Buffer Systems in Mammals

Buffer Systems

• Bicarbonate-Carbonic Acid Buffer System
  • Principle mammalian buffer system
  • Acids combine with Bicarbonates in the blood
    • Neutral Salts (Bicarbonate Salts) – conjugate base
    • Carbonic Acid (Weak Acid)
  • In blood circulation, bicarbonate and carbonic acid exists in 2 different forms:
    • Bicarbonate: HCO3-
      • Measured to determine pH
      • Normal range: 21 - 28 mmol/L (21 - 28 meq/L)
    • Carbonic Acid (unstable): H2CO3
      • Readily dissociated into H2O and CO2 once it reaches the blood circulation
      • This fraction of blood, plasma or serum includes the undissociated carbonic acid and the physically dissolved anhydrous C02
  • In blood circulation, CO2 concentration is higher than HCO3, the symbol cdCO2 (conc.of dissolved C02) is frequently used and measured from pCO2 multiplied by the solubility coefficient (0.03) of CO2.
    • Normal range: 1.05 –1.45 mmol/L.

Propanol

• Beta receptor blocking drug (Class II)
• Used in the treatment of angina pectoris, hypertension, and coronary artery disease
• Suppresses the conversion of T4 to T3
  • Helpful in patients with thyrotoxicosis
• Therapeutic Range: 50-100 ng/ml
• Toxic Effect:
  • Hypotension
  • Peripheral edema
  • Ventricular fibrillation

Alpha Blockers

• Significant effect on the heart function and circulatory system activity
• Alpha receptors normally promote constriction of the arterioles
• Blocking constriction promotes dilation of vessels and lowers blood pressure as well as reducing the heart work in some situations.
• Alpha-blocking drugs also inhibit the actions of one of the adrenal hormones, norepinephrine, that raise blood pressure as part of the fight-or-flight response.
• Generic names (trade names): doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin)
• Effects: Lower high blood pressure and may reduce the heart workload in heart failure.
• Possible side effects:
  • Orthostatic hypotension: Drop in blood pressure when a person stands up abruptly
  • Dizziness and fainting may occur.

Vancomycin

• Example: Vancomycin HCl
• Glycopeptide - effective against gram (+) cocci and bacilli
• Supplemental therapy with cyclosporine and tacrolimus
• Decreases renal allograft rejection
• Half Life: 17hrs

Leflunamide

• Inhibits lymphocyte proliferation
• For the treatment of rheumatoid arthritis

Anti-Neoplastic

• Drugs to prevent/inhibit the development of neoplasm or tumor
• Therapeutic monitoring is not readily aided by therapeutic monitoring because the correlation between the plasma concentration and therapeutic benefits is hard to establish.
  • Varies according to the type of neoplasm the patient has.

Methotrexate

• Example: Otrexup, Rasuvo
• Also an immunosuppressive agent
• Inhibits DNA synthesis in all cells by blocking dihydrofolate reductase
• Leucovorin is used to reverse action of methotrexate
  • Methotrexate dose followed by Leucovorin because the neoplastic cell proliferate rapidly.
    • The DNA synthesis will be most affecting the anti-neoplastic cell and after inhibition of DNA synthesis, we will be reversing the action thru Leucovorin
• Half Life: 5-9hrs
• Therapeutic range for trough specimen: 20 mg/ml
• Adverse Effects: Insomnia, tachycardia, seizures, arrhythmias, cardiorespiratory arrest

Phenytoin

• Example: Dilantin
• Anticonvulsant drug that is effective against generalized tonic-clonic seizures
• Works by suppressing repetitive neuronal firing (mainly in the motor cortex of the brain) through blocking sodium channels and reducing calcium influx
  • Also works by blocking the release of excitatory neurotransmitters in synapses
• It stabilizes the neuronal membrane by inhibiting the repetitive firing of neurons, which leads to a decrease in the amplitude and frequency of action potentials.
  • This helps to prevent seizures by reducing the likelihood of synchronized neuronal activity
• Also known to have antidepressant effects.
• Half Life: 12 - 42 hours
• Not fully absorbed from the GIT
  • IV administered

Neuroleptics (Antipsychotic Major Tranquilizer)

• Examples: Risperdal, Olonzapine ( Zyprexa), Quetiapine ( seroquel), Aripiprazole (abilify)
• Block the action of dopamine and serotonin in the limbic system.
• 2 classes:
  • Phenothiazines (chlorpromazine)
  • Butyrophenones (haloperidol)
• Toxic effects: cholestasis, orthostatic hypotension, aplastic anemia, muscle rigidity

Sample Collection

• Serum or plasma – specimen of choice
• Timing of specimen collection: Single most important factor in TDM
• Trough concentrations: Drawn right before the next dose.

Explore the Bicarbonate-Carbonic Acid Buffer System, which is the principal buffer system in mammalian blood. This quiz covers how acids combine with bicarbonates and the roles of carbonic acid in regulating blood pH levels. Test your understanding of these essential biochemical processes.