Pharm Focused Review PDF

Pharm Focused Review 1. Dementia o Neurocognitive o Formation of neurofibrillary tangles (hyperphosphorylated Tau proteins) and plaques (B-amyloid or neuritc), cortical atrophy, and neuronal (cholinergic, glutametrgic) destruction and loss. o Alzheimer Disease (AD) - most common type o Slow, progres...

Pharm Focused Review 1. Dementia o Neurocognitive o Formation of neurofibrillary tangles (hyperphosphorylated Tau proteins) and plaques (B-amyloid or neuritc), cortical atrophy, and neuronal (cholinergic, glutametrgic) destruction and loss. o Alzheimer Disease (AD) - most common type o Slow, progressive decline in cognition o CAUSES OF DEMENTIA o Apolipoprotein E (ApoE) involved in cholesterol transport linked to the development of AD o Advanced age o Traumatic brain injury o Lack of social and cognitive engagement o REVERSIBLE CAUSES OF DEMENTIA o Medications: Anticholinergics, antipsychotics, benzos, H2 blockers o Metabolic disorders: Dehydration, thyroid disorders, hyponatremia, hypercalcemia o Intracranial infection: Meningitis, neurosyphilis, tumor, toxoplasmosis o Miscellaneous: Toxins (lead, mercury, ETOH), Vitamin B12 deficiency, Depression and psychoses 2. Pt with Alzheimer DiseaseèTx Acetylcholine levels are decreased and an excessive stimulation of glutamate causes neuronal toxicity. Slow, progressive decline in cognition. Tx: 1st Cholinesterase inhibitors (CIs) (Cholinergic SE: N&V, diarrhea). once daily for: o Mild to moderate AD § Donepezilè SE: N&V, ¯HR, syncope. If nightmare/imsomnia, give in AM. Taken with or without food. § Rivastigmineè SE: N&V, HA, fatigue, dyspepsia. Initial response within 12 wk. § GalantamineèSE: N&V, HA, dizziness, dyspepsia. Cont. severe hep/renal impairment § If no effect within 3-6 months, try another CI. o Moderate to severe AD § Memantine (Namenda)èSE: dizziness, confusion, HA, HTN, anxiety. May be used in conjunction to CIs. Blocks activation of NMDA receptors during abundance of glutamate. 2nd a trial of a second CIs may be granted Avoid anticholinergic agents like diphenhydramine. SELECTED AGENTS FOR NONCOGNITIVE SYMPTOMS o In patients receiving antipsychotics for noncognitive symptoms (agitation, delusion, hallucinations), response is usually seen within 1st day of tx. § Antipsychotic agents § Risperidone (Risperdal) § Olanzapine (Zyprexa) o Response to antidepressants (anxiety, depression, sleep disorders), response is usually seen within 4-6 wks. o Benzodiazepines o Assess for suicidal ideation. Goals: increase length of time of self-sufficiency, delaying need for nursing home, reduce burden to caregiver. 3. Alzheimer’s èmeds beneficial and contraindicated that make symptoms worth “Don’t prescribe cholinesterase inhibitors (ChEIs) for dementia without periodic assessment for perceived cognitive benefits and adverse gastrointestinal effects” Cholinesterase inhibitors like tacrine, donepezil, galantamine, and rivastigmine can interact with other drugs, potentially leading to increased cholinesterase inhibitor levels and more cholinergic adverse effects. Tacrine, donepezil, and galantamine are metabolized by the P450 enzyme system, while rivastigmine is metabolized differently, making it less prone to these interactions. This distinction may offer an advantage, as rivastigmine could have fewer drug interactions and lower risk of cholinergic side effects. 4. Antipsychotic medèextrapyramidal symptoms a. Muscle stiffness (rigidity) b. Tremors c. Restlessness d. Involuntary movements (dyskinesia) e. Akathisia (a feeling of inner restlessness and inability to sit still) § § § § § § Antipsychotics treat conditions such as schizophrenia, hallucinations, and violent behaviors. Elderly individuals receiving psychotropic therapy require close monitoring due to potential severe side effects like EPS, tardive dyskinesia, dystonic reactions, and anticholinergic effects. Older antipsychotic drugs like haloperidol, fluphenazine, and trifluoperazine carry a higher risk of EPS compared to newer atypical antipsychotics. Newer atypical antipsychotics like risperidone and olanzapine are better tolerated but may lead to weight gain and metabolic changes. Caution is needed with risperidone in Parkinson's disease patients. Aripiprazole, a partial dopamine agonist, is a newer option for psychosis in Alzheimer's disease but may cause dose-related somnolence. For patients intolerant to traditional antipsychotics, anticonvulsants like divalproex, carbamazepine, oxcarbazepine, and lamotrigine are used, but they come with risks like hyponatremia and serious rashes. Close monitoring is essential. 5. Antipsychotic SE Drowsiness Weight gain Movement disorders (tremors, stiffness, restlessness) Metabolic changes (blood sugar, cholesterol) Sexual dysfunction Increased risk of diabetes and cardiovascular problems Changes in blood pressure 6. Best candidate for antipsychotic treatment èPt may have symptoms like hallucinations, disorganized thinking. Schizophrenia At least 2 of the following core symptoms must be present for ≥1 month: Delusions (fixed, false beliefs) Hallucinations (auditory > visual disturbances) Disorganized thought (derailed or incoherent speech) Grossly disorganized/catatonic behavior (hyper- or hypoactive movements that are often repetitive) Negative symptoms (diminished emotional expression, poverty of speech and thought, amotivation, lack of social interest) First-line treatment is with an atypical antipsychotic given lower potential for extrapyramidal side effects. o Atypical (2nd generation) Risperidone, olanzapine, ziprasidone, aripiprazole, quetiapine, paliperidone, iloperidone, asenapine, lurasidone, clozapine, brexpiprazole, cariprazine, pimavanserin (Parkinson disease–related psychosis) o Typical (1st generation) § Haloperidol, chlorpromazine, fluphenazine, trifluoperazine, perphenazine, thioridazine, thiothixene, loxapine Medication choice is based on clinical and subjective response and side-effect profile: o Sensitivity to extrapyramidal adverse effects: atypical o For least risk of tardive dyskinesia: quetiapine, clozapine o For least risk of metabolic syndrome: aripiprazole, ziprasidone, lurasidone, perphenazine, brexpiprazole o For least risk of QTc prolongation: aripiprazole § Avoid use of thioridazine and ziprasidone in patients with a prolonged QT interval. For poor compliance/high risk of relapse: Injectable form of long-acting antipsychotic may be used. o Haloperidol, fluphenazine, risperidone, olanzapine, aripiprazole, and paliperidone § 7. Labs before antipsychotics è liver function, EKG, UA The following labs are used to assess for comorbidities and baseline values prior to antipsychotic initiation: Electrocardiogram (ECG) for baseline QTc CBC, blood chemistries, TSH, hemoglobin A1C, Lipid panel Pregnancy test, if indicated 8. Alzheimer/Dementia èBZD are least helpful for memory problemsèstay away from anxiolytics o Benzodiazepines are sometimes used to address behavioral issues in dementia, although they are typically reserved for anxiety or episodic agitation due to their limited effectiveness compared to antipsychotics. o The use of anxiolytics in these patients should be approached with caution due to their potential adverse effects, such as sedation, confusion, and increased risk of falls. 9. Pt education èBZD: ETOH, ­ risk for addition/tolerance, Xanax controlled in Europe due to cognitive impairment Benzodiazepines (alprazolam [Xanax], lorazepam [Ativan], temazepam [Restoril]): MOA: binds receptors at several sites within the CNS, including the limbic system and reticular formation; effects may be mediated through GABA receptor system; increase in neuronal membrane permeability to chloride ions enhances the inhibitory effects of GABA; the shift in chloride ions causes hyper polarization (less excitability) and stabilization of the neuronal membrane ADE: drowsiness, impaired motor function, memory loss, dependency Interactions: ETOH, OCP, erythromycin Pts previously treated for anxiety: assess for drug seeking behavior (rule-out dependence). Pts with hx of prescription med/alcohol/substance abuse can become dependentèBuspirone (drug of choice) Children approved: clorazepate, chlordiazepoxide, diazepam, and alprazolam. Elderly: start in low doses. May interact with contraceptives. Benzodiazepines and alcohol have additive effects and can potentiate sedation, respiratory depression, and cognitive impairment. Patients should be advised to avoid alcohol while taking benzodiazepines. Not abruptly discontinue benzodiazepines due to the risk of withdrawal symptoms. Reserved for acute situations or specific phobias due to their addictive potential. 10. BZD & ETOH èexacerbate existing depression 11. Status epilepticus TxèAtivan 12. Education èBZD § Concurrent benzodiazepine and opioid use can cause severe sedation, respiratory depression, coma, and death. § Benzodiazepines like temazepam pose risks of abuse, misuse, and addiction, potentially leading to overdose or death. § Prolonged use of benzodiazepines can result in significant physical dependence and withdrawal reactions. 13. OpioidsèEduc. Pt addiction Opioid tolerance occurs with chronic use, requiring dose increases for pain relief. Dependence results in withdrawal symptoms upon abrupt cessation or rapid dose reduction. Tolerance and dependence can develop quickly (2-3 d), but they shouldn't deter aggressive pain management. Even short-term opioid use can lead to dependence, with withdrawal symptoms ranging from mild tremors to flu-like symptoms. Severe withdrawal in tolerant individuals may include increased respiratory rate, sweating, and anorexia. Patients with chronic pain may display drug-seeking behavior, which can be due to uncontrolled pain rather than addiction. Pseudo-addiction resolves with adequate pain management. Addiction is a chronic disease characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving. True addiction is rare in the general population, with about a 10% incidence. Substance abuse history is important but beyond the scope here. 14. Pain in pregnancy ècodeine can be used 15. Antidepressant èmaleè intimacy engagementèSE: no drive, no orgasm Side effects from SSRIs are often temporary. Sexual side effects, like decreased libido or delayed ejaculation in men and anorgasmia in women, are common and may persist without intervention. Managing treatment-related sexual dysfunction may involve reducing the SSRI dosage or switching to antidepressants without such effects, like bupropion, nefazodone, or mirtazapine. Other strategies include using sildenafil (Viagra) or buspirone. Antidepressants with major ADE sexual dysfunction: § SSRIs: Paroxetine, Fluoxetine, Sertraline, Fluvoxamine § SNRIs: Venlafaxine, Levomilnacipran § Novel drugs: Vortioxetine Treatment of this dysfunction is available, but lowering the dose without compromising efficacy may be the first strategy. If the symptoms persist, cyproheptadine (Periactin), amantadine (Symmetrel), and yohimbine (Yohimex) may benefit some patients. In addition, sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra) may benefit some male patients who suffer from this sexual side effect. 16. Quality life improvement è antidepression med associated with ­ sexual dysfunction and least Paroxetine is comparatively associated with the highest rate of sexual side effects. Fluvoxamine may be the least likely in the class to cause sexual dysfunction. 17. Antidepressants èNo in pregnancyèescitalopram (Lexapro)/sertraline (wt risks) § Studies on SSRIs in pregnant patients show varied results, especially regarding newborn outcomes. Late exposure to SSRIs in the third trimester can lead to various adverse effects in newborns, including respiratory distress, apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, and seizures. Close monitoring and individualized treatment are crucial for pregnant patients with major depressive disorder. § Paroxetine has been associated with fetal cardiac defects when used during pregnancy. § During pregnancy, escitalopram and desmethylcitalopram cross the placenta and are found in the amniotic fluid. If treatment for major depressive disorder is initiated for the first time during pregnancy, escitalopram can be considered. § Sertraline crosses the human placenta. If treatment for major depressive disorder is initiated for the first time during pregnancy, sertraline is one of the preferred SSRIs. Serum concentrations may be decreased in the third trimester; however, due to the wide therapeutic reference range, dose adjustments may not be needed. 18. Escitalopram (Lexapro) èissues in baby lungs 19. No MAIOs in pregnancy § Adverse events have been observed in animal reproduction studies. 20. Common mistakes providers made when prescribing Practitioners may make mistakes in drug therapy by: § Misunderstanding drug safety regulations. § Ignoring clinical trial data. § Mishandling controlled substances. § Overlooking generic drug options. § Neglecting interactions with complementary medicine. § Failing to consider patient-specific factors. § Providing inadequate disposal guidance. § Not monitoring patients adequately. These errors can lead to safety issues, inefficiencies, and compromised treatment outcomes. 21. Antidepressant medsèTime tx takes to be effective 8-12 wksèto optimize dose correctly Acute Treatment Phase è The goal of drug therapy in the acute treatment phase is to treat the patient until full remission. The duration of this phase is 6 to 8 weeks and potentially up to 12 weeks with apparent improvements occurring within the first 1 to 2 weeks. 22. Parkinson’s differentialsè1st èMeds can cause symptomsèrule out other cause § A progressive neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra and other dopaminergic regions of the brain. § Cardinal symptoms include resting tremor, rigidity, bradykinesia, and postural instability. § Differential Dx: Secondary parkinsonism (drug induced: reversible; may take weeks/months after offending medication is stopped; often bilateral symptoms): o Neuroleptics (most common cause); Antiemetics (e.g., prochlorperazine and promethazine), metoclopramide; SSRIs; Calcium channel blockers (e.g., flunarizine and cinnarizine); Amiodarone; Lithium /valproic acid; Amphotericin B; Estrogens Medication Goal: Improve motor and nonmotor deficits in Parkinson's disease (PD). First Line: o Options: Levodopa, dopamine agonists (Pramipexole, Ropinirole, Rotigotine, Apomorphine), MAO-B inhibitors (Selegiline, Rasagiline, Safinamide) o o Levodopa with carbidopa remains most effective, especially for bradykinesia. Dopamine agonist use versus levodopa is debated due to adverse events and motor fluctuations. o MAO-B inhibitors like rasagiline or Catechol-O-Methyltransferase Inhibitors (COMT) inhibitors like entacapone can help manage dyskinesias with levodopa. Second Line: o Options: β-adrenergic antagonists, amantadine, anticholinergics. o Dopamine agonists (ergot) are less preferred due to higher adverse events. o Treatment for levodopa-induced complications: Entacapone or rasagiline for end-of-dose wearing off; amantadine for dyskinesias. o FDA approved istradefylline for "off" episodes. o Anticholinergic agents are avoided except for tremor control. o Anticholinergics: antagonize acetylcholine receptors, regulates muscle movement: Trihexyphenidyl (Artane), Benztropine (Cogentin) Additional Medications: o NMDA antagonist amantadine can be used in patients with dyskinesia. o COMT inhibitors: Entacapone is preferred over tolcapone due to hepatotoxicity. o Apomorphine for off episodes in advanced disease, administered subcutaneously. 23. GADèBusparè2 wks to make effect Buspirone (BuSpar) is an anxiolytic drug effective for generalized anxiety disorder (GAD). Unlike benzodiazepines, it has low abuse potential. Absorbed quickly but with extensive metabolism, it's less effective in patients needing immediate relief. Adverse effects, like nausea and dizziness, are rare. Its therapeutic effect may take 1-2 weeks, requiring patient education for compliance. 24. ETOH +GAD è Buspar GAD tx: § 1st SSRI or SNRIèuseful for anxiety disorder as well as a coexisting comorbidity § 2nd Buspirone or Imipramine è takes 1-2 wks for effect. § 3rd adjunctive therapy with pregabalin or buspirone è Select agent based on drug onset, half-life, and patient metabolism. Do not use if patient is alcohol or drug dependent. May be first-line drug in motivated patients with acute anxiety to a time-limited stress. o Patients with a history of prescription medication abuse and substance or alcohol abuse can become drug dependent. Buspirone, a non-addicting drug, is a choice for their treatment regimen. 25. Panic attack A discrete period, in which there is a sudden onset of intense apprehension, fearful- ness, or terror, often associated with feelings of impending doom. During these attacks, symptoms such as shortness of breath, palpitations, increased heart rate, blurred vision, clammy skin, chest pain or discomfort, choking or smothering sensations, and fear of “going crazy” or losing control are present. First-Line Therapy SSRIs. èlong timeèeffect begin 2-4 wks BZD: Alprazolam (Xanax) is the only BZD approved by the FDA for PD, but clonazepam (Klonopin) is also used. èShort time BZDs are used along with an SSRI if rapid relief from anxiety is needed. Monitor symptoms, assess for side effects, and gradually increase the dosages of SSRIs and alprazolam or clonazepam if needed Second-Line Therapy TCA and monitored for effectiveness in decreasing panic attacks and controlling the severity of anxiety or panic symptoms while causing tolerable adverse events. Third-Line Therapy MAO inhibitors can be very effective in controlling panic attacks. Before the patient begins therapy, however, the practitioner must assess his or her willingness to avoid the many tyramine-containing sympathomimetic drugs and foods, which can interact with MAO inhibitors to precipitate serious, life-threatening reactions. In addition, the patient should be referred to a psychiatrist for intensive therapy. 26. BZD + ETOHè­ risk for respiratory depression 27. Situational anxietyèmajor lossè BZD Acute stressèloss of jobèXanax 28. Know Schedules Schedule 1 drugs § heroin and LSD § high potential for abuse § not available for regular use, except for investigational purposes with approval from the DEA. Schedule 2 drugs § certain amphetamines and barbiturates § valid medical use but a high potential for abuse. § In emergencies, they may be prescribed by phone but require a written prescription within 72 hours and cannot be refilled. Schedule 3 drugs § certain narcotics (codeine) and nonbarbiturate sedatives § potential for abuse lower than Schedule 2 drugs. § They can be verbally ordered and refilled up to five times within 6 months. Schedule 4 drugs § lorazepam (Ativan) § low potential for abuse and limited physical dependence. § They include nonnarcotic analgesics and antianxiety agents. Schedule 5 drugs § least potential for abuse and contain a moderate amount of opioids. § antitussives and antidiarrheals § include medications with small amounts of narcotics. 29. Categories for pregnancy A è Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote. è folic acid, thyroid hormone B è Either animal reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal reproduction studies have shown an adverse effect (other than decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters). è erythromycin, penicillin C è Either studies in animals have revealed adverse effects on the fetus and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk. è labetalol, nifedipine, angiotensin- converting enzyme (ACE) inhibitors D è There is positive evidence of human fetal risk, but benefits from the use in pregnancy may be acceptable despite the risk. è glyburide, diazepam, aspirin, ACE inhibitors X è Studies in animals or human beings have demonstrated fetal abnormalities, or there is evidence of fetal risk based on human experience, or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. èoral contraceptives, lovastatin, isotretinoin 30. FDA Studies è A, B, C, …èhave study been done in animals/humans Preclinical Trials: § Testing conducted in animals. § Evaluates efficacy, toxic effects, and adverse reactions. Phase I Clinical Trials: § Initial evaluation of the drug. § Involves 20 to 100 healthy volunteers. § Focuses on absorption, distribution, metabolism, and elimination. § Determines effective dosage ranges and administration routes. Phase II Clinical Trials: § Tests conducted on several hundred patients with the targeted disease. § Similar focus as Phase I, but drug effects monitored in patients with the disease. Phase III Clinical Trials: § Large-scale trials involving several thousand subjects. § Double-blind studies comparing the new drug with existing treatments. § Lasts several years to discover most risks and adverse effects. § FDA evaluates data for approval or rejection of the new drug. Phase IV Clinical Trials: § Post-marketing surveillance. § Drug released on a limited basis initially. § Long-term monitoring of effectiveness and safety in a broader population. § Comparative studies with other available drugs. § Monitoring of adverse drug reactions and impact on quality of life. 31. Polypharmacyèelderly Polypharmacy Impact on Elderly Patients: Significant contributor to morbidity and mortality in elderly individuals. Increased risk due to multiple chronic illnesses requiring drug therapy. Common chronic conditions like osteoarthritis necessitate long-term medication use. NSAIDs commonly used for pain management can lead to gastrointestinal complications. Treatment of NSAID side effects with additional medications may cause further complications. Adverse Drug Reactions (ADRs): Account for 30% of hospital admissions in individuals over 65. Approximately 106,000 deaths attributed to medication problems, with 15-65% of cases being preventable. Preventable by avoiding inappropriate medications, effective communication, and patient education. Factors Contributing to Polypharmacy: Varied symptoms and complaints associated with multiple chronic illnesses. Patient belief that medication will resolve health issues. Provider pressure to prescribe medication to meet patient expectations. Stockpiling of discontinued medications, often due to cost concerns. Sources of Polypharmacy: "Poly-providers": Patients seeing multiple specialists without coordination. Lack of primary care oversight in patients seeing multiple specialists. Uninformed prescribing practices leading to avoidable side effects and complications. Patient self-prescription of over-the-counter medications without awareness of interactions. 32. Medications that exacerbates depressions Drug use associated with depression Alcohol BZDsècan cause depressionè The main adverse events of BZDs include drowsiness, ataxia, cognitive and memory impairments (more pronounced in the elderly and sensitive individuals), and rare occurrences of rage, excitement, and hostility, particularly after overdoses. Additional side effects may include increased depression, confusion, headache, GI disturbances, menstrual irregularities, changes in libido, urticaria in cases of drug hypersensitivity, and interactions with other medications.==> Flumazenil used for BZD overdose. Opioids Antihypertensives § Reserpine § Methyldopa § Diuretics § Propranolol § Clonidine Oral contraceptives Steroids 33. Antidepressants: until 4 wks to feel better warning boxèsuicidal ideation § 19-25 yr è (­ risk) § Elderly è(¯ risk) Boxed Warning: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults. In depressed adolescents, antidepressants, especially SSRIs, might initially boost energy and initiative before improving mood, potentially increasing suicide risk. This effect is more pronounced in patients under 25. However, SSRIs don't raise suicide risk in those aged 25-64 and can reduce it in those over 65. 34. Somatic symptomsèno physiological causeèin children/teenagersèabdominal pain The most common somatic symptom in children and teenagers is abdominal pain, often occurring in the absence of any identifiable physical cause. Other common somatic symptoms in this age group include headaches, fatigue, and musculoskeletal pains. These symptoms can sometimes be manifestations of underlying psychological distress or stressors. 35. OCDè1st line SSRIs o First-Line Therapy: o Use of SSRI recommended by APA. o Clomipramine or SSRIs like fluoxetine, sertraline, fluvoxamine can be effective. o Monitor symptoms and side effects, adjust dosage if needed. o Therapy may continue for up to 1 year if response is good. o Second-Line Therapy: o Alternative SSRI or buspirone may be considered. o Monitor response to drug therapy and refer for supportive therapy. o Third-Line Therapy: o If first and second-line treatments are ineffective or unacceptable, consider different but effective treatment. o Assess for adverse effects and potential drug-seeking behavior. o Buspirone may be an option for those with history of substance abuse. 36. Antipsychotic èQT, neuroleptic malignant syndrome o Antipsychotic medications can cause QT interval prolongation, increasing the risk of arrhythmias and sudden cardiac death. o They also carry the risk of neuroleptic malignant syndrome (NMS), a serious condition characterized by hyperthermia and altered mental status. o Early recognition and intervention are vital for managing NMS effectively. 37. 1st line tx elderly depression è citalopram (Celexa) o No TCA because of anticholinergic effects o No Trazodone èsedating, no safe for elderly. Antidepressant Drugs 1st line: o SSRIs: most commonly prescribed (Fluoxetine, citalopram, paroxetine, escitolopram) § Safe if overdosed § Indication – depression, anxiety – inhibits reuptake of serotonin; fluoxetine for children 8 and up; escitalopram 12 and up; pregnancy referral § Absorption – dosing starts low and increase after 4 weeks. Onset of action 1-2 weeks with episodic treatment 4-6 months after recovery; elderly decreased renal and hepatic function, albumin levels; ½ starting dose. § Elimination – metabolized by the liver; cytochrome p450 titrate before DC; ethnic considerations § Adverse effects – nausea, insomnia, decreased libido; hyperactivity in serotonin storm/bipolar nd 2 line o SNRIs: (venlafaxine, duloxetine) § Increase the relative concentrations of both serotonin and norepinephrine, with more serotonergic or noradrenergic activity depending upon the dose § Easy to tolerate § D/C slowly, titrate down § Indications – poor tolerance or response to SSRI; may be preferred depending on history § Absorption – inhibits serotonin and norepinephrine, slight dopamine; noradrenergic activity (norepinephrine in transmission of nerve impulse); start low and increase over 2 – 4week interval § Elimination – liver metabolites; p450 enzymes; avoid abrupt DC § Adverse effects – insomnia, HTN, constipation, headache 3rd line o TCAs: § Potent inhibitors of the reuptake of norepinephrine and exert fewer effects on serotonin § High doses needed; first line pain control § Cholinergic side effects o α2-Noradrenergic antagonists/mixed serotonin blockers: (mirtazapine–Remeron) § Similar to TCAs § Causes sedation § Alleviate depression while increasing appetite and decreasing insomnia o Serotonin 2A antagonists and serotonin reuptake inhibitors: (trazodone) § Weak serotonin receptor antagonist that also blocks serotonin reuptake to a lesser degree. § Highly sedating at therapeutic doses § Often used to treat insomnia at lower doses o MAOIs: (Phenelzyne, tranylcypromine) § § Lead to a decreased degradation of norepinephrine, serotonin, and dopamine in the synapse. Broad spectrum, hypertensive crisis severe adverse reaction (life threatening!), avoid tyramine-containing foods 38. Bipolar disorder/hesitant about med + hx of suicidal attempts è Lithium è narrow safety profile o Lithium is primarily used to treat bipolar disorder, including acute mania, acute episodes with mixed features (labeled use), acute hypomania (off-label use), or acute bipolar major depression (alternative agent) (off-label use). o For most patients, a therapeutic response occurs with serum concentrations between 0.8 and 1.2 mEq/L; some respond to lower levels (eg, 0.6 mEq/L). For treatment of acute severe mania, typically given in combination with an antipsychotic or antiseizure drug. o It's crucial to monitor serum lithium levels closely due to its narrow safety profile. The dosage varies by age and weight, with adjustments for pediatric and older adult patients. o It's contraindicated in severe cardiovascular or renal disease and interacts with many drugs. Side effects can be significant, including lithium toxicity, which is closely related to serum levels and can occur even at therapeutic doses. It's vital to manage interactions carefully and adjust doses as necessary. 39. opioid withdrawal treatmentèmed no usedèmultiple suicidal attemptsèlithium small safety profile 40. Bipolar disorderècorticosteroidsècan increase mania o o o o o o o o o o o Increased appetite and weight gain Fluid retention leading to bloating and increased blood pressure Mood changes, including irritability, mania, and anxiety Insomnia or disrupted sleep patterns Increased risk of infections due to immune suppression Osteoporosis and increased fracture risk Muscle weakness and atrophy Glaucoma and cataracts, particularly with topical or high-dose use Gastrointestinal issues like heartburn and ulcers Skin changes such as thinning, bruising, and stretch marks Adrenal suppression/DM with long-term use 41. Anxiety/migraine/­BP/­HRèBB First-line abortive treatments Mild to moderate attacks: o Acetaminophen o NSAIDs o Aspirin-acetaminophen–caffeine (Excedrin Migraine) Moderate to severe attacks: o Triptans when OTC agents fail for mild to moderate attacks OR first line for moderate to severe attacks § Sumatriptan èrapid onset § Rizatriptan § Naratriptan èslow onset but long half-lives § Zolmitriptan § Frovatriptan èslow onset but long half-lives § Eletriptan o Antiemetics: dopamine antagonists o Contraindications: Avoid triptans and ergots in coronary artery or uncontrolled hypertension. Precautions Frequent use of acute-treatment drugs can result in MOH (especially Excedrin, triptans, butalbital). o Triptan common adverse reactions: chest pain, flushing, weakness, dizziness, and paresthesias. Recommend trying more than one triptan before considered a class failure. Second-line abortive treatment Ubrogepant Rimegepant Dihydroergotamine: drug of choice in status migrainosus and triptan resistance or failure. Lasmitidan Schedule V controlled substance. Patient should not drive following 8 hours; safe with CV risk factors. First-line preventive treatment: Lifestyle modifications, trigger reduction, CBT Consider prophylactic treatment if: o Quality of life is severely impaired o ≥6 headache days per month, ≥4 headache days per month of moderate severity, or ≥2 headache days per month of severe impairment o Migraines not responding to abortives o Frequent, long, or uncomfortable auras Preventive treatment of migraine: divalproex, topiramate, metoprolol, and propranolol to reduce frequency. A mitriptyline, venlafaxine, lisinopril, and candesartan are other options. o Beta-blockers and calcium channel blockers are effective prophylaxis. o 42. Abortive therapy for migraine HA § Triptans: Medications like sumatriptan and rizatriptan constrict blood vessels and block pain pathways. § NSAIDs: Ibuprofen and naproxen reduce pain and inflammation. § Acetaminophen: Provides relief for mild migraines, often combined with caffeine. § Ergotamines: Drugs like ergotamine and dihydroergotamine constrict blood vessels and block pain pathways. § Anti-nausea medications: Metoclopramide or prochlorperazine can relieve nausea and vomiting. 43. Red flag symptoms for HA Red flag symptoms for headaches include: § Sudden onset of severe headache § Headache associated with neurological symptoms like weakness, numbness, or visual disturbances § Headache after head injury § Headache accompanied by fever, stiff neck, rash, or confusion § New headache in individuals over 50 years old § Headache worsened by coughing, exertion, or sexual activity § Headache that wakes a person from sleep § Headache in patients with a history of cancer or HIV/AIDS § Progressive headache that increases in severity and frequency § Headache triggered by certain activities or positions § The pain is disabling, burning, or boring and centered around one eye and is described by patients as being more severe than childbirth or passing a kidney stone. § Contraceptive use 44. Pt unable to close eye/one side of faceèartificial tears o Diseases and abnormalities of tear production and maintenance of tear film o The most common lacrimal disorder is dry eye syndrome (keratoconjunctivitis sicca). o Lacrimal duct disorders usually result in overflow tearing. o System(s) affected: skin/exocrine o History § Dry sensation in eyes § Foreign body sensation § Blurry vision § Itching § Ocular pain § Photophobia § Burning § Occasional tearing due to excessive reflex tearing o Patient’s symptoms usually worsen in dry, smoky environments while reading, driving, or using a computer for extended periods. First Line Preservative-free artificial tears: 1 drop in each eye several times a day to prevent discomfort (1) Ophthalmic lubricating ointment may be used in each eye at bedtime (2)[A]. Lacrisert time-release cellulose. Second Line If inflammatory component ètopical immunosuppressives such as cyclosporine 0.05% (Restasis). Topical lifitegrast (Xiidra), Tyrvaya (nasal varenicline) Emerging therapies: topical androgens, secretagogues (e.g., oral pilocarpine), cytokine-blocking agents, and a P2Y2 receptor agonist (diquafosol). 45. ETOH èbruising/jaundice/no eatingèHepatic failure What to expect in treatment?... Variceal Hemorrhage Prophylaxis Dilated submucosal esophageal veins connecting the portal and systemic circulations Most commonly results from portal hypertension (typically a result of cirrhosis) First Line Not actively bleeding. NSBB Carvedilol: 6.25 mg daily is more effective than NSBB o Propranolol: 20 mg BID increase until heart rate decreased by 25% from baseline o Nadolol 80 mg daily; increase as above o Contraindications: severe asthma NSBBs and EBL reduce rate of rebleeding to a similar extent, but β-blockers reduce mortality, whereas ligation does not. Second Line Obliterate varices with esophageal ligation if not tolerant of medication prophylaxis. During ligation: proton pump inhibitors, such as lansoprazole 30 mg/day, until varices obliterated Ascites § Pathologic accumulation of fluid in the peritoneal cavity and the most common complication of cirrhosis. First Line Sodium restriction and diuretics o Spironolactone o Furosemide Diuretic-intractable/refractory ascites defined as: o Persistent or worsening ascites despite maximum doses of spironolactone (400 mg/day) and furosemide (160 mg/day) for at least 1 week o Recurrence of grade 2 or 3 ascites within 4 weeks of achieving minimal ascites. o Diuretic induced complications like hepatic encephalopathy, hyponatremia to