Unit 5 Exam Flashcards
Treatment of MDD in Children
Fluoxetine (Prozac) - >8 years
Escitalopram (Lexapro) - > 12 years
Adjunctive Therapy for MDD
St John’s Wort
SAMe
Omega-3 (efficacy not confirmed)
Folate
St. John’s Wort Risks/Interactions
Increased risk for serotonin syndrome if used with other antidepressants.
Activates CYP450 and has the potential to interact with other meds metabolized by CYP 450 system → Decreases levels of warfarin, theophylline, oral contraceptives, indinavir
SAMe (S-Adenosyl Methionine) MOA
Some data suggest effectiveness
Helps produce and regulate hormones and maintain cell membranes.
Folate Indications
Recommended if the patient has partial response to antidepressants.
Can be taken along with antidepressants.
Benzodiazepine MOA
Binds to GABA-A receptors (inhibitory receptor) in the brain causing them to increase the opening of chloride channels along the cell membrane, leading to an inhibitory effect on cell firing.
Benzo Discontinuation
Taper should take 3-6 months (depending on dose)
Abrupt DC is life-threatening.
Short Acting Benzos
Alprazolam (Xanax) - 6-20 hrs
Oxazepam (Serax) - 8-12 hrs
Intermediate Acting Benzos
Lorazepam (Ativan) - 10-20 hrs
Long Acting Benzos
Chlordiazepoxide (Librium) - 30-100 hrs
*Diazepam (Valium) - 30-100 hrs
*Longest half-life
SSRI Onset of Action
Effects of these drugs become apparent within 4-6 weeks of treatment.
Length of therapy for first episodes of depression is 4-6 months AFTER recovery.
Continued treatment beyond the point of recovery drastically reduces the relapse potential over 1-3 years.
*Monitor for serotonin syndrome-med interactions
Examples of SSRIs
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Paroxetine (Paxil, Pexeva)
Sertraline (Zoloft)
Common Tricyclic antidepressant side effects
Most common → sedation, orthostatic hypotension, and anticholinergic effects (urinary retention, dry mouth, blurred vision, constipation).
Known to cause sexual dysfunction.
The most dangerous adverse effect → cardiac toxicity (AV block, QT prolongation, and ventricular tachycardia).
Other adverse effects: diaphoresis, seizures, hypomania, and yawngasm.
Can exacerbate dementia in older adults.
Best treatment of anxiety/agitation in dementia
Benzodiazepines
Used for periodic anxiety and agitation in older adults with dementia.
SNRI MOA
Potent inhibition of neuronal uptake of serotonin and norepinephrine and the weak inhibition of dopamine reuptake.
SSRIs are considered more safe than SNRIs d/t more SE.
SNRI Examples
Desvenlafaxine (Khedezla, Pristiq) - Treats depression and GAD.
Duloxetine (Cymbalta, Drizalma, Irenka) - Treats anxious and somatic S/S.
Levomilnacipran (Fetzima)
Milnacipran (Savella)
Venlafaxine (Effexor)
Side Effects of Bupropion (Wellbutrin)
Increases sexual desire and pleasure.
Acts as a stimulant, suppresses appetite.
Lowering the seizure threshold especially when combined with alcohol.
Bupropion (Wellbutrin) Interactions
Sertraline, fluoxetine, and paroxetine (because they are all CYP450 inhibitors) - can increase bupropion levels.
Can be given together but must be monitored.
MAOIs can increase the risk of bupropion toxicity.
Mirtazapine (Remeron) Uses
Atypical antidepressant
Patients with insomnia, agitation, restlessness, or anorexia and weight loss.
Sedating effects of mirtazapine tend to diminish with acclimation and also ten to be less pronounces with higher doses.
Mirtazapine (Remeron) Side Effects
Sedation (at initiation and low doses)
Appetite increases
Weight gain
Dry mouth
Constipation
Avoid in obese patients because of increased appetite/weight gain.
Discontinuation Syndrome
A non-life threatening syndrome of flu-like symptoms that may occur after abrupt cessation of an SSRI.
Can be minimized by gradually tapering the dose.
Onset depends on half-life of the drug and how long it takes to get out of the body and body to realize its missing.
Effexor and Paxil - most commonly associated.
Treatment of Insomnia
1st line - Hypnotics
2nd line - Sedating Antidepressants
3rd line - Orexin receptor agonists.
*First gen antihistamines can be used.
1st Line Treatment of Insomnia - Hypnotics
Benzos
Benzo receptor agonists
Melatonin receptor agonists
2nd Line Treatment of Insomnia - Sedating Antidepressants
TCAs - Sinequan (Doxepin)
Trazadone
3rd Line Treatment of Insomnia - Orexin receptor agonists
Suvorexant (Belsomra)
First-Gen Antihistamines
Diphenhyramine (Benadryl)
Doxylamine succinate (Unisom)
Examples of Benzos Used for Insomnia
Intermediate agents - Temazepam (Restoril), Ativan, Estazolam (ProSum)
Rapid onset - Flurazepam (Dalmane), Quazepam (Doral)
Examples of Benzo Receptor Agonists (BZRA) Used for Insomnia
Eszopiclone (Lunesta)
Zolpidem (Ambien)
Caution for complex behaviors like sleep-driving.
Examples of Melatonin Receptor Agonists Used for Insomnia
Ramelteon (Rozerem)
1st line if used alone, 2nd if alternating with a BZRA
Special Considerations with the Treatment of Insomnia (Peds/Old/Preg)
Children: Melatonin for a limited amount of time.
Elderly: antihistamines or short-intermediate acting benzo.
Pregnant: Unisom is only Category A agent for sleep.
Treatment Order for Restless Leg Syndrome (RLS)
1st line - Dopamine agonists or Gabapentin Enacarbil (Horizant) - gabapentin prodrug.
Other - Opioids, benzos, anticonvulsants, and iron.
Non-Pharmacologic Treatment of RLS
Mental alerting activities, cessation of alcohol, nicotine, and caffeine.
*** Avoid any meds that precipitate or worsen RLS (antidepressants, dopamine ANTAgonists).
Correction of underlying serum iron deficits.
Treatment Order of Generalized Anxiety Disorder
1st line - SSRIs or SNRIs
2nd Line - TCAs and Buspar
Novel agents - Pregabalin (Lyrica)
Examples of TCA for GAD
Imipramine (Tofranil) is the only TCA with an indication for GAD (effective for controlling panic attacks too).A
Atypical Antipsychotics Use for GAD
Not FDA-approved for anxiety disorders but can be used as adjunctive therapy in patients who did not respond to or are intolerant to conventional therapies.
Atypical Antipsychotics Used for GAD
Aripiprazole (Abilify)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
Olanzapine (Zyprexa)
Side Effects of Opioids
Respiratory depression
Sedation
Confusion
Nausea/vomiting
Pruritus
Miosis
*Constipation
Urinary retention
*NEVER develop a tolerance to constipation
Treatment of Opioid Related Constipation
Prophylactic bowel regimen →
Mild stimulant or
Osmotic agent plus/minus
Stool softener
Acetaminophen (APAP) MOA
Unknown, but it is postulated that pain may be mediated through PG inhibition in the CNS as a cyclooxygenase-3 (COX-3) inhibitor.
Non-steroidal anti-inflammatory Drugs (NSAIDs) MOA
Cyclooxygenase, consisting of the isoforms COX-1 and COX-2, is the enzyme involved in the formation of PGs.
Aspirin causes irreversible inactivation of COX-1 and COX-2, whereas nonaspirin NSAIDs cause reversible inactivation.
Nociceptive Pain
Occurs as a result of nerve receptor stimulation following a mechanical, thermal, or chemical insult.
Considered purposeful or functional pain because the pain tells you to stop doing whatever is causing discomfort.
Includes somatic, visceral, and inflammatory.
Somatic Pain
Associated with muscle, skin, or bone injury is often well localized.
Visceral Pain
Affects internal organs (ex: pancreatitis).
Inflammatory Pain
Results from the release of pro-inflammatory cytokines at the site of tissue injury.
Inflammatory pain may be present in acute pain from bruises or infection and chronically from rheumatoid arthritis or osteoarthritis.
Neuropathic Pain
Caused by abnormal signal processes in the central nervous system (CNS).
Pain can be peripheral or central in origin and is no longer protective in nature.
Examples of Neuropathic Pain
Peripheral neuropathies include pain from diabetes and postherpetic neuralgia.
Central neuropathic pain syndromes include pain from multiple sclerosis, spinal cord injuries, migraine, and post-stroke syndrome.
Feels electric-like, burning, tingling, stabbing, or shooting pain.
Opioid Potency Ratios
Oral morphine: oral hydromorphone is 4:1
Oral morphine:oral oxycodone is 1.5:1
Oral morphine: IV hydromorphone is 20:1
Opioid Tolerance
Increased dosage needed to produce the same effect.
Opioid use Disorder/Dependence
Signs and symptoms of withdrawal upon abrupt cessation, rapid dose decrease, or administration of antagonist.
DSM-5 OUD
2 of 11 criteria must be met within the span of a year to diagnose OUD
DSM-5 OUD Criteria (11)
Increased amounts of opioids are used, or the duration of use is longer than intended
Persistent desire or unsuccessful efforts to cut down or control opioid use
Excessive time spent in efforts to obtain, use, or recover from opioid use
Strong desire or craving for opioid use
Opioid use despite resultant inability to fulfill obligations
Continued opioid use despite interference with personal interactions, social obligations, and/or work
Elimination or reduction in activities because of opioid use
Continued opioid use despite the risk of harm or injury
Continued opioid use despite understanding that opioid-related physical or psychological problems exist and are caused or worsened by the use of an opioid
Increased doses of an opioid are needed to achieve the effect previously achieved with a smaller dose (tolerance)
Symptoms of withdrawal occur when opioid dose is decreased (withdrawal)
Symptoms of Opioid Withdrawal
Withdrawal symptoms range from mild tremors to sweating and fever and mimic flu-like symptoms.
Anxiety, yawning, sweating, tearing, runny nose, pupils widen (dilate), goosebumps, muscle twitching, N/V, diarrhea, abdominal cramps, and muscle + bone pain.
Severe Opioid Withdrawal Symptoms
Increased respiratory rate
Perspiration
Lacrimation
Mydriasis
Hot and cold flashes
Anorexia
Examples of Anticonvulsants used to treatment neuropathic pain
Anti-epileptics:
Gabapentin
Pregabalin (Lyrica)
Side effects of Anti-convulsants/Anti-epileptics
Nausea, sedation, dizziness, weight gain and ataxia.
Start at night time because of the risk of sedation.
Over time, patients become tolerant of sedation.
Treatment of Opioid Overdose
Respiratory depression can cause death.
Naloxone (Narcan)
Diagnostic Studies to Order for Complications of NSAID Use
Assessing kidney function (serum creatinine) for long-term NSAID use.
Endoscopy for suspected NSAID-induced ulcers.
Why Codiene May not Achieve Pain Control
Codeine is a pro-drug and conversion to morphine is facilitated by hepatic CYP2D6 enzyme action.
The CYP2D6 genotype is associated with polymorphism, causing variability of CYP2D6 activity, effecting the amount of morphine converted from codeine.
The metabolism of codeine to its active metabolite, morphine, is pharmacogenetically determined.
Individuals with more than one copy of the “normal” gene producing the cytochrome P450 enzyme 2D6 (CYP2D6) will be ultra-rapid metabolizers and, in the case of codeine, will produce MORE morphine than expected; this will have a much greater effect on the patient.
In contrast, if the patient DOES NOT have the normal gene present, the patient will be considered a poor metabolizer, and those patients with variations in the gene-producing CYP2D6 will have LESS metabolism.
Acetaminophen Dosing
Normal maximum dose: 4,000 mg/ day
Older adult maximum dose: 3,000 mg/day
Lower maximum doses are recommended when two or more alcoholic drinks per day: 2,000 mg/day
Medical Cannabis Contraindications
Neuro disorders, dyskinetic disorders, pts w/ psychosis (esp w/ hx or risk of suicide attempts, schizophrenia, or bipolar disorder).
Pregnant or breastfeeding women, adolescents, and neonates.
Severe cardiopulmonary disease severe liver or kidney disease.
Cannabis Use Disorder
A problematic pattern of cannabis use leading to clinically significant impairment or distress.
Cannabis withdrawal syndrome
Arise within 8 days of stopping cannabis use in daily users or almost daily users in people who have been using it over several months.
Mild depression, cravings, irritability, mood swings, aggression, sleep disorders, loss of appetite, and lack of concentration.
Different Types of Cannabinoids
Delta 9 tetrahydrocannabinol (THC)
CBD
CBN
THCV
Types of Synthetic Cannabinoids
Marinol (Dronabinol)
Syndros (Dronabinol)
Cesamet (Nabilone)
Epidiolex (Cannabidoil)
Pharmacokinetics of Cannabinoids
Metabolized extensively by the liver → Consider monitoring liver enzymes
Half-life is estimated at 18-32 hours
Highly protein bound → monitor warfarin, cyclosporin, or amphotericin B).
Cannabinoids Bioavailability
Rapid bioavailability (31%) and peak plasma concentration (< 10 min) with aerosolization or vaporization (inhalation).
Bioavailability of only 6% from enteral delivery due to significant first-pass metabolism in the liver (edibles).
Symptoms of Cannabis Overdose
Common adverse effects of cannabis include dizziness, reddened eyes, dry mouth, dysphoria, ataxia, sedation, changed visual perceptions, altered sense of time, and bronchitis.
Caution in the older person → sedation and ataxia.
No CB receptors on the brain stem → no resp. depression.
Biguanides - Metformin Side Effects
GI upset (N/V/D/gas/loss of appetite/metallic taste).
Adverse events: lactic acidosis (especially with CKD/AKI).
GI upset rare in late therapy: new onset N/V → lactic acidosis
**LEAST likely to produce hypoglycemia
Sulfonylureas Side Effects
Weight gain
Adverse events: hypoglycemia, sulfa allergy.
Associated ww alcohol abuse and overexertion.
Thiazolidinediones Side Effects
Sodium retention, weight gain, fat redistribution.
Adverse events: Hepatotoxicity, CHF exacerbation, risk of bladder CA, hypoglycemia in combination with other oral antidiabetics, decreased effectivity of OCP’s
Use alternative contraception!
Meglitinides Side Effects
Weight gain, GI upset
Adverse events: Hypoglycemia, upper respiratory infections, headache, arthralgia, back or chest pain, constipation/diarrhea
Avoid with BB’s or alcohol
Alpha Glucosidase Inhibitors Side Effects
GI upset due to delayed carbohydrate absorption (abd distention, gas, diarrhea).
Incretins Side Effects
N/V/D/Dyspepsia
Adverse events: Pancreatitis
Hypoglycemia in combination with a sulfonylurea
DPP4 Inhibitors Side Effects
Nausea at onset of therapy, upper respiratory infections, UTI’s, headaches
Adverse events: Hypoglycemia in combination with a sulfonylurea,
Additional postmarketing reports for Sitagliptin: hypersensitivity reactions, Steven Johnson syndrome, potentially fatal pancreatitis, hepatic enzyme elevations.
SGLT2 Side Effects
UTI’s, candida vulvovaginitis, weight loss,
Adverse events: Hypotension, dehydration, hyperkalemia, renal insufficiency, mycotic infections.
Dopamine Receptor Agonist Side Effects
Nausea
Adverse events: Somnolence, fatigue, dizziness, vomiting, HA, orthostatic hypotension.
Amylin Analog Side Effects
Nausea
Adverse events: vomiting, HA, anorexia.
Rapid Acting Insulin Examples
Aspart (Novolog)
Glulisine (Apidra)
Lispro (Humalog)
Rapid Acting Insulin Timing
Meal-time insulin, based on daily need or carb content.
Onset 10-30 mins, peak 30-90 mins.
Short Acting Insulin Examples
Regular (Humulin or Novolin)
Velosulin (Insulin pump)
Short Acting Insulin Timing
Onset 30-60 mins
Peak 2 hours
Intermediate Acting Insulin Example
NPH
Intermediate Acting Insulin Timing
Onset 1-2 hours, peak 4-12 hours
Combined with rapid or short-acting
Long Acting “Basal” Insulin Examples
Glargine (Lantus)
Detemir (Levimir)
Degludec (Tresiba)
Long Acting “Basal” Insulin Timing
Peakless
Biguanide Ex./MOA/Indications
Metformin
MOA: Decreases hepatic glucose production and increases peripheral insulin sensitivity
Little/no risk of hypoglycemia, no weight gain, and cheap.
Sulfonylureas Ex./MOA/Indications
Glipizide, Glimepiride and Glyburide
MOA: Stimulate beta cells of the pancreas
Effective early in the disease process
Promote weight gain
Cheap as generics and come in short and long acting forms
Thiazoladinediones Ex./MOA/Indications
Pioglitazone (Actos)
MOA: Bind to peripheral skeletal cells, improve insulin sensitivity and decrease resistance
Takes 4-6 weeks to work
Causes Na+ retention so contraindicated in HF and RF
Causes weight gain/fat redistribution (*Arn mentioned twice in her DB response)
Meglitinides Ex./MOA/Indications
Repaglinidine (Prandin)
Nateglinide (Starlix)
MOA: stimulate a rapid short burst of insulin
Effective in patients that become hypoglycemic with sulfonylureas
Effective for patients with irregular meal schedules
Alpha Glucosidase Inhibitors Ex./MOA/Indications
Acarbose (Precose)
MOA: Inhibit glucose absorption in gut
Poorly tolerated due to GI upset
DPP4 Inhibitors Ex./MOA/Indications
“-agliptin”
MOA: block GLP-1 and increase the amount of circulating incretins
Weight neutral
Nausea at onset of therapy
Few contraindications besides t1dm, renal failure and pancreatitis
Combination Antidiabetic Medications Therapy
DPP4 should not be prescribed together with GLP1 because GLP1 medication produces natural GLP 1, so the DPP4 enzyme doesn’t affect it.
DPP4 + Sulfonylureas = Hypoglycemia
SGLT2 can be prescribed in non-DM patients. Can be prescribed in metformin to preserve kidney function, reduce MACE, and weight loss.
Metformin Contraindications
CHF, pregnancy, heavy ETOH use, Cr > 1.4.
Must be DC’d before contrast material.
Metformin Monitoring
Initiate therapy and evaluate in 3 months.
Goal is an a1c of less than 7%.
Metformin can potentially lower a1c by 1.5-2%
Metformin Side Effects
GI (N/V/D/Bloating/Gas/loss of appetite).
Hypothyroidism Medications
Levothyroxine (T4):Synthroid or Levoxyl (*brand name=best)
Thyroid Replacement Alternatives = Cytomel (pure T3) and Armour thyroid (Dessicated thyroid combination, variable T3).
Hyperthyroidism Medications
1st line: Methimazole (Tapazole)
Propylthiouracil (PTU)
Radioactive Iodine- 131I or Lugols (SSKI) for pts w/ persistent symptoms despite using Tapazole or PTU → Destroys & shrinks the thyroid, which can help w/the removal.
Adjunctive Hyperthyroidism Medications
Beta-blockers (propranolol, atenolol) can help with symptoms (HR, anxiety).
Lithium- blocks the release of thyroid hormone from the gland.
Glucocorticoids reduce conversion T3→ T4 (prednisone, hydrocortisone)
Monitoring Treatment of Thyroid Disorders
Monitor TSH & Free T 4 (TSH Goal 0.5-4.5 mIU/ml) every 4 to 6 weeks until the patient is stable
Steady-state 6-8 weeks after initiating treatment
Patient should start to feel symptom relief in 2-4 weeks
Once at a therapeutic level, check every 6 months and then eventually can be checked annually.
Thyroid Medications with Life-Threatening Side Effects
PTU & methimazole can cause fatal agranulocytosis.
(Rare, occurs more w/ PTU than methimazole).
PTU BB warning for severe liver injury
Levothyroxine- increases the risk of cardiac events (arrhythmias, HF), esp in pts w. pre-existing disease.
Signs + Symptoms of Agranulocytosis
If the patient is experiencing any symptoms of illness (sore throat, fever) or flu-like symptoms - it could be agranulocytosis - check and monitor CBC!
*CBC and full LFTs before treatment initiation.
Oral Antidiabetic Medications
Biguanide → Metformin
Sulfonylureas → Glipizide, Glimepiride and Glyburide
Thiazolidinediones (TZDs) → Pioglitazone (Actos)
Meglitinides → Glinides → repaglinide (Prandin) and nateglinide (Starlix)
Alpha Glucodase Inhibitors → Acarbose (Precose)
Dipeptidyl Peptidase 4 (DPP4) Inhibitors → Liptins → sitagliptin (Januvia), saxagliptin (Onglyza) and Linagliptin (Tradjenta)
Incretin Mimetics (Glucagon Like Peptide 1 (GLP1) Receptor Agonist) → semaglutide (Rybelsus) → only GLP1 in the oral form. Good for patients who have injection phobia and would rather take a pill.
Sodium-Glucose Transporter 2 (SGLT2) → Flozins → canagliflozin (Invokana), dapagliflozin (Farxiga) and empagliflozin (Jardiance).
Injectable Antidiabetic Medications
Incretin Mimetics (Glucagon Like Peptide 1 (GLP1) Receptor Agonist)
“-Tides” → exenatide (Byetta, Bydureon), liraglutide (Victoza) and dulaglutide (Trulicity).
Treatment Hyperthyroidism in Pregnancy
Propylthiouracil (PTU) drug of choice
Use the lowest possible dose; the dose usually decreases as pregnancy progresses, and increases again after birth.
No radioactive iodine because it crosses the placenta
No Methimazole first trimester- birth defects (can restart in 2nd and 3rd)
PTU preferred in Breastfeeding (textbook).
