pH is the measure of acidity or alkalinity in the body’s fluids, particularly the blood. This value is strictly regulated within a narrow range of 7.35 to 7.45; significant deviation indicates a serious health threat. The body’s ability to keep this value constant is called homeostasis, and disruptions are known as acid-base disorders. Drugs can significantly affect the body’s pH balance by interfering with the systems responsible for maintaining this equilibrium.
The Body’s pH Control System
The body employs three primary defense lines to maintain blood pH within its healthy, slightly alkaline range. Chemical buffer systems provide the immediate, first response to any change in acid or base load. The most important is the bicarbonate buffer system, which uses carbonic acid and bicarbonate ions to quickly absorb or release hydrogen ions, minimizing sudden pH shifts.
The second defense system is the respiratory system, which offers rapid control over volatile acids. Carbon dioxide, a byproduct of metabolism, combines with water to form carbonic acid. By adjusting the rate and depth of breathing, the lungs can quickly expel or retain carbon dioxide, raising or lowering the blood’s acid content within minutes.
The renal system provides the third and most powerful line of defense, though it is the slowest, taking hours to days to fully activate. The kidneys manage non-volatile acids by selectively reabsorbing bicarbonate, a base, back into the blood. They also excrete excess hydrogen ions into the urine, ensuring the long-term fine-tuning of the acid-base balance.
Mechanisms of Drug-Induced pH Disruption
Drugs disrupt pH homeostasis by targeting either the respiratory or the metabolic (renal) mechanism. Respiratory acid-base disorders occur when a drug affects the central nervous system’s control over breathing or directly impairs lung function. For example, sedatives like opioids can suppress the brain’s respiratory drive, causing reduced breathing rate and depth.
Slower breathing leads to the retention of carbon dioxide, causing an increase in carbonic acid and a drop in pH, resulting in respiratory acidosis. Conversely, some drugs can over-stimulate the respiratory center, causing excessive carbon dioxide expulsion. This leads to a decrease in acid and a rise in pH, known as respiratory alkalosis.
Metabolic acid-base disorders are the most common drug-induced pH problems. They occur when a drug interferes with the body’s ability to process or excrete non-volatile acids or bases, often involving the kidneys’ handling of bicarbonate and hydrogen ions. The resulting conditions are classified as metabolic acidosis (too much acid) or metabolic alkalosis (too much base).
Medications That Cause Metabolic Acidosis
Metabolic acidosis is characterized by a loss of bicarbonate or excessive acid accumulation, causing the blood pH to drop below 7.35. Several common medications and substances can induce this condition. For instance, high doses of salicylates, the active component in aspirin, can lead to a severe form of acidosis.
Salicylates disrupt cellular energy production by uncoupling oxidative phosphorylation and interfering with the Krebs cycle. This forces the cells to rely on anaerobic metabolism, causing a rapid buildup of organic acids, specifically lactic acid and ketoacids. The accumulation of these acids creates a high anion gap metabolic acidosis, a serious and potentially life-threatening condition.
The diabetes medication Metformin is well-known for its rare but severe association with lactic acidosis. Metformin is thought to inhibit the liver’s ability to clear lactate from the blood, allowing this acid to accumulate and overwhelm the body’s buffer systems. Patients experiencing severe metabolic acidosis may exhibit Kussmaul respirations—deep, labored, and rapid breaths—representing the body’s attempt to compensate by blowing off carbon dioxide.
Excessive alcohol consumption also contributes to metabolic acidosis, often by causing alcoholic ketoacidosis. When alcohol is metabolized, it generates cofactors that inhibit the normal metabolic processes that prevent ketone body formation. This leads to the overproduction of ketoacids, strong non-volatile acids that consume the body’s bicarbonate stores, lowering the blood pH.
Medications That Cause Metabolic Alkalosis
Metabolic alkalosis is defined by an excessive amount of base (bicarbonate) or extreme acid loss, leading to a blood pH above 7.45. Diuretics, particularly loop diuretics like furosemide and thiazide diuretics, are the most frequent drug causes of this condition. These medications increase the excretion of sodium and water, causing volume depletion and chloride loss.
This volume depletion triggers a compensatory mechanism in the kidney tubules that enhances the reabsorption of bicarbonate and increases the excretion of hydrogen ions, effectively making the blood more alkaline. The loss of chloride also contributes, as the kidney attempts to conserve negatively charged ions, often reabsorbing bicarbonate instead of chloride.
The overuse of certain antacids, such as those containing calcium carbonate, can directly introduce a large alkali load. This excessive ingestion, often combined with underlying kidney issues, can lead to calcium-alkali syndrome. The large influx of calcium and carbonate ions overwhelms the body’s ability to excrete the base, causing bicarbonate levels to rise significantly.
Symptoms of metabolic alkalosis are often related to the associated loss of electrolytes, such as potassium, and may include muscle weakness, muscle twitching, or mental confusion. The body attempts to correct this high pH by reducing the respiratory rate to retain carbon dioxide, which acts as an acid.