Overactive Bladder Treatment

Overactive Bladder/Urinary Retention

• First line treatment includes oxybutynin, tolterodine, and darifenacin
• These medications decrease intravesicular pressure, increase capacity, and reduce bladder contractions and frequency
• Effective for overactive bladder, enuresis, and neurogenic bladder

Geriatric Considerations:

• Antimuscarinics treat overactive bladder
• First-generation antihistamines treat seasonal allergies
• Antidepressants & atypical antipsychotics treat depression
• Older adults are more sensitive to antimuscarinic drugs due to changes in pharmacokinetics, increased blood-brain barrier permeability, and reduced cholinergic neurotransmission
• Even single doses of potent antimuscarinics can affect delayed recall and hippocampal brain volume

Β3-Adrenergic Agonist

• Mirabegron is administered orally at 25-50 mg daily
• Mirabegron MOA causes detrusor muscle relaxation during the storage phase, reducing irritative voiding symptoms and incontinence episodes
• It's a second-line option for overactive bladder/incontinence
• Efficacy occurs in 4-8 weeks
• Contraindicated with creatinine clearance less than 15ml/min, ESRD, hepatic impairment, uncontrolled HTN
• Watch out for urinary retention and elevated BP
• Other beta3-selective adrenergic receptor agonists include vibegron

Other Overactive bladder Medications

• Medications: Oxybutynin, Solifenacin, tolterodine and Trospium block muscarinic receptors, reducing uninhibited detrusor muscle contractions and irritative voiding symptoms
• Side effects: dry mouth, constipation, tachycardia, blurred vision
• Adverse drug reaction: Acute urinary retention can occur if poor detrusor contractility is present
• In all individuals, it's essential to ensure that the post-void residual urine volume remains below 150 mL.
• Consider this if they also are on an antihistamine, due to increased drying effects

Alzheimer's/Dementia

• Aim is to sustain and optimize functional capabilities and independence
• Donepezil reverses cholinesterase, enhancing acetylcholine duration in synapses

Donepezil Details

• It readily penetrates the blood-brain barrier, yielding a 7-fold greater concentration in the central nervous system than in plasma
• Used for mild to moderate Alzheimer's
• Can lead to minor enhancements in cognition and everyday tasks
• Some patients don't respond because they lack pre-synaptic acetylcholine release as the illness advances
• Common adverse effects are nausea, vomiting, diarrhea, abdominal pain, anorexia, and bradycardia
• Cholinergic side effects occur in about 20% of those on typical doses

Alzheimer's Disease- Cholinesterase Inhibitors

• Aricept response is variable, with 30-50% showing no benefit and 20% showing above-average results
• Alzheimer's is linked to a deficiency of cholinergic neurons, especially ones that extend from subcortical parts such as the nucleus basalis
• Donepezil is typically taken at a 5-mg dose daily, which is increased to 10 mg for moderate conditions if tolerated.
• Rivastigmine is a carbamylating medication that has both oral and skin application options
• Galantamine is another AChE inhibitor
• AEs- Nasopharyngitis, diarrhea, nausea, and vomiting

Rivastigmine (Exelon)

• It's a slower-acting carbamate version that inhibits acetylcholinesterase
• Used to treat mild to moderate Alzheimer's, Parkinson's disease, and Lewy bodies
• AEs- Cholinergic side effects, nausea, diarrhea, anorexia, wt. Loss

Namenda MOA

• NMDA receptor/channel antagonist that decreases extra-synaptic receptors
• NMDA receptor/channels may safeguard nerves by preventing excessive glutamate-induced excitotoxicity
• Indications: Moderate to severe Alzheimer's
• Generates a small effect to reduce the progression of the disease
• Does not appear to be helpful for the slight kind of Alzheimer's
• Adverse effects include mild headache or dizziness, kidneys excrete the drug, and dosages must be lowered for those with serious kidney issues

Migraine First Line

• First-line treatments involve NSAIDs
• Second-line treatments involve Triptans
• Third-line treatments involve Ditans and Gepants

Adjunct medications for N/V

• Prokinetic antiemetics offer relief such as domperidone or metoclopramide

Preventative tx for migraine

• For individuals affected for 2 or more days a month
• First line: Beta blockers like propranolol, topiramate, and candesartan
• Second line: Flunarizine, amitriptyline, and sodium valproate
• Third line: CGRP monoclonal antibodies

Managing migraine in older people

• Comorbidities + secondary headaches occur due to adverse events

Managing migraine in children

• Consider bed rest, ibuprofen for tx and propranolol, amitriptyline, and topiramate for prevention

Managing migraine in pregnant/breastfeeding woman

• paracetamol for acute treatment, if possible, avoid preventive treatment

Ergot Alkaliods

• Ergot is a product of a fungus (Claviceps purpurea) that grows on rye and other grains
• Pharmacological effects occur due to effects as partial agonists or antagonists of serotonergic, dopaminergic, and adreneric receptors
• Ergotamine and dihydroergotamine are headache medicines
• Used only for intense headaches like migraines

Ergot side effects

• Nausea, dizzy, abnormal heartbeat and muscle pain

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist

• Monoclonal antibodies and non-peptide small molecules
• Emerging therapeutic class for acute and preventative migraine treatment
• Most common side effect hypersensitivity at infection sites
• High % of patients probably experience unrelated side effects

CGRP Atogepant side effects

• Constipation, nausea, fatigue, wt. Loss
• It can be used in patients in Renal failure

BOTOX (Botulinum Toxin A) Mechanism of Action

• Blocks the delivery by binding AND entering motor nerve terminals while preventing the release of acetylcholine

BOTOX EFFECTS

• Peripheral acting and antispasmodic
• Inhibit the SNARE proteins, inhibiting the releaSe of ACh

Topiramate (Topamax)

• Second-gen anti-epileptic drug to treat epilepsy and migraines, BMI higher than 30
• Blocks gated sodium channels, decreases excitability
• Decreases membrane depolarization

Topiramate side effects

• Somnolence, fatigue, weight loss, and nervousness occurs as well as kidney stones
• Kidney tests
• Off label for neuropathic pain, ETOH withdrawal and HA

Seizures

• Review questions about
• Wellbutrin depression
• Goal: seizure freedom with minimum amount of side effects

Seizures Therapeutic Goal

• If monoTx isn't therapeutic, 2nd-generation, with new MOA, must be added to plan
• Tx is epilepsy-specific
• Need the right # and doses until seizures are better, OR adverse
• Draw on drug for selection, medication AND patient
• Plasma measurements facilitate optimized
• BUT, impact of those medications DOES influence clinical AND recommended guidelines
• Condition checkup immediately after increasing the level

Major Classes

• Hydantoins
• Carbamazides
• Sultonamides

Action of Anti Seizures

• Includes modulation AND action on GABAa receptors
• Inhibitors include levetiracetam, topiramate, licosamide, phenytoin, valproic acid, and zonisamide against focal seizures
• It can be limited to a neuron's ability to fire

Phenytoin (Dilantin) Effects

• Stabilizes membrane
• Antiseizure DOES effect CNS depression!

Dilantin Use

• Can help focal AND all types of seizures except absence/ trigeminal neuralgia EXCEPT for those with slow rhythm
• BBW and has lots of receptors AND either great OR bad
• Low effect with 10mg/L , mild horizontal nystagmitis
• Check labs, preg AND dentistry + Dextro Scan

Benzodiazepines

• Trade name endings with pam + lam
• Gaba mediated and receptor b/w subunits

Benzodiazepines use and Actions

• Includes seizures AND treating absence
• Long-term use AND treatment + seizures
• Diaze and loraze both have roles in seizures
• Pk- Many Benzes have long lives
• ALL have anti anxiety and sedating properties

Flumazenil

• Benzodiazepine action antagonist

Topiramate effects

• Reduces seizure and has kidney effects

Levetiracetam/ keppra/

• To treat all aspects of seizures
• Monitoring baseline and cretan
• S/S: Depression and psychosis

##Valproate

• BBW:Hepato/terato pancreatitis
• S/S: tremors/ Sedations
• Esp checks, esp. benxos

Anxiety drugs

• SSRis, NRIS, all for long term use
• Benzodiazepine + short term

Antipsychotics

• Target all 3, but with dopamine at best.