecting duct is similar to the thin section of the nephron loop, as the medulla becomes saltier more water leaves the duct.

And that's the kidney! It actually makes a lot of sense and it's a really cool organ.