Pharm - Cough Suppressants Decongestants, Mucolytics Flashcards
what is the physiological definition of a cough? and definitions of phases
3 phase expulsive motor act
1 - inspiratory phase
2 - compressive phase - forced expiratory effort against a closed glottis
3 - expulsive phase - opening of glottis and rapid expiratory outflow
what is the clinical definition of a cough
forced expulsive maneuver, usually against a closed glottis, which is associated with a characteristic sound
define acute cough
one lasting less than 3 weeks
define subacute cough
one lasting 3 to 8 weeks
chronic cough
one lasting greater than 8 weeks
what are the nonpharmacologic treatment modalities for cough?
- eliminating irritants
- hard candies such as Jolly Ranchers (stay so hard, you can suck me for a long time, oh muh gah)
- Lozenges
- Humidifiers, or vaporizers
- Hydration
what are the 2 broad categories of pharmacological treatment options for cough
1 - antitussives
2 - expectorants
when are antitussives the drug of choice? (what type of cough)
nonproductive cough
when are expectorants the drug of choice?
productive cough w/ thick secretions
what are the 3 systemic antitussive agents
Dextromethorphan
Diphenhydramine
Codeine
what are the 2 topical antitussive agents
Camphor
Menthol
what is the only FDA approved expectorant
Guaifenesin
what is the MOA of dextromethorphan?
suppresses the cough reflex by a direct action on the cough center in the medulla of the brain
what is dextromethorphan metabolized into and by what enzyme? what is the activity of this new product?
it is metabolized into dextrorphan by CYP2D6
dextrorphan is as active as the parent drug
what is dextromethorphan’s potency and relation to opiods
it is a non opiod, but has equal potency to codeine
what are the other actions of dextromethorphan and dextrorphan? why is this important?
they increase levels of serotonin
this increase in serotonin levels contributes to the ability to abuse this drug - it causes dissociative hallucinogenic effect at 12 to 75 times the TD
How is dextromethorphan protected in a pharmacy? wht age restrictions?
it must be kept behind the counter, must show ID to purchase it
18 in most states
21 in Mississippi (for obvious reasons)
what are the side effets of dextromethorphan?
dizziness, drowsiness, nauseau, upset stomach, vomiting, diarrhea, irritability, excitability, light headedness, and trouble sleeping
what is the major contraindication for dextromethorphan?
Monoamine oxidase inhibitor antidepressants - cause really high levels of serotonin - can cause convulsions and cardiac arrest
what are some other contraindications for dextromethorphan?
advanced respiratory insufficiency or hepatic disease
and if the pt is allergic to any ingredients of the product
how can you remember that dextromethorphan is contraindicated w/ MAOIs?
the Libby Zion story - she was on antidepressants, became sick, checked into hospital, residents prescribed her some codeine like drug, and she died b/c of cardiac arrest
Dad sued, now we have restrictions on number of hours residents can work each week
Diphenhydramine has 3 MOAs, what are they?
1) antihistamine-H1 receptor antagonist
2) suppresses the cough reflex by a direct effect on the cough center
3) antitussive effects due to its anticholinergic / antimuscarinic effects
what line therapy is Diphenhydramine for nonproductive cough caused by irritation? what are some of its other common uses?
2nd line
common cold, allergic rhinitis, chronic urticaria, motion sickness, parkinsonism, insomnia
what are the side effects of diphenhydramine? they are sort of in 2 categories based on the diff MOA
drowsiness and respiratory depression - due to direct effect in the brain
blurred vision, dry mouth, urinary retention, constipation - due to anticholinergic, antimuscarininc effects
What are the contraindications for diphenhydramine? again, these are in categories based on MOA
prostate hypertrophy, urinary obstruction, peptic ulcer - b/c of antimuscarinic effects
Asthma, COPD - b/c of depression of respiration
MAOIs - again, serotonin syndrome / toxicity
what is codeine - what does it do and what is it related to?
an opiod analgesic and antitussive related to morphine
what receptors does codeine act on
acts on mu receptors
compare the affinity of codeine and morphine for the mu receptor
codeine has a lower affinity than morphine for the mu receptor
what is the MOA of Codeine
it depresses the cough reflex by a direct action on the cough center in the CNS
what happens to Codeine in metabolism
about 10% of codeine is metabolized (by CYP2D6) to morphine and other products - individuals w/ high level of this enzyme will build up more morphine
what are the side effects of Codeine (think about MOA - it has side effects in common w/ other 2 antitussives)
constipation, sedation, respiratory depression (all the opiods do this) - result of action in CNS
histamine release, vasodilatoin, orthostatic hypotension, and dizziness
what are the contraindications for Codeine?
hypersensitivity, labor of premature birth, pregnancy category C, prostatic hypertrophy, individuals on sedatives, in patients with acute respiratory depression, asthma or COPD, following tonsillectomy and or adenoid surgery
What is the MOA of the topical agent Camphor?
it activates the TRPV1 and TRPA1 channels on the cough receptor afferent nerves, intially activates them and then desensitizes them
what is the MOA of the topical agent menthol?
it acts on TRPM8 channels, initially activating then desnsitizing them
is Guaifenesin used for chronic cough?
no
what is Guaifenesin used for?
symptomatic relief of ineffective productive coughs - chest congestion
what is the MOA of Guaifenesin?
loosens and thins lower respiratory trat secretions by increasing the volume and reducing the viscosity of secretions
What is Guaifenesin used for in veterinary medicine, and why?
it is used to induce and maintain anesthesia in horses in llama
it does not have any analgesic effect, it simply causes muscle relaxation
because the horses and llamas have a violent reaction to the analgesics like propofol and others
what are the side effects of Guaifenesin
dizziness, dry mouth, rash, diarrhea, drowsiness, nausea, vomiting, stomach pain, diarrhea, uric acid nephrolithiasis (in large doses)*
what is contraindication for Guaifenesin
hypersensitivity
what are the nasal decongestants? how do they affect histamine? what are they commonly formulated with?
vasoconstrictive drugs that reduce nasal decongestion
they do not affect release of histamine or any other mediators involved in the allergic reaction
commonly formulated with antihistamines
what is the MOA of nasal decongestants
alpha-adrenergic agonist (sympathomimetic) - constricts blood vessels throughout the body
what is the effect of nasal decongestants
reduces supply of blood to the nose
decreases the amount of blood in the sinusoid vessels
decreases mucosal edema
what is a direct acting alpha antagonist used as a nasal decongestant?
Phenylephrine
what is the MOA of pseudoephedrine?
indirectly acting sympathomimetic - it binds presynaptic terminal, causes NE to be released into the synaptic cleft
(same moa as ampehtamine)
How is PE metabolized?
rapidly by MAO (Monoamine oxidase) and COMT (catechol-O-methyl transferase) in the GI mucosa, liver, and other tissues - does not have long duration of aciton
How is Pseudoephedrine metabolized?
only to a minor extent, by N-demethylation to norpseudoephedrine
between Pseudoephedrine and Phenylephrine, which one gets into the brain better?
pseudoephedrine - it has longer duration of action, and it is not metabolized by MAO
which between pseudoephedrine and phenylephrine has a better bioavailability?
pseudoephedrine
but both have a short half life
what are the side effects of phenylephrine?
can increase BP at high doses, will see reflex bradycardia b/c phenylephrine has no effects on B receptors in heart
what are the side effects of Pseudoephedrine
Pseudoephedrine induces the release of NE so it activates everything
CV stimulation: increase BP, tachycardia, palpitation, arrhythmias
CNS stimulation: restlessness, insomnia, anxiety, tremors, fear, or hallucinations
which pt populations are most likely to experience the side effects of systemic decongestants?
children and elderly
what are two effects that can result from overuse of the systemic decongestants?
1) can cause infection due to vasoconstriction and inability to clear bacteria
2) rebound congestion - ischemia as a result of local vasoconstriction or local irritation by the drug
what are two notable precautions or contraindications for phenylephrine use and why
1) bradycardia - due to the reflex increase in vagal tone because of PE
2) heart block - again, due to the increase vagal tone
what is one major contraindication for pseudoephedrine and why
hyperthyroidism - hyperthyroidism causes increase in expression of beta adrenergic receptors - never give medication to a pt w/ hyperthyroidism that will increase NE - this will lead to heart problems
what are two other precautions and contraindications for the use of systemic decongestants
uncontrolled HTN
ventricular tachycardia
what is an alpha agonists that is used as a topical spray nasal decongestant? available OTC
oxymetazoline
what is the MOA of oxymetazoline?
direct alpha 1 adrenergic agonist
what are two other drugs that have similar MOAs as amphetamine (increase release of NE) and thus have the potential for abuse?
Levamfetamine
Benzedrex
what effect does amphetamine have at high doses?
hallucinogenic
Mucolytics are used in diseases where there is increased mucus production - some examples are
cystic fibrosis
COPD
Bronchiectasis
Respiratory infections - TB
what are 4 non-pharmacologic ways to facilitate mucus clearance
provide adequate hydration
remove causative factors
optimize tracheobronchial clearance
reduce inflammation
what are 4 examples of expectorants?
Iodinated glycerol
Guiafenesin
Bromohexine
N-acetyl cysteine
what is the MOA of iodinated glycerol
promote the production of serosal fluid that is more watery
what is the MOA of bromohexine?
secretolytic, increases the production of serous mucous in the respiratory tract and decreases the viscosity of phlegm
what is the MOA of N-acetyl cysteine
breaks the disulfide bonds by substituting a sulfhydryl radical
what is a side effect of N-acetyl cysteine
bronchospasm
what are the 5 mucolytics we talked about?
1) N-acetyl cysteine
2) Sodium Bicarbonate
3) Dornase alfa (pulmozyme)
4) amiloride
5) Denufosol Tetrasodium
what do we need to know about sodium bicarbonate (MOA)?
it is a 2% sodium bicarb solution - used to increase the pH of mucus by weakening carbohydrate side chains
what is the MOA of Dornase Alfa?
it is a DNAse enzyme that digest extracellular DNA - it reduces viscosity of secretion during an infection this way
what are the indications for Dornase Alfa (pulmozyme)?
used in cystic fibrosis, chronic bronchitis, or bronchietasis
what is an important point about dornase alfa, i.e. when won’t it work?
has no effect on non-infected sputum
what are the side effects of pulmozyme (dornase alfa)?
voice alteration, pharyngitis/laryngitis, rash, chest pain, conjunctivitis
what is the contraindication of Pulmozyme (dornase alfa)?
pts hypersensitive to Chinese Hamster Ovary cell products (Abteen)
what is the MOA and indication for amiloride
diuretic that can be given by aerosol for pts w/ cystic fibrosis
when is amiloride not very effective
bronchial asthma
what is the MOA of Denufosol Tetrasodium? make note of which receptors it activates
enhances mucosal hydration and mucus clearance by activating Cl- secretion and inhibiting epithelial Na+ transport via activation of P2Y2 receptors (the same receptors as for ATP)
