The Finite

All right, STOP get out your notes and listen

About to start a cascade of mem’rization

Svensson & Lill both say we gotta know

The importance here of Pharmacology’s role

Xenobiotics, toxins attack

Cytochrome 450 deals with that crap

Enzymes, conjugating functional groups

Better solubility, all a part of Phase II

Glucoronidation, so polar, you’ll see

Metabolites ending all up in your pee

And if you’re tamoxifen? Just need a hydroxy.

Binds like estrogen a hundred fold more tightly

Bioactivation of a product therapeutic

if you had breast cancer it’s a way to try to treat it.

[CHORUS]
P-Four-Fifty, Cytochrome P-four-fifty(x4)

Packing heme and stuck to a membrane,

Gonna need electrons from your reductase

Aromatic hydroxylation? Can’t wait.

Can also dealkylate, oxidize, deaminate.

Sulfoxidation, what the hell’s that?

Just add a carbonyl, just stuck where the sulfur’s at.

Ketoconazole? Inhibitor that’ll fight

Off other substrates, bumping up their half-life.

Mechanism-based? Whoa, that’s suicide.

Gonna need that enzyme resynthesized.

Binding moeities, 2C, cimetidine

inhibits not Advil, but raises your warfarin

What the hell?! It’s the same damn enzyme,

But they’re in the active site at the same time!

[Chorus]

Induction! From this biochem crosstalk

Metabolism gets kicked up another notch

Transcription! for more enzyme production

Common substrates means drug interactions

Metabolite toxicity? I don’t know!

Like P-A-H, gives you cancer down below

So no more cigarettes or char-grilled cattle meat

Hey, you can always just freaking boil it.

[Chorus]

C-Y-P-3-A-4 does a third of all drugs

but anti-fungal azos leave it stopped up.

When he takes midazolam and alfentanyl,

Upped levels of both mean that his diaphragm is still

Tell the nurse to run and get him a ventilator

and get set to defend yo’self from the prosecutor

Grapefruit, messing with 3A4’s career

It works lopinavir, not so with ritonavir

Mash em up, Kaletra’s got longer action

Just avoid citrus; it’s packing Naringinin

On to Phase II, UGT’s right next door

Adding glucoronide makes things more polar

Doesn’t matter, O or N or S

UGT will add a sugar right onto it.

Don’t forget SULT conjugating glutathione

To catecholamines, phenolics, and the steroid hormones

Let that be it. Please say that’s where it ends.

Whoa, whoa, we still got patient variance!

[Chorus]

Race, sex, nutrition and location

Personal genetic mutation variation

Environmental stuff may just activate

Enzymes to go ahead & upregulate

Giving chloramphenical to some newborns

Only to find in the morning, their color is all gone.

Whoops, we forgot about their immature UGT

And accidentally dosed them all the way to toxicity

Hypervariable, just look at that graph!

So when you dose, please triple check your math.

With just efflux pumps, the poor kid’s helpless

So please don’t give harsh drugs to the fetuses.

[Chorus]

Alcoholic cirrhosis, active chronic hepatitis

Less first pass blood flow, less enzymes going at it

Then there’s the elderly, where everything’s slower

Less blood flowing round and the liver mass is lower

Not to mention probably all the polypharmacy

Making their liver a pharmaceutical potpourri

All the random individual genetic factors,

Makes us poor, or ultrafast metabolizers

Like that mama with the morphine in her breast milk excreting

If only she had started with some formula and bottle feeding.

So take heed from this lyrical poet,

This exam won’t be easy and deep down we all know it.

Now the coffee wears off and we finally get to snooze

Only because the action of CYP 1A2

[Chorus]