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.

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.

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....

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

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.

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.

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.