Asthma/COPD/Colds/Allergies/GI Flashcards
1
Q
destruction of walls in acinus diminishing SA for gas exchange and loss of elastic recoil
A
emphysema
2
Q
asthma is ___ inflammatory response that results in ___ bronchial hyperreactivity to various stimuli
A
chronic
reversible
3
Q
W/ Asthma, inflammatory mediators act either directly on \_\_ or through \_\_ to produce an exaggerated bronchoconstrictive response with: 1. 2. 3. 4.
A
smooth muscle
neural pathways
- Edema
- Cellular infiltration
- Mucus plugs
- Epithelial denudation (late response)
4
Q
describe the pathophysiology of exercise induced bronchoconstriction
A
-Inhalation of large volume of relatively cool, dry air alters
airway surface osmolality –> primary stimulus
-Attenuated when the inspired air is humidified and brought closer to body temperature
5
Q
describe the early asthmatic response
A
- Immediate bronchoconstriction (↓ FEV) and vascular leakage caused by mediators from mast cells (histamine and cysteinyl leukotrienes (C4, D4).
- LTB4 and other cytokines (IL-4, IL-5, TNF [tumor necrosis factor]) are responsible for recruitment of inflammatory cells involved in the late reaction (infiltration and activation).
6
Q
describe the late asthmatic response
A
Delayed (4-6 hrs) bronchoconstriction and bronchial hyperreactivity following epithelial damage; mediated by ECP (eosinophil cationic protein), MBP (major basic protein), and cytokines from eosinophils and neutrophils
7
Q
COPD inflammation is largely mediated by
A
macrophages-neutrophils-CD8 T lymphocytes
8
Q
what mediators result in acute bronchospasm (bronchoconstriction, microvascular leakage, mucus secretion)
A
acetylcholine
leukotrienes**
9
Q
what mediators result in chronic inflammation hyper-reactivity (inflammatory cell infiltration and activation and epithelial damage)
A
leukotrienes
LTB4
eosinophils
neutrophils
10
Q
5 Asthma Treatment Goals
A
- Control chronic symptoms (including overnight)
- Maintain normal activity (including exercise)
- Maintain normal pulmonary function
- Prevent acute episodes
- Avoid adverse medication effect
11
Q
describe the mechanism of bronchodilation w/ B-adrenergic receptors for asthma and COPD tx
A
B2: Gs= + AC= increase cAMP= bronchial muscle relaxation
*inhale is best route due to fast onset
12
Q
Side Effects of B2 adrenergic or sympathomimietic drugs
A
- Skeletal muscle tremor (β2 receptors)
- Tachycardia, palpitations, anxiety, insomnia (β1 receptors)
- Dry mouth (anticholinergic- M)
- Black Box Warning for salmeterol (LABA)
- Increased risk of asthma related deaths
- Should not be used without an inhaled corticosteroid
13
Q
side effects of antimuscarinic agents used w/ asthma and COPD
A
- drying of upper mouth and airways
2. caution if comorbid glaucoma, symptomatic BPH, or bladder neck obstruction
14
Q
How to glucocorticoids work
A
- inhibit T cell activation
- inhibit cytokine production
- inhibit eosinophil recrutiment
- inhibit mast cell migration
- inhibit mediators from eosinophils and mast cells
- vasoconstrict= reduce airway edema
*go to med bc they work everywhere
**anti-inflammatory
15
Q
how to cromyolns work
A
- inhibit mediators from eosinophils and mast cells
- inhibit eosinophil chemotaxis
**anti-inflammatory
16
Q
how to leukotriene inhibitors work
A
- inhibit leukotriene synthesis
- block leukotriene receptor
**anti-inflammatory
17
Q
side effects of oral, parenteral corticosteriods w/ short course, high dose use?
A
- hyperglycemia
- sodium retention
- hypertension
- hypokalemia
- GI bleeding
- CNS distrubance
- insomnia
18
Q
side effects of oral, parenteral corticosteriods w/ chronic use
A
- immunosuppression
- growth suppression
- thinning of skin
- osteoporosis
- cataract formation
- adrenal gland suppression
19
Q
side effects of inhaled steroids
A
*less systemic effects but still local effects possible
- thrush
- dysphonia/hoarseness– vocal cord weakness
* 1 and 2 due to improper administration technique
HD:
- monitor for HPA axis (for adrenal gland suppression)
- bone density (osteoporosis)
- eyes (cataracts, glaucoma)
20
Q
Advantages: Oral (vs inhalational administration of corticosteroids) administration increases compliance (esp. in children). Few adverse effects since __ are produced only at sites of inflammation. Relative to corticosteroids, less effect on airway symptoms / reactivity / inflammation, but equal in reducing frequency of exacerbations.
A
leukotriene inhibitors
21
Q
Side effects of leukotriene inhibitors
A
- some are non-responders
- Zileuton may cause problems with liver dysfunction, so must perform regular liver function tests; must be given four times daily.
- Zafirlukast can interfere with warfarin metabolism.
22
Q
• Mechanism: Anti-inflammatory action via prevention of antigen-induced release of inflammatory mediators from sensitized mast cells. Also inhibit pulmonary afferent nerve fiber receptors that contribute to cough and reflex bronchoconstriction and can suppress the activating effects of chemotactic peptides (cytokines) on neutrophils, eosinophils, and monocytes
A
cromolyn sodium
23
Q
• Advantage: Has action to reduce both early and late phase bronchospastic response, useful in exercise-induced and antigen-induced asthma, as well as nonspecific airways reactivity. Minimal risk of systemic adverse effects
A
cromolyn sodium
24
Q
Side effects of cromolyn sodium
A
- Limited to use as prophylactic agent, must be given prior to expected exposure to precipitant of asthma attack as it will NOT abort an attack once initiated;
- less effective in severe asthma.
- bronchospasm,
- wheezing,
- cough [these effects can be minimized by drinking water and/or by using of β2 agonist prior to treatment
25
* Mechanisms of action: Bronchodilator and anti-inflammatory via various mechanisms including:
* Inhibition of phosphodiesterase-nonselective (high concentrations)
* Effect on calcium transport
* Adenosine antagonist
* Effect on prostaglandin synthesis
Theophylline
26
• Advantage: Prolonged duration of action (oral) - administration at dinner can target nocturnal asthma. Rapid onset of action if given intravenously (but rarely used today).
Theophylline
27
Side effects of theophylline
1. Low margin of safety (generally avoid switching brands),
2. risk of adverse effects related to blood level:
3. insomnia,
4. GI disturbances (nausea, vomiting),
5. headache,
6. anxiety;
7. seizures and
8. arrhythmias (at higher levels).
9. NOT available via inhalational route. Requires monitoring of serum concentration levels.
28
• Mechanism: Inhibition leads to increases in cAMP levels in pulmonary inflammatory cells (neutrophils, T-lymphocytes, macrophages) resulting in suppression of a myriad of inflammatory responses underlying COPD (chemotaxis, phagocytosis, and release of proinflammatory mediators [lipid mediators, cytokines, chemokines, reactive oxygen species, and hydrolytic enzymes]).
PDE-4 inhibitor
(rolumilast)
NOTE: not also a bronchodilator like theophylline (a nonselective PDE inhibitor).
29
• Advantage: Administered once daily via oral route. Reduces numbers of exacerbations in patients with severe COPD along with modest improvement in lung function. Reserve for refractory disease.
PDE-4 inhibitor
| rolumilast
30
side effects of PDE-4 inhibitor
| rolumilast
1. Nausea and
2. diarrhea most common side effects leading to discontinuation;
3. weight loss in 8%.
4. Psychiatric effects also observed (6% → insomnia, depression, anxiety
31
• Mechanism: A recombinant humanized monoclonal antibody that will bind free IgE in the circulation, preventing IgE attachment to mast cells and basophils and blocking the cellular response to allergens.
Omalizumab
32
• Advantages: An option for patients with moderate to severe persistent asthma, with high levels of antigen-specific IgE (i.e., a strong allergic component), who have been inadequately controlled despite maximal therapy with other asthma medications. Some studies have shown omalizumab treatment led to reduced inhaled corticosteroid use and decreased asthma exacerbations.
Omalizumab
33
• Mechanism: Splits disulfide linkages between mucoproteins resulting in decreased viscosity of pulmonary mucus secretions - BUT no evidence that thinning secretions induces clinical improvement. Also possesses antioxidant properties.
mucolytics
34
side effects of mucolytics
1. trigger bronchospasm (always give w/ bronchodilator)
2. N/V
3. stomatitis
4. rhinorrhea
35
black-box warning due to risk of anaphylaxis
Omalizumab
36
• Mechanism: Bronchodilation via action blocks vagal nerve component (parasympathetic) to oppose bronchospastic response and increased mucus secretion.
antimuscarinic agent (ipratroprium)
37
• Advantage: Relatively rapid onset of action. May be more effective than β-adrenergic agonists in COPD (bronchitis or emphysema)
antimuscarinic agent (ipratroprium)
38
in viral cold symptoms] [primary use in allergic rhinitis, minor role
antihistamines
39
(vasoconstrictors) [primary use in allergic
| rhinitis and viral cold infections]
decongestants
40
[some use in coughs associated with viral
| cold symptoms, allergic rhinitis, asthma, COPD]
antitussives
41
[some utility in viral cold infections-COPD]
expectorants
42
[some utility in viral cold infections-COPD]
mucolytics
43
describe the CV effects from histamine
H1 (increase IP3/DAG)
- vasodilation via increased No synthesis= hypotension, nasal congestion, reflex tachycardia
- increased cap. permeability (edema, hives, shock, rhinorrhea)
H2 (increased cAMP)
-cardiac stimulation and vasodilation
44
describe the GI effects from histamine
H1:
-SmM contraction= cramps
H2:
-increase gastric acid secretion
45
describe the bronchiolar SmM effects from histamine
H1:
| -Bronchoconstriction--- hyperactive responds in asthma
46
describe the neuron effects from histamine
H1
| stimulate nerve endings- pain, itching
47
Describe the anaphylactic reaction effects from histamine
H1:
| -Urticaria, abdominal cramps, laryngospasm, bronchospasm, decreased BP, shock
48
tx of anaphylatic rxn from histamine
Histamine plus other mediators are released from mast cells necessitating treatment with epinephrine
- Antihistamines, while effects are additive with epinephrine,
are not sufficient alone
49
how does cromolyn sodium affect histamine
prevents histamine release from mast cells
50
describe H1 receptor blocking agents for an antihistamine agent
-Reversible and competitive block with neglible H
blocking effects
1st generation agents: have additional blocking actions
at non H
2nd generation agents relatively selective for H1
receptors
51
uses/effects of antimuscarinic receptor blocking agents for an antihistamine agent
1. Sedation (more in 1st generation bc less CNS penetration in 2nd generation)
2. Prevent N/V and motion sickness: block M and H1 (1st gen. only)
3. block of secretions: may be beneficial or SE: dry mouth, UR, blurred vision, constipation (1st gen only)
52
use of sodium channel block for antihistamine
local anesthetic action
| -most often used topically first
53
α1-adrenergic receptor block (esp. promethazine) can cause what when used for an antihistamine
orthostatic hypotension in suspected individuals
54
compare 1st and 2nd generation antihistamines
1st:
- more sedation*
- more CNS penetration*
- more antimuscarinic actions*
- prevent N/V/motion sickness*
- Metabolized by liver
- short duration of action (4-8hrs)*
2nd:
- highly H1 selective
- less sedation
- no block of secretions
- no prevention of N/V/motion sickness
- less antimuscarinic actions
- longer actions (12-24 hrs)
- metabolic and/or renal elimination
55
2nd generation antihistamines
- fexofenadine/ Allergra
- cetirizine/ Zrytec
- loratadine/ Claritin
56
use of antihistamines
1. allergic reactions (rhinitis and urticaria) -- H1 receptor block
* 1st and 2nd generation OTC
Chronic use may diminish clinical effectiveness - can try
switch to different class)
*1st generations have additional uses
57
what is the best drug class to help w/ allergic disordres
antihistamines
*helps w/ sneezing, pruritus, rhinorrhea, congestion (a little)
NOT w/ inflammation
Rapid onset!
(2nd best= corticosteroids but slower onset ie.nasal steroids)
58
additional uses of 1st generation antihistamines
1. Cough suppression (Na channel blocker)??
2. Motion sickness (H1 and M block)
3. N/V (H1 and M block)--Meclizine-dimenhydrinate
4. Sleep aid for insomnia (H1 and M block)-- diphenhydramine- doxylamine
59
Side effects of antihistamines
1. Sedation (mostly 1st gen.)
2. Additive CNS depression w/ alcohol and other CNS depressants (more with 1)
3. Antimuscarinic actions: dry mouth
4. paradoxical excitation
5. postural hypotension
6. GI: Decreased appetite, N/V, constipation
60
what are 1st generation antihistamines
Dimenhydrinate
Diphenhydramine/Benadryl
Meclizine
61
what is the main inflammatory mediatory in RSV colds that leads to symptoms
bradykinins
*Mast cell mediators (histamine) have MINOR role in the viral inflammatory response so antihistamines have minimal efficacy for treating cold sx
62
Most common cold symptoms appear 1-3 days after infection and can be explained by the actions of BK including:
1. Pain via activation of nociceptors
2. Nasal stuffiness via dilation of blood vessels
3. Nasal fluid hypersecretion via increased capillary
permeability plus parasympathetic reflex mechanisms
4. Cough via activation of irritant sensory receptors
63
main inflammatory mediators of allergies vs viral colds
Allergies: LTs, Histamine
Viral Colds: BK
64
what is the MOA for topical decongestants
stimulate alpha1- receptors of nasal BV dilated by histamine or BK--> vasoconstriction
* promotes drainage, improves breathing
* *PROMT effect relative to oral decongestants
65
SE of topical decongestants
1. Rebound congestions (rhinitis medicamentosa) due to ischemia-local irritation (restrict to 2x/day for 3-4 days)
66
ex of topical decongestants
1. Phenylephrine (Neosynephrine)-- most effective, shorter duration
2. Oxymetazoline (Afrin)-- longer acting, use 2x day
67
describe the MOA of oral decongestants
Stimulate α1 receptors of nasal BV dilated by histamine or bradykinin --> vasoconstriction
-increases neuronal release of NE
**NO REBOUND congestiong bc drugs are delivered systemically
68
side effects of oral decongestants
Systemic actions can cause:
1. headaches,
2. nausea,
3. dizziness,
4. increased BP
5. palpitations
*at chronic or high doses
(use w/ caution if hx of HTN or arrhythmia)
69
examples of oral decongestants
1. Pseudoephedrine (Sudafed)- safest/effective vasoconstrictor oral agent
2. Phenylephrine (Sudafed PE) - substrate for hepatic MAO so variable interpatient blood levels
70
Why is sudafed such a hassel to get from the pharmacy?
similar compound to methamphetamine (just remove a hydroxyl group and you have meth)
71
antitussives target what?
cough center mu (u) receptors in CNS
72
Antitussives are best used when?
1. Reduce frequency of cough, esp. dry, non-productive cough
2. Excessive coughing can be discomforting, self-perpetuating
73
MOA for antitussives and examples
*both central and peripheral actions
1. Most effective agents are agonists at endogenous µ-
opioid receptors to depress the cough center in brain stem (ex. codeine, dextromethorphan, hydrocodone)
2. Diphenhydramine (Benylin, OTC) is generally less effective, working
through antihistaminic and/or local anesthetic actions
74
Effective antitussives at lower doses - less physiological /
| psychological dependence
opioid drugs (controlled substances)
ie. codeine, hydrocodone (in Tussionex)
75
Side effects of Codeine, hydrocodone when used as an antitussive
1. nausea
2. drowsiness
3. constipation
4. allergic rxns (pruritus less common)
76
Most commonly used OTC cough suppressant.
| Variable effectiveness
Dextromethorphan (in Robitussin DM)
77
Antitussive agent that is an opioid agonist, but does not depress respiration or
predispose to addiction (only l-isomers do this)
Dextromethorphan (in Robitussin DM)
78
Side effects of Dextromethorphan (in Robitussin DM)
Mild
1. drowsiness
2. GI upset
3. can produce PCP-like effects and coma at doses 50-100x therapeutic value (Robo-tripping)
79
Dextromethorphan (in Robitussin DM) has what effects at a low/therapeutic dose (15-30 mg) vs drug abuse dose (500-1500mg)
15-30mg: antitussive: block mu receptors
500-1500mg- blcok of NMDA glutamate receptors
80
Safe and somewhat effective antitussive
Diphenhydramine (Benylin, OTC)
81
Side effects of Diphenhydramine (Benylin, OTC)
1. Sedation
2. antimuscarinic effects
*gerater propensity for SE than dextromethorphan
82
Tetracaine (local anesthetic) congener antitussive
Benzonatate (Tessalon Perles)
83
Guidelines for tx of cough in adult due to common cold
1. 1st generation antihistamine/decongestant (e.g.,
brompheniramine / pseudoephedrine)
2. Naproxen (tid x 5 days): blocks inflammation that
stimulates cough afferents
**2nd generation antihistamines ineffective
84
Guidelines for tx of cough in adult due to upper airway cough syndrome (postnasal drip)
1st generation antihistamine/decongestant (e.g.,
| brompheniramine / pseudoephedrine)
85
"-prazole"= blocks ___
"-itidine"= blocks ___
-prazole blocks ATPase --> PPI
(in parietal cell)
-itidine blocks H2 receptor--> H2 antagonist
86
___ is the tx of choice for ACUTE ulcers and given along these agents will lead to ulcer healing
___ is necessary to reduce rates of recurrence though
acid suppression
Abx
87
what type of organism is H. pylori
Gram Neg bacilli
| facultative anaerobe
88
what is 1st line tx for H. pylori
```
Triple therapy (10-14 days)
-PPI BID + Clarithromycin + Amoxicillin ( or Metronidazole if PCN allergy)
```
89
what is 1st Line alternative OR salvage therapy for H. pylori
```
Quadruple therapy (0-14 days)
PPI + Bismuth + Tetracycline + Metronidazole
```
90
Anti-secretory drug categories for PUD
PPIs
H2 antagonist
*all antisecretory agents cause an increase in gastric pH
91
Cyctoprotective drugs for PUD
Sucralfate (Carafate®) Misoprostol (Cytotec®)--> "-prostol"= prostaglandin inhibitor
92
describe the MOA for PPIs
Prodrug--> enters systemic circulation--> diffuse into parietal cells--> activated in canaliculi to sulfenamide--> then trapped
- Irreversible inactivates H+K+ATPase
* Only inactivates active pumps --> 2-5 days for steady state effect
93
when should you take a PPI
Best BEFORE a meal--> Cp max then coincides w/ max pump secretion
94
how are PPIs metabolized?
CYP450 enzyme in rapid first pass metabolism --> consider lower dose in pts w/ severe hepatic disease
95
uses of PPIs
1. GERD (most effective agent)
2. PUD (faster sx relief than healing H2 antagonists)
3. NSAID induced ulcers (prevention and tx)-- often used in critcically ill
4. Prevention of stress gastritis
5. Zollinger-Ellison syndrome
96
Side effects from PPIs
* remarkably safe
- Mild
1. HA
2. abdominal pain
3. Constipation
4. diarrhea
97
side effects from chronic use of PPIs (over 1 yr, erosive esophagitis)
1. Hypergastrinemia -- no tolerance but may contribute to rebound increases in gastric acidity upon stopping-- tapper
2. increase fx risk? decreased Ca2+ absorption
3. decreased Mg2+ absorption
98
Drug-drug interactions w/ PPIs
* due to actions on CYP450
| - Omeprazole may inhibit conversion of antiplatelet agent clopidogrel to active form
99
MOA of H2 receptor antagonists
Competitive reversible block of H2 receptors – basolateral
| membrane
100
compare the actions of H2 receptor antagonists and PPIs
1. H2 antagonists less efficacious than PPIs – generally requires bid dosing
2. More rapid onset of action than PPIs in acute gastritis
3. Better at block of nocturnal (H2) than meal-stimulated
(ACh-gastrin) acid secretion
101
describe the PK of H2 receptor antagonists
1. Rapidly absorbed (advantage in acute gastritis)
2. Major route of elimination is renal excretion
3. Dosage reduction in renal dysfunction (esp. in elderly)
102
uses of H2 receptor antagonists
1. GERD if infrequent (if frequent requires BID)
2. PUD-- largely replaced by PPIs
3. Stress-related gastritis- reduce bleeding when given IV
103
Side effects of H2 receptor antagonists
Generally well tolerated
1. CNS dysfunciton- AMS (more common w/ cimetidine w/ renal dysfxn)
2. Endocrine effects w/ Cimetidine - gynecomastia
104
drug drug interactions w/ H2 receptor antagonists
Cimetidine inhibition of CYP450 metabolism, which increase the effects or toxicity of many drugs
105
MOA of Sucralfate (Carafate)
Sulfated disaccharide Aluminum salt selectively binds to necrotic ulcer tissue to form a protective barrier
- Activated by acidic pH – give on empty stomach – 2-4 / day
- Not absorbed
106
Side effects of Sucralfate (Carafate)
few side effects
1. constipation
107
MOA of Misoprostol (cytotec)
Prostaglandin analog - acts on epithelial cell to ↓ H+
| secretion - ↑ mucus-bicarbonate
108
what is Misoprostol (Cytotec) used
NSAID induced ulceres
109
Side effects of Misoprostol (Cytotec)
1. diarrhea
2. uterine stimulation/cramping
3. CONTRAINDICATED in pregnancy bc of increase uterine motility
110
Most effective agent for preventing NSAID-induced ulcers:
PPIs
Omeprazole (prilosec) or Esomeprazole (nexium)
111
Antacids raise pH of stomach contents to ___
4
112
PK of antacids
1. should be nonabsorbable-- wil raise urinary pH about 1 when used in ulcer tx
2. should be long-acting but must be given every 2 hrs
113
side effects of antacids
no adverse effects
| but diarrhea- constipation is common
114
drug-drug interactions of antacids
None generally avoid by spacing dose around other drugs
115
examples of gastric antacids
1. Calcium (as carbonate- Tums)
2. Aluminum
3. Magnesium (Milk of Magnesium)
116
adverse reactions of calcium antacids
1. rebound secretion
2. safe but not for chronic use
3. CONSTIPATION
4. hypercalcemia
117
adverse reactions of aluminum antacids
1. CONSTIPATION
| 2. chronic intake may lead to CNS toxicity
118
adverse reactions of magnesium antacids
1. osmotic DIARRHEA
| 2. retention of Mg if renal disease
119
avoid sodium bicarbonate antacid/neutralizing agent if:
- pregnant
- CHF
- HTN
- edema
- renal failure
*conditions exacerbated by fluid retention
120
drugs associated w/ inducing constipation
1. Antimuscarinic agents
2. drugs w/ antimuscarinic SE (1st generation antihistamines, tricyclic antidepressants, typical antipsychotic agents)
3. Antacids (calcium and aluminum)
4. Ca2+ channel blockers (esp. verapamil)
5. opioid analgesics
6. 5HT3 antagonists
121
Laxative classification by mechanism of action
1st- bulk forming
2nd- Saline (osmotic): increases fluid volume
3rd- stimulant (irritant): stimulates enteric nerves
Prevent: Wetting agents: moistens to ease passage
122
management of simple constipation
1. proper diet (20-30g daily)
2. exercise (esp. abdominal muscles)
3. adequate fluid intake (6-8 8oz/day)
123
what laxative is usually recommended first
Psyllium
| fiber/bulk forming
124
Psyllium MOA
physiologic mechanism: facilitates passage and stimulate peristalsis via absorption of water --> bulk expansion
125
adverse reactions w/ psyllium
may combine and interact w/ other drugs (ie. digoxin/salicylates) so space dosing
126
MOA of saline (osmotic) cathartics
Non-absorbable ions --> osmotic retention of intestinal
| water --> increased peristalsis
127
examples of saline (osmotic) cathartics
1. milk of magnesia, magnesium citrate
2. polyethylene Glycol- electrolyte solutions (PEGs)- Miralax
3. Lactulose
4. Phosphage enema--> reserved for fecal impaction
128
when is milk of magnesia most commonly used
1. Most used for mild to moderate constipation
2 Avoid in renal dysfunction as long term use can lead to electrolyte imbalances
129
• Bowel cleansing prior medical procedures
• Contain Na+-K+ salts to prevent net transfer of
electrolytes
High volume solutions of polyethylene glycol (saline osmotic cathartics)
130
-For difficult to treat constipation
• Daily dose for treatments less than 2 weeks duration
• Excessive use may lead to electrolyte depletion
smaller volume solutions of polyethylene glycol (saline osmotic cathartics)
131
MOA of lactulose
Dissacharide metabolized by colonic bacteria to low
| MW acids --> osmotic diarrhea --> increased peristalsis
132
examples of stimulant laxatives
1. Bisacodyl
2. Senna
3. Castor Oil
133
MOA of Bisacodyl (stimulant laxative)
↑ peristaltic activity via local irritation (PG-NO) --> accumulation of water and electrolytes --> ↑ motility
134
adverse reactions of Bisacodyl (stimulant laxative)
potentially dangerous side effects
1. electrolyte/fluid deficiencies
2. severe cramps
*most widely abused class- but safe for chronic use
in recommended doses
135
MOA of castor oil
1. Contains a triglyceride that is hydrolyzed in the gut to
ricinoleic acid
- Acts primarily in the small intestine --> stimulate fluid/
electrolyte secretion and speed intestinal transit
136
Castor bean also contains __, an extremely toxic glycoprotein
ricin
137
examples of Stool-wetting agents and Emollients
1. Docusate (colace)
2. Lubricant (mineral oil)
*used for prevention
138
A surfactant that acts as stool-softener (facilitates
| admixture of aqueous and fatty substances)
Docusate (colace)
*Often used in combination with stimulant laxative
when initiating opioid analgesic therapy
ROLE IS PRIMARY PREVENTION
139
Coats fecal contents preventing colonic absorption of fecal water
Lubricant (mineral oil)
140
Peripherally acting opioid antagonists for patients taking opioids for non- cancer pain that have failed laxative therapy
1. Methylnatrexone (Relistor)- expensive but doesn't cross BBB
2. Naloxegol (Movantik)- binds primarily to opioid receptors in GI tract only
141
drugs that induce diarrhea
1. Abx (esp. broad spectrum)
2. Colchicine
3. Digoxin
4. Magnesium antacids
5. Misoprostol
6. Muscarinic agonists
7. Resperine
8. SSRIs
142
Classes of drugs that tx diarrhea
1. Opioids
2. Polycarbophil
4. Adsorbents
5. Probiotics
143
MOA of Loperamide (Imodium)
```
Opioid receptor agonist affecting intestinal motility (µ),
intestinal secretion (δ), and absorption (µ and δ)
-anti-secretory activity against cholera toxin (good for travelers diarrhea)
```
144
side effects of Loperamide (Imodium)
1. can cross BBB and cause:
- CNS (euphoria and decreased RR)
- Cardiac toxicity (prolonged QT)
2. CNS depression (esp. in children)
3. paralytic ileus
4. may worsen Shigella infections
*low addition liability for acute use due to water solubility (difficult to dissolve and then inject)
145
what drug is approved by the FDA to use for diarrhea AND constipation
Polycarbophil (Mitrolan)
146
examples of Adsorbents
```
Charcoal
Bismuth subsalicylate (pepto Bismol), Kaolin, pectin
```
147
what drug has an association w/ Reye's Syndrome in children under 12y/o
bismuth subsalicylate
*AVOID USE
148
Taken after each loose bowel movement until controlled
- Manages mild to moderate diarrhea
- “Formed stools” and perception of decreased fluidity, but small effect on fluid volume excreted
adsorbents
149
MOA of probiotics
Suppress growth of pathogenic organisms --> restore
| normal flora --> possible role in antibiotic-associated, viral, or Traveler’s diarrhea
