Overactive bladder drugs

Overactive Bladder/Urinary Retention

• Overactive bladder, enuresis, and neurogenic bladder may be treated with oxybutynin, tolterodine, and darifenacin.
• Oxybutynin, tolterodine, darifenacin decrease intravesicular pressure, increase capacity, reduce bladder contractions, and decrease frequency
• Older adults exhibit increased sensitivity to antimuscarinic drug effects due to pharmacokinetic changes, increased BBB permeability, and reduced cholinergic neurotransmission.
• Cholinergic pathways from the basal forebrain to the hippocampus and cerebral cortex are crucial for cognition, and potent antimuscarinic drugs can negatively impact delayed recall.
• Mirabegron, a B3-adrenergic agonist, can be used as a second-line treatment for overactive bladder/incontinence, taking 4-8 weeks for efficacy.
• Mirabegron is contraindicated with creatinine clearance <15ml/min, ESRD, hepatic impairment, and uncontrolled HTN.
• Vibegron, is another ẞ3-selective adrenergic receptor agonist

OXYBUTYNIN (DITROPAN, DITROPAN XL), SOLIFENACIN (VESICARE), TOLTERODINE (DETROL, DETROL LA), Trospium (Sanctura)

• These medications work by blocking muscarinic receptors, which reduces uninhibited detrusor muscle contractions, thereby reducing irritative voiding symptoms
• Common side effects include dry mouth, constipation, tachycardia, and blurred vision.
• ADR: May cause acute urinary retention in patients with poor detrusor contractility
• ALWAYS CHECK A POST VOID RESIDUAL, URINE SHOULD BE LESS THAN 150 ML

Alzheimer's/Dementia

• Alzheimer's Disease aims to maintain and maximize the patient's functional ability and independence
• Donepezil (Aricept) is a reversible cholinesterase inhibitor, increasing intra-synaptic levels of acetylcholine to alleviate Alzheimer's cholinergic symptoms
• Donepezil readily crosses the BBB, resulting in 7-fold higher concentration in the CNS compared to plasma
• Indications: mild to moderate Alzheimer's disease, produces a small improvement in cognition and daily activities
• Lack of response in some patients may result from the loss of pre-synaptic release of acetylcholine, due to disease progression
• Common side effects include nausea, vomiting, diarrhea, abdominal pain, and anorexia, Cardiovascular bradycardia
• Approximately 20% of patients experience cholinergic side effects at typical doses of Donepezil
• Rivastigmine is a reversible cholinesterase inhibitor, it is orally effective but twice daily

Rivastigmine (Exelon)

• Used to treat mild to moderate Alzheimer's disease, Parkinson's disease dementia
• Has fewer side effects when adminsitered via a transdermal patch (3-times less nausea & vomiting)
• Is cleared renally
• Memantine Drug Class: NMDA receptor/channel antagonist
• MOA: that block of NMDA receptor/channels may be neuroprotective by reducing excessive (pathologic) glutamate-induced excitotoxicity.

Memantine (Namenda)

• Used to treat moderate-severe Alzheimer's disease only: reduces rate of clinical deterioration
• Side Effects: mild headache or dizziness.
• Excreted in the kidneys, dose reduction advised in renal impairment.

Migraine Management

• Acute migraine first-line medications: NSAIDs (acetylsalicylic acid, ibuprofen or diclofenac potassium)
• Second-line medication Triptans: combine with fast-acting NSAIDs when triptans provide insufficient pain relief
• Third-line medications: Ditans and Gepants
• Recommended preventative treatments: beta blockers, topiramate, and candesartan
• Avoid preventive treatments in women who are pregnant or breastfeeding

5HT1B/1D Receptor Agonists: The Triptans

• Triptans are effective in the acute treatment of migraine (with or without aura) but use for migraine prophylaxis is not intended.
• Treatment should begin as soon as possible after the onset of a migraine attack
• Oral dosage forms of the triptans are the most convenient to use.
• Triptans can cause paresthesias, asthenia and fatigue, flushing, feelings of pressure, tightness, or pain in the chest, neck, and jaw; drowsiness; dizziness; nausea; and sweating and can cause serotonin syndrome
• Triptans: contraindications
• Contraindicated with a history of ischemic or vasospastic CAD (including history of stroke or TIAs), cerebrovascular or peripheral vascular disease, hemiplegic or basilar migraines, or ischemic bowel diseases.

Ergot Alkaloids

• Ergot is the product of a fungus (Claviceps purpurea) that grows on rye and other grains.
• Used only to treat severe, throbbing headaches like migraine and cluster headaches
• Side effects include:Nausea and vomiting, Dizziness, Numbness and tingling, High blood pressure, Slow or fast heartbeat
• Triptans start to work faster than ergot alkaloids and cause fewer side effects. But their pain relief effects don't last as long.

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist

• Can be divided into monoclonal antibodies and non-peptide small molecules, also known as gepants
• Most common side effect of Galcanezumab (Emgality), erenumab (Aimovig) and fremanuzumab (Ajovy): hypersensitivity
• Atogepant is dosed at 10 mg daily in patients with severe and end-stage renal disease
• Adverse effects reported during the clinical studies of atogepant include constipation, nausea, fatigue, weight loss, and decreased appetite

BOTOX (Botulinum Toxin A) (Migraines)

• BOTOX Cosmetic produces partial chemical denervation of the muscle resulting in a localized reduction in muscle activity muscle may also atrophy
• The botulinum toxins bind to cholinergic neurons, enter the cell, and cleave SNARE proteins, thereby inhibiting vesicular release of ACh.

Topiramate (Topamax)

• Used to manage and treat epilepsy and migraine, and it is in the second-generation anti-epileptic drugs class of drugs. Used for chronic weight management for individuals with a BMI > 30.
• MOA: blocks voltage-gated sodium channels, enhancing GABA (A) receptor activity, and reducing membrane depolarization by AMPA/Kainate receptors:
• Common Side Effects: tiredness, fatigue, weight loss, nervousness
• Kidney Issues: Potential for kidney stones and monitor creatinine and bicarbonate used for neuropathic pain, psychotropic drug-induced weight gain, alcohol use disorders

Seizures

• If the therapeutic goal is not achieved with monotherapy, a second anti-seizure drug, preferably with a different MOA, can be added, or a switch made.
• Measurement of drug concentrations in plasma facilitates optimizing antiseizure medication, especially when therapy is initiated, after dosage adjustments, in the event of therapeutic failure, when toxic effects appear, or when multiple-drug therapy is instituted.
• General adverse effects: fatigue, ataxia, diplopia, SIADH, rash, GI upset, confusion and prolonged use can cause decreased BMD and ViD deficiency.

Anti-Seizure Meds (general MOA)

• ASD's act by modulating sodium, potassium, or calcium ion channels or by enhancing y-aminobutyric acid (GABA) neurotransmission
• Additional actions include modulation of synaptic release and diminishing synaptic excitation mediated by ionotropic glutamate receptors
• MOA: Blocks Na+ channels. Increases GABA-mediated inhibition. Decreases Ca2+ influx.
• Adverse effects are based mostly on levels/concentrations of medication

Hydantoins: Phenytoin (Dilantin)

• Stabilizes neuronal membrane by either increasing efflux or decreasing the influx of Na+ *Must replace folic acid with Second-or third-degree AV block or Sinoatrial block
• Exerts antiseizure activity without causing general depression of the CNS
• Side effects based on plasma concentrations (less than 10 mg/L --> Rare side effects, 10-20 mg/L --> Occasional mild horizontal nystagmus on lateral gaze, twenty to 30 mg/L --> Nystagmus, Thirty to 40 mg/L --> Ataxia, slurred speech, tremor, nausea, and vomiting, etc...)

More specific Anti Seizure Med Details

• Benzodiazepines, indications: seizure disorders - absence seizures, akinetic seizures status epilepticus (e.g. lorazepam) clonazepam and clorazepate -long-term treatment of certain types of seizures.
• Flumazenil antagonizes the actions of benzodiazepines and It can wear off before the benzodiazepine it is reversing!
• Valproate, a medication of the Carboxylic acid derivatives class has a Black Box warning of Hepatotoxicity, teratogenicity, and pancreatitis

Anxiety

• Tx depends on patient’s type of anxiety and whether immediate relief is important
• 1st line for chronic anxiety are SSRI’s, SNRI’s , and buspirone
• for situational relief is Beta- adrenergic antagonists

Selective Serotonin Reuptake Inhibitor (SSRI)

• Drug class to drug: Venlafaxine, Desvenlafaxine, Duloxetine, levomilnaciopran, milnacipcan
• Side effects can be nausea, constipation , headache, and weight gain

Atypical Antidepressant

• Serotonin (5HT), Norepinephrine are effected
• Mechanism of Action is Inhibit serotonin transporter (SERT) and norepinephrine transporter (NET) leading to enhanced serotonergicnoradrenergic neurotransmission
• Medication- Trazodone

Lithium

• May interact with ACEIS, ARBS, and diuretics (increases levels)
• Side effects: tremors, seizures and cognitive impairments and Renals effects may occur
• Key Actions: can lead to to lithium lowering and decreased suidality and neuroprotective

Treatment/Management

• Acute Psychotic: (transient symptoms), Low of Anti psychotic is preferred to reduce side effects because there are not FDA APPROVE for those types of situations
• Longterm: Clozapine can treat but there is significant advance effect (schrizophenia ex) -Anticholinergic effects may worsen delirium and/or dementia

Monoamines and their effects:

• Acetylcholine- Muscle control, memory formation, memory formation, excitatory.
• Dopomine- Reward pathways, cognition, voluntary motion- Imbalances with release and reuptake of stimulants
• Histamine- Wakefullness temperature, -

Dopamine

• Dopamine -Controls motivation, pleasure, and motor function -Deficiancy is linked to oarkison but overactivity is linked with schrizophenia

Nerepinephrine

• Regulates autonomoic nervous system functions includin BP, Alertesss - Beta Blockers reudce Hyptertension are example
• H1 receptors - Sedation an weight gain
• Beta Blockers -Propanolol

ADHD

• 1st line treatment- stimulants (addreall)
• methylphenydrate- a mild stimulant- helps you regulate/ focus
• children - can’t take
• adults - first line
• don’t give a person with glaucoma because of the hypertensive crisis and can see with anxiety in generad
• Monitor growth rate- it’s on slides- what you watch in chart and other important med points for exams
• Monitor for anxiety- what else we concerned for
• Side effects- nervousness insomnia, anorexia, etc
• Cautions- children not growing may need a break at least but there are a high potential of getting abuse
• Anotomoxine (Strattera)Key Paiteint Councilign Points- Avouid activities requiring , grow rate