Carbonic anhydrase inhibitors - Fixing pretty much everything

  • class of drugs that inhibit (wait for it...) carbonic anhydrase (CA), an enzyme with a variety of functions specific to different parts of the body, enabling it to be used to treat a number of seemingly unrelated diseases
  • include acetazolamide (Diamox), methazolamide (Neptazane), topiramate (Topamax) and zonisamide (Zonegran)
  • are structurally related to sulfonamide antibiotics ('sulfa drugs'), from which they were developed
    • carbonic anhydrase inhibitors, thiazide diuretics and sulfonylurea antidiabetic drugs were all developed from sulfonamide antibiotics, after it was noticed that, in addition to killing bacteria, the antibiotics produced 'side effects' including diuresis, metabolic acidosis, and increased insulin secretion from the pancreas
  • things that these drugs can fix:
    • glaucoma - decrease the formation of aqueous humour, which reduces intraocular pressure
    • idiopathic (benign) intracranial hypertension - decrease the formation of cerebrospinal fluid (CSF), which reduces intracranial pressure
    • hypertension, congestive heart failure, cirrhosis with ascites - increase urine production (diuresis) so that you lose more fluid than normal, lowering blood volume and thus blood pressure (since PV=nRT, natch)
      • note: CA inhibitors are rarely used as diuretic agents since there are lots of other drugs capable of doing the same thing, only better
    • hyperkalemic periodic paralysis - increase urinary potassium excretion
      • note: can lead to mild hypokalemia (too little potassium in the blood) that can cause fun side effects like numbness and parageusia (things tastes weird)
    • mild altitude (mountain) sickness - increase urinary bicarbonate excretion, which increases the plasma concentration of hydrogen ion and thus relieves the effects of respiratory alkalosis that occur at high altitudes (the reduced availability of oxygen at higher altitudes stimulates respiratory centres in the brain resulting in increased ventilation, decreasing the plasma concentration of carbon dioxide and thus hydrogen ion)
    • cystinuria and hyperuricosuria - increase urinary bicarbonate excretion, alkalinizing urine so as to maintain acidic substances such as cystine and uric acid, which would normally precipitate out and form stones, in solution
    • epilepsy and migraine - increase cerebral blood flow and raise carbon dioxide levels in the brain, also block sodium channels and glutamate receptors and/or enhance GABA activity
Masereel B et al. Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. J Med Chem. 2002 Jan 17;45(2):312-20.

5 chemically inspired comments:

Orri said...

Correct me if I'm wrong, but doesn't the Ideal Gas Law refer to . . . well, gases? (As opposed to liquids like blood.) Also, even according to PV=nRT, it wouldn't make sense for a decrease in volume to accompany a decrease in pressure with constant temperature. The issue is, we're talking about a different kind of volume. With gases, decreasing the volume means decreasing the size of the container holding the gas, which increases the pressure. With liquids, decreasing the volume means decreasing the amount, which would be accompanied by a decrease in moles (n) as well as in pressure. However, as I said before, liquids don't follow the ideal gas law.

CND said...

Dear orri,

Yeah, you're correct. I was trying to be all show-offy and neglected to actually think. Your criticism is appreciated.

David said...

Not necessarily true for the second part Orri, decreasing the volume of a liquid with constant moles increases the pressure on the liquid, and can cause it to turn solid, or you can do the reverse and boil the liquid by removing pressure. I do have to say I screamed a little on the inside when I saw the Ideal Gas Law.

Anonymous said...

Here is a fun tip.... Hyperventilate for about 30 seconds to 1 minute.. Immediately inhale an increased level of O2 from an oxygen tank to give elevated levels of O2 in the blood. Assuming your don't use too much O2 and fry your lungs you should be able to hold your breath for around 7 to 8 minutes and not feel the dyer need to take a breath... it should keep those CO2 sensors from triggering and the H+ concentration in the CSF should be fairly stable.. With the elevated O2 in the blood you will have a while for the pH to stable itself. (side note: O2 sensors are worthless anyways since they only kick in seconds prior to passing out).. The oxygen tank is mainly for pH regulation.. Lots of time for CO2 to catch up..

Margaret said...

Topiramate is a weird drug. In addition to seizures and migraines, it's used for tremor, and off-label uses include weight loss, bipolar disorder, and bulimia.

Patients sometimes complain that these drugs make thing taste funny. And soda tastes flat, because the CA inhibitor kills the bubbles :-(