Manual of Equine Anesthesia and Analgesia. Группа авторов
hypotension via antagonism of alpha1‐adrenergic receptors.
Antagonize dopamine receptors, which can prevent dopamine‐induced increases in RBF.
Benzodiazepines
Little effect on RBF or GFR.
Opioids
Little effect on RBF or GFR.
In some species, morphine increases the release of ADH resulting in an inhibition of diuresis, and this is accompanied by an increase in chloride excretion.
NMDA antagonists
Increase RBF and renal vascular resistance.
As the dose increases, renal sympathetic nerve activity increases. This decreases RBF while increasing renal vascular resistance.
Ketamine can inhibit dopamine transporter proteins in the kidney but the clinical significance is uncertain.
Ketamine and its metabolites are highly dependent on renal excretion.
Propofol
Minimal effects on RBF or GFR.
E Intermittent positive pressure ventilation
Increases in intrathoracic pressure reduce venous return. This decreases right and left ventricular preload.Cardiac output decreases as a result.The effect on cardiac output is more pronounced in hypovolemic patients.
Baroreceptors become activated, initiating a cascade of neurohormonal mechanisms to stimulate the kidney to decrease GFR and increase tubular reabsorption.
Other mechanisms involved are:Release of ADH.Stimulation of the RAAS.Stimulation of the sympathetic nervous system.Inhibition of tonic vagal influences.
This results in decreased urine volume, decreased renal plasma flow, and retention of sodium and water.
F Stress
Stress associated with anesthesia and surgery can result in the release of catecholamines, aldosterone, ADH, and renin.
This results in decreased RBF and GFR, leading to fluid retention.
These effects resolve over time after anesthesia.
V Diuretics
There are several different classes of diuretics with different mechanisms of action, ultimately resulting in increased urine production.
See Table 5.1 for a summary of the diuretic classes.
Table 5.1 Site and mechanism of action of diuretics.
| Diuretic Class | Examples | Site of Action | Mechanism of Action |
|---|---|---|---|
| Osmotic diuretics | Mannitol | PCT | Inhibits Na+ and water reabsorption |
| Carbonic anhydrase inhibitors | Acetazolamide | PCT | Inhibits activity of carbonic anhydrase |
| Loop diuretics | Furosemide | Thick ascending limb of LOH | Inhibits Na+‐K+‐Cl− cotransporter |
| Thiazide diuretics | Hydrochlorothiazide | DCT | Inhibits Na+‐Cl− cotransporter |
| Potassium sparing diuretics – Aldosterone inhibitors | Spironolactone | Collecting duct | Inhibits aldosterone receptor |
| Potassium sparing diuretics – Sodium channel blockers | Amiloride | DCT | Inhibits Na+ channel |
PCT – Proximal convoluted tubule.
LOH – Loop of Henle.
DCT – Distal convoluted tubule.
A Osmotic diuretics (e.g. mannitol)
Inhibit water and sodium reabsorption predominantly at the PCT with some effects on the descending LOH and collecting duct.
Expand extracellular fluid and plasma volume, increasing RBF.This will lead to medullary washout and an inability to concentrate urine.
They are filtered through the glomerulus and increase osmotic pressure in the tubule. This reduces transmembrane water flow.
Note: glucosuria will also induce an osmotic diuresis.
B Carbonic anhydrase inhibitors (e.g. acetazolamide)
Acetazolamide is highly protein bound and is not filtered by the glomerulus.It is secreted by the proximal tubule.Secretion is GFR dependent.
It inhibits the activity of membrane and cytoplasmic carbonic anhydrase in the PCT, preventing reabsorption of bicarbonate. This results in decreased activity of the Na+/H+ exchanger, causing more sodium to remain in the filtrate.
Increases renal excretion of Na+, K+, HCO3−.
Results in a proximal renal tubular acidosis.
Can cause metabolic acidosis.Hence, its potential use as a treatment for metabolic alkalosis.
Other clinical uses of acetazolamide include glaucoma and neurologic disorders.
In equine practice, their main use is in horses likely to be affected by a hyperkalemic periodic paralysis (HYPP) episode.
Use in potential HYPP episodes: (see HYPP Chapter 38)
Acetazolamide may be administered to horses prone to develop HYPP in order to increase potassium excretion prior to an anesthetic event, for example. It is generally recommended that acetazolamide be administered for a minimum of two days prior to anesthesia.
C Loop diuretics (e.g. furosemide)
Furosemide is the most commonly used diuretic in horses.
Furosemide inhibits the Na+‐K+‐Cl− cotransporter in the luminal membrane of the thick ascending limb of the LOH.It binds specifically and reversibly to the Cl− binding site of the transporter's transmembrane domain.
Because this transporter reabsorbs about 25% of