Week 6 Respiratory and Gout Flashcards
Asthma
Chronic inflammatory disorder of the airways
50% results from an immune response to an allergen
Allergen binds to IgE on mast cells
Mast cells release mediators (DRUGS TARGET THESE)
Mediators cause bronchoconstriction and airway inflammation
COPD
3rd leading cause of death
Irreversibel symptoms from:
Chronic bronchitis (chronic cough with excessive sputum production)
Emphysema– enlargement of airspace within the bronchioles/alveoli
Diagnoses: FEV1/FVC= <0.7 (70%)
Inflammation from mediators inhibits protease inhibitors who protect and maintain alveoli integrity; without them enzymes break down elastin
Anti Inflammatory
Glucocorticoids
Budesonide and Fluticasone
MOA: < release of inflammatory mediators (histamine, leukotrienes, and prostaglandins)
USE: Asthma prophylaxis and COPD exacerbation mangement
ADE: inhaled: oral thrush; long term adrenal suppression and bone loss
ORAL glucocorticoids can cause toxicity and should not be first line
PT ED: intended for prevention not acute attacks; rinse mouth post use
Anti Inflammatory
Leukotriene Receptor Antagonists
Zilueton; Zafirlukast (prototype)
Montelukast (TESTED ON) Only one approved for children 1-3
MOA: high affinity for leukotriene receptors in the airway on pro-inflammatory cells blocking receptor activation
Use: prophylactic and maintenance therapy for asthma; prevention of EIB exercise inducted bronchospasm
ADE: possible neuropsychiatric impact (mood/ suicide)
PT ED: Cannot be used for quick relief from an attack
Provider considerations: SABA preferred for EIB
Anti Inflammatory
Other Category (1 drug)
Cromolyn
Inhaled agent that suppresses bronchial inflammation
Use: Prophylaxis in mild to moderate asthma
Less effective than glucocorticoids; not preferred
Only prescribe is pt has an issue with glucocorticoids
SAFEST DRUG
Admin via nebulizer
Anti Inflammatory Life Stages
inhaled glucocorticoids are preferred tx for children, pregnant women, breastfeeding, and inhaled is safer than systemic in all categories for older adults
MABS Monoclonal Antibodies
OmalizuMAB
Tx asthma
MOA: forms complex with IgE reducing amount of IgE available to bind with mast cells limiting mediator release
Approved for ages 6 and ^ for allergy related asthma not controlled by glucocorticoids
Sub Q injection; half life 26 days
Once stopped, will take IgE 1 year to return to pretreatment levels
Phosphodieterase 4 Inhibitor
Roflumilast
MOA: target ^ cAMP to inhibit inflammation
Use: mange COPD w/ primary chronic bronchitis component; exacerbation prophylaxis
ADE: headache, insomnia, GI (N/V/D weight loss, reduced appetite)
Bronchodilators
Anticholinergic Drugs
IpraTROPIUM/ TioTROPIUM
IpraTROPIUM
SAMA
MOA: Blocks muscarinic receptors in bronchi reducing bronchoconstriction
USE: COPD approved
ADE: minimal dry mouth or irritation of pharynx
***PT ED: Risk for ^ interocular pressure; frequent eye exams with glaucoma
TioTROPIUM
Long acting muscarinic antagonist (LAMA)
Same use/ effects peak 3 hours; last 24 hours
Each dose more relief; plateau at 8 days
ADE: dry mouth; less common anticholinergic effects: can’t see, can’t pee; can’t spit, can’t shit)
Bronchodilators
Beta 2 Agonists SABA
Albuterol/ Xopenex/ Levalbuterol/ Proair/ Proventil
Use: 1st line acute asthma attacks; prophylaxis EIB
MOA: activates B2 receptors; smooth muscle in lung promotes bronchodilation
Dose: 1-2 breaths
Pt ED: cannot be used for prolonged prophylaxis, only for acute attack and EIB prophylaxis
PRN
Albuterol in Neonates: prevent BPD, relive brochospasm, TTN, viral bronchiolitis (all little research)
Intra-tracheal albuterol and surfactant; positive effect in reducing Intubation- Surfactant Extubations failure
Bronchodilators
Beta 2 Agonists LABA
Salmeterol/ Formoterol/ Arformoteral
MOA: activates B2 in lung
Use: longterm prophylaxis in pts with frequent asthma attacks; Preferred in COPD
PT ED: Take on a fixed schedule
BLACK BOX: Asthma related deaths from monotherapy
Bronchodilator
Unknown Mechanism
Methylxanthine
MOA: unknown
USE: maintenance therapy for asthma; nocturnal asthmatics; not for COPD
ADE: r/t toxicity; NV and tachy-dysrythmias
If toxic dose, stop dosage and consider charcoal
PT ED: Drug interactions: caffeine, tobacco, phenobarb, phenytoin, rifampin, and fluoroquinolone abx
Bronchodilator Life Stage
SABAs are for children >2
Methylxanthines for any age (neonates)
Preg: beta 2 agonists exceed risk of uterine relaxation and poor oxygen delivery to fetus
Anticholinergics are the safest
Breastfeeding: avoid methyxanthine
Older: systemic anticholinergics BEERS list
Methyxanthine risk of toxicity; avoid
Treatment Goals ASTHMA
Reduce impairment
Reduce Risk
Severity of illness:
Intermittent: Step 1
Mild persistent: Step 2
Moderate persistent: Step 3
Sever persistent: Step 4/5
Step 1: PRN SABA
Step 2: daily low dose ICS and PRN SABA/// OR/// PRN concomitant ICS and SABA
Step 3: Daily and PRN combo of low-dose ICS–Formoterol
Step 4: Daily and PRN combo medium dose–Formoterol
Step 5: Daily medium high dose ICS-LABA + LAMA and PRN SABA
Step 6: Daily high dose ICS-LABA +oral systemic corticosteroids and PRN SABA
Treatment Goals for COPD
Reduce Symptoms
Reduce Risk
Diagnosis: GOLD assessment
0-1 Moderate exacerbations not leading to hospitalization:
Group A: bronchodilator
Group B: long acting bronchodilator (LABA or LAMA)
> 2 moderate exacerbations or >1 leading to hospitalization:
Group C: LAMA
Group D: LAMA or LAMA + LABA or ICS + LABA
Allergic Rhinitis
Inflammatory disorder affecting upper airway
Sneezing, rhinorrhea, pruitis, nasal congestion
Main cause: Dilation and increased permeability of nasal blood vessels
Triggered: airborne allergens that bind to mask cells
Seasonal: hay fever, occurs in spring and fall, fungus, pollen, weed grass, trees
Perennial: Indoor allergens, pet dander, dust mites
Allergic Rhinitis
Drug Categories and Drugs
Inranasal Glucocorticoid: Beclomethasone
Antihistamine: Azelastine/Loratadine
Intranasal Sympathomimetics: Phenylephrine; oxymetazoline
Oral Sympathomimetics: Psuedoephendrine
Allergic Rhinitis
Glucocorticoids
Beclomethasone/ budesonide/ fluticasone propionate/ triamcinolone
prevent inflammatory response to allergies; reduce symptoms
ADE: nasal irritation, burning/ itching, sore throat, nose bleeds, headache
MOST EFFECTIVE
Metered dose spray
Admin daily
Allergic Rhinitis
Antihistamines
Azelastine/ Olopatadine
H1 receptor antagonist
first line for mild to moderate rhinitis
more effective taken prophylactically
Relieves sneezing and nasal itching but not congestion
ADE: sedation, dry nose, dry mouth, constipation, urinary hesitancy
Sympathomimetics (Decongestants)
Psuedoephendrine
Activate A1 adrenergic receptors on nasal blood vessels
Only relieves congestion
ADE: Rebound congestion, CNS stimulation, CV impact, abuse
TX Allergic Rhinitis based on chief complain
Nasal Decongestion: glucocorticoids and oral decongestant
Intermittent sneezing and rhinorrhea: oral and internasal antihistamine
Mild symptoms: oral antihistamine
Moderate to severe: nasal glucocorticoids. intranasal antihistamines, and combo therapy
Cough
Not all cough is useful
irritation of bronchial mucosa reflex
Opiod antitussive, non opioid antitussive, expectorants, mucolytics
Cough opioid antissive
Codeine, hydrocodeine
Suppress cough
1/10 of the dose for pain (10-20mg PO)
Not recommended in kids
Cough Non opioid antissive
Dextromethorphan
Acts in CNS
Can cause euphoria
10-30mg Q 4-8 hours
Diphenhydramine
Antihistamine
mechanism to suppress cough is unclear
Can cause Sedation
Benzonatate Decreases cough by decreasing sensitivity of respiratory tract stretch receptors
Avoid in children < 10
adopt dose 100mg TID
Cough Expectorants and Mucolytics
Expectorants Efficacy??
Guanifenesin
makes cough more productive
Mycolytics
Acts directly with mucus to make more watery
Acetycysteine and hypertonic saline
Cold Combo Remedies
Nasal Decongestant
Antitussive
Analgesic
Antihistamine (suppress mucus secretion)
Caffeine (offset sedation from antihistamine)
Do not use in children; especially antihistamines and codeine
>1 yr: honey for sore throat
>2 yr: mentholated chest rubs (VICKS) for cough
Acetaminophen and ibuprofen for discomfort
Rheumatoid Arthritis
Autoimmune inflammatory disease
Attacks joints (hands, wrists, knees)
lining of joined becomes inflamed causing damage to tissue
can attack HRT/Lungs/Eyes
Diagnose: pain/stiffness/tenderness in more than one joint, on both sides
Management of Rheumatoid Arthritis
Goal: Relieve symptoms, mange pain, maintain function of joints, delay disease progression
DMARDS: Disease Modifying Antirheumatic Drugs
conventional, biological, targeted
take time to work (weeks-months)
Nonsteroidal Anti-inflammatories: manage pain while waiting for DMARDS
Glucocorticoids directly injected into joint for flare ups and relief while waiting on DEMARDS
DMARDS: Conventional: First line drug
Methotrexate
Faster acting than other DMARDS (3-6 weeks to therapeutic range)
MOA: Folate antagonist (inhibit DNA)
Immunosuppression 2/2: reducing activity of the B and T lymphocytes
ADE:
BLACK BOX: fatal toxicities to bone marrow, liver, lungs, kidneys, hemorrhagic enteritis, gastrointestinal perforation
Can cause fetal death and congenital abnormalities
Supplement with folic acid 5mg/week: reduce GI/hepatoxicity
Avoid drugs: with liver injury, alcohol, myelosupression
Reduces response to vaccines
live vaccines are contraindicated
Prior to stating: vaccine PNA, Flu, HepB, HPV, Herpes zoster
DMARDS: Conventional: 2nd Line
Leflunomide
2nd line therapy
Equally as efficacious
More expensive and hazardous!!!!
Prodrug
MOA: Inhibits Tcell proliferation and antibody production
ADE: diarrhea; respiratory infection, reversible alopecia and rash
Pancytopenia, SJS, peripheral neuropahty; intestinal disease and severe hypertension
Hepatotoxic and Immunosupresive
Teratogenic:
3 steps to clear system for pregnancy: D/C drug/ Cholestyramine dosed for ll days/ plasma drug levels <20mcg/L (may stay in body up to 2 years if drug is not given)
NSAIDS: risk of inhibiting metabolism and ^ drug level in body
Rifampin: ^ Leflunomide levels in body do not admin together
DMARDS Conventional Sulfa
Sulfasalazine
can slow profession of joint deterioration
GI reactions; skin reactions; liver injury; none marrow suppression
Avoid in Sulfa allergy
DMARDS Conventional Hydro
Hydroxychloroquine
used only on combo with Methotrexate
MOA in RA unknown
Delayed onset 3-6 months
ADE: retinal damage (directly related to dose levels), caridomyopathy, QTc prolongation, Hypoglycemia
DMARDS Biologics
TNF Inhibitors
Etanercept
Inflixmab
Adalimumab
Golimumab
Certolizumab Pegol
Etanercept: first available; inhibit tumor necrosis factor to prevent inflammation
Mod-Sever RA
Superior to methotrexate
ADE: RISK FOR INFECTION/SEPSIS/DEATH
injection site reactions
children-lymphoma
May ^ HRT failure; ^risk of cancer, ^ risk of liver injury
Reduce vaccine efficacy
Infliximab Admin IV
similar to Etanercept
DMARDS Biologics
B-lymphocyte Depleting Agents
Rituximab
Reduce # of B Lymphocytes which cause attach on joints
CD20 monoclonal antibody
Mod-severe RA in combination with methotrexate in patients who have not responded to TNF inhibitors
Admin IV
ADE: infusion reaction 80%; premeditate: antihistamine, acetaminophen, methylprednisone
Mucocutaneous reactions: SJS, TEN, lichenoid dermatitis (1-3 weeks after)
Hep B reactivation
Progressive multifocal leukoencephalopathy (severe infection of CNS; d/c if seen immediately)
DMARDS Biologics
T cell Activation Inhibitors
Abatacept
T cells inhabit the synovium of joints in pts with RA; cause autoimmune attach
MOA: bings to antigens presenting T cells
Mod-Severe RA
< symptoms in mod-severe polyarticular juvenile idiopathic arthritis
ADE: Headache, upper respiratory infection; nausea
IMMUNOSUPRESSION
Blunts vaccine effectiveness
NOT WITH TNF inhibitors (^risk infection)
But yes with conventional DMARDS
DMARDS Biologics
Interleukin 6 receptor antagonist
Tocilizumab
Expensive
Only used when not responding to other DMARDS
Only combine with methotrexate; all others ^risk of infection
ADE: infection; neutropenia; thrombocytopenia; GI perf; liver
DMARDS Biologics
Interleukin 1 receptor antagonists
Anakinra
Mod-severe RA and not responding to other drugs
ADE: Severe infection
Targeted DMARDS
Janus Kinase Inhibitors
Tofacitinib Baricitinib
Prevents activation of STAT pathway
Failed other DMARD treatment
ADE: long term unknown; risk for serious infection
RA Recommendations
1st DEMARD moderate disease: Methotrexate
Glucocorticoids: if conventional DMARD prescribed with a therapeutic dose in 3-6 weeks recommended not to use; however, >3 months wait then use
Low disease RA: Hydroxchloroquine over csDMARDs
Admin of methotrexate
initially oral is recommended over sub q
Titrate to a dose of 15mg within 4-6 weeks
Not tolerating weekly dosing; try split dose of oral or sub q weekly and increase folic acid before switching to an alternative DMARD
RA Lifespan DMARD
children taking TNF risk for lymphoma
Pregnant: TNF cat B, Hydroxychloroquine and sulfasalazine cat B
Azathioprine is teratogenic
Leflunomide: 3 step process to clear system before trying to get pregnant; toxic to fetus
Methotrexate toxic to fetus
Do not take DMARDS while breastfeeding
Older: > risk for infection
Gout
recurring inflammatory disorder that can be painful and disabling
Sever joint pain; hyperuricemia (>6 crystal formation)
Risk: Male, onset, alcohol, red meat, CHF, HTN, DM, Metabolic syndrome, kidney dysfunction
Diagnose: blood uric levels, uric acid crystals in affected joints
only diagnosed during a flair up
First sign: big toe in 50% of cases
Acute Attack Gout
Colchicine
Anti inflammatory
gout attack: ^ dose, relief in hours
Prevention low dose
Administer with ULT to prophylactically prevent flare ups which waiting for ULT to be effective
ADE: N/V/D
Myelosuppression (leukopenia)
Myopathy
Interacts with STATINS/ PGP inhibitors or CYP3A4 inhibitors
Long Term Gout
Reduce urate
goal: uric acid level 6 or lower to dissolve or prevent crystals
Allopurinol
MOA: Xanthine oxidase inhibitor
ADE: N/V/D; cataract formation; bone marrow suppression; rash
Drug drug: theophylline and WARFARIN
Probenecid
MOA: acts at renal tubules to inhibit reabsorption of uric acid
Delay therapy if onset of acute attack: will take wks/months for drug
ADE: N/V/D, rash, hypersensitivity, G6PD deficiency
Renal injury: weeks to months to lower uric acid; crystals can form initially; reduce the risk by drinking 3 liters of water daily to alkalinize urine
Pegloticase IV Admin
last line for those nor responding to oral
very expensive
ADE: anaphylaxis in 6% pt
40% infusion reactions
provide antihistamine and glucocorticoid prior to admin
Gout Management
Urate lowing therapy not recommended in patients experiencing first attack
ULT for subcutaneous tophi, radiographic damage; frequent flare ups (>2 annually)
Not recommended in pts with asymptomatic hyperuricemia
Gout ULT First line
Allopurinol > Probenecid> Pegloticase
Admin NSAIDS, colchicine, steroids for anti-inflammatory prophylaxis when starting a UTL and continue for 3-6 months
Random MABS
Bezlotoxumab: C Diff; combine with abx for bacterial tx
Erenmab: migraine; monthly sub q injection
ADE: immune reaction, anaphylaxis, cytokine release syndrome (manage with tocilizumb), derm/GI/liver toxicity
