Renal Pharmacology & The Urinary System, Pt. 4 Flashcards
What is the sympathetic innervation of micturition? What 2 effects does it have? What does it result in?
hypogastric n with NE on β3 receptors
- relaxation of detrusor muscle
- contraction inner urethral sphincter (α1)
inhibition of micturition
What is the parasympathetic innervation of micturition? What 2 effects does it have? What does it result in?
pelvic n with ACh on M3 receptors
- contraction of detrusor muscle
- relaxation of inner urethral sphincter
activation of micturition
What is the somatic innervation of micturition? What effect does it have? What does it result in?
pudendal n with ACh on N receptors
contraction of external urethral sphincter
continence
What are the 5 steps to micturition?
- progressive filling of bladder causes the bladder wall to stretch
- when tension rises above the threshold, sensory signals will reach the spinal cord and from there the micturition center (pons) and to the thalamus
- from the thalamus, signals reach the cerebral cortex to become aware of bladder distension and discomfort
- pelvic nerve causes detrusor to contract and the urethra to relax
- internal and external sphincter open and urine exits the body
What are the 4 major micturition disorders? What does treatment target?
- hypotonic urethra
- hypertonic urethra
- hypocontractile bladder
- hypercontractile bladder
end organ receptors (postganglionic receptors)
What is the most common cause of hypocontracile bladder? What are some other causes?
atonic bladder caused by sacral or suprasacral neurologic lesions
- acute/chronic overdistention of the bladder
- general muscle weakness
- dysautonomia
What drug class is the main treatment for hypocontractile bladder? What drug is the first choice?
parasympathomimetic drugs
Bethanechol
What are common adverse reactions of Bethanechol? In what cases is use contraindicated?
parasympathetic signs - hypersalivation, defecation, increased GI motility (cramping)
- urinary and GI obstruction
- ulcerative GI disease
What are some common causes of hypercontractile bladder? What does it result in?
congenital, inflammatory, masses, neurologic disorders, idiopathic
failure in the bladder’s filling capacity causing involuntary bladder contractions to occur at low pressures/volumes and incontinence
What is the main drug class used to treat hypercontractile bladder? What drug is used?
anticholinergic drugs
Oxybutynin - antispasmodic and local anesthetic action
What are common adverse effects of Oxybutynin? In what cases is use contraindicated?
sedation, urine retention, vomiting, diarrhea
- glaucoma
- cardiac disease
- GI obstruction
What is a secondary drug class used to treat hypercontractile bladder? What drug is used?
tricyclic antidepressants
Imipramine - anticholinergic and adrenergic that facilitates urine storage by blocking NE and EPI reuptake
What are common adverse effects of Imipramine?
- tremors
- seizures
- tachycardia
- excitability
In what animals is hypotonic urethra common? What does treatment include?
middle-aged, early neutered/spayed, medium- to large-breed dogs (German Shepherd, Doberman, Pinschers, Old English Sheepdogs, Springer Spaniels, Boxers, Rottweilers, Weimeraners, Irish Setters)
hormone supplementation causing adrenergic receptor upregulation via reproductive hormones in the lower urinary tract, maintaining mucosal integrity, collagen fiber content, blood supply enhancement by estrogen
What reproductive hormones are used to treat hypotonic urethra? What other hormone can also be used?
- diethystilbestrol (DES), silbestrol, estriol
- testosterone propionate
gonadotropin-releasing hormone (GnRH) analogs - deslorelin, buserelin
What adverse signs are associated with estrogen hormone therapy for hypotonic urethra?
- signs of estrus
- bone marrow suppression (check blood count)
- pyometra
- behavioral changes
What adverse effects are associated with testosterone hormone therapy for hypotonic urethra?
- aggression
- behavioral changes, like humping
- prostatic disease
- perianal issues - hernia
How do GnRH analogs treat hypotonic urethra?
re-establishes negative feedback that causes the production of sex hormones
What hormonal drug being tested in women may be able to treat hypotonic urethra? What are some possible adverse effects?
Duloxetine, a serotinin and NE reuptake inhibitor
- nausea
- fatigue
- insomnia
- constipation
- diarrhea
- headache
What sympathomimetic drugs are used to treat hypotonic ureter? How do they work?
alpha-adrenergic agonists - Phenylpropanolamine, Ephedrine
enhances urethral closure via endogenous NE release and alpha receptor stimulation in blader neck and urethra
What adverse effects are associated with Phenylpropanolamine and Ephedrine treatment for hypotonic urethra? When is used contraindicated?
- tachycardia
- hypertension
- restlessness
- anorexia
cardiac/hypertensive patients, renal disease, diabetes mellitus
What is hypertonic urethra? What are the 2 major treatments?
inappropriate urethral resistance caused by obstructions, leading to inflammation, spasms, and then urine retention
- alpha-adrenergic antagonists
- striated muscle relaxants
What is the first choice for treating hypertonic urethra? What adverse effects are associated? In what animals is it not used?
alpha-adrenergic antagonists, Phenoxybenzamine and Prazosin, to decrease muscle tone
hypotension, GI upset, tachycardia
rats - phenoxybenzamine is potentially carcinogenic
In what 4 cases is alpha-adrenergic antagonist usage contraindicated?
- glaucoma
- cardiac disease
- diabetes mellitus
- renal failure
In what 2 situations are striated muscle relaxants especially helpful for hypertonic urethra? Which one is most commonly used?
- patients with upper motor neuron lesions
- cats with functional urethral obstructions, since they have more striated muscle in their urethra
Diazepam
What adverse effects are associated with Diazepam usage for hypertonic urethra? When is its use contraindicated?
- sedation
- polyphagia
- paradoxical excitement
- hepatotoxicity
hepatic disease and pregnancy
