Drugs for Test 2 Flashcards
1
Q
Ondansetron (Zofran), Granisetron (Kytril), Dolasetron (Anzemet)- MOA and ROA
A
5-HT3 Antagonists
Antagonism of the 5-HT3 receptor in the chemo-receptor trigger zone
ROA- oral, rectal, IM, IV
2
Q
Ondansetron (Zofran), Granisetron (Kytril), Dolasetron (Anzemet)- Indications
A
5-HT3 Antagonists
Treatment and prevention of postoperative N/V
Chemotherapy- induced N/V
3
Q
Ondansetron (Zofran), Granisetron (Kytril), Dolasetron (Anzemet)- ADRs
A
HA
Dizziness
Diarrhea
ABD pain
4
Q
Metoclopramide (reglan), Trimethobenzamide (tigan), Phenothiazines- Prochlorperazine (compazine), promethazine (phenergen)- MOA
A
Dopamine Antagonists
Antagonist of D2 receptors of the CTZ
At higher doses metoclopramide also blocks 5-HT3 receptors
ALSO PROMOTES GASTRIC EMPTYING AND SMALL INTESTINE PERISTALSIS- PROKINETIC EFFECT
5
Q
Metoclopramide (reglan), Trimethobenzamide (tigan), Phenothiazines- Prochlorperazine (compazine), promethazine (phenergen)- contraindications
A
GI- HEMORRHAGE, OBSTRUCTION OR PERFORATION Cautious use in pts w/ depression Pheochromocytoma Seizure Use w/ caution in children
6
Q
Metoclopramide (reglan), Trimethobenzamide (tigan), Phenothiazines- Prochlorperazine (compazine), promethazine (phenergen)- ADRs
A
EXTRAPYRAMIDAL EFFECTS
RESTLESSNESS, ANXIETY, DROWSINESS, FATIGUE, HALLUCINATIONS
CV- HTN, HPOTN, AV BLOCK, BRADYCARDIA
AGRANULOCYTOSIS
7
Q
Promethazine (Phenergen)-MOA
A
Antihistamine
Blocks H1-> effectiness appear to be with motion sickness and vestibulochoclear dz
Antagonist of D2 receptors in the CTZ
8
Q
Promethazine (Phenergen)- ADRs
A
Dry mouth, dizziness
PARKINSONIAN SYMPTOMS (DYSKINESIA, DYSTONIAS, AKATHISIA)
NEUROLEPTIC MALIGNANT SYNDROME
Blood dyscrasias
9
Q
Promethazine (Phenergen)- Cautions
A
BPH
Urinary retention
Glaucoma
10
Q
Dronabinol (Marionol)- MOA and Side effects
A
MOA is not well defined
SE- drowsiness, sedation, increased appetite
11
Q
Psyllium (metamucil), Methylcellulose (Citrucel), Polycarbophil (Fibercon)- MOA
A
Bulk forming laxatives
Increases the volume of non-absorbable solid residue with water, distending the colon and stimulation peristaltic activity increasing the rate of colonic transit
12
Q
Psyllium (metamucil), Methylcellulose (Citrucel), Polycarbophil (Fibercon)-Primary Uses and contraindications
A
CONSIDERED 1ST LINE FOR BEDRIDDEN OR GERIATRIC WITH CHRONIC CONSTIPATION, GOOD IN PREGNANCY
Contraindication- pts w/ stenosis, ulceration or adhesions, and fecal obstruction
13
Q
Psyllium (metamucil), Methylcellulose (Citrucel), Polycarbophil (Fibercon)- ADRs
A
Flatulence
ABD distention
Gastrointestinal obstruction
14
Q
Psyllium (metamucil), Methylcellulose (Citrucel), Polycarbophil (Fibercon)- drug interactions
A
BINDS DRUGS & REDUCES ABSORPTION- SEPARATE FROM OTHER MEDICATION ADMIN
15
Q
Psyllium (metamucil), Methylcellulose (Citrucel), Polycarbophil (Fibercon)- other uses
A
- The ability of these agents to absorb water makes them useful for RELIEVING SX OF MILD DIARRHEA
- Several months use can RELIEVE SX OF IBS
- LOWERING CHOLESTEROL
16
Q
Docusate sodium (Colace)- MOA
A
Emollient
Surfactant brings water into stool, facilitates mixing of aqueous and fatty materials within intestine, increase H20 and electrolyte secretion in small/ large bowel
17
Q
Docusate sodium (Colace)- uses
A
To avoid straining
After MI, rectal surgery, opiates
1ST LINE PREGNANT WOMEN
Onset 1-3 days
18
Q
Docusate sodium (Colace)- contraindication
A
Fecal impaction
Signs and sx of appendicitis
19
Q
Mineral Oil- MOA
A
Lubricant
Coats stool (allows easier passage), inhibits colonic absorption of water
Onset- 6hrs-3 days (oral or rectal)
20
Q
Mineral Oil- Use and contraindications
A
Used mainly for prevention (to avoid straining and after MI or rectal surgery)
CHRONIC USE IS DISCOURAGES
CAUTION-AVOID IN ELDERLY, ASPIRATION RISK AND DECREASE ABSORPTION OF FAT-SOLUBLE VITAMINS (DEAK)
May leak from anal sphincter
21
Q
Lactulose- MOA
A
Osmotic agent
Disaccharide that is metabolized by bacteria in the colon to low-molecular weight acids = osmotic effect
Not considered a 1st line therapy
22
Q
Lactulose- Uses and SE
A
MOST COMMONLY USED IN PTS W/ HEPATIC ENCEPHALOPATHY
Side effects- flatulence, cramps, electrolyte imbalance
Oral dose soften stools in 1-3 days
23
Q
Sorbital- MOA
A
Osmotic agent
Monosaccharide creates an osmotic gradient when used as a 70% solution
Hyperglycemia
Oral dose soften stool in 1-3 days
24
Q
Magnesium hydroxide (milk of magnesia), Magnesium sulfate (Epsom salts), Sodium phosphate (fleets enema), Magnesium citrate (citrate of magnesia)- MOA
A
Saline cathartics
Mg++ or Na+ salts are POORLY ABSORBED; THEY INCREASE THE WATER CONTENT OF THE BOWEL THROUGH OSMOSIS
Onset- 30min-6hrs (oral), 5-30min (rectal)
25
Magnesium hydroxide (milk of magnesia), Magnesium sulfate (Epsom salts), Sodium phosphate (fleets enema), Magnesium citrate (citrate of magnesia)- Contraindications
Impaired renal function
Mg and Na accumulation
CHF
No sodium for HTN pts
26
Caster oil- MOA and use
MOA- metabolized to ricinoleic acid (stimulates secretory pathways)
Decreased glucose absorption
Promotes intestinal motility
Not for routine use
27
Glycerin Suppository- MOA, Use, ADRs
```
MOA- osmotic action in rectum
Onset <30 min
May cause rectal irritation
Very safe laxative and can be used in children
Intermittent use
```
28
Polyethylene Glycol (Miralax)- MOA and use
Glycerin/hyperosmotic
MOA- osmotic
Use- 17g mixed in water or juice, usually 2wk duration but chronic is okay
Relatively safe, OK for children
29
Polyethylene glycol (PEG, GoLYTELY)- MOA
Glycerin/hyperosmotic
| Osmotoc agent that causes retention of water resulting in softer stool and more frequent defecation
30
Polyethylene glycol (PEG, GoLYTELY)- USE
For COLONIC CLEANSING BEFORE DIAGNOSTIC PROCEDURES
| Note- 4 liters over 3 hrs, NOT FOR CHRONIC USE. AVOID IN PTS W/ INTESTINAL OBSTRUCTION
31
Bisacodyl (Dulcolax) MOA
Stimulant laxative
Diphenylmethane derivative
Stimulate nerve plexus of the colon
onset 6-8 hrs PO; 1-6 hrs PR
32
Bisacodyl (Dulcolax)- Contraindications and ADRs
SHOULD NOT TAKE W/IN 1 HR OF ANTACIDS, MILK OR MILK PRODUCTS
Intestinal cramping
CAN CAUSE FLUID AND ELECTROLYTE INBALANCE
PINK COLORED URINE AND FECES
Long term use- could cause damage to the nerve plexi resulting in deterioration of intestinal function
ATONIC COLON
33
Senna (Senokot)- MOA
Stimulant laxative
Anthraquinone laxative
MOA- increased peristalsis
34
Senna (Senokot)- ADRs
YELLOW-BROWN TO RED COLORED URINE
LARGE DOSES CAN PRODUCE NEPHRITIS
Long term use- CAN CAUSE DAMAGE TO THE NERVE PLEXI (resulting in deterioration of intestinal funciton), STONIC COLON
35
Senna (Senokot)- contraindications
Contraindications- PREGNANCY AND ACUTE INTESTINAL INFLAMMATION
36
Lubiprostone (Amitiza)- MOA
Chloride-channel activator…works by increasing fluid secretion locally in the small intestine by activating the ClC-2 chloride channel
37
Lubiprostone (Amitiza)- Side effects and contraindications
Side effects- nausea and diarrhea
| Contraindications- INTESTINAL OBSTRUCTION AND PREGNANCY
38
Methylnaltrexone- MOA
Peripherally acting antagonist of mu
Expensive
Does not cross the blood brain barrier
Reduced the effects of opioids peripherally (not centerally)
39
Opiates and Derivates, Loperamide, Diphenoxylate, Paregoric, Difenoxin- MOA
Antimotility
Slow intestinal transit
Prolong contact and absorption
Increase gut capacity
40
Opiates and Derivates, Loperamide, Diphenoxylate, Paregoric, Difenoxin- Caution
Addiction potential
| Worsen diarrhea if infectious
41
Lomotil- Onset and Contraindications
Clinical benefit usually w/in 48 hrs
If no benefit in 10 days, change therapy
Contraindications- C. diff or entertoxin
42
Loperamide (Imodium)- MOA
Acts directly on intestinal muscles to inhibit peristalsis, prolonging transit time
43
Loperamide (Imodium)- Onset and contraindication
Clinical benefit usually w/in 48 hrs
Contraindications- Pts w/ a fever exceeding 101 F (38.3c), acute ulcerative colitis, ABX associated colitis, and children under 2
44
Kaolin-pectin, polycarbophil, attapulgite- MOA
Adsorbents
Absorb nutrients, toxins, drugs, and digestive juices
Effectiveness unproven in trials, many do not require RX.
45
Cholestryamine (Questran)- MOA
Absorbs bile salts and C. diff toxin
46
Pepto-Bismol-MOA and Onset
Bismuth subsalicylate
Stimulates absorption of fluid and electrolytes across the intestinal wall
Onset- <48 hrs
47
Pepto-Bismol- Side effects
Not for kids Reyes syndrome
Blackened stool and tongue
Salicylism
Can induce gout attacks
48
Pepto-Bismol- Interactions
Anticoagulants and tetracycline; May interfere with radiologic studies
49
Octreotide (Sandostatin)- MOA
Antisecretory
Blocks the release of serotonin, direct inhibitory effects
Reduces motility and facilitates water absorption from the gut
50
Octreotide (Sandostatin)- Use and onse
Official indication- control sx in pts with metastic vasoactive intestinal peptide-secreting tumor associated diarrhea
Off labe use- tx of refractory diarrhea
Onset- 1-3 days up to a week
51
Octreotide (Sandostatin)- ADRs
BRADYCARDIA
| HYPERGLYCEMIA
52
Atropine- MOA
Anticholinergic
| Blocks vagal tone and prolongs gut transit time
53
Atropine- ADRs and contraindications
ADR-anticholinergic side effects
| Contraindicated- glaucoma, prostatic hypertrophy
54
Lactobacillus-MOA
Bacterial replacement
| Restores normal flora and intestinal function
55
Lactobacillus- ADRs and contraindications
Intestinal flatus
| Contraindicated in immuno-compromised patients
56
Lactase Enzymes-MOA and Use
MOA- replaces lactase enzyme deficiency
| Use- only useful in lactose intolerance
57
Zinc
Substantial data supporting zinc in diarrhea as adjunct to ORS
Reduction of Stool output
Reduction of diarrhea duration
MOA is unknown, possibly action on intestinal ion transport
58
Antacids- MOA
```
Neutralize acid to raise intragastric pH
Decrease activation of pepsinogen
Increased LES pressure
Benefit- rapid onset
Disadvantage- short duration
```
59
Antacid- Side effects
```
GI- diarrhea or constipiation
- diarrhea: magnesium
-constipation: aluminum
-Gas: calcium, sodium bicarbonate
Sodium bicarbonate products can cause fluid overload in pts. with CHF, renal failure, cirrhosis, pregnancy, or any salt-restricted diet; avoid in anyone taking supplemental calcium or with renal dysfunction
```
60
Antacid- Drug interactions
alter gastric pH, increase urinary pH, adsorbing medications, physical barrier to absorption, form insoluble complexes
Clinically significant- abx- quinolone, isoniazid, tetracycline, ferrous sulfate, quinidine, sulfonylurea
61
Antacids- Precautions
Use of med >14 days needs evaluation for barrett's esophagus and upper GI pathology due to increased risk
Pts excessively using antacids should be treated w/ rx drugs, and is considered more significant disease.
62
H2 receptor antagonists- MOA
Reversibly inhibit histamine-2 receptors on parietal cells
63
H2 receptor antagonists- USE
On-demand therapy for intermittent mild to moderate GERD symptoms
Preventive dosing before exercise/meals
Prescription strengths needed for more severe symptoms or for maintenance dosing
Less effective than PPIs in healing erosive esophagitis
64
What drugs are H2 receptor antagonists?
```
Ranitidine (Zantac)
Cimetidine (tagamet)
Nixatidine (Axid)
Famotidine (Pepcid)
Pepcid Complete
These resemble histamines
```
65
H2- receptor antagonist- Absorption, fate, and excretion
H2 receptor antagonists are rapidly & well absorbed after oral admin.
Peak conc. 1-2 hours
Oral bioavailability of nizatidine ~ 90%
-Whereas first-pass metabolism limits bioavailability of the other compounds to ~50%,
A large part of these drugs are excreted unchanged in the urine and therefore may need a reduction in dosage w/renal impairment.
66
H2- receptor antagonist- side effects
Well tolerated
HA, somnolence, fatigue, dizziness, constipation or diarrhea
Thrombocytopenia: rare, reversible
67
H2- receptor antagonist- Drug interactions
Cimetidine
-Inhibition of metabolism of warfarin, phenytoin, nifedipine, propranolol
Acidic environment required for absorption
-Ketoconazole, itraconazole, ferrous sulfate
68
Antacids vs H2-receptor antagonist
Combination more effective than antacid therapy alone
69
What are the names of the PPIs?
Prototypes- omeprazole (prilosec)
| Other agents- Lansoprazole (prevacid), esomeprazole (nexium), pantoprazole (Protonix), rabeprazole (aciphex)
70
Proton pump inhibitor- MOA
- Inhibit the action of the H+,K+ -ATPase.
- All considered prodrugs in that they need to be activated to be effective. They need the acidic environment (H+) to work.
- Requires 18 hours to synthesize new H+,K+ -ATPase molecules
71
Proton pump inhibitor- ADRs
Generally uncommon
N/D/C
HA, dizziness, somnolence
May have higher incidence of community-acquired pneumonia
-Clinical significance unclear
-Pts with asthma, COPD, immunocompromised, young or elderly may be at risk
72
Proton pump inhibitors- Drug interactions
P450s
Omeprazole, lansoprazole, esomeprazole and pantoprazole metabolized by P450 enzymes (rabeprazole metabolized thru nonenzymatic reduction pathway)
Omeprazole and esomeprazole reduce metabolism of: Diazepam, Phenytoin, warfarin
73
Promotility agents- Side effects
Limited side effect profile:
CNS effects: drowsiness, irritability, extrapyramidal effects
--Metoclopramide (Reglan): contraindicated in Parkinson’s Dz, mechanical obstruction, concomitant use of other dopamine antagonists, anticholinergics, and pheochromocytoma
--Bethanechol (Urecholine): may increase acid production, not well tolerated due to cholinergic side-effects (usually used for the bladder and not intestines)
--Fatal cardiac dysrhythmia: cisapride
74
Sulcralfate- MOA
Mucosal protectant
Non-absorbable aluminum salt
Compared to H2-receptor antagonist for mild esophagitis
Less effective in refractory esophagitis
75
Sulcralfate (Carafate)- Chemistry and effects
- When the pH is below 4, an extensive polymerization & cross-linking of sucralfate to form a sticky, viscid, yellow-white gel.
- The gel adheres to epithelial cells and adheres very strongly to the base of ulcer craters.
76
Sulcralfate (Carafate)- Clinical utility
- Effective at promoting healing in PUD
- As a maintenance therapy--more efficacious in duodenal than gastric ulcers.
- Used to prevent stress ulcers
- More effective when administer prior to meals than after since acid is needed for activation.
77
Sulcralfate (Carafate)- ADRs
Constipation - A3+
Dry mouth
Abdominal discomfort
78
Sulcralfate (Carafate)- drug interactions
Phenytoin
Tetracycline
Fluroquinolone Antibiotics
Digoxin
Ketocanazole
Better to administer these meds 2 hrs before sucralfate
DO NOT administer w/ agents that decrease acid
79
What is the three drug regimen for peptic ulcer dz?
```
P= PPI
A= Amoxicillin
C= Clarithromycin
```
OR
P=PPI
M==Metronidazole
C=Clarithromycin
80
what is the drug of choice for PUD?
PPIs
81
What is the 4 drug regimen for peptic ulcer dz?
P=PPI (or H2 blcoker)
B= Peto bismol
M=Metronidazole
T=tetracycline (or amox, or clarithro)
82
Bismuth Subsalicylate (pepto-bismol)- beneficial effects
Cytoprotection through enhanced secretion of mucus and HCO3-.
Inhibit pepsin activity.
Accumulate bismuth subcitrate in craters of gastric ulcers.
Antibacterial effects: Reduce bacterial adherence to mucosal cells, Damage bacterial cell walls.
Promote healing of both gastric and duodenal ulcers
83
Bismuth Subsalicylate (pepto-bismol)- ADRs
- Reaction of bismuth w/bacterial H2S leads to bismuth sulfide causing a black color to the oral cavity and to feces.
- Aspirin ADRs
84
Prostaglandin Analogs- MOA
- Misoprostol is a synthetic analogue of prostaglandin E.
- Imitates the action of endogenous prostaglandins (PGE2 and PGI2) in maintaining the integrity of the gastroduodenal mucosal barrier.
- Promotes healing.
85
Prostaglandin analogs- Indications
Ulcer healing
| Ulcer prophylaxis w/ NSAID use
86
Prostaglandin Analog- contraindications
Hypotension
Breastfeeding
Pregnant
87
Prostaglandin Angalog- ADRs
Diarrhea
| Constipation
88
Inhaled corticosteroids-MOA
Depress the inflammatory response and edema in the respiratory tract and diminish bronchial hyper-responsiveness.
- -Reduced mucous production
- -Decreased local generation of prostaglandins and leukotrienes, with less inflammatory cell activation (decreased inflammation)
- -Adrenoceptor up-regulation
- -Long-term reduced eosinophil and mast-cell infiltration of bronchial mucosa.
89
Inhaled corticosteroids- ROA
Metered dose inhaler
Oral
IV for severe asthma attack
90
Inhaled corticosteroids- Indications
- Most EFFECTIVE long-term control therapy for persistent asthma
- Only therapy shown to reduce the risk of death from asthma even in low doses
- Often used in combination with β2 agonist or other asthma agents.
91
Inhaled corticosteroids- response to therapy?
- Symptoms improve in 1-2 weeks; max in 4-8 weeks
- FEV1 and peak expiratory flow require 3-6 weeks for max improvement
- BHR improvement in 2-3 weeks; max 1-3 months
* *Note- inhaled corticosteroids must be used regularly to be effective.
92
Inhaled corticosteroids- contraindications and ADRs
Contraindication- caution in growing children
ADRS:
Local
Oropharyngeal candidiasis (Thrush)
Dysphonia
Reflex cough and bronchospasm
Potential systemic effects- not seen if low regular doses are being used
Hypothalamic-pituitary-adrenal suppression
Impaired growth in children
Dermal thinning-Dose Dependant
Osteoporosis and glaucoma
93
Inhaled corticosteroids- Adverse effects in adults
Bone mineral density
--Data suggest cumulative dose relationship
If risk for osteoporosis consider bone-protecting therapy
Ocular effects
--High cumulative lifetime exposure may increase prevalence of cataracts
--Increase risk of glaucoma if family history
94
How can you reduce the potential for adverse effects in inhaled corticosteroids?
- Using a holding chamber (spacer)
- Rinse mouth (rinse and spit) after inhaler use
- Using lowest dose possible- if controlled on low dose don’t give them medium or high dose
- Using in combination with long-acting beta2-agonists (LABA)
95
What are the medication names of inhaled corticosteroids?
```
Fluticasone (Flovent, Flovent Diskus)
Budesonide (Pulmicort Flexhaler, Pulmicort Respules)
Beclomethasone HFA (Ovar)
Flunisolide (Aerobid, aerobid-M)
Triamcinolone (Azmacort)
Mometasone (Asmenex)
Ciclesonide (Alvesco)
```
96
What are the ICS and LABA combinations?
Fluticasone/salmeterol (Advair Diskus, Advair HFA)
| Budesonide/formoterol (Symbicort HFA)
97
What are the long acting beta2 agonists (LABAs)?
```
Salmeterol (Serevent)
Formoterol (Foradil)
Fluticasone/salmeterol (advair)
Budesonide/formoterol (symbicort)
Arformoterol tartrate (Brovana)
Formoterol fumerate (Perforomist)
```
98
LABA's use
Not a substitute for anti-inflammatory therapy
Not appropriate for monotherapy
Beneficial when added to inhaled corticosteroids
Not for acute symptoms or exacerbations
--20 minutes for onset (salmeterol)- that’s too late
99
LABAs
Tolerance with chronic administration
Partial loss of protective effect against- Methacholine, Histamine, Exercise
Bronchodilator response not decreased
Responsiveness to SABA slightly decreased
100
What is the black box warning associated with Long acting beta 2 agonists (LABA)?
May increase the change of severe asthma episodes, and death when those episodes occur
Trying to get rid of this not entirely accurate.
Taking this drug in combo with a steroid DECREASES risk of death but taking it alone could increase asthma and death.
101
LABA- interactions
- Concomitant use of CYP3A4 inhibitors increase salmeterol plasma levels
- Avoid: Ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin
- -Prolonged QTc intervals
- -Palpitations
- -Tachycardia
102
What are the Leukotriene receptor antagonists?
Montelukast (Singulair)
Zafirlukast (Accolate)
Zileuton (Zyflo)
103
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- MOA
--Competitively antagonize leukotriene receptors D4 and E4 in the bronchiolar muscle, antagonizing endogenous leukotrienes causing bronchodilation.
Zileuton inhibits 5-lipoxygenase—an enzyme necessary for leukotriene synthesis.
Endogenous leukotrienes are thought to cause airway narrowing which is sometimes seen with the use of NSAIDs.
104
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- ROA and indications
Oral
| Alternative tx of mild persistant asthma
105
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- Contraindications
Pregnancy
Caution in elderly
Zileuton is contraindicated in patients with active liver disease
106
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- ADRs
GI disturbances (stomach pain, heartburn)
HA
Zileuton and Zafirlukast liver toxicity
Zafirlukast and montelukast can increases respiratory infections in elderly patients
107
Montelukast (Singulair), Zafirlukast (Accolate),
| Zileuton (Zyflo)- drug interactions
Zafirlukast
Interaction with Warfarin – increase in prothrombin time (~35%)
Food can reduce bioavailability
Take 1 hour before or 2 hours after meals
Zileuton
Theophylline – doubles theophylline concentration
Warfarin – increase prothrombin time
Propranolol- doubles propranolol AUC
108
What are the methylxanthine drugs?
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline
109
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- MOA
Methylxanthine
Appear to increase cAMP levels in the bronchial smooth muscle cells by inhibiting phosphodiesterase, an enzyme which catalyses the hydrolysis of cAMP to AMP. Increased cAMP relaxes smooth muscle, causing bronchodilation
110
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- Route and indications
Oral
Aminophylline-IV in severe asthma attacks
Use- refractory patients and used as monotherapy and combination therapy w/ ICS
111
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- Contraindications
Not recommended in children < 4 years
Cardiac disease
HTN
Hepatic impairment
112
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- drug interactions
--Infrequently used due to narrow therapeutic window, drug-drug interactions and safer alternatives
--Significant drug/disease interactions
Viral illness, CHF, cirrhosis, cigarette smoking,etc
--Significant drug/drug interactions
Cimetidine, macrolides, quinolones, etc
CYP1A2 and 3A4 substrate
113
Theophyllline (Theo-24, Theochron, Theolair)
| Aminophylline- adverse effects
Nausea, irritability, insomnia, headache, vomiting
--Less frequent when dosing is low and slow
Tachyarrhythmias
Ventricular arrhythmias, seizures
Seizures reported with concentrations of 25 mcg/mL
Minor side effects do not always occur before severe, life-threatening effects
114
What are the mast cell stabilizers?
```
Cromolyn sodium (intal)
Nedocromil (tilade)
```
115
Cromolyn sodium (intal), Nedocromil (tilade)- MOA and ROA
Mast stabalizers
stabilize mast cells preventing the release of inflammatory mediators
Route- Inhaled
116
Cromolyn sodium (intal), Nedocromil (tilade)- Indications
Patients pregnancy
117
Cromolyn sodium (intal), Nedocromil (tilade)- ADRs
```
Mast stabalizers
Cough
Transient bronchospasm
Throat irritation
Neocromil has a bitter taste
Note: Must be utilized regularly for several weeks before effects are noted. Not indicated for acute asthma.
```
118
Omalizumab (Xolair)- MOA
Immunomodulator
Recombinant monoclonal antibody that binds IgE on mast cells and basophils limits release of mediators of allergic response
119
Omalizumab (Xolair)- indications
For moderate-to-severe persistent asthma in patients 12 years of age or older who are not controlled on other therapies (not first line therapy Reserved )
120
Omalizumab (Xolair)- Safety profile
```
Black Box Warning for anaphylaxis
Anaphylaxis in 0.1% of patients
May develop after any dose
70% of reactions within 2 hours
May be delayed up to 24 hours
Cost-effectiveness and long-term efficacy unknown at this time
```
121
Systemic corticosteroids-MOA
Decrease inflammation by suppression of migration of leukocytes and reversal of increased capillary permeability.
122
Systemic corticosteroids- indications and ROA
Control chronic symptoms in people with severe asthma
Can be used for maintenence but mainly used for acute asthma
Oral therapy preferred over IV
123
What are the quick relief treatments for asthma?
Bronchodilators
--Short Acting Beta2-adrenoceptor agonist
Albuterol: Ventolin® HFA, Proventil® HFA, Proair® HFA- DOC
Pirbuterol: Maxair®
Metaproterenol
Levalbuterol: Xopenex®- r enantimer of albuterol
124
Beta2-adrenoceptor agonist- MOA
- β2-adrenoceptors are located on the airway smooth muscles and respond to epinephrine.
- Stimulation of β2-adrenoceptors leads to a rise in intracellular cAMP levels and subsequent smooth muscle relaxation and bronchodilation.
- β2-adrenoceptor agonist may also prevent activation of mast cells as a minor effect
- β2-adrenoceptor agonist are potent bronchodilators with little if any β1 stimulating properties.
125
Beta2-adrenoceptor agonist- Indications
Relieve bronchospasm during acute exacerbations
Pretreatment for exercise induced bronchoconstriction
Treat the symptoms of asthma but not the underlying disease.
Does not improve control of symptoms
Alone in mild asthma
Adjunct to corticosteroids
126
Beta2-adrenoceptor agonist- ADRs
Fine tremor
Tachycardia
Hypokalemia w/ high doses- albuterol encourages potassium to go intracellulary
Some patients have increased risk of exacerbations, some have decreased lung function
Does not appear to occur with prn use
Short-acting beta agonist such as albuterol are the only inhaled agents indicated for acute asthma attacks therefore also used as rescue inhalers.
127
What are the anticholinergic (Antimuscarinics)?
Ipratropium (Atrovent)
| Tiotropium (Spiriva, Handihaler)
128
Anticholinergics- Ipratropium (Atrovent), Tiotropium (Spiriva, Handihaler)- indications
- Relief of acute bronchospasm
- Not indicated for chronic therapy
- Ipratropium may provide additive effects to B2-agonists, in acute setting
- Alternative for patients with B2-agonist intolerance
- Treatment of choice for bronchospasm due to B-blockers
129
Anticholinergics- Ipratropium (Atrovent), Tiotropium (Spiriva, Handihaler)- MOA
Parasympathetic vagal fibers provide a bronchoconstrictor tone to the smooth muscle of the airways. Activated by reflex with stimulation of sensory receptors in the airway walls.
Muscarinic antagonists act by blocking muscarinic receptors, especially M3 subtype, which responds to this parasympathetic brochoconstrictor tone.
130
Anticholinergics- Ipratropium (Atrovent), Tiotropium (Spiriva, Handihaler)- Contraindications
Glaucoma
| Pregnancy
131
Systemic Corticosteroids- Indication
- -Important in the treatment of severe acute exacerbations
- -Prevent progression of asthma exacerbation
- -Reduce need for referral to ER and hospitalization
- -Prevent early relapse after emergency treatment
- -Reduce morbidity of the illness
- -More than three courses/year → re-evaluate asthma management plan
132
Oxygen
Administered to any patient in respiratory distress except COPD patients who retain CO2. Caution should be used in these patients not to administer too much O2 to depress their respiratory drive.
It increases alveolar oxygen tension and decreases the work of breathing necessary to maintain arterial oxygen tension.
133
What are the aminosalicylate drugs?
Sulfasalazine
| Mesalamine
134
Sulfasalazine (Azulfidine)-MOA
Aminosalicylate
| Metabolized by intestinal bacteria to to the active component 5-aminosalicylate (5-ASA) and sulfapyridine (mesalamine)
135
Sulfasalazine (Azulfidine)- use
Most commonly used for inducing and maintaining remission
| Response can take 2-3 weeks
136
Sulfasalazine (Azulfidine)- contraindications
SALICYLATE HYPERSENSITIVITY
| Renal impairment- monitor SCr
137
Sulfasalazine (Azulfidine)- side effects
NOT WELL TOLERATED
N/V, heartburn, anorexia
HA
HYPERSENSITIVITY RXNS (RASH, FEVER)- DO NOT USE IN PTS W/ SULFA ALLERGY
BLOOD DISORDERS (ANEMIA, THROMBOCYTOPENIA, GRANULOCYTOPENIA)
CAN IMPAIR FOLIC ACID ABSORPTION
IDIOSUNCRATIC RXNS (HEPATOCELLULAR INJURY, AGRANULOCYTOSIS, LUPUS-LIKE SYNDROME)
LOW SPERM COUNTS
138
Mesalamine (Asacol, Rowasa, Pentasa, Canasa)- MOA
Aminosalicylate
Unclear various effects on inflammatory process
Formulations vary and target different parts of the colon
Mesalamine or suppositories for rectosigmoid disease
Delayed release formulations of mesalamine for Crohn’s ileitis
Response is slow
139
Mesalamine (Asacol, Rowasa, Pentasa, Canasa)- side effects
Local itching and mild rectal irritation with topical enemas
| Idiosyncratic rxns: pleuropericarditis, pancreatitis, nephrotic syndrome
140
What are the corticosteroids?
Prednisone, Budesonide, Prednisolone, Hydrocortisone, Methyprednisolone (available in a syrup)
141
Corticosteroids- MOA
Anti-inflammatory effects
Improves Symptoms
Improves disease severity
142
Corticosteroids-ROA
PO
IV- hospitalization for parenteral
Topical: suppositories, foams, enemas (effective in distal colonic inflammation)
143
Corticosteroids- tapering
Induction of response takes 7-14 days
Taper by 5mg/wk prednisone or equivalent
Budesonide taper: 9mg6mg3mg
Inability to taper is indication for amtimetabolite and/or infliximab therapy
Parenteral steroid indicated in pts failing to respond to 7-14 days of high dose oral prednisone or equivalent
144
Corticosteroids- monitoring for complications
Glucose intolerance/ metabolic abnormalities
Hyperkalemia
Hyponatremia
glucose
Greater risk for adrenal insufficiency and infections
N/V
Postural hypotension
Long-term therapy (>3mo)
Bone density
Annual eye exam
145
What are the immunosuppressives?
6-Mercaptopurine (6-MP)
| Azathioprine (Imuran)
146
What is azathiprine (imuran)?
A prodrug metabolized to 6-MP
147
Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- MOA
Antagonizes purine metabolism; inhibits DNA, RNA and protein synthesis
Steroid-sparing achieve or maintain control and allow reduction or discontinuation of steroids
148
Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- Toxicity bone marrow and pancreas5
```
Bone marrow suppression 2-5%
Dose related
Managed by dose reduction/withdrawal
Leukopenia, thrombocytopenia, pancytopenia
RISK OF LYMPHOMA 4 FOLD INCREASE
```
Pancreatitis 1.3-3.3%
Dose independent
Occurs within 3-4 weeks of start
Resolves with stopping drug
149
Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- Toxicity GI effects, others, and Infections
GI effects
N/V, abdominal pain
Occurs early, improves with time or with dose reduction
Other
Fever, rash, arthralgias
Dose independent
Infections
Disseminated CMV, herpes zoster, pneumonia, Q fever, viral hepatitis
Occur without leukopenia
Increased risk if combined with steroids
150
Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- drug interactions
```
Inhibition of metabolism leading to increased myelosuppression
Sulfasalazine, mesalamine
Allopurinol
Aspirin
Furosemide
```
151
What is the immunodulator drug?
Methotrexate
152
Immunodulator- Methotrexate- MOA
Folic acid antagonist with anti-inflammatory effects
Reduces steroid needs
Improves disease control
153
Immunodulator- Methotrexate- ADRs
Nausea
| Elevated transaminases- huge problem have to monitor for LFT
154
Immunodulator- Methotrexate- Toxicities
Leukopenia
N/V
Absolute contraindication in pregnancy (Category X)
--Stop therapy 3 months prior to conception
--Folate supplementation prior to conception
--Contraindicated in breastfeeding
Hypersensitivity pneumonitis (rare)
Hepatic fibrosis
--Most significant in long term therapy
--Risk with >1500 mg total cumulative dose and daily dosing
--DC if moderate/severe fibrosis or cirrhosis found on biopsy
155
Cyclosporin (Neoral or Sandimmune)-MOA
MOA: inhibits production and release of IL-2 inhibits activation of T-lymphocytes
Concomitant IV steroids recommended
Cyclosporin alone unable to maintain remission
Requires “bridging” with AZA or 6-MP
Convert IV to PO
PO dose is 2x IV dose
Wean off cyclosporin and steroids over next few months
156
Cyclosporin (Neoral or Sandimmune)- toxicities
```
HTN
Hypertrichosis- abnormal hair growth on the body
ELECTROLYE ABNORMALITIES
NEPHROTOXICITY
Opportunistic Infections
Requires PCP prophylaxis
```
157
Tacrolimus (Prograf)-MOA
inhibits T-lymphocyte activation
| Fungus (streptomyces)
158
Tacrolimus (Prograf)- adverse reactions
```
Tend to resolve with dose reductions
HA
Increased serum creatinine
Nausea
Insomnia
Leg cramps
Paresthesias
Tremors
```
159
What are the monoclonal antibodies?
Infliximab (Remicade)
Adalimumab (Humira)
Natalizumab (tysabri)
160
Infliximab (remicade)- MOA
Monoclonal Antibodies
Monoclonal antibody that binds to TNF-alpha
Inhibits inflammatory cytokines, inhibits leukocyte migration and activation of neutrophils
161
Infliximab (remicade)- Contraindications
```
NYHA class III/IV heart failure
Dose should not exceed 5mg/kg in other pts with congestive heart failure
```
Hepatitis
Reactivation of hepatitis B
Autoimmune hepatitis
Discontinue use with LFTs 5x ULN
162
Infliximab (remicade)- antibodies to infliximab
Increased risk of infusion rxn, shorter duration of response
| regularly scheduled less immunogenic than episodic
163
Infliximab (remicade)- Toxicities infections and infusion reactions
INFECTIONS
Bacterial, mycosal, mycobacterium
Higher TB rates with more extrapulmonary involvement
INFUSION REACTIONS
During or after (1-2 hrs)
HA, dizziness, nausea, erythema at site, flushing, fever, chills, chest pain, cough, dyspnea, pruritis
Mechanism unclear- not IgE type 1
Doesn’t occur till after 1st infusion; not at every infusion
164
Infliximab (remicade)- Toxicities delayed hypersensitivity, autoantibodies, and malignancy and lymphoproliferative disorder
Delayed hypersensitivities
3-14 days after infusion
Myalgia, arthralgia, fever, rash, pruritis, dysphagia, urticaria, HA
Resolve spontaneously or require steroids
Prednisone 40mg PO or methylprednisolone 100mg IV 30 min before
Risk factor: long interval between treatments
Autoantibodies
15-40% develop anti-dsDNA ANA
Development of drug-induced lupus rare
Reversible with DC
Malignancy and lymphoproliferative disorder
Longstanding CD and tx with immunosuppression more likely to develop lymphomas
165
Adalimumab (Humira)- MOA
recombinant fully-human immunoglobulin-1 anti-tumor necrosis factor (TNF)-alpha monoclonal antibody
Evaluate for TB before starting therapy
166
Adalimumab (Humira)- Side effects
BLACK Box Warning of serious infections
TB, invasive fungal, other opportunistic infections
Rash, injection site rxn, HA, URI, development of autoantibodies to drug, development of anti-nuclear antibodies (ANA)
Risk of reactivating hepatitis B
167
Natalizumab (tysabri)- MOA
recombinant immunoglobulin-4 monoclonal antibody
168
Natalizumab (tysabri)- adverse effects
Major adverse effect: progressive multifocal encephalopathy
169
What are the antibiotics used to treat IBD?
```
Metronidazole (Flagyl)
Ciprofloxacin
Metronidazole + ciprofloxacin
Rifamixin
Clarithromycin
```
170
Metronidazole (Flagyl)- indications
For treatment of ileocolitis or colitis
Failure to respond to sulfasalazine
For treatment of abscesses, rectovaginal fistulas, proctocolectomy wounds
Low dose maintenance therapy to minimize recurrence of perineal disease
171
Metronidazole (Flagyl)- ADRs
GI upset, metallic taste, paresthesias, antabuse-like rxn
172
Ciprofloxacin
Effective in resistant disease when used in combination with standard tx
173
Metronidazole + ciprofloxacin
Improve and can promote closure of fistulas
| Tend to recur once drugs stopped
174
Rifamixin
Data from open-label trial found statistically significant response in mild-moderate disease
175
Clarithromycin
Response in pts otherwise unresponsive
176
Opiates
Provide symptomatic relief of diarrhea
Diphenoxylate/atropine, codeine, tincture of opium, paregoric, loperamide
MOA: inhibits excessive GI motility and GI propulsion
