Module 7 CNS Lecture Notes PDF

Module 7: CNS Lecture Notes Anticholinergic E8ects: >drugs that antagonize acetylcholine (chief neurotransmitter) >inhibit transmission of parasympathetic nerve impulses *dry mouth, blurred vision, constipation, drowsiness, trouble urinating, tachycardia (antidepressa...

Module 7: CNS Lecture Notes Anticholinergic E8ects: >drugs that antagonize acetylcholine (chief neurotransmitter) >inhibit transmission of parasympathetic nerve impulses *dry mouth, blurred vision, constipation, drowsiness, trouble urinating, tachycardia (antidepressants, antipsychotics, drugs for insomnia) Prescribing principles: >Consider a patients total anticholinergic burden >Educate about OTC drugs that have an anticholinergic eAect Neurotransmitters: >Norepinephrine: *primary neurotransmitter *CNS and parasympathetic nervous system *causes increase in BP (SNRIs) >Dopamine >Acetylcholine >Serotonin: *within the enteric nervous system (digestive and CNS) *plays a role in vasoconstriction, inhibition of gastric secretion, and stimulation of smooth muscle contraction *brain: aAect mood, appetite, temperature regulation, and sleep >GABA >Glutamate Antidepressants: (SSRIs, SNRIs, TCAs, MAOIs, Atypical) >SSRIs: (increases circulation of serotonin) *inhibits CNS neuron reuptake of serotonin (minimal eAect on reuptake of NE or dopamine) *Paroxetine (Paxil: FDA approved 1992), Citalopram (Celexa), Fluoxetine (Prozac), Sertraline (Zoloft) >SNRIs: (increases the circulation of serotonin AND NE) *inhibits neuronal reuptake of serotonin and norepinephrine (weak inhibitor of dopamine reuptake) *Venlafaxine (EAexor: FDA approved 1993), Desvenlafaxine SR (Pristiq), Duloxetine (Cymbalta) Why are SSRIs and SNRIs e8ective – Depression/Anxiety: >Serotonin: *function- includes regulation of mood and aggression >NE: *function- alertness and focus >Symptom relief approx. 4 weeks – varies SSRI-SNRI: >Take several weeks before pt feels therapeutic eAect *may require adjunct therapy >Similar SE and AE *r/t increase in serotonin at specific serotonin receptor subtypes *aAect on other hormones (testosterone and dopamine) **Sexual dysfunction; may last for months – often not reported *insomnia *weight loss initially and then weight gain Safety Considerations SSRI SNRI Paroxetine (Paxil) Venlafaxine (EAexor) Pregnancy- Adverse eAect in the newborn Adverse eAects: *Educate about contraception and when planning Venlafaxine (EAexor) - HTN or become pregnant >switch to a safer option >if unplanned pregnancy – discontinue QT prolongation Both: transient – GI disturbances, nausea, bowel changes, HA, fatigue, agitation SSRI – SRNI (Safety Considerations) >Both: serotonin syndrome; increased with MAOIs >Serotonin syndrome – rare but serious *confusion, agitation, clonus, fever, tremor, hyperreflexia, respiratory failure, and death *BBW: antidepressants increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor for clinical worsening or suicidal thoughts and behaviors >Adverse EAects: *abrupt discontinuation – withdrawal symptoms (somatic and psychological) **electric shock to the brain – transient – may be related to the lower serotonin levels *activations of mania or hypomania **Avoid antidepressants as monotherapy – pts with bipolar disorder SSRI and SNRI – Special Populations >Sertraline (Zoloft) is one of the safest to use both in pregnancy and breastfeeding >Paroxetine (Paxil): slight increase in congenital cardiac malformations during the first trimester – newborn persistent pulmonary hypertension if taken in the third trimester >Elderly: (antidepressants may require dose reduction >65 years) *possibility of clinical adverse events: **cardiovascular, CNS, falls, fractures Bupropion (Wellbutrin) Trazodone Norepinephrine and Dopamine Reuptake Serotonin Modulator Inhibitors (NDRIs) Benefits: improved focus/concentration, Benefits: improves symptoms in mildly depressed reduction in appetite, less weight gain, increased pts with insomnia libido, and greater motivation/energy *oA label for insomnia: greatest sedative eAect Adverse E8ects: may increase the frequency and Contraindicated with MAOIs and other severity of seizures in pts with known seizure serotonergic drugs disorder (at higher doses D2D interactions with MAOIs Increased risk of suicidal thoughts and behaviors in pediatric and young adults – closely monitor all antidepressant-treated patients for clinical worsening and for emergence of suicidal thoughts and behaviors Antidepressants (pt concerns) >SSRIs and SRNIs *weight gain, sexual dysfunction, sleepiness (transient), insomnia (transient) >Bupropion (Wellbutrin)  *weight gain – less likely when compared to SSRIs and SNRIs *sexual dysfunction – less likely when compared to SSRIs and SRNIs Atypical Antidepressant >Trazadone >Inhibits reuptake of serotonin; blocks histamine1 and aplha1 adrenergic receptors *strong sedative eAects; oA-label sleep agent >Safety Concerns: *daytime grogginess, postural/orthostatic hypotension, bleeding risk – increases with antiplatelets and/or anticoagulants *BBW: increased risk for suicidal thought and behaviors in pediatric and young adults – closely monitor all depressant-treated patients for clinical worsening and for emergence of suicidal thoughts and behaviors Antidepressants Tricyclic Antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Block the reuptake of norepinephrine and Inhibition of the enzyme (monoamine oxidase) serotonin responsible for the breakdown of neurotransmitters (epinephrine, NE, dopamine, and serotonin) Amitriptyline (Elavil – FDA approved 1983) Isocarboxazid (Marplan – FDA approved 1959) Clomipramine (Anafranil) Phenelzine (Nardil) Doxepin (Sinequan) Imipramine (Tofranil) TCAs >May benefit pts with depressive symptoms and trouble sleeping >May benefit people with diAiculty sleeping secondary to neuropathic pain >S/E: Anticholinergic >Safety Issues: *prolonged QT interval *Cardiac dysrhythmias/cardiac toxicity **especially in the event of an overdose >Many D2D Interactions *MAOIs, CNS depressants, sympathomimetics and other anticholinergic drugs MAOIs >Not commonly prescribes in primary care *many adverse eAects **CNS stimulation, orthostatic hypotension, hypertensive crisis – dietary tyramine *D2D interaction **drugs that increase NE (increase BP) **drugs that block serotonin reuptake (increased risk for serotonin syndrome) *Must follow a special diet **excludes fermented or aged products **fermented and aged meat and cheeses, red wine and some fruits and vegetables Antidepressants >Consider eAects that may be beneficial for the patient >A pt with fatigue may benefit from taking a drug that stimulates the CNS (bupropion) >A pt with chronic pain may benefit from a TCA eAective in relieving chronic pain/neuropathic pain >Follow up in a week: peds/adolescents/young adults (when starting antidepressant medication) Depression – initiating pharmacotherapy >Rule out bipolar disorder prior to prescribing any antidepressant – risk of mania *mood disorder questionnaire >Rule out hypothyroidism prior to starting antidepressants More on Antidepressants >When to wean *Do not stop abruptly **withdrawal symptoms **stopping or reducing – reports of electrical sensations (or brain zaps) perceived as occurring inside the brain *Serotonin Syndrome – seen with overdose, D2D interactions, adding other serotonergic drugs >Contraindications: generally do not use with other serotonergic agents or within 14 days of MAOIs *however half-life of drug to be considered Ezketamine (Spravato)* (nasal) N-Methyl-D- Brexanolone (Zulresso) *(2019) (IV) Aspartate (NMDA) Receptor Antagonist Zuranolone (Zurzuvae) *(2023) (oral) Modulator of GABA receptors Depression treatment resistance: Postpartum Depression: *FDA approved 2019 *pregnancy – may cause fetal harm *administered under the direct supervision of a *breastfeeding – seen in breast milk health care provider BBW: Esketamine* BBW: *Sedation and dissociation *Excessive sedation or sudden loss of *Respiratory depression consciousness (during administration) - Zulresso *Abuse and misuse *Impaired ability to drive or engage in other *suicidal thoughts and behaviors potentially hazardous activities - Zurzuvae Anxiety >Generalized: *SSRI (escitalopram (Lexapro)) *SNRI (Venlafaxine (EAexor)) *Benzodiazepine (Lorazepam (Ativan)) *NonBenzo (Buspirone (Buspar)) *Antihistamine (Hydroxyzine (Vistaril)) *BetaBlocker (Propanolol (Inderal) *Herbal (St. John’s Wort) Anxiolytics – Drugs used to reduce anxiety Azapirones (nonbenzo) Benzodiazepines Buspar impacts neurotransmitters in the brain, Binds to specific receptors on the postsynaptic such as serotonin and dopamine. GABA neuron at several sites within the central Specifically, it is a serotonin receptor agonist, nervous system thereby enhancing the which means that it increases action at inhibitory e8ect of GABA serotonin receptors in the brain Buspirone (Buspar) Alprazolam (Xanax), Lorazepam (Ativan), Diazepam (Valium Why are Benzodiazepines indicated – Anxiety >MOA – enhances the inhibitory eAect of GABA >FYI: GABA, an inhibitory neurotransmitter, produces a calming eAect *GABA functions: reduce arousal, aggression, anxiety, and excitation >May be considered in GAD while waiting for the therapeutic eAects of SSRIs and SNRIs >May be used for acute anxiety (short-term) >Avoid in individuals with hx of substance use – misuse of meds Benzodiazepines – Safety considerations >Chronic/long-term use: avoid abrupt withdrawal *taper to reduce acute withdrawal reactions, which can be life-threatening *can also result in seizures >CYP3A inhibitors (itraconazole, ketoconazole) >Acute narrow-angle glaucoma (ophthalmic emergency) *eAect on pupillae muscles >Suppress respiratory drive >BBW: risk from concomitant opioid use; abuse, misuse, addiction, dependence, and withdrawal reactions Benzos – Special Populations >Caution: older adults, alcohol or substance abuse; sleep apnea >Pregnancy: teratogenic eAects have been observed with some benzos *Alprazolam, Lorazepam, Diazepam >Breastfeeding: *risk vs benefits *can accumulate to toxic levels in breastfed infant *lorazepam lower levels in breastmilk – shorter half-life compared to other benzos Azapirones (non-benzo) >Buspirone (Buspar) *increases action at serotonin receptors in your brain – alleviates anxiety **used as adjunct with SRIs or 2nd line if SRIs are not tolerated **known to help relieve adverse sexual eAects of SRIs **not intended for PRN use **no potential for abuse Antihistamine (hydroxyzine) Beta Blocker Herb Anxiolytic eAects – activity at Blocks response from beta- CNS eAects – improves mood, muscarinic serotonergic and adrenergic stimulation resulting decreases anxiety, and somatic dopaminergic receptors in the in decreased HR, myocardial symptoms CNS contractility, BP, and myocardial O2 demands Hydroxyzine (Atarax, Vistaril) Propranolol (Inderal) St. John’s Wort *Performance anxiety disorder (oA-label use) Antihistamine – relive sx of anxiety >Hydroxyzine (Vistaril) >Anxiolytic e8ects – activity at muscarinic serotonergic and dopaminergic receptors in the cns *use: relieve anxiety symptoms > Watch out for anticholinergic eAects: especially in the elderly (BEERS criteria) >Pregnancy: Considered safe for short term treatment of anxiety/insomnia Beta Blocker >Propranolol (Inderal) >Blocks response from beta-adrenergic stimulation (non-selective) B1 and B2 *Use: performance anxiety **controls tremors, sweating, tachycardia, and palpitations when taken about 1 hour prior to event/performance – immediate release tablets *non-sedating **ALTHOUGH it can cause fatigue, some drowsiness, bradycardia, wheezing/bronchospasms, erectile dysfunction >Try out in advance of the event (10-20mg) **should not be taken if pt is already on a beta blocker or has other cardiac issues CAM – Herbs >St. Johns Wort *CNS eAect ** improves mood, decreases anxiety, and somatic symptoms >D2D interactions: SSRIs, other antidepressants, benzos >Oral contraceptive (substrate) – St John’s Wort is a CYP34A inducer *Accelerating the metabolism of oral contraceptives – reducing the eAectiveness of the OC *Barrier method of conception should be added TEST YOUR KNOWLEDGE Which class of drugs are used to treat anxiety disorders (SATA) a. Benzodiazepines b. Stimulants c. CCB (calcium channel blockers) d. SSRIs e. MAOIs Your patient requires more education when they say: a. I may not feel an immediate eAect from my anxiety medication b. OTC herbal medications have no adverse eAects c. OTC medications may interact with other medications Which statement is true about SNRIs? a. Paroxetine (Paxil) may increase BP b. Venlafaxine (EAexor) may increase BP c. Propranolol (Inderal) needs to be used with caution in pts with conduction issues True or False SSRIs and SNRIs are safe when paired with MAOIs False (serotonin syndrome and hypertensive crisis) True or False Paxil is safe to use in pregnancy False (switch to safer option, discontinue if pregnant) Insomnia – Benzodiazepines (Long Acting) >Related to depressant actions in the CNS >Promote sleep & induce muscle relaxation >Estazolam (ProSom); Flurazepam (Dalmane); Temazepam (Restoril) *potentiate the actions of GABA *indicated for short-term use (10 days) *include good sleep-hygiene (pt education) >Special Populations *high risk in elderly pts *Pregnancy **In utero exposure to benzos has the potential to cause harm to the fetus. Teratogenic eAects have been observed in some studies Benzodiazepines – Sedative (Safety) >Estazolam (Prosom); Flurazepam (Dalmane); Temazepam (Restoril) >Azoles (CYP34A inhibitors) >BBW: *risk for concomitant use with opioids *abuse, misuse, and addiction *dependence and withdrawal reactions Insomnia – nonBenzodiazepines >Eszopiclone (Lunesta) (C-IV): for chronic insomnia >Zaleplon (Sonata) (C-IV): short-term treatment >Zolpidem (Ambien) (C-IV): short term treatment *Adjust dose: lower dose for females than males **morning after: higher blood levels in females; impairs activities that require alertness >Safety: *BEERS criteria: inappropriate use in elderly 65 and older *BBW: Complex sleep behaviors, including sleep-walking, sleep driving, and engaging in other activities while not fully awake, may occur following use. Some of these events may result in serious injuries, including death Melatonin (OTC) >Adults 3-5 mg daily in the evening over 4 weeks *Immediate-release melatonin 1 to 2 mg given 1 hour prior to bedtime *May be useful in elderly patients *Pediatric pts useful >Pregnancy/Lactation: *lack of evidence ADHD – Stimulants >Methylphenidate (Ritalin) *usually the first choice *eAective in 75% of children *Common SE: Insomnia, restlessness, decreased appetite (weight loss) *Not to be used with pre-existing heart disease or cardiac symptoms *May lower the seizure threshold >BBW: abuse and dependence ADHD – Non-Stimulant >Atomoxetine (Strattera) (NE reuptake inhibitor) *sleep problems, anxiety, fatigue, upset stomach, dizziness, dry mouth *rare adverse eAects: liver damage * QT prolongation reported *BBW: increased suicidal ideation in children and adolescents >Clonidine (Catapres) – alpha 2A adrenergic agonists *can be used alone or as an adjunct to another ADHD medication *helps impulsivity and hyperactivity, modulating mood level *can help tics, worsened from stimulants and sleep problems *adverse eAects: fatigue, dizziness, dry mouth, irritability, behavior problems, low blood pressure >Antidepressant: Bupropion (Wellbutrin) *ADHD in adults (oA-label) Bipolar Disorder >mood disorder that is characterized by episodes of mania, hypomania, and major depression >mood stabilizing drugs: *antimanic drugs: reduce acute symptoms of mania/hypomania without causing a switch to the opposite polarity **lithium, second generation antipsychotics, antiepileptics >Lithium carbonate (Lithobid): mood stabilizer (antimanic agent) *monitor lithium levels **toxicity can occur at doses close to therapeutic levels *monitor kidney function *D2D interactions: NSAIDs, diuretics, ACEIs, metronidazole *Pregnancy: cardiac malformations during 1st trimester (avoid if possible) *Hypothyroidism with long term use *BBW: Lithium toxicity is closely related to serum lithium levels and can occur at doses close to therapeutic levels Schizophrenia >A chronic psychotic illness *disordered thinking, reduced ability to comprehend >Numerous hypotheses related to the cause *neurotransmitters: dopamine, GABA, acetylcholine >Antipsychotic *2nd generation antipsychotic: *Clozapine (Clozaril): **antagonist of dopaminergic and serotonergic receptors, alpha-adrenergic, histamine h1, and cholinergic **Schizophrenia **oA label: bipolar disorder, treatment resistant *SE/AE: sedation and weight gain, anticholinergic eAects **QT prolongation **risk of HTN and hyperglycemia *Similar 1st generation antipsychotics **sedation – orthostatic hypotension, death in the elderly **less likely to cause EPS *BBW: severe neutropenia (agranulocytosis), seizures, orthostatic hypotension, bradycardia, syncope, increased mortality in elderly patients with dementia-related psychosis Antipsychotic Agents >1st generation antipsychotics *as a class older drugs – varying degress block receptors for dopamine, acetylcholine, histamine and NE *common SE: anticholinergic eAects and sexual dysfunction >Haloperidol (Haldol): Schizophrenia *EPS, QT prolongation, monitor: CBC, electrolytes, heart, and liver function *BBW: increased mortality in elderly with dementia-related psychosis TEST YOUR KNOWLEDGE Which statement is true about antipsychotics? a. 1st line SNRIs (monitor BP) b. 1st generation antipsychotics (monitor CBC, electrolytes, and liver) c. 1st line SSRIs (as a rule monitoring not required) Antiepileptic drugs may also be used to treat bipolar disorders. True or false. True Carbamazepine (Tegretol) Valproic Acid Depakote Lamotrigine (Lamictal) Seizures Seizures Seizures Bipolar disorder Bipolar disorder Bipolar disorder Depression is a concern EAicacy reduces with Oral contraceptive a CYP D2D interactions: carbapenem antibiotics – inducer of Lamictal (reduced *CYP inducer (OC and folic acid) imipenem/cilastatin levels) *grapefruit juice (increase the Increased fetal neural tubes levels of Tegretol) defects BBW: serious dermatologic BBW: risk of pancreatitis, BBW: serious skin rash conditions – TEN and SJS hepatotoxicity, and it is Aplastic anemia and teratogenic agranulocytosis AED – Phenytoin (Dilantin) >use: seizures >Adverse E8ects: ** hepatitis, blood dyscrasias, gingival hyperplasia, suicidal ideation, SJS >Many D2D interactions – CYP involvement >Food: high protein diet may reduce the absorption of Dilantin >Pregnancy: increased risk of congenital malformations >Lactation: do not appear to adversely aAect infant *When discontinuing oral formulation, taper dose gradually; abrupt discontinuance can cause exacerbation of seizures >BBW: cardiovascular risks associated with rapid infusion AEDs Patient Education: >Decreased contraceptive eAects with AEDs *Ideal contraceptive methods are progestin-only **progestin-only pills **progestin-based injections **implants or IUDs TEST YOUR KNOWLEDGE Which of the following statement is true about an AED drug? a. MAOIs should not be taken with a high protein meal b. Dilantin should not be taken with a high protein meal c. MAOIs are safe to take with fermented and aged foods Which of the following statement is true about AEDs? a. Paxil is teratogenic b. Dilantin is teratogenic c. Levodopa avoid high protein meals Alzheimer’s Diseae >Donepezil (Aricept) *Cholinesterase Inhibitors *use: mild to moderate symptoms *AE: cardiac, GI, and weight loss *D2D interactions: **anticholinergic agents **1st generation antihistamines >Memantine (Namenda) *N-Methyl-D-Asparate (NMDA) receptor antagonists *use: moderate to severe *AE: CNS eAects (dizziness) >No cure: Aricept can improve cognition and prolong independent function TEST YOUR KNOWLEDGE What should we expect with drug therapy for patients with Parkinson’s Disease? a. A drastic increase in cognitive function b. Increase in the quality of life c. A continuous increase in symptom management Parkinson’s - **Goal of treatment: enhance quality of life** >Levodopa and Carbidopa (Sinemet) *Levodopa: crosses BBB; Carbidopa: increases the availability of dopamine *reduces symptoms by increasing dopamine synthesis *high protein foods can reduce therapeutic responses >Contraindication: MAOIs (concurrent use – hypertensive crisis), narrow angle glaucoma >AE: hypotension, psychosis >D2D Interactions: antipsychotics, MAOIs, anticholinergics BBWs: >Carbamazepine (Tegretol): Dermatologic reactions Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), aplastic anemia and agranulocytosis >Valproic Acid (Depakote): risk of pancreatitis, hepatotoxicity; teratogenic >Antidepressants: increase the risk of suicidal thoughts and behaviors in pediatric and young adult pts >Benzodiazepines: risk from concomitant opiod use; abuse, misuses, addiction, dependence, and withdrawal >Brexanolone (Zulresso): excessive sedation or sudden loss of consciousness (during administration) >Methylphenidate (Ritalin): abuse and dependence >Atomoxetine (Straterra): ADHD; suicide risk in children and adolescents >Litium: lithium toxicity >Haloperidol (Haldol): antipsychotic; increased mortality with elderly patients >Clozapine (Clozaril): increased risk of death in elderly with dementia related psychosis; severe neutropenia, agranulocytosis, cardiac issues, and seizures Drugs known to prolong the QT Interval: >Chlorpromazine (antipsychotic) >Citalopram (Celexa) – antidepressant (SSRI) >Escitalopram (Lexapro) – antidepressant (SSRI) >Thioridazine – 1st generation antipsychotic >Donepezil (Aricept) >TCAs – antidepressant >Haloperidol (Haldol) – 1st generation antipsychotic >2nd generation antipsychotics >Trazodone (atypical antidepressant) >Clozapine (Clozaril): 2nd generation antipsychotic