Acid Base Disorders Pharmacology (Zhang)

What medications are used to treat acute severe metabolic acidosis?

What medications are used to treat acute severe metabolic acidosis?

sodium bicarbonate, tromethamine (THAM), carbicarb, dichloroacetate

What is tromethamine (THAM)?

sodium-free organic amine that combines with H+ to form a buffer in the body → acts as an osmotic diuretic

What is a physiochemical benefit to THAM?

it can penetrate cells and neutralize acidic anions

What is Carbicarb?

mixture of sodium carbonate and sodium bicarbonate

What is the MOA of Carbicarb and its intended effect?

limits generation of CO2 → appears to correct intracellular acidosis

What is the MOa of dichloroacetate?

facilitates aerobic lactate metabolism by stimulating the activity of dehydrogenase, thus reversing hyperlactatemia

In Type 1 Metabolic Acid-Base disorders (volume-mediated processes), what are its causes?

GI disorders (vomiting, diarrhea), diuretic therapy (thiazides, loops)

In Type 2 Metabolic Acid-Base disorders (volume-independent processes), what are its causes?

excessive mineralcorticoid activity (excessive mineralcorticoid drug use), Liddle’s syndrome, profound K+ depletion, Mg2+ deficiency

In Type 3 Metabolic Acid-Base disorders (unclassified), what are its causes?

alkali administration

What is the main therapy for type 2 metabolic acid-base disorders?

treat cause of mineralcorticoid excess

What is the pathophysiology of respiratory alkalosis?

Hyperventilation (cause of alkalosis = decrease in PCO2 when ventilatory excretion exceeds metabolic production, negative CO2 balance primarily caused by an increase in ventilatory excretion of CO2)

What can hyperventilation develop from (what is the stimulation in the body that causes the action of hyperventilation, not the acid-base imbalance)?

(1) increase in neurochemical stimulation, (2) voluntary or mechanical (iatrogenic) hyperventilation

What can be causes of central stimulation of respiration in respiratory alkalosis? (drug-based)

catecholamines, theophylline, nicotine, salicylates

Respiratory acidosis occurs when lungs fail to excrete carbon dioxide leading to a lower pH, this can be a result of conditions that… (2)

(1) centrally inhibit respiratory center, (2) diseases that interfere with pulmonary perfusion or neuromuscular function, and instrinsic airway or parenchymal pulmonary disease

The central pathway of inducing respiratory acidosis can be caused by what medications?

anesthetics, opioids, sedatives

Which of the following results in Elevated Anion Gap Metabolic Acidosis?

1. failure to reabsorb bicarbonate in proximal tubule

2. failure to excrete acid in the distal tubule

3. GI bicarbonate loss

4. Accumulation phosphates bc of renal failure

Accumulation phosphates bc of renal failure

What is the mechanism of action of dichloroacetate in Acute Severe Metabolic Acidosis?

1. combines with H+ from carbonic acid to form bicarbonate and cationic buffer

2. facilitates aerobic lactate metabolism by stimulating the activity of lactate dehydrogenase

3. acts as a proton acceptor to prevent or correct acidosis

facilitates aerobic lactate metabolism by stimulating the activity of lactate dehydrogenase