Patient overdoses on paracetamol. A few hours since ingestion. Administer Sodium Bicarbonate or Ammonium Chlor

Question

This is the complete question:
A patient is brought into hospital having overdoesd on the weak acid, paracetamol (pKa = 9.5). It has been a few hours since they ingested the drug so it is decided to facilitate clearance of the drug by adjusting the patient's urinary pH. Determine if you would administer sodium bicarbonate (makes urinary pH~8) or ammonium chloride (makes urinary pH~4) to facilitate excretion of paracetamol. Explain the rationale behind your selection based on the principles of pharmacokinetics.

Answer 1

yes, everybody's right, administer sodium bicarb to make the urine alkaline. i'll try to put the explanation based on the principles of pharmacokinetics in a detailed but easily understandable way(but if you want the gist of it, just go right ahead to the 2nd to the last paragraph):

you have to understand first that the final composition of urine actually excreted depends largely on the transport of solutes and water across the renal cells of the kidney tubuli. The transport may be by passive diffusion or by active transport. In the case of passive diffusion, transfer in either direction depends on the PRINCIPLES OF DIFFUSION (concentration gradient, pH,pka, lipid solubility, etc). It is assumed that ONLY THE UNIONIZED FORM OF A DRUG CAN PASS THE MEMBRANE. Why? In passing through a membrane, the drug molecule dissolves in the lipid material of the membrane (remember that our membrane is a bilipid layer). So, the drug has to be lipid-soluble for it to be absorbed, and remember that water is polar and ionized, oil or lipids therefore are nonpolar and unionized (that's how i can easily recall if i forget which one is polar, nonpolar).

Since ions usually have no lipid solubility they cannot permeate. However, most drugs are electrolytes, either weak acids or weak bases (paracetamol being a weak acid). But here's another thing to remember: THE UNIONIZED MOIETY of weak electrolytes IS USUALLY LIPID SOLUBLE. Therefore, the pka of the drug and pH at the absorption site will determine the degree of drug being unionized and absorbable.

look at the henderson-hasselbach equation for weak acids:

pH = pKa + log ( [A] / [HA] )

where [A] is the molar concentration of the salt which is the ionized moiety while [HA] is the molar concentration of the acid which is the unionized moiety.

***((If you're wondering how [A] became the ionized moiety and [HA] the unionized, read this succeeding explanation in these parentheses or if not you can skip it: At a certain pH, the relative concentration of the ionic and the molecular moieties of a drug are given by the Henderson-Hasselbach equation.For a weak acid HA which ionizes according to this equation:
HA + H2O = H30 (Hydronium ION) + A (ANION),
the dissociation constant is:
Ka = [H3O] [A] / [HA]
where Ka is the dissociation constant, [A] is the molar concentration of the acidic anion, [H3O] is the molar concentration of the hydronium ion, and [HA] is the molar concentration of the UNDISSOCIATED ACID.
and now you can see which one is IONIZED and which one is UNIONIZED.))**

Going back to the HH equation for weak acids, if we INCREASE the pH (make it alkaline), there would be more of the IONIZED moiety than the unionized. but if we DECREASE the pH (make it acidic), there would be more of the UNIONIZED than the ionized.

now, what do we want to happen? we want to excrete an acidic drug. if we want to excrete an acidic drug, we wouldn't let it be reabsorbed into the kidney tubules. so, we try to make it more IONIZED than UNIONIZED since we know if it is UNIONIZED, it can be reabsorbed into the kidney tubules. Hence, we increase urinary pH in the patient overdosed with paracetamol to facilitate its urinary clearance.

***SIMPLY PUT, a base and acid put together becomes polar/ionized, but a base and a base or an acid and acid becomes nonpolar/unionized and unionized drugs are reabsorbed into the kidney tubules, so if the drug is acidic and we want to excrete it, we adjust the urinary pH by making it alkaline to make it POLAR/IONIZED so that it can be excreted, not reabsorbed.

That's all really, I just got into the details in case you might need to actually defend your answer with, i dunno, deeper details?! hehe.. hope this helps, and hope i was able to give a clear picture. God bless! :)

Answer 2

You already got a very detailed answer to your question- Sodium Bicarbonate will be administered.

In brief explanation, a paracetamol overdose can cause abnormalities of glucose metabolism leading to metabolic acidosis (blood pH below 7.35 will confirm that condition).

Other blood components (such as potassium, glucose, ketones, or lactic acid) may be above normal ranges. While the level of BICARBONATE in the blood will be low. The acidic blood going to be filtered by the kidneys will produce an acidic urine. Thus in the presence of metabolic acidosis, the urine pH may fall below 4.5.

Administering sodium bicarbonate obviously will change the blood pH, and will increase blood level of bicarbonate which will increase the urine pH above 4.5.

Answer 3

Give NaHCO3 to alkalinize the urine, ion trapping the weak acid (from the blood to the urine in the renal tubules).

Clinically, you can alkalinize the urine by giving a single IV bolus of NaHCO3 at 1-2 mEq/kg and following with a constant infusion of D5W containing NaHCO3 (100-150 mEq/L) and KCl (20-40 mEq/L) at 1.5-2.5 cc/kg/h to produce a urine flow of 0.5-1 cc/kg/h. You should closely monitor the serum electrolytes (e.g. by venous gas) and urine pH (using urine dipsticks) to maintain the urinary pH between 7.5-8.

N.B. The mainstay Tx of paracetamol OD is the NACC protocol (using a nomogram)! Early i.v. administration of NACC (brand name Mucomyst), within 8 hours of ingestion is nearly 100% hepatoprotective. I've given it several times to a single (psych) patient who had OD'd on Tylenol (Paracetamol in the UK) more than 10 times when I was working in the emergency department.

See my (long) answer to "Why make urinary pH alkaline after an overdose with paracetamol?"

Answer 4

acetadote. go!