Renal and Urinary Disease Pharmacology

Question 1

Aluminum Phosphate/Aluminum carbonate

Answer 1

historically common phosphate-binding drug-decreases phosphate in plasma and increases secretion, overall reduced availability of aluminum products has reduced their use
-ADVERSE EFFECTS:
Generally well-tolerated. Concern in human medicine for CNS toxicity. Currently no evidence for this in veterinary medicine.
Binds, reduces oral bioavailability of some PO drugs: e.g. Tetracyclines, Fluorquinolones

Question 2

Calcium Carbonate

Answer 2

Available as combined calcium carbonate/magnesium carbonate preparation for dogs
-Calcium carbonate is used as a phosphorus binding agent for treating hyperphosphatemia associated with chronic kidney disease and as a calcium supplement in animals with chronic hypocalcemia. It could also be used as an oral antacid but is rarely recommended for this purpose in small animals.

Question 3

What are some adverse affects of Calcium Carbonate?

Answer 3

-ADVERSE EFFECTS
Generally well tolerated. Constipation can occur.
Hypercalcemia is possible, should be monitored, particularly when used with HCTZ diuretics.
Binds, reduces oral bioavailability of some PO drugs: e.g. Tetracyclines, Fluorquinolones

Question 4

Sevelamer

Answer 4

Limited veterinary experience, may be used when aluminum/calcium phosphate binders are not tolerated
-Sevelamer binds phosphorus in the gut; when combined with decreased phosphorus in the diet it can substantially reduce serum phosphorus levels. Sevelamer binds bile acids, which interferes with fat and fat-soluble vitamin absorption. It also reduces serum low-density lipoproteins and total cholesterol.

Question 5

What are sevelamars adverse effects?

Answer 5

ADVERSE EFFECTS
May reduce absorption of certain vitamins, consider vitamin supplementation
Multiple DDIs relating to sevelamer binding and reducing oral bioavailability of other drugs/vitamins

Question 6

Darbepoetin

Answer 6

modified form of human erythropoetin (EPO) with extended half-life Vs. human EPO
injectable preparation, used in dogs and cats

Question 7

What are the adverse effects of darbepoetin?

Answer 7

ADVERSE EFFECTS:
Vomiting/diarrhea, hypertension (~50%), seizures (15% dogs), pyrexia,
PRCA (Pure red cell aplasia) 6-8% in dogs and cats
Injectable preparations

Question 8

Calcitriol

Answer 8

Vitamin D analog (Vitamine D3) that is used in dogs and cats for treatment of hypocalcemia and chronic kidney disease (CKD)

Question 9

What are the adverse effects of calcitriol?

Answer 9

ADVERSE EFFECTS:
Hypercalcemia, hypercalciuria, hyperphosphatemia
Administer on empty stomach to minimize promotion of calcium absorption and risk for hypercalcemia
Injectable, Oral preparations

Question 10

Prazosin

Answer 10

alpha-1 adrenergic antagonist, reduces sympathetic tone to treat functional urethral obstruction in dogs/cats

Question 11

What are the adverse effects of Prazosin?

Answer 11

ADVERSE EFFECTS
Hypotension, use with caution in CKD patients
Lethargy, dizziness
Vomiting/diarrhea/constipation

Question 12

Amitryptaline

Answer 12

tricyclic antidepressant (TCA): inhibits reupdake of serotonin and other neurotransmitters in CNS.
May reduce anxiety in cats with FIC, no direct effect on bladder
-Amitriptyline (and its active metabolite, nortriptyline) is a tricyclic antidepressant (TCA) with a complicated pharmacologic profile that includes blockage of serotonin and norepinephrine reuptake pumps (thereby increasing neurotransmitter concentrations), sedation, and central and peripheral anticholinergic activity

Question 13

What are the adverse effects of Amitryptaline?

Answer 13

ADVERSE EFFECTS:
TCAs have several adverse effects: anticholinergics (xerostomia, tachycardia, urine retention), antihistaminics (sedation). Cardiotoxicity at high doses.
In cats, reduced grooming, weight gain, sedation
Bitter taste
-The most likely adverse effects include sedation and anticholinergic effects; there is risk for serotonin syndrome when amitriptyline is used concurrently with serotonergic drugs.

Question 14

Buspirone

Answer 14

Anti-anxiety agent, azapirone drug class. Agonist at serotonin 5-HT1a receptor
-Buspirone is an anxioselective agent. Thus, unlike benzodiazepines, buspirone does not possess any anticonvulsant or muscle relaxant activity and little sedative or psychomotor impairment activity. Buspirone does not have significant affinity for benzodiazepine receptors and does not affect GABA binding. It appears to act as a partial agonist at serotonin (5-HT1A) receptors and as an agonist/antagonist of dopamine (D2) receptors in the CNS. In neurons, buspirone slows neuronal serotonin depletion.
-

Question 15

What are the adverse effects of Buspirone?

Answer 15

ADVERSE EFFECTS
Generally well tolerated. Mild sedation
Do not use with MAOIs

Question 16

Clomipramine

Answer 16

TCA
-Although the exact mechanism of action of TCAs is not fully understood, it is believed that their most significant effects result from preventing neurotransmitter reuptake at the neuronal membrane. Clomipramine is predominantly an inhibitor of serotonin (5-HT) reuptake, but it also has effects on norepinephrine and possibly other neurotransmitters.

Question 17

What are the adverse effects of Clomipramine?

Answer 17

-similar to amitryptaline
The primary adverse effects reported in dogs are anorexia, emesis, diarrhea, dry mouth, elevation of liver enzymes, and sedation/lethargy/depression. Significant ECG abnormalities were not identified in small studies in dogs25,26 or cats.21 One case of a dog developing pancreatitis after receiving clomipramine has been published.27
Cats have been reported to be more susceptible than dogs to develop adverse effects, including anticholinergic effects (eg, dry mouth, mydriasis, urine retention, constipation), sedation, and diarrhea; this may be the result of slower elimination of the active (desmethyl) metabolite in cats.
Adverse effects reported in birds include ataxia, drowsiness, and regurgitation.
Although therapeutic effects may take several weeks to be seen, adverse effects can occur early in the course of treatment.

Question 18

Fluoxetine

Answer 18

Selective serotonin reuptake inhibitor (SSRI)
-Fluoxetine is a highly selective inhibitor of the presynaptic reuptake of serotonin in the CNS with negligible effects on other neurotransmitters (eg, dopamine, norepinephrine). In dogs and cats, fluoxetine has anxiolytic and anticompulsive effects and may reduce aggressive behaviors by decreasing reactivity.

Question 19

What are the adverse effects of Fluoxetine?

Answer 19

ADVERSE EFFECTS
Generally better tolerated than TCA’s.
Lethargy, decreased appetite (dogs)
Nervousness, anxiety, tremors, anorexia, vomiting

Question 20

Phenylpropanolamine

Answer 20

Sympathomimetic used primarily to treat acquired urethral sphincter hypotonus in spayed dogs
use with caution in dogs with glaucoma, prostatic hypertrophy, hyperthyroidism, diabetes mellitus, cardiovascular disorders, and/or hypertension
NOTE: HUMAN ABUSE POTENTIAL precursor to methamphetamine

Question 21

What are the adverse effects of Phenylpropanolamine?

Answer 21

ADVERSE EFFECTS:

restlessness, irritability, hypertension, anorexia

Question 22

Estriol

Answer 22

• -Short-acting estrogen approved for treating estrogen-responsive urethral sphincter mechanism incompetence (USMI) in ovariohysterectomized female dogs
• -Not dosed by animal’s weight. Dosage should be tapered to the lowest effective dose.
• -Use is contraindicated in male dogs, intact female dogs, dogs less than 1 year of age, pregnant or lactating dogs, dogs that have polyuria and polydipsia (PU/PD), dogs that are pregnant or lactating, or dogs receiving other estrogen medications.

Question 23

What are the adverse effects of Estriol?

Answer 23

ADVERSE EFFECTS
GI: inappetence, vomiting
Endocrine: swollen vulva,
Risk of myelotoxicity low relative to other estrogens