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What is the definition of a COUGH?
A voluntary OR involuntary RESPIRATORY tract REFLEX
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What is the CLASSIFICATION and CAUSE of an ACUTE cough?
- LESS than 3 weeks
- Caused by: Viral URI or OTHER conditions (pulmonary emboli, pneumonia)
- Related to POST NASAL DRIP
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What is the CLASSIFICATION and CAUSE of a SUBACUTE cough?
- 3-8 Weeks
- Caused by: Post infectious Cough, Bacterial Sinusitis
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What is the CLASSIFICATION and CAUSE of a CHRONIC cough?
- 8 Weeks
- Most COMMON: Post Nasal Drip, Pulmonary Conditions (asthma), GERD
- ALSO: CHF, Medications (ACEI--20% due to inhibition of bradykinin break down, Non-selective Beta-blockers---due to bronchioconstriction)
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What are the CAUSES of a CHRONIC cough in children?
- Foreign body ASPIRATION
- Esophageal MOTILITY Disorders
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Why do ACE INHIBITORS cause a COUGH?
They STOP the breakdown of BRADYKININ
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Why do Non-selective BETA-BLOCKERS cause a COUGH?
They cause BRONCHIOCONSTRICTION
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What are the TWO TYPES of Coughs?
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What is a PRODUCTIVE Cough?
- Wet or "CHESTY"
- CLEARS secretions from LRT
- Coughing up MUCUS
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What is a NONPRODUCTIVE Cough?
- Dry or "HACKING"
- No PHYSIOLOGIC purpose
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What are (6) COMMON Complications with a COUGH?
- Exhaustion
- Insomnia
- Muscle Pain
- Hoarseness
- Excessive Sweating
- Urinary Incontinence
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What are (4) LESS COMMON Complications with a COUGH?
- Heart Arrythmias
- Syncope--- passing out
- Stroke--- due to increased Intracranial Pressure
- Rib Fractures--- due to Osteoporosis
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A TRIAD of symptoms that usually occur with the common COLD, FLU, & ALLERGY?
- Cough
- Nasal Congestion
- Allergy
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What is the MECHANISM of the COUGH REFLEX?
Irritants/Particulates----(Inflammatory Mediators)---- Sensory Nerve Stimulation---- CNS Cough Reflex Center= MEDULLA
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What is the COUGH REFLEX Center?
MEDULLA
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What can TRIGGER (5) the COUGH REFLUX?
- Allergens
- Pathogens
- Enviro Pollutants
- Job Exposures
- Mucosal [Ion]/osmolarity
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The ____________________________ is the SENSORY nerve ENDINGS of respiraory epithelium.
AFFERENT Nerve Pathway
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The Afferent Nerve Pathway contains receptors SENSITIVE to ___________________________ & __________________________.
- MECHANICAL Stress
- Specific CHEMICAL Transmitters
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__________________________ are activates by ONE OR MORE mechanical stimuli.
Rapidly Acting Stretch Receptors (RAR)
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What MECHANICAL Stimuli activate RARs?
- Lung Inflation
- Bronchospasm
- Light Touch
- Physical changes---triggered by histamine from mast cells
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________________________________ are activated DIRECTLY or SENSITIZED by a wide range of chemicals, but are realtively INSENSITIVE to mechanical stimuli.
CHEMORECEPTORS
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Whats CHEMICALS activate Chemoreceptors?
- Capsaicin
- Bradykinin
- Adenosine
- PGE2
- Substance P
- Neurokinin A
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What FIBERS carry informations from CHEMORECEPTORS?
Bronchopulmonary C-fibers (Slow, thin unmyelinated nerve fibers)
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Bronchopulmonary C-fibers RELEASE ________________________.
TACHYKININS------Substance P, Neurokinin A, Bradykinin
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What FIBERS carry information from STRETCH & CHEMORECEPTORS?
Broncopulmonary A-delta fibers (Fast, thick myelinated nerve fibers)
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Where to BOTH FIBERS (C & A-delta) JOIN to carry senssory Info to the CNS?
Afferent Branch of the VAGUS NERVE
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Where do extensive SYNAPSES from the VAGUS occur?
The nulceus of the TRACTUS SOLITARIUS--associated with the Solitary Nucleus
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Where is the Nucleus of the TRACTUS SOLITARIUS Located?
Upper MEDULLA OBLONGATA (each side)
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What FUNCTIONS does the Nucleus of the TRACTUS SOLITARIUS play a role in?
- BP regulation
- Cough Reflex
- Gag Reflex
- Sneeze Reflex
- Vomitting
- Inspiration
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What happens with the SUPPRESSION of the Medulla Oblongata?
- Increased Threshold to elicit Cough
- Decreased Cough Reflex
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What is the COORDINATION of Nerve Impulses in the EFFERENT PATHWAY?
- CLOSE Epiglottis (following deep inspiration)
- SYNCHRONIZED Contraction (of diaphragm, intercostal and abdominal muscles)
- COUGH Rapidly (expel 2-3L of air)
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What (4) MAJOR NERVES are involved in the EFFERENT Pathway of a COUGH?
- Vagus--coordinates muscles
- Glossopharngeal--closes epiglot, controls pharynx
- Phrenic--enervates diaphragm
- Trigeminal--afferent sensory fxn from scalp to chin
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What are the PHARMACOLOGICAL Interventions of the CNS for a COUGH?
- Opiod Receptor Agonists--Codeine, Hydrocodone
- Dextromethorphan
- Antihistamines--diphenhydramine, chlorpheniramine, brompheniramine, promethazine
- Benzonatate
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What are the PHARMACOLOGICAL Interventions used LOCALLY for a COUGH?
- Local anethetics
- Benzonatate
- Tachykinin receptor antagonists
- Antihistamines
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EXCLUSIONS to Self-Care:
COUGH?
- Fever (if only symptoms are fever and cough)
- Unintended Weightloss
- Drenching PM Sweats
- Hemoptysis
- Hx or Symp of underlying disease with Cough
- Foreign Object Aspiration
- Drug-associated (suspected)
- Cough > 7days
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NON-PHARMACOLOGICAL Therapy for a COUGH?
- Cool Mist Humidifiers & Vaporizers
- Lozenges/Hard Candy
- Hydration
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Avoid using COUGH & COLD medications in KIDS under the AGE ____________.
TWO
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The 3 OPIOID Receptors TYPES?
- Mu, Kappa, Delta
- ---GPCRs w/ 7 transmembrane domains
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Which RECEPTOR SUBTYPE for Opioids is associated with the MOST effects?
Mu--Analgesia, Sedation, Respiratory Depression, Decreased GI Motility
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What are (8) IMPORTANT Opioid Receptor Agonists?
- Euphoria--dream-like sense of well-being
- Sedation & Drowsiness
- Anti-Anxiety
- Analgeisa
- N/V
- Respiratory Depression
- Miosis
- Constipation
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The __________________ expresses HIGH LEVELS of _________ opioid receptors.
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The Agonist activity of the _______ receptor ___________________ CHEMICAL and ELECTRICAL activity of the neurons.
- Mu
- SUPPRESSES--- increases cough treshold & decreases cough reflex
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Where is the Mu RECEPTOR located?
Membrane of NEURONAL CELLS
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What type of SYSTEM does MORPHINE affect?
The Brain's PAIN & REWARD system
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What provides a REWARD SENSATION or a feeling of RELIEF from TENSION when our basic needs are satisfied?
DOPAMINERGIC "pleasure-reward" Neural Tract
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How does AGONIST ACTIVITY at Opioid Receptors contribute to ABUSE & ADDICTION?
They FLOOD the pleasure-reward system with ARTIFICIAL high levels of DOPAMINE
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What is the difference between ABUSE & ADDICTION?
- Abuse: Self-Admin of drug in a disapproved manner with adverse consequences
- Addiction: Behavioral Pattern characterized by compulsive drug use
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What are the OPIATES typically used as ANIT-TUSSIVES?
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What is this DRUG and what is a DISTINCT characteristics?
- CODEINE
- methylated hydroxyl
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What is this DRUG and what are (2) DISTINCT characteristics?
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What EFFECTS & USAGES does CODEINE have?
(Explain the REASON behind each USAGE)
- Antitussive: May involve DISTINCT receptors that bind codeine itself
- Analgesic: Codeines conversion to Morphine
- Pro-emetic: Causes N&V
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How is Codeine METABOLIZED?
Demthylation at -OMe sites via CYP2D6 enzymes to MORPHINE
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What DRUGS INTERACT with Codeine?
- CNS Depressants: additive adverse effects
- 2D6 Inhibitors: decrease metabolism of codeine to metabolism
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Explain GENETIC POLYMORPHISM as it pertains to CODEINE?
- Good Metabolizers can convert codeine to morphine to have an analgesic effect.
- Poor Metabolizers cannot convert codeine to morphine but still have anttussive effect from codeine
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What is the DOSING for CODEINE?
- Adult: 10-20mg Q4-6 hrs (Max 120mg daily)
- Not recommended for kids <2 [as a cough suppressent]
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What are the ADVERSE EFFECTS of CODEINE?
- N&V
- Sedation
- Dizzieness
- Constipation
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What are the CONTRAINDICATIONS of CODEINE?
Known codeine or morphine HYPERSENSITIVITY
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What are the PRECAUTIONS/WARNINGS of CODEINE?
- Impaired Respiratory Reserve
- Pre-existing Respiratory Depression
- Addicts
- Taking Sedative or Alcohol
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What is considered an OVERDOSE for CODEINE?
- 0.5-1g in opioid naive patients
- ---respiratory depression & cardiopulmonary collapse
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What is CODEINE's pregnancy category?
- C: Not near tern
- D: at high doses OR prolonged exposure
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What is this DRUG and what is a DISTINCT Characteristic?
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HYDROCODONE has _________x's the potency and efficacy of Codeine as an ___________________.
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What additional PRODUCT can Hydrocodone be PAIRED WITH comapred to Codeine?
- CHLORPHENIRAMINE
- Tussionex: Chlorpheniramine (8mg) & Hydrocodone (10mg) 5ml Q12h (10ml/24hrs)-- not recommended <6 yr
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What is HYDROCODONE's pregnancy category?
- C: Not near term
- D: at high doses OR prolonged exposure
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What is this DRUG and it's DISTINCT characteristics?
- DEXTROMETHORPHAN
- SIMILIAR structure but NOT an OPIOID
- LACKS analgesic, respiratory depressant, abuse effects that opioids have
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Why does DEXTROMETHORPHAN retain its ANTITUSSIVE effects?
- Activations of SIGMA receptors
- BLOCKS MAOI receptors
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What can happen when taking HIGH doses of DEXTROMETHORPHAN?
(3 Step Process)
- Acute Euphoria, halluciantions
- Dysphoria & craving upon withdrawl
- Psychological dependence
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What is the DOSING for DEXTROMETHORPHAN?
- 10-20mg Q4hr
- 30mg Q6-8hr
- 60mg Q12hr
- Max 120mg daily
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What are the ADVERSE EFFECTS of Dextromethorphan at USUAL doses?
- Drowsiness
- N&V
- Stomach Discomfort OR Constipation
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What DRUGS interact with DEXTROMETHORPHAN?
- CNS depressants
- 2D6 Inhibitors
- Monoamine Oxidase Inhibitors (MAOI)
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What 2D6 INHIBITORS canNOT be taken with Dextromethorphan and WHY?
- Paroxetine, Fluoxetine, Sertraline
- They inhibit serotonin re-uptake--dextro also inhibits re-uptake of dextro = LOTS of free serotonin ---- Increase risk of Serotonin Syndrome
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Why CAN'T MAOIs be taken with Dextromethorphan?
- MAOIs decrease the metabolism of serotonin
- -----which leads to Serotonin Syndrome
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What are the (7) MAIOs?
- Isocarboxazid
- Linezolid
- Phenelzine
- Selegiline
- Rasagiline
- Procarbazine
- Tranylcypromine
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What are the (9) 2D6 Inhibitors?
- Amiodarone
- Paroxetine
- Fluoxetine
- Sertraline
- Desipramine
- Imipramine
- Cimetidine
- Diphenhydramine
- Terbinafine
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What are the CONTRAINDICATIONS of Dextromethorphan?
- Must wait 14 days after MAIO is stopped to admin Dextro
- Known hypersensitivity
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What is Dextromethorphan's PREGNACY category?
C: because there are no controlled human studies
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What is the CENTRAL Mechanism of BENZONATATE?
Increases trigger threshold of MEDULLARY cough reflex
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What is the PERIPHERAL Mechanism of BENZONATATE?
- ANESTHETIC action on peripheral nerve endings
- ---bind to INTRACELLULAR portion of voltage-gate Na+ channels
- ----------decrease rate of membrane depolarization
- ----------increase threshold for excitability
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What is this DRUG and it's DISTINCT characteristics?
- BENZONATATE
- Strutually similiar to other ester-type local ANESTHETICS (tetracaine)
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The is the DOSING of BENZONATATE?
- Initial 100mg TID PRN
- As often as 100mg Q4hr PRN
- Max dose 600mg daily
- Not recommended <10yrs
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What are the ADVERSE EFFECTS of Benzonatate?
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What is the MAJOR counseling point of BENZONATATE?
DO NOT CHEW
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How do Antihistamines affect CENTRAL Antitussive Mechanisms?
Depress Medullary Activity via blocking H1 receptors
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How do Antihistamines affect PERIPHERAL Antitussive Mechanisms?
Have Local ANESTHETIC affects via blocking Na+ channels of peripheral nerves
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What are FIRST GENERATION Anti-histamines?
- Diphenhydramine
- Chlorpheniramine
- Brompheniramine
- (Central and Peripheral effects)
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Dosing, Adverse Effects, Drug Interactions & Pregnancy:
PROMETHAZINE & CODEINE
- Promethazine (6.25mg) & Codeine (10mg) 5ml Q4-6hr (max 30ml/24hr)
- Constipation, N/V, Sedation
- 2B6 & 2D6 Inhibitors
- Prometh:C Codeine: C/D
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What are the 2B6 & 2D6 Inhibitors?
- Desipramine
- Paroxetine
- Sertraline
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What is the DOSING for DIPHENHYDRAMINE for a Cough?
- 1/2 dose of cold/allergy
- Normally: 25mg Q4h (max 150mg daily)
- >6yrs
- Pregnancy category: B
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What are the reason to use CAMPHOR & MENTHOL to treat a cough?
- Counter irritant effects
- COLD abd MENTHOL sensitive receptor-1
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What is the COUNTER-IRRITANT effect for Camphor & Menthol?
The distraction of the CNS for an irritant because of change in temperature
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What are the TWO names for the clones menthol receptor?
- Cold & Menthol sensitive receptor-1
- Transient receptor potential channel M8
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What TWO ways does the menthol receptor help relieve a cough?
- Senses COLD at peripheral nerve endings
- Menthol-induced Ca release from presynaptic Ca stores potentiates sensory synaptic transmission
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What are Pro-tussives used for?
To help bring up mucus in a productive cough
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What is GUAIFENESIN used as?
Expetorant
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What is the MECHANISM of Gauifenesin?
- Increases VOLUME of secretions
- Reduces the VISCOSITY of secretions
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What other FACTOR also increases the volume of respiratory secretions?
OSMOLARITY--- draws fluid out of respiratory tract into mucosal tissue
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What is the DOSAGE of Gauifenesin?
- 200-400mg Q4 hr OR 1200mg BID
- Max daily 2400mg
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What are the ADVERSE EFFECTS of Gauifenesin?
- N/V, stomach pain
- Dizziness
- Headache
- (Not common in normal dosage)
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What are the DRUG INTERACTIONS of Gauifenesin?
NONE
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What are the CONTRAINDICATIONS of Gauifenesin?
Known Hypersensitivity
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What is the PREGNANCY Category of Gauifenesin?
C
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What will NOT break up mucus that is already formed?
Gauifenesin
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What WILL break up mucus that is already formed and WHY?
- Mucolytics---lyzes disulfide bonds in mucuproteins presnet in mucus and decreases viscosity
- (facilitates removal of mucus/irritants by promoting productive cough)
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WHEN should you refer a patient with a COUGH?
- Cough > 7days
- Cough worsens
- Development of other exclusions--fever
- Only symptoms cough and fever >101
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