Exam+%234+Review+Outline copy copy.docx

**Outline -- Exam \#4** **\~ 65 questions total** **\*\*Know your strong inhibitors and inducers\*\*** **PD/AD** - **Medications (when used?, AEs, DDIs, prescribing considerations)** - **DA replacers - Levodopa/carbidopa (sinemet)** - **Use:the carbidopa allows more of the do...

**Outline -- Exam \#4** **\~ 65 questions total** **\*\*Know your strong inhibitors and inducers\*\*** **PD/AD** - **Medications (when used?, AEs, DDIs, prescribing considerations)** - **DA replacers - Levodopa/carbidopa (sinemet)** - **Use:the carbidopa allows more of the dopamine to reach CNS by inhibiting decarboxylation of DA in intestine and peripheral tissues. Most effective drug for PD motor, 1^st^ line** - **AE: dyskinesias (reduce dose)** - **DDI: \*pyridoxine diminishes levodopa, \* MOA inhibitors cause HTN crisis d/t cathecholamine increase** - **Considerations: full effect takes months,** - **DA agonists -- Pramiprexole, apomorphine** - **Use: \*apomorphine for acute management** - **AE: confusion, hallucinations, impulse control, sleep attacks , orthostatic hypotension** - **DDI:** - **Considerations: 1^st^ line for younger pts and mild to moderate symptoms, reduce dose for renal, add levodopa for advanced disease** - **COMT inhibitors -- entacapone** - **Use: increase % of levodopa reaching brain** - **DDI: methyldopa, dobutamine, isoproterenol** - **AE:** - **Considerations: ALWAYS with levodopa-carbedopa** - **MAO-B inhibitors -- selegyline** - **Use:** - **AE: serotonin syndrome, HTN crisis** - **DDI:** - **Considerations: early treatment to delay levo-carbi need, take early in day to reduce insomnia, max 10mg** - **Anticholinergics -- benztropine** - **Use** - **AE** - **DDI: AchE inhibitors, cholinergic agonists, anticholinergics** - **Consideration: used later in disease process, useful for tremor** - **Cholinesterase inhibitors -- Rivastigmine, Galantamine** - **Use:** - **Riva: 1^st^ line for mild to moderate Alzheimer's** - **Galán: mild to moderate AD, possible effect on glutamate and serotonin** - **AE:** - **DDI: Galan: anticholinergics, 3A4 inhibitors** - **Considerations: riva highest potential actions, d/c after 6 mo if no improvement, adjust for renal/hepatic** - **Riva: oral and patch forms not 1:1, do not adjust sooner than q2-q4w** - **Galan: do not adjust sooner than q4w** - **NMDA antagonists -- memantine** - **Use: for moderate to severe Alzheimer's** - **AE:** - **DDI: none** - **Consideration: renal dose, can adjust weekly** - **General** - **Managing motor fluctuations** - **Prescribing considerations** - **Monitoring** - **Pt record on/off time journal, sleep disorders, dep/ anxiety** - **Falls risk** - **Avoid high protein meals** **Epilepsy** **\*\*don't need to know loading or maintenance doses\*\*** - Medications (novel uses, Contras/AEs, toxicities, DDIs, PK, monitoring) - Phenytoin / Fosphenytoin - Use: generalized tonic clonic, partial complex \*fosphenytoin safe IV route - Contraindication: pregnancy, renal or hepatic disease - AE: skin rashes, hirsutism, gingival hypertrophy, hypotension, dysrhythmia - Toxicities: nystagmus, ataxia, coma, delirium, psychosis, depression - DDI: valporic acid - PK/monitoring: inhibition @ Na channels, decreased in hypoalbuminemia, RF or DDIs. PLASMA levels: 10-20 total, 1-2 unbound PHT - Carbamazepine - Use: generalized tonic clonic, partial complex. Other: bipolar, trigeminal/glossopharyngeal neuralgias - CI: hypersensitivity to TCAs, bone marrow suppression, MOAI use - AE: hyponatremia, bone marrow suppression, rash, pruritos, teratogenic - Toxicities: - DDIs: potent inducer, avoid grapefruit - PK/Monitor: inhibition @ Na channels. Serum: 4-12 mg/ml - Valproic Acid - Use: all seizures. Other: bipolar, migraine - CI: hepatic disease, urea cycle disorders, pancreatitis, pregnancy - SE: hepatotoxicity, pancreatitis, weight gain, no sedation/affect on cognitive skills, hair loss, increased bruising - Toxicities: - DDI: increase levels of phenobarbital and phenytoin, carbapenem antibiotics ( decrease level of VPA) - PK/monitoring: inhibit Na, suppress Ca, GABA transmission effect, decrease degradation of GABA and increase GABA synthesis. SERUM: 50-100 mcg/ml - Phenobarbital \* not 1^st^ line - Use: generalized tonic clonic, complex partial - CI: intermittent porphyria, respiratory depression with dyspnea/ obstruction, adjusted dose for liver disease - AE: drowsy, ADHD (kids), **dependence**, teratogenic, overdose, ostemalacia - Toxicities: CNS depression and death. Moderate toxicity: nystagmus/ ataxia - DDI: **potent inducer** - PK/monitor: serum: 15-40 mcg/ml. Potentiates GABA effects - Oxcarbazepine - Use: generalized tonic clonic, complex partial - CI: pregnant - AE: sedation, cross sensitivity with carbamazepine, teratogenic, Steven's Johnson syndrome, toxic epidermal necrolysis, hyponatremia - Toxicities: - DDI: decrease contraceptives, increase phenytoin, alcohol causes CNS effects - Pk/monitoring: - Lamotrigine - Use: all seizures - CI: - AE: CNS: blurred vision, diploid, dizzy/ headache, small risk of cleft palate terotogenic - Toxicities: RASH (d/c at first sign of rash) - DDI: inducers and inhibitors - PK/monitoring: TITRATION - Benzodiazepines - Use: generalized tonic clonic, myoclonic, complex partial. Other: anxiety, sedation - CI: liver disease (clonazepam) - AE: fatigue, sedation, aggressiveness or confusion - Toxicities: - DDI: CNS depressants - PK/monitoring: increase gaba activity Cl channel opening. Weight based dosing for clobazam - General: - Drug selection, initiation and discontinuation principles - Dosing principles - Patient education: medical alert tag - Which drugs used for other conditions? - What are the common concerns with AEDs? (e.g., teratogenic, enzyme induction -- DDIs, rash, serum monitoring, PK issues) - Key AEs of concern with each drug? **Migraine Headache** - Medications (contras/AEs, DDIs, prescribing considerations) - NSAIDs: 1^st^ line for mild to moderate - CI: - Tension headache/ migraines - DDI: - Consideration: overuse may cause rebound headache, no more than 10 has per month - APAP - CI: - DDI: - Consideration - **"Triptans": stimulate serotonin receptors/ interrupt release of gene related peptide** - **CI: complicated migraines, heart disease, prior MI, Uncontrolled HTN, ischemic stroke, angina, pregnancy** - **AE: can mimic angina worth pressure, tightness or warmth in neck/chest/throat/jaw** - **DDI: serotonin increasing meds (SSRIS, MOAIs), ergots, triptans** - **Consider: not effective for treating/preventing aura or migraine prophylaxis, non oral forms for rapidly intensifying headache** - **"Ergots"** - **CI: same as triptans** - **DDI: CYP3A4 inhibitors** - **Consider: 4 hr for relief, 2^nd^ dose if no response, may cause rebound headache (ergotamine)** - **AE:transient cerebral anxiety, nausea, vomiting** - Metoclopramide - CI: - DDI: - Consider: - Prophylaxis medications (e.g., BB, CCBs, TCAs, AEDs) - Verapamil: cluster headache prophylaxis, may develop tolerance - Amitryptyline: good for adolescents, dry mouth, constipation, weight gain - Propranolol: CI: asthma, DM, athletes, kids. Not a failure until 3+ months of use - Tópamax/ valporic acid - What should be avoided: APAP alone, opioids - General: - Types of headaches - Difference between rescue and prophylaxis therapy - Treatment principles **Antipsychotics** - Medications (Use, Contras/AES, DDIs, monitoring) - FGAs: Haloperidol (high), chlorpromazine (low) - Use: block dopamine receptors. HAL: schizo, psychosis, Tourette's. Chlorpromazine: schizo, psychosis,nausea, hiccups - Contraindicated: - AE: sedation, hypotension. Chlorpromazine: low eps, more anticholinergic - DDI: QT prolonging drugs, anticholinergics, p450 inhibitors - Monitor: for EPS (medical emergency), Haloperidol can cause Neuroleptic malignant syndrome - \*lower risk for EPS but high risk for metabolic effects - SGAs: Risperidone, olanzapine, clozapine - Use: - CI: - AE: weight gain, diabetes, dyslipidemia, seizures, EPS, hypotension - DDI: same as FGA - Monitor: low dose in elderly, can switch between SGAs. Monitor WBC with clozapine - \*less expensive - General - TIMA algorithm (general approach, initial v. treatment‐resistant pts) - Drug selection, expected response - EPS/NMS (what is each? How to treat?) - EPS: acute dystonia, Parkinsonism, akathesia, Tardive dyskinesia - Acute dystonia: medical emergency treat with Benadryl IV or benztropine IM - Akathisia: treat with decreasing dose, beta blocker or benzo - -NMS: body temp \>38, autonomic dysfunction, seizure - Treatment : d/c, dantrolene, bromocriptine or benzos - SGAs -- which have worse AEs over others?, monitoring - Dosage forms **Major Depressive Disorder** - Medications (Use, **AEs**, **DDIs**, **prescribing considerations**, Education/monitoring) - SSRIs: fluoxetine, sertraline, citalopram - Use: 1^st^ line - AE: serotonin syndrome - DDI: fluoxetine/paroxetine potent 2D6 inhibitor, fluoxetine moderate 3A4 inhibitor, Serotonin syndrome with 5HT drugs - Consider: - Education: 1^st^ line , taper off with short half life, elderly start low, take in Am to minimize insomnia - SNRIs: venlafaxine - Use: serotonin norepinephrine reuptake inhibitor - Ae: consider duloxetine if liver dysfunction or alcohol use - DDI: 3A4, 2D6 , 1A2 substrates, caution: 3A4 or 2d6 inhibitor - Consider: taper off, titrate to minimize nausea, monitor BP closely - Education: do not abruptly stop, take with food - Atypical ADs: bupropion, mirtazapine - Use: bupropion 1^st^ line, option for pt experience sexual dysfunction, mirtazapine good choice for low appetite elderly - AE - DDI: MAOIs, cyp2d6. Mirtazapine: no DDI - CONSIDER: avoid in pt with seizure risk - EDU - TCAs: nortriptyline, amitriptyline - USE - AE: lethal in overdose (to gastric lávage, IV bicarb for dysrhythmia - DDI: MAOIs, anticholinergics, sympathomimetics, CNS depressants - CONSIDER: narrow therapeutic, depressed patient no more than 1-week supply - EDU - CI: history of epilepsy or CV disease - MAOIs: phenelzine - USE: 3^rd^ line - CI: patient taking other antidepressants - DDI: MANY - CONSIDER - EDU: no tyramine high foods, - St. Johns wort (DDIs) - USE - AE: photosensitization - DDI: cyp p450 enzyme inducer, PGP inducer, serotonin syndrome with ADs - Consider: not much evidence, lack of standardization - General concepts: - Phases of treatment/how long - Pharmacotherapy considerations (drug selection, response, etc) - Patient education - 1st line v. 2nd or 3rd line drugs **Bipolar Disorders** - Medications - Lithium (PK, DDIs, Use, AEs, toxicity) - Elimination is renal, changes in Na or fluid can change lithium levels, (hyponatremia+ decreases lithium elimination ) - DDI: thiazide, NSAIDS, ACEIS, salt restricted diet - Consideration: first line for euphoric pt, narrow therapeutic index, 0.8-1.4 range for acute to, 0.6-1.2 for maintenance. Levels q 3-6 months - Toxicity: \>1.5 tremor, ecg changes, 2-2.5: ataxia, coma, death, \>2.5: seizure & death - General concepts: - Manic, depressive, relapse/drugs for each (see my summary slide) - AEDs, SGAs -- when used? - SGAs: depressive episodes, manic episodes, mainly maintenance phase - Monitoring **Anxiety** - Medications (use, PK, AEs, DDIs, safety, monitoring ) - SSRI/SRNI (same as above) \*1^st^ and 2^nd^ line - Benzos - Safety: taper to avoid withdrawal, abuse potential - CI: elderly, substance abuse, hepatic impairment - Buspirone - DDI: strong 3A4 inducers or inhibitors, MOAIs, - Start low titrate q 2-3 days max dose 20-30 - General; - Treatment algorithm ‐ GAD - Onset of effect, treatment principles, monitoring **Sleep Disorders** **\*\*do not need to know sleep disorders other than insomnia for exam\*\*** - Medications (Use, Contras/AES, DDIs, monitoring) - Benzos - DDI: reps depression when used with other depressants, - Consider: short acting only for insomnia - Education: sleep hygiene, no alcohol/opiods/ short term use, rebound insomnia - **BZDRAs: zolpidem, zaleplon, eszopliclone** - **half-life shortest to longest** - **zaleplon, zolpidem, eszoplicone** - **DDI: resp dep with other depressants** - **Dose reduction for liver dysfunction, no alcohol** - **Ramelteon: 1^st^ line for insomnia** - **Ci: preggy, liver failure** - **Great option for substance use history** - Diphenhydramine - FDA approved for insomnia\* - AE: Will cause daytime sedation, anticholinergic effects - Trazadone (good when pt on ADs, AEs) - Use for depression and insomniacs - Mostly inpatient - General - Treatment algorithm -- insomnia - nonRx measures - drug‐related causes - ideal drug **ADHD/Autism** - Medications - Stimulants: methylphenidate, dextroamphetamine - \*ADHD - Schedule 2: tolerance and dependence - CI: symptomatic disease, glaucoma, severe anxiety, prior illicit or stimulant drug abuse - Education: first dose in AM, last dose before 4 pm, withdrawal from abrupt use - Overdose: dizzy, confused, hallucination, paranoid, palpitations, dysrhythmias, HTN - Dosage forms: IR v SR v ER, patch formulation causes hypersensitivity - - Nonstimulants: atomoxetine - DDI: MOAIs, 2D6i - Considerations: 2^nd^ or 3^rd^ line, weight based, 4 week onset, expensive - SGAs: risperidone, aripiprazole - Stereotyped/repetetive behaviors, self injury behavior Irritability and agression\* - - SSRIs: fluoxetine - General - Prescribing considerations - Safety/ monitoring Behavioral therapies 1^st^ line **Pain/Anti‐inflammatory Agents** - Medications - Opioids (how they differ, when to use one over the other, PK, comparative doses, DDIs, AEs) - Fentanyl- 80x more potent as morphine - \- chronic pain=patch - Lowest dose for patch 12 mcg/hr - Increase dose as much as 15% if fever develops - Morphine= duration 4-6 h - Oxycodone - Methadone - Half life 15-55 hours can accumulate, for chronic or drug abuse treatment - Hydromorphone - Tramadol - Increased risk for seizures @ 400 mg/day - Partial agonists: ceiling effect - Avoid butorphenol or pentazocine will cause withdrawal symptoms in patients on full agonist. - Ceiling effect "reduced analgesic effect" - *Drugs to avoid: Meperidine, Codeine -- why? what is the harm?* - *Codiene is the prodrug of morphine, cyp2d6 metabolize codiene to morphine.* - *7-10% don't have the enzyme for conversion of codiene* - *Meperidine: can cause seizures d/t toxic metabolites normeperidine accumulation with renal dysfunction* - *Meperidine only appropriate in post surgical rigors, ampho-b induced rigors, drug allergy to all other opioids* - NSAIDs (AEs, Uses, DDIs, Toxicity) - Aspirin (Cox1/Cox2 -- irreversible) - AE: bleeding, Reye's syndrome, salicylism (tinnitus, sweating, headache, dizzy) - Od will cause salicylism - Ibuprofen (Cox1/Cox2) - Reversible both cox ½ - SE: GI, cross hypersensitivity to aspirin, CV risk, Steven Johnson syndrome - AE in pregnancy - Celebrex (Cox2) - Reversible inhibition, ex only - SE: **CV risk**, cross hypersensitivity to aspirin, sulfonamide ax - Acetaminophen (no anti‐inflammatory) - Inhibit cox in CNS only, max dose 4000 mg /day - Hepatotoxicity with more than 4g/ day - Other: Lidocaine patch, TCAs, Gabapentin/Pregablin, Duloxetine, NSAID topicals - General: - Chronic v. acute pain treatment ‐ which drugs? - ***Tx of chronic pain, opioid considerations, MME calculations, PDMP, CDC guidelines for chronic pain Tx with opioids*** - Differences between NSAIDs and opioids; Tylenol and NSAIDs - Overdose management: aspirin, APAP, opioids **Substance Use Disorders** - Medications (Use, MOA, prescribing considerations, DDIs, Monitoring) - Benzodiazepines - Naltrexone - Moa: blocks cravings for alchy, and pleasurable effects - AE: sedation, anxiety, liver toxicity, GI effects - DDI: opiods - Considerations: MUST be opioid free with negative urine screen, wear medic alert - Acamprosate - Reduces unpleasant feelings assoc. with abstinence - Tablets three times daily - AE: diarrhea, suicide ideation rare - Consideration: do not give if crcl \