Pharm Kelsey and Amy Flashcards
1
Q
Can Conventional Synthetic drugs treat other conditions?
A
Yes - Cancer, Chron’s, RA, Ulcerative Colitis
2
Q
Conventional Synthetic Drugs
A
Hydrocholorquine, Sulfasalazine, Leflunomide, Methotrexate
3
Q
How do you decide what drug to use?
A
Drug safety, efficacy, disease severity, cost, patient experience
4
Q
What is the initial treatment choice for RA?
A
Methotrexate
5
Q
MOA for Methotrexate
A
Anti-inflammatory inhibits dihydrofolate reductase (inflammatory factors) which prevents folic acid (FH2) from converting to active form (FH4)
6
Q
What must be given in combo with Methotrexate?
A
Folic Acid
7
Q
What does Folic Acid supplementation prevent?
A
Reduces risk of folate depleting reactions Methotrexate Toxicity
8
Q
Folic Acid prophylactic dose
A
1 gram
9
Q
Methotrexate route of admin
A
PO, IM, SubQ
10
Q
Methotrexate AE
A
Nausea, diarrhea, hepatotoxicity, alopecia, new cough, SOB, myelosuppression
11
Q
Methotrexate contraindication
A
Hepatic Impairment
12
Q
What to monitor with methotrexate use
A
CBC, creatinine, LFT (every 4-8 wks), signs of infection
13
Q
What to avoid when taking methotrexate
A
Pregnancy, alcohol
14
Q
What DMARDs medication is category X for pregnancy?
A
Methotrexate
15
Q
What does methotrexate cause if taken when pregnant?
A
Spontaneous abortion, myelosuppression in fetus, limb defects, CNS abnormalities
16
Q
Cautious measures with methotrexate
A
Birth control and dose adjustment for renal impairment
17
Q
Signs of methotrexate toxicity
A
Stomatitis, diarrhea, nausea, alopecia, myelosuppression (fever, infection, easy bruising, bleeding), elevation in liver fxn tests
18
Q
What do you give to prevent Methotrexate Toxicity? What do you give if Methotrexate Toxicity occurred?
A
Folic Acid or Leucovorin (cancer drug)
19
Q
What does Leucovorin provide in the active form?
A
Folic Acid (X-FH4)
20
Q
MOA for Hydroxychloroquin
A
Unknown
21
Q
Use for Hydroxychloroquin
A
Low RA disease activity
22
Q
Can Hydroxychloroquin be combined?
A
Yes - with methotrexate or sulfasalazine
23
Q
Hydroxychloroquin route
A
Oral
24
Q
Hydroxychloroquin AE
A
Nausea, diarrhea, headache, vision changes, skin pigmentation
25
Hydroxychloroquin onset time
Slow must use for 6 mo to determine if effective
26
When would Hydroxychloroquin be a good choice?
Renal, hepatic, or bone marrow suppression
27
What to monitor with Hydroxychloroquin use?
Annual eye exam
28
Sulfasalazine MOA
Unknown
29
When is Sulfasalazine used?
For low RA disease activity
30
Sulfasalazine onset time?
Slow onset - must use for 6 mo to determine if effective
31
When would Sulfasalazine be a preferred option?
Pregnancy!
32
Can you combine Sulfasalazine?
Yes - with methotrexate or hydroxychloroquin
33
What is Sulfasalazine's route of administration?
Oral
34
How do you dose Sulfasalazine?
Start with low dose and titrate up slowly
35
Sulfasalazine AE
Nausea, abdominal discomfort, diarrhea, leukopenia, myelosuppression, rash, yellow-orange discoloration, photosensitivity (easily sunburn!)
36
What is a contraindication to taking Sulfasalazine?
Sulfa allergy
37
Who should avoid taking Sulfasalazine?
Those with hepatic impairment
38
Why should you adjust the dose of Sulfasalazine
Renal impairment status
39
What to monitor when taking Sulfasalazine
CBC every 2-4 weeks for 3 mo, then every 3 mo
40
MOA of Leflunomide
Inhibits t-lymphocyte response which halts the inflammatory cascade
41
What type of half life does Leflunomide have?
Long
42
How should you start a patient on Leflunomide?
Loading dose followed by a maintenance dose
43
Can you combine Leflunomide?
Yes - with Methotrexate, but it INCREASES RISK OF HEPATOTOXICITY!
44
How can you discontinue Leflunomide abruptly?
Give cholestyramine (removes from body quickly)
45
Why would you want to discontinue Leflunomide abruptly?
Pregnancy or toxicity
46
When should you use Biological DMARDs
If a patient fails trail of conventional DMARDs or used in combo with a conventional DMARD in early aggressive disease.
47
Do conventional or biological DMARDs work faster?
Biological
48
Can Biological DMARDs be used with methotrexate?
Yes
49
What do you base your choice of Biological DMARDs of off?
Comfort level, severity of disease, prognosis, frequency/route of administration, patient's comfort level, cost, insurance
50
Who should avoid using Biological DMARDs?
Patients with serious infections, demyelinating disorders, hepatitis
51
Who should avoid using TNF antagonists?
Patients with heart failure
52
What other conditions use Biological DMARDs?
Patients with cancer and chrons
53
What are the classes of Biological DMARDs?
TNF antagonists, Interleukin-1 receptor antagonist, Costimulation modulators, Anti-CD20 monoclonal antibody, Anti-interleukin-6 receptor antibody
54
What are the drug names of the TNF Antagonists?
Etanercept (Enbrel)
Adalimumab (Humira)
Infliximab (Remicade)
Golimumab (Simponi)
Certolizumab (Cimzia)
55
What are the adverse reactions of TNF Antagonists?
Injection site reactions and Infusion reactions (can be helped by using topical corticosteroids, antipruritics, analgesics, rotate site).
56
What should you monitor in TNF Antagonists?
Serious infection
57
What should you screen for before giving a TNF Antagonist?
TB (could reactivate if TNF is inhibitied. TNF involved in forming granulomas that wall off TB) and Hepatitis
58
What is the MOA of TNF Antagonists?
Prevent action of TNF, causing a reduction in inflammation
59
What are the signs of an infusion reaction? What should you do if someone has a reaction?
Rash, urticaria, flushing, headache, fever, chills, nausea. Treatment is to temporarily d/c, slow infusion rate, corticosteroids/antihistamines.
60
What is the route of administration of Infliximab?
Given IV
61
What is the route of administration of Adalimumab (Humira)
SubQ
62
What is the route of administration of Golimumab (Simponi)
SubQ or IV
63
What are the drug names of Costimulation Modulators?
Abatacept (Orencia)
64
What is the MOA of Costimulation Modulators?
Blocks T cell signaling and activation (prevents response)
65
What are the adverse effects of Costimulation Modulators?
Headache, infection, infusion reaction, injection site reaction
66
What should you monitor Costimulation Modulators?
Infection
67
What is the use of Costimulation Modulators?
Monotherapy or combo therapy after inadequate response of methotrexate and/or anti-TNF
68
What are the Anti-CD20 Monoclonal Antibody drug names?
Rituximab (Rituxan)
69
What is the MOA of Anti-CD20 Monoclonal Antibody?
Causes B lymphocyte depletion in bone marrow and synovial tissue. Fewer B lymphocytes to cause inflammation response.
70
Do patients with rheumoatoid factor postive RA have a better or lesser response to Anti-CD20 Monoclonal Antibody?
Better
71
What is the Black box warning of Anti-CD20 Monoclonal Antibody?
Fatal infusion reactions, severe mucocutaneous reactions
72
When should you use Anti-CD20 Monoclonal Antibodies?
As LAST resort - HIGH RISK
73
What is the AE of Anti-CD20 Monoclonal Antibody?
Infusion reaction
74
What should you monitor for when taking Anti-CD20 Monoclonal Antibody
Infection
75
What are the Anti-interleukin-6 Receptor Antibody drug names?
Tocilizumab (Actemra)
76
What is the MOA of Anti-interleukin-6 Receptor Antibody?
Blocks interleukin-6 (causes joint damage, disease activity, and anemia)
77
What is the route of administration for Anti-interleukin-6 Receptor Antibody?
IV or SubQ
78
When would you use Anti-interleukin-6 Receptor Antibody?
After Biological DMARDs have failed
79
What is the AE of Anti-interleukin-6 Receptor Antibody
Elevated LFT/Total Chol/Trigs/HDL, nasopharyngitis, infection
80
What to monitor when using Anti-interleukin-6 Receptor Antibody
Infection, LFTs
81
Targeted Synthetic drug names
Tofacitinib
82
What is the MOA of Targeted Synthetic?
Inhibits specific kinases
83
What is the route of administration for Targeted Synthetic?
Oral
84
When would you use Targeted Synthetic drugs?
To treate moderate or severe RA
85
Can you combine Targeted Synthetic drugs?
Yes - with conventional DMARDs (but you can use it as monotherapy)
86
What is the AE of Targeted Synthetic drugs?
Infection, headache, HTN, elevated LFTs, diarrhea, worsening lipids
87
When should you adjust the dose of Targeted Synthetics?
When there is renal or hepatic impairment
88
What should you monitor when taking Targeted Synthetics?
CBC, hemoglobin, lipids, LFTs, infection
89
How should you think about Biosimilar drugs?
As "generic" Bio Originators
90
What DMARD medication is the drug of choice during pregnancy?
Sulfasalazine
91
What other RA medications are ok for pregnancy?
Low dose corticosteroids, hydroxychloroquine, azathioprine
92
What is the MOA of acetaminophen?
Centrally acting analgesic and antipyretic with minimal anti-inflammatory properties
93
What is the onset of acetaminophen?
One hour
94
What is the use of acetominophen?
Mild to moderate pain in general
95
What is the drug name for acetominophen?
Tylenol (APAP)
96
Can APAP be combined?
Yes - with NSAIDs (APAP has equal efficacy as NSAID)
97
What is the max daily dose for APAP?
4000 mg per day
98
What is the max dose of APAP given at a time
1000 mg at a time
99
What is the AE for APAP?
Renal toxicity, hepatic toxicity, GI upset
100
What is the leading cause of acute liver injury?
Acetaminophen Toxicity
101
What can cause Acetaminophen toxicity?
Overdose - many meds contain APAP
102
What can cause CHRONIC Acetaminophen Toxicity?
> 4g daily dose, use of alcohol (2.5 g daily in those drinking 2-3 beverages)
103
What can cause ACUTE Acetaminophen Toxicity?
200 mg/kg or 10g or 10x overdose
104
What are the common signs/sx's of acute APAP toxicity?
Nausea, vomiting, abdominal pain
105
What is elevated after 24 hours of APAP ingestion?
ALT and AST
106
When do ALT and AST peak after ingestion or APAP?
2-3 days
107
What are the more serious effects of acute APAP toxicity?
Liver and renal dysfunction, hyperglycemia, lactic acidosis, coma, death (if serum concentration of APAP is > 500 mcg/mL)
108
True or false: hepatic and renal function return to normal if a Pt survives APAP overdose?
True!
109
What are the mild signs/sx's of chronic supratherapeutic APAP overuse?
ALT elevation, malaise, nausea, vomiting, abdominal pain, hepatotoxicity
110
What are the severe signs/sx's of chronic supratherapeutic APAP overuse?
Jaundice, hypoglycemia, coagulopathy, renal failure, fulminant hepatic failure encephalopathy, death
111
How do you treat mild/moderate supratherapeutic overuse of APAP?
1: Obtain APAP concentration in blood. 2: Start acetylcysteine (if risk of hepatic injury)
112
What is considered mild/moderate supratherapeutic APAP overuse?
If >200 mg/kg ingested or if >10 g ingested, or if APAP concentration can't be measured, or if concentration is >150 mcg/mL at 4 hours post ingestion
113
How do you treat severe supratherapeutic APAP overuse
ER care: intubation, fresh frozen plasma, vasopressors, dialysis, airway management, fluid resuscitation
Start acetylcysteine if hepatic injury risk
114
What is acetylcysteine used for?
Hepatic injury due to severe APAP toxicity
115
What is one of the safest analgesics?
APAP
116
What analgesic is preferred for Pts with mild-moderate pain with hypertension or kidney issues?
APAP
117
What is the MOA of NSAIDs?
All NSAIDs block COX1 and COX2. Has analgesic and antipyretic activities by blocking COX1 and COX2, which causes inhibition of prostaglandins
118
What does COX1 affect?
Gastric mucosa (increase muscus, bicarb), kidney (dilate afferent arteriole), platelets (promote normal function)
119
What does COX2 affect?
Normally undetectable, but increases at sites of inflammation and local tissue injury
120
What COX does selective NSAIDs preferentially block?
COX2
121
What COX does nonselective NSAIDs preferentially block?
Not selective for either
122
What are the nonselective NSAIDs drug names?
Aspirin, salsalate, etodolac, diclofenac, indomethacin, nabumetone, ibuprofen, naproxen, meloxicam, prioxicam, prioxicam, sulindac, ketorolac
123
What nonselective NSAIDs are over-the-counter?
Aspirin, ibuprofen, naproxen
124
What are the selective COX2 inhibitors?
Celecoxib
125
What is the use of NSAIDs?
Used in mild-moderate pain in general. Can be combined with APAP.
126
What is the route of administration with NSAIDs?
Oral, topical
127
What is the efficacy of APAP compared to NSAIDs?
They are equal
128
What is the onset of pain relief with NSAIDs?
1 hour
129
What is the onset of anti-inflammatory effects?
2-3 weeks of continuous therapy
130
What do you choose NSAIDs based on?
Patient preference, previous response, tolerability, dosing frequency, cost, GI and CV risk. if one doesn't work, try another NSAIDs
131
What is the route of administration of Diclofenac?
Gel, solution, patch
132
What are the adverse effects of Diclofenac?
NSAID specific are minimal. Appilcation site dermatitis, pruritus, and phototoxicity.
133
What joints should be used with Diclofenac?
Superficial joints. Hands, wrists, elbows, knees, ankles, feet.
134
What is the dose of Diclofenac?
Depends on the joint.
135
What are the pros of using Diclofenac?
Minimized systemic exposure. Has comparable pain relief to oral NSAIDs.
136
What are the contraindicatations of Ketorolac?
CV disease, GI/peptic ulcer risk, advanced renal impairment, high bleeding risk (on anticoagulants), concomitant NSAIDs.
137
What is the use of Ketorolac?
Commonly used for acute moderately severe pain that requires analgesia at opioid level. Initiate in office/ED with IM or IV then followu p to 5 days oral.
138
How long can you use Ketorolac?
5 days maximum, only for adults
139
What should you take Ketorolac with?
Food
140
What is Salicylism?
Toxic syndrome that occurs due to excessive doses of aspirin, salicylic acid, consuming oil of wintergreen (5mL). Cuased mixed repiratory alkalosis and metabolic acidosis (anion gap). Can occur due to acute overdose (150mg/kg or 6.5g aspirin) or chronic overdose.
141
What are the signs and symptoms of Salicylism?
Severe headache, nausea, vomiting, tinnitus, confusion, increased pulse, increased repiratory rate, can progress to seizures, coma, cerebral/pulmonary edema, death
142
What is the treatment of Salicylism?
Urine alkalinization (sodium bicarb), hemodialysis, emergency care PRN
143
What are the adverse reactions of all NSAIDs, especially in eldery?
GI (COX1 related), renal insufficiency, hepatic dysfunction, increased cardiovascular risk (COX2 related), CNS effects, increased BP/fluid retention, rarely causes tubulointerstitial nephropathy renal papillary necrosis.
144
What are the adverse reactions of COX1 inhibitors?
Adverse effects on gastric mucosa (asymptomatic gastric/duodenal mucosal ulceration), direct irritant effect on GI (nausea, dyspepsia, anorexia, abdominal pain, flatulence, diarrhea), perforation, gastric outlet obstruction, GI bleeding
145
What are the adverse reactions of COX2 inhibitors?
Increased risk of CV events. Degree of COX2 selectivity (dose, potency) dictates how much CV event risk.
146
What selective COX2 inhbitor has the strongest association with CV events?
Celecoxib
147
What nonselective NSAIDs have the strongest association with CV events?
Diclofenac, ibuprofen
148
What increases the CV risk the most?
Selective COX2 inhbitor
149
What NSAID should you use with patients at high risk fo GI complications and low risk for CV events?
Celecoxib (selective COX2 inhibitor)
150
What NSAID should you use in high CV risk patients?
Use nonselctive NSAID, Naproxen. Has the lowest CV event risk. Should also be on aspirin.
151
If high GI risk, use
Gastroprotection to nonselective NSAID or lower Gi risk NSAID (selective COX2 NSAID, celecoxib)
152
If high CV risk +Gi risk
Add gastroprotection and use nonselective NSAID (naproxen)
153
If low CV and GI risk
Use nonselective NSAID
154
NSAID contraindications/cautions
At risk for peptic ulcers or GI risk, bleeding risk, renal insufficiency, uncontrolled HTN, HF. Caution if NSAID/asprin sensitive asthma.
155
NSAIDs and pregnancy
Risk of feal bleeding. Possibly contraindicatied, associated with miscarriage in 1st trimester. Contraindicated after 30 weeks/3rd trimester, promotes closure of ductus arteriosus.
156
NSAID interactions
Aspirin, warfarin, oral hypoglycemics, antihypertensives, lithium. Due to high protein binding, detrimental renal effects, antiplatlet activity.
157
What medication is used to stop gout attacks?
Colchicine
158
Can you use colchisine for an acute gout attack if already taking it for prophylaxis or recently taken (in last 14 days)
No!
159
Could you give colchisine 48 hours after the acute attack begins?
No - it only works if given right away (<36 hrs)
160
What fraction of people respond to colchisine w/in the first 24 hours of attack?
2 out of 3
161
What is the MOA of Colchisine?
It interferes with the migration of neutrophils to sites of inflammation induced by deposits of monosodium urate crystals in synovial fluid anti-inflammatory
162
Is Colchisine an analgesic or uricosuric (clears uric acid)?
No
163
Is there a generic Colchisine drug?
No - it is brand name only (more expensive)
164
Is Colchisine FDA approved?
Yes - recently! And now properly labeled and the dose changed (lower)
165
What are the AE of Colchisine?
Toxicity
166
What are the signs that Colchisine toxicity could happen?
Nausea, vomiting, diarrhea, abdominal pain
167
What are the signs that Colchisine toxicity HAS happened?
Myopathy, bone marrow suppression (neutropenia)
168
What should you be cautious of when taking Colchisine?
Renal insufficiency (toxicity is more likely adjust the dose!)
169
What kind of therapeutic window does Colchisine have?
Low
170
What class of drugs does Colchisine interact with?
P-glycoprotein or strong CYP3A4 inhibitions
171
What specific drugs does Colchisine interact with?
Clarithromycin, Verapamil, Ritonavir, Cyclosporine, Ranolazine
172
What should you do if Pt is experiencing numerous AE on Colchisine?
Adjust dose or try NSAIDs
173
What is urate lowering therapy used for?
To prevent future gout attacks
174
What is the criteria for using urate lowering therapy?
Recurrent attacks (>2xyear), Tophi, CKD Stage 2 or worse, past urolithiasis
175
In what ways can urate lowering therapy prevent future gout attacks?
Either decrease uric acid production or increase uric acid secretion
176
What is the goal of urate lowering therapy?
Decrease uric acid levels and prevent crystal formation
177
What are the FIRST LINE Urate Lowering Therapy drugs?
Allopurinol and Feboxostat
178
What are the ALTERNATE Urate Lowering Therapy drugs?
Probenecid
179
What are the REFRACTORY Urate Lowering Therapy drugs?
Pegloticase
180
Should you continue using Urate Lowering Therapy drugs during an acute flare?
YES! That is the key of urate lowering therapy
181
What is the most common Urate lowering therapy drug?
Allopurinol and Feboxostat
182
MOA of Allopurinol?
Both drug and metabolite reduce uric acid concentrations by inhibiting xanthine oxidase
183
What does xanthine oxidase do?
Produces uric acid
184
What is the primary metabolite of Allopurinol?
Oxypurinol
185
What is the route of Allopurinol administration?
Oral
186
What clears Allopurinol from the body?
Kidneys
187
What is the half life of Allopurinol?
2-3 hours
188
What is the half life of Oxypurinol?
24 hours
189
What is the dosing of Allopurinol?
Once daily
190
Why would you adjust the dose of allopurinol?
Based on renal function (decrease if renally impaired)
191
Should you start Allopurinol with a high dose?
No - start with low, then increase q2-5 weeks prn and as tolerated
192
What uric acid level should you titrate the dose of Allopurinol to?
<6 mg/dL or <5 mg/dL
193
What is the max dose of Allopurinol?
800 mg daily
194
What should you also give when initiating allopurinol during an acute gout attack?
Low dose colchisine or NSAID
195
What does allopurinol do?
Prevents inflammation and crystal formation
196
What causes crystals?
Rapid uric acid concentration shifts
197
What should you monitor when taking Allopurinol?
Serum uric acid levels Q 2-5 weeks during titration, every 6 mo after target level is reached
198
What interacts with Allopurinol?
Theophylline, Warfarin, Azathioprine, 6-mercaptopurine (can simply lower the doses of these), and Ampicillin (rash)
199
What are the AE of Allopurinol?
Nausea, diarrhea, maculopapular rash
200
What can Allopurinol AE progress to?
Stevens-Johnson Syndrome or Allopurinol Hypersensitivity syndrome
201
What are the sx's of Stevens-Johnson Syndrome?
Severe expression of erythema multiforme, top layer of affected skin dies and sheds, skin and mucous membranes affected - can lead to death!
202
When does Stevens-Johnson Syndrome usually occur?
1-2 weeks after initiation
203
Where are Stevens-Johnson Syndrome patients treated?
Burn unit
204
What are the sx's of Allopurinol Hypersensitivity Syndrome?
Severe desquamating skin lesions, high fever (>39 C), hepatic dysfunction, leukocytosis with predominant eosinophilia, renal failure
205
When does Allopurinol Hypersensitivity usually occur?
Highest risk in in first months
206
Is a mild skin rash a sign of Allopurinol Hypersensitivity?
No - you can actually desensitive patients with this reaction to be able to take Allopurinol
207
What can you screen for to determine if Pt is at risk for Allopurinol Hypersensitivity?
HLA B*5801
208
What groups are more at risk for Allopurinol Hypersensitivity?
Koreans with stage 3+CKD, Han Chinese or Thai descent
209
When is it ok to give Allopurinol to HLAB*5801 positive pts or Pts with history of A Hypersenstivity?
NEVER
210
What is the MOA of Febuxostat?
Xanthine oxidase inhibtor that acts to decrease uric acid
211
What should you give during initiation and titration of Febuxostat?
Low dose colchicine or NSAID to prevent gout attack
212
What are the cons of Febuxostat?
Expensive
213
What are the pros of Febuxostat?
Structurally different than allopurinol, so if someone has an allergic reaction they can take Febuxostat
214
What is use of Febuxostat?
If allopurinol is not tolerated or need additional therapy to reach uric acid level.
215
What are the contraindications of Febuxostat?
CrCl <30
216
What are the adverse effects of Febuxostat?
Nausea, arthralgias, rash, transient elevation of hepatic transaminases
217
What should you monitor when on Febuxostat?
Liver function tests at baseline, 2 months, 4 months, periodically.
218
What is the MOA of Probenecid?
Uricosuric. Blocks reabsorption of uric acid, increasing its excretion.
219
What are the contraindications of Probenecid?
History of urolithiasis, urate nephropathy. Avoid if CrCl <50.
220
What are the adverse reactions of Probenecid?
Generally well tolerated, nausea, fever, rash, hepatic toxicity, uric acid kidney stone formation
221
Who is Probenecid not advised for?
Urate overproducers. It also less effective as renal function declines.
222
What is the MOA of Pegloticase?
Recombinant form of uricase, an enzyme that exists in nonprimates to convert uric acid into soluble product that is easily excreted.
223
When should you use Pegloticase?
When other therapies don't work
224
What are the severe AE of Pegloticase?
Gout flares, infusion reactions, anaphylaxis
225
What is the route of Pegloticase administration?
IV (which is inconvenient)
226
What are the contraindications of Pegloticase?
G6PD deficiency (risk of hemolysis and methemoglobinemia)
227
What must you screen for before you give Pegloticase?
Methemoglobinemia
228
Pros and Cons of Single Inhaler Products
Pro- Easier to adjust specific dose
229
Pros and Cons of Combination Inhaler Products
Pro- May increase adherence
Con- Lose dosing flexibility
230
Pros and Cons of Nebulizers
Pros- Helpful if patient can't use inhaler (very young, difficulty breathing, etc.)
Cons- Not as portable, can be loud
231
General Monitoring Considerations
-Efficacy/symptoms/control
-Adverse effects
-Inhaler technique
-Adherence
232
Respiratory- Bronchodilator Sub Categories
Beta agonists
Anticholinergics
Methylzanthines (theophylline)
233
Respiratory- Anti-inflammatory Sub Categories
Corticosteroids
Immunomodulators
PDE-4 Inhibitors
234
Beta2 Adrenergic Agonists MOA
-Relax airway smooth muscle by direct stimulation of B2 receptors in airway (bronchodilation)
-Also increase clearance and transport of mucus in airways
-Also stabilize mast cell membranes
235
Beta2 Adrenergic Agonists Adverse Effects
Tachycardia
Tremor
Hypokalema
Palpitations
Sleep disturbance (higher doses of LABAs)
-Inhaled preferred (Adverse effects not as severe)
236
SABA Use in Treatment
Most effective agents for reversing acute airway obstruction caused by bronchoconstriction
SABAs are best at bronchodilating
-1st line for acute asthma
-1st line for chronic asthma symptoms
-1st line for preventing exercise induced bronchospasm
-Used for rescue prn use in COPD
237
SABA Onset and Duration
Onset- 5 min
Duration- 4-6 hours
238
SABA Delivery
Inhaler
Nebulizer
239
SABA Drug Names
Albuterol
Levalbuterol
Terbutaline
240
Dosing of SABA
Typically dosed 1-2 puffs every 4-6 hours
241
Considerations of Levalbuterol
R-enantiomer of albuterol—equally effective, no fewer side effects (despite marketing)
242
LABA Drug Names
Salmeterol
Formoterol
Arformoterol (R enant of formoterol)
Indacaterol*
Olodaterol*
Vilanterol *
*longer acting
243
LABA Onset and Duration
Onset:
-Salmeterol: 30 min
-Formoterol: 5 min
Duration: 12-24 hours initially, decreases to 5 hours with chronic use
244
LABA Delivery
Inhaler (alone, combo with ICS)
Nebulizer
245
LABA Black Box Warning
Not for monotherapy in chronic asthma: increase risk of severe asthma exacerbations and asthma related deaths—must use with ICS
Monotherapy in COPD is common
(but add a SABA for rescue med)
246
Inhaled Anticholinergics MOA
MOA: anti-inflammatory; inhibit the effects of acetylcholine on muscarinic receptors in airways causes bronchodilation
-Protect against cholinergic-mediated bronchoconstriction
-May decrease mucus secretion
247
Adverse Effects of Inhaled Anticholinergics
Blurred vision Dry mouth
Urinary retention
Metalic taste (ipratropium)
Constipation
Tachycardia
Precipitation of narrow-angle glaucoma
Urinary retention
Increased CV events (with ipratropium, esp in CV disease or CKD)
248
AVOID Ipratropium in COPD + CV disease
Aclidinium: CV risk also
249
Inhaled Anticholinergic Drug Names
Ipratropium bromide Tiotropium bromide*
Aclidinium bromide
Umeclidinium bromide*
Glycopyrrolate
250
Delivery of Inhaled Anticholinergics
Inhaler
Nebulizer (ipratropium)
251
Onset of Inhaled Anticholinergics
Ipratropium 15 min
(not a rescue med, too slow)
Tiotropium 30 min
Aclidinium < 30 min
252
Duration of Inhaled Anticholinergics
Ipratropium 4-8 hours
Tiotropium >24 hours
Aclidinium < 24 hours
253
Methylxanthines MOA
MOA: anti-inflammatory + causes bronchodilation by inhibiting phosphodiesterase and antagonizing adenosine
-Act as a bronchodilator at high concentrations
-Anti-inflammatory effect at low concentrations
254
Methylxanthines Drug Name
Theophylline
255
Methylxanthines Considerations
-Narrow therapeutic index
-Life-threatening toxicity
-Many important drug interactions
-Only for patients who cannot use Inhaled meds or if symptomatic despite appropriate use of Inhaled meds
256
How is Theophylline metabolized?
By CYP1A2, CYP2E1, CYP3A4
257
Theophylline Drug Interactions
alcohol
ciprofloxacin diltiazem
erythromycin
oral contraceptives phenytoin propranolol
verapamil
258
Theophylline Target Serum Concentration
Target serum concentration: 5-15mg/L
< 10: little bronchodilation (more anti-inflammatory: 5-10)
10-20: bronchodilation
> 15: increased adverse effects
(headache, nausea, vomiting, insomnia)
> 20: more serious adverse effects
(cardiac arrhythmias, seizures)
259
Theophylline Pharmacokinetics
Dose changes, drug interactions, hepatic function, cigarette/marijuana have VARIABLE EFFECT on serum concentration
Tobacco increases clearance, current smokers may need higher dose
260
Theophylline Adverse Effects
Heartburn
Restlessness
Insomnia
Irritability
Tachycardia
Tremor
With increased dose-
Nausea
Vomiting
Seizures
Arrhythmias
261
Corticosteroids MOA
MOA: decrease airway inflammation, attenuate airway hyperresponsiveness, minimize mucus production/secretion, improve response to beta 2 agonists
262
Delivery of Corticosteroids
Inhalers
Oral
Injectable
263
Inhaled Corticosteroid Drug Names
Beclomethasone
Budesonide
Ciclesonide
Flunisolide
Fluticasone
Mometasone
*many in combo with LABAs
264
Onset of Inhaled Corticosteroids
12 hours; 2+ weeks for max effect
265
Inhaled Corticosteroid Considerations
-Equally effective at equipotent doses
-Cigarette smoking decreases response need higher dose
266
Local Adverse Effects of Inhaled Corticosteroids
Oralpharyngeal candidiasis (thrush)
Cough
Dysphonia (hoarse voice)
-drug deposited in mouth/throat/swallowed—rinse mouth after use; use spacer
-decrease dose decrease hoarseness
267
Inhaled Corticosteroids Interactions
Potent inhibitors of CYP3A4 (ritonavir, itraconazole, ketoconazole, etc) + high doses of ICS : cause Cushing syndrome and adrenal insufficiency
268
What factors vary the response of Inhaled Corticosteroids
Age
Genetics
Smoking status
Race
269
Consideration of Inhaled Corticosteroids
Abrupt discontinuation exacerbations
Changed dose does not increase exacerbation risk
270
Systemic (oral) Corticosteroids Drug Names
Prednisone
Prednisolone
Methyprednisolone
271
Use of Systemic (oral) Corticosteroids
Acute exacerbations of asthma or COPD
(rarely, some patients may be on longer term—serious cases)
272
Onset of Systemic (oral) Corticosteroids
4-12 hours
-Therefore start early in exacerbation
-Continue 3-10 days until symptoms resolve
-Taper off is not necessary (short course)
273
Adverse effects of Systemic (oral) Corticosteroids (also Inhaled Corticosteroids)
**More likely if long term, high dose, systemic route
**Adrenal suppression
**Decreased bone mineral density
**Skin thinning
**Cataracts
Easy bruising
**Steroid myopathy
Insomnia
Increased appetite
Agitation/irritation
Weight gain (longer term)
274
Systemic (oral) Corticosteroids Interactions
Potent inhibitors of CYP3A4 (ritonavir, itraconazole, ketoconazole, etc) + high doses of ICS : cause Cushing syndrome and adrenal insufficiency
275
Systemic (oral) Corticosteroid Considerations
-Minimize as much as possible if chronic therapy necessary
(once daily, every other day, taper off)
-AVOID LONG TERM use if possible
(unfavorable risk vs benefit, steroid myopathy can occur)
276
Leukotriene Receptor Antagonists MOA
MOA: anti-inflammatory; act to antagonize the leukotriene receptor
-Improve FEV1
-decrease asthma symptoms
-decrease SABA use
-decrease asthma exacerbations
-Steroid sparing
277
Leukotriene Receptor Antagonists
Montelukast
Zileuton
Zafirlukast
278
Adverse Effects of Leukotriene Receptor Antagonists
Generally few
-Hepatotoxicity (zileuton and zafirlukast)
-Sleep disorders
-Aggressive behavior
-Suicidal thoughts
-Eosinophilic granulomatosis with polyangiitis (rare)
-Angioedema
-Urticartia
279
Leukotriene Receptor Antagonists monitoring
Liver function monitoring at onset and frequently thereafter (Zileuton)
280
Leukotriene Receptor Antagonists drug interactions
CYP2C9 drugs (significant: zileuton, zafirlukast)
281
Monteleukast Considerations
Generally well tolerated, few interactions, minimal monitoring
282
Immunomodulator (Omalizumab) MOA
Anti-inflammatory; inhibits binding of IgE to receptors on mast cells and basophils; results in inhibition of inflammatory mediator release/attenuation of early and late phase allergic response
283
Immunomodulator Drug Name
Omalizumab
(recombinant humanized monoclonal anti-IgE antibiody)
284
Delivery of Immunomodulator
Subcutaneous q2-4 weeks in office/clinic ($$$)
285
Immunomodulator AE
Injection site reactions
-Bruising
-Redness
-Pain
-Stinging
-Itching
-Burning
Anaphylactic Reactions (rare, but can happen anytime)
-Monitor after injection
-Give epinephrine prescription
Increased risk of CV and cerebrovascular events
Increased risk of cancer
286
Phosphodiesterase-4 Inhibitor MOA
Reduce inflammation by inhibiting breakdown of cAMP; do not cause direct bronchodilation
Used for preventing COPD exacerbations or for select chronic bronchitis patients
287
AE of Phosphodiesterase-4 Inhibitor
Much more likely than other meds
-Diarrhea
-Weight loss
-Nausea
-Headache
-Insomnia
-Decreased appetite
-Abdominal Pain
-Anxiety
-Depression
-Increased suicidality
288
Interactions of Phosphodiesterase-4 Inhibitor
-Theophylline (both inhibit PDE-4)
289
Cromolyn MOA
MOA: decreases bronchospasm through anti-inflammatory effect
(may not have more benefit than a placebo)
290
Cromolyn Considerations
Less effective & less cost effective than ICS
-Reserve for patients who can't tolerate ICS
2nd line therapy for exercise induced asthma
291
Smoking Cessation Meds
Nicotine replacement
(nicotine gum, lozenges, patches, inhaler, nasal spray)
Bupropion SR
Varenicline
292
Smoking Cessation Considerations
Lowered risk of
COPD, Lung cancer, Cancer, CV disease, Infertility
Slows rate of decline in pulmonary function
(important in asthma and COPD)
Difficult! (often takes multiple quit attempts)
Patients need support, drugs can help!
293
The 5 A's for Brief Intervention
Ask: Identify and document tobacco-use status for every patient at every visit
Advise: Urge every tobacco user to quit
Assess: Is the tobacco user willing to make a quit attempt at this time?
Assist: Use counseling and pharmacotherapy to help patients willing to make a quit attempt
Arrange: Schedule follow-up contact, preferably within the first week after the quit date
294
The 5 R's to Motivate Smokers Unwilling to Quit at Present
Relevance: Tailor advice and discussion to each smoker
Risks: Help the patient identify potential negative consequences of tobacco use
Rewards: Help the patient identify the potential benefits of quitting
Roadblocks: Help the patient identify barriers to quitting
Repetition: Repeat the motivational message at every visit
295
Nicotine gum/inhaler/lozenge/spray considerations
-Provides nicotine at a fixed dose
-Used prn for cravings
296
Nicotine patch considerations
-Can be worn 24 hours/day
-Provides a consistent delivery of nicotine
-Reduces cravings; doesn't take them away
-can be Used in combo with prn nicotine replacement
-8 week treatment longer treatment
-Change patch Q24 hours
Remove overnight if insomnia/weird dreams
297
Nicotine replacement therapy dosing
Increase chances of quitting by 50-70%
Dosing/strength based on # cigs/day, if smoke immediately upon waking
298
Nicotine Gum considerations
-Chew gum until it tingles
park it in cheek until it no longer tingles
-Repeat until gum no longer tingles
-Do not eat/drink 30 min after use
-AVOID if dentures/braces
299
Nicotine Lozenge considerations
-Dissolve in mouth
-Do not eat/drink 30 min after use
-Contains 25% more nicotine than gum
300
Bupropion SR MOA
Antidepressant (Blocks reuptake of dopamine and NE)
Doubles the odds of smoking cessation compared to placebo
301
Bupropion SR considerations
-can combine with NRT -May benefit patients with Depression/history of Depression
-Not 1st line for adolescents
302
Bupropion SR AE
Dry mouth
Insomnia (take early in day)
Lowers seizure threshold
303
Bupropion SR contraindicated
-history of seizures
-history of eating disorder
-Use of MAOI in past 14 days (risk of hypertensive reactions)
304
Black Box Warning of Bupropion SR
-May increase suicidality in patients with Depression
-Adolescents/young adults have Increased suicide risk while on antidepressants
305
Bupropion SR Interactions
-MAO-is
-Drugs that lower seizure threshold (antipsychotics, antidepressants, Theophylline, systemic corticosteroids)
306
Varenicline MOA
Nicotinic receptor partial agonist. Reduces cravings/withdrawal. Blocks effects of smoked nicotine
(works better than bupropion)
307
Varenicline considerations
Use as monotherapy
Do not combine with NRT or bupropion
Begin 1 week before quit date; continue 12-24 weeks
308
Varenicline AE
Insomnia
Black Box Warning of Varenicline
309
Black Box Warning of Varenicline
Neuropsychiatric symptoms
-Changes in behavior
-Hostility
-Agitation
-Depressed mood
-Suicidal thoughts and behavior
-Attempted suicide
310
Varenicline Cautions
Increased risk of CV events
311
Smoking Cessation, Special Populations: Pregnant Women
-NRTs increase risk of birth defects
-Other meds not tested for safety/Efficacy
-Quitting smoking important encourage (without drugs)!
312
Smoking Cessation, Special Populations: Coronary Heart Disease
Caution with bupropion
-Cardiotoxic at high doses
-Widens QRS complex
Caution with varenicline
-Increased CV events
NRT: generally benefits>risks
Caution at immediate post MI
Caution with serious arrhythmias
Caution with worsening angina
313
Asthma is characterized by...
Airway narrowing
-Hyper-responsiveness—triggers cause exaggerated narrowing
-Results from smooth muscle contraction, Increased mucus secretion, airway edema, remodeling
Inflammation
-Initiated by trigger that induces immune response (immediate and later)
314
Chronic asthma severity is based on...
Current Disease Impairment
-Frequency and severity of symptoms
-use of short acting B2 agonists (SABAs)
-Pulmonary function
-Impact on normal activity
-Quality of Life
Future Risk
-Potential for future severe exacerbations
-Potential for asthma-related death
-Potential for progressive loss of lung function (esp. adults)
-Potential for reduced lung growth (children)
-Occurrence of drug-related Adverse effects
315
Chronic Asthma Tx Goals
-Prevent chronic/troublesome symptoms
-SABA use infrequent (< 2 days/week)
-Maintain normal/near normal Pulmonary function
-Maintain normal activity levels
-Prevent exacerbations/ED visits/hospitalizations
-Prevent progressive loss of lung function
-Minimize Adverse effects
316
Acute Asthma classification
Not based on chronic classification (because anyone with asthma can have life threatening attacks!)
-Mild: dyspnea with activity; PEF (peak expiratory flow) >70%
-Moderate: dyspnea limits activity; PEF is 40-69%
-Severe: dyspnea interferes with conversation or occurs at rest; PEF < 40%
-Life threatening: not able to speak; PEF <25%
317
Acute Asthma Tx goals
-Correct significant hypoxemia
-Reverse airflow obstruction rapidly
-Reduce likelihood of exacerbation relapse/recurrence of severe airflow obstruction in future
-Prevent death!
Mortality: usually due to
inappropriate assessment of severity/insufficient treatment or referral for medical care (TAKE IT SERIOUSLY!)
318
Treating Asthma Considerations
-AVOID triggers (Prevent attacks)
-Quick relief meds (STOP attacks/RELIEVE symptoms)
-Long-term control meds (PREVENT attacks, DECREASE/SLOW damage)
319
Non pharmacologic treatment
Avoid triggers
Allergens/irritants/foods/comorbid conditions
Influenza/pneumococcal vaccines recommended!
Drugs
Nonselective beta blockers (including eye drops)
Avoid unless benefits > risks
Selective BB (low dose) are better option!
Aspirin-sensitive asthma (Samter's Triad)
Often co-occurs with rhinitis, nasal polyps and asthma
Acute asthma can occur in minutes of aspirin or other NSAIDs
AVOID!
320
Quick Relief Meds for Asthma
ALL ASTHMA PATIENTS NEED SABA
Pretreatment with SABAs block early phase response to antigen/trigger
SABAs are best at bronchodilating
-1st line for acute asthma
-1st line for chronic asthma symptoms
-1st line for preventing exercise induced bronchospasm
Chronic Use: PRN (shorter duration of action if used chronically/all the time)
Exacerbation: Double the dose of SABA during exacerbation + schedule the dose
321
Intermittent Astma Tx
SABA for dealing with symptoms
-infrequent trigger exposure
-Exercise-induced bronchospasm
-Seasonal asthma
-can pretreat with SABA before Exercise
322
Persistant Chronic Asthma Tx
SABA for PRN use
Daily long term control therapy
323
Control Therapy: First Line
ICS
-Most effective monotherapy (1st line)
-Additional agents can be added if needed
-LABAs Most effective add on (not for monotherapy)
-LTRAs 2nd best add on
ICS + LABA preferred therapy
For age 5+ with moderate persistent asthma
324
Control Therapy: Alternatives
LTRAs as monotherapy for mild persi
Monoclonal antibodies
-Reserved for patients with uncontrolled severe symptoms
(expensive, risk of anaphylaxis)
Immunotherapy
-for patients with asthma triggered by allergies + Adverse effects with meds or comorbid allergic conditionsstent asthma (if patient prefers to avoid ICS, less effective than ICS)
325
Step Up Therapy
-Initiate with low-dose treatment
-increase intensity at later visits if control is not achieved
326
Step Down Therapy
-start with high dose regimen
-Reduce intensity as control is achieved
327
Monitoring Asthma
After initiating med
2-6 weeks
If controlled asthma
q1-6 months
Consider step down if well controlled for > 3 months
328
COPD cause
Caused by repeated inhalation of noxious particles/gasses
SMOKING: 85-90% of cases
Leads to chronic inflammation & pathologic changes that cause obstruction
329
Goals of COPD Tx
-smoking cessation
-Symptom reduction (Reduce inflammation, bronchodilation)
-Improve Exercise tolerance
-Maintain/Improve Quality of Life
-Prevent/treat exacerbations (hospitalizations)
-SLOW disease progression
-Reduce mortality
330
COPD Tx
Smoking cessation
Drug therapy
-short acting bronchodilators
-LONG acting bronchodilators
-Inhaled corticosteroids
Supplemental therapy
-Oxygen (Goal: O2 sat >90%)
Pulmonary Rehab
-Exercise training
-smoking cessation
-Nutrition counseling
-Education
Vaccinations
-Pneumococcal
331
COPD Tx Based on Gold Guidelines
PATIENT GROUP
RISK/SYMPTOMS
INITIAL TREATMENT
A
low risk, fewer symptoms
Short acting anticholinergic
Or
SABA
B
low risk, more symptoms
LABA
Or
Long acting anticholinergic
C
high risk, fewer symptoms)
ICS + LABA or
Long acting anticholinergic
high risk, more symptoms
ICS + LABA or
Long acting anticholinergic
332
COPD Tx: Bronchodilators
ALL patients: short acting bronchodilator (SABA OR short acting anticholinergic)
Step 1: Initiate with monotherapy bronchodilator (LABA or long acting anticholinergic)
Step 2: if needed, LABA + long acting anticholinergic OR LABA + ICS
Step 3: if needed, could consider LABA + long acting anticholinergic + ICS
333
COPD Tx: Corticosteroids
Inhaled corticosteroids:
-For severe, v. severe COPD or frequent exacerbations not controlled by 1st line long acting bronchodilator
-monotherapy less effective than in combo with LABA
-Reduces inflammation
Oral corticosteroids
-For exacerbations (3-10 days)
-not recommended for LONG TERM treatment
334
COPD Tx Contraindication
Antitussives
-Cough is important—clears secretions
-not for LONG TERM treatment
335
Other meds possible used in COPD
Beta Blockers
-May be beneficial due to CV effects & B2 receptor up regulation (means inhales B2 agonists might work better)
-Selective B1 blockers preferred
Azithromycin prophylaxis
-Reduces incidence of acute exacerbation in some patients
-risk of LONG TERM use
-risk of QT prolongation
-More study needed
Leukotriene modifers
-May improve lung function(?), dyspnea, QoL, but studies are inadequate
