CARDINAL MANIFESTATION - Symptoms: frequent nasal discharge, a sensation of liquid dripping into the back of the throat, and

(ADULT) frequent throat clearing. However, postnasal drip may also be "silent," so that the absence of these
symptoms does not necessarily exclude the diagnosis.
APPROACH TO PATIENTS WITH COUGH - PE: Clues on physical examination are a cobblestone appearance to the nasopharyngeal mucosa
Subjective (things you have to ask in history): and the presence of secretions in the nasopharynx.
- Onset of cough *Because the symptoms and signs of postnasal drip are nonspecific, there are no definitive criteria for
o Acute – less than 3 weeks its diagnosis, and it is ultimately the response to therapy that secures the diagnosis. When an alternative
o Subacute – 3 – 8 weeks specific cause for cough is not apparent, empiric therapy of postnasal drip should be attempted before
o Chronic - > 8 weeks embarking on an extensive diagnostic work-up for other etiologies. Radiographic evidence of mucosal
- What makes the cough worse thickening is a relatively nonspecific finding, and radiographic studies generally are not indicated unless
- If it produces sputum empiric treatment of chronic rhinitis has failed.
- Time of occurrence during the day - Treatment:
- Pattern of coughing o For Allergic Rhinitis, Nonallergic Rhinitis with Eosinophilia (NARES), Vasomotor Rhinitis:
- Cough occurs only with certain allergic exposures / exercise in cold air (Asthma)  Intranasal glucocorticoids are the most effective therapy for symptoms of allergic
*Regardless of cause, cough often worsens upon first lying down at night, with talking, or with the hyperpnea rhinitis. It is generally effective in reducing cough within the first few days, but may take
of exercise; it frequently improves with sleep. up to two weeks to achieve maximal effect. If the patient responds, therapy is continued
for approximately three months.
Objective (Things you have to assess):  Oral and nasal antihistamines, oral decongestants, oral leukotriene receptor
antagonists, and other agents.
- Suggest presence of cardiopulmonary disease: Wheezing / crackles
 If without evidence for allergic rhinitis in whom nonallergic rhinitis may be more likely:
- Examination of auditory canals and tympanic membranes – for irritation in stimulation of Arnold’s
 Perform a diagnostic trial with an oral first generation antihistamine
nerve
(eg, brompheniramine, chlorpheniramine, clemastine) or a combined
- Exam of nasal passageways (Rhinitis / Polyps), nails for clubbing
antihistamine-decongestant (eg, brompheniramine-pseudoephedrine).
 First generation antihistamines are preferred over second generation ones
Assessment:
(eg, cetirizine, fexofenadine, loratadine) due to the stronger anticholinergic effect,
Common etiologies of Chronic Cough: but concern over the sedating effects may limit their use. Improvement in the cough
1) Chronic idiopathic cough (aka Cough Hypersensitivity Syndrome) should lead to further evaluation for the cause of the rhinitis (eg, allergic,
- It is often experienced as a tickle or sensitivity in the throat nonallergic, or rhinosinusitis) and optimization of the long-term treatment.
- Occurs more often in women o For patients with suspected nonallergic UACS who are not candidates for use of an oral first
- typically “dry” or at most productive of scant amounts of mucoid sputum generation antihistamine (eg, due to excess somnolence):
- can be exhausting, interfere with work, and cause social embarrassment  Other options include intranasal administration of one of the following: azelastine,
o PLAN glucocorticoid, and ipratropium bromide. However, azelastine may cause somnolence
 Once serious underlying cardiopulmonary pathology has been excluded, an attempt at cough even with intranasal use.
suppression is appropriate.  Intranasal ipratropium bromide significantly reduces the rhinorrhea associated with
 Most effective are narcotic cough suppressants, such as codeine or hydrocodone, which are perennial nonallergic rhinitis and has few side effects
thought to act in the “cough center” in the brainstem o Lack of improvement in cough after one to two weeks of empiric therapy for UACS is evidence
- Warning: The tendency of narcotic cough suppressants to cause drowsiness and that UACS is not the cause of the cough.
constipation and their potential for addictive dependence limit their appeal for longterm o However, in the presence of nasal symptoms or signs, a sinus CT scan should be performed
use. before completely excluding the possibility of UACS as a cause of cough. When sinusitis is
 Dextrometorphan - centrally acting cough suppressant with fewer side effects and less efficacy documented by plain radiograph or sinus CT scan, treatment is guided by whether the patient
than the narcotic cough suppressants has acute (less than 12 weeks) or chronic sinusitis.
- Thought to have a different site of action than narcotic cough suppressants and can be
used in combination with them if necessary 3) Asthma
 Benzonatate is thought to inhibit neural activity of sensory nerves in the cough-reflex pathway. It - Second leading cause of persistent cough in adults
is generally free of side effects; however, its effectiveness in suppressing cough is variable and - Most common cause in children
unpredictable - Symptoms: Cough due to asthma is commonly accompanied by episodic wheezing and
dyspnea; however, it can also be the sole manifestation of a form of asthma called "cough variant
2) Upper Airway Cough Syndrome asthma". Cough variant asthma can progress to include wheezing and dyspnea.
- Several studies suggest that upper airway cough syndrome related to postnasal drip is a common o Asthma-related cough may be seasonal, may follow an upper respiratory tract infection, or
cause of subacute and chronic cough. Underlying reasons for postnasal drip include allergic, may worsen upon exposure to cold, dry air, dust, mold, or to certain fumes or fragrances. A
perennial nonallergic, and vasomotor rhinitis; acute nasopharyngitis; and sinusitis. cough accompanied by wheezing or dyspnea, or one that occurs following initiation of beta-
- Once secretions are present in the upper airway, cough is probably induced by stimulation of blocker therapy also suggests asthma.
cough receptors within the laryngeal mucosa. - A diagnosis of asthma is suggested when the patient is atopic or has a family history of asthma.
 - In some cases, the cough is accompanied by reversible airflow obstruction. In other patients,
baseline spirometry is normal, but airways hyperreactivity can be demonstrated by
bronchoprovocation testing. However, in a patient with persistent cough, the presence of
reversible airflow obstruction or a positive bronchoprovocation test does not necessarily prove
that the cough is secondary to asthma. One study, for example, evaluated the utility of spirometry
pre- and post-bronchodilator in predicting that asthma was responsible for cough. Spirometry was
falsely positive in 33 percent of patients, and methacholine challenge was falsely positive in 22
percent.
- Thus, the best way to confirm asthma as a cause of cough is to demonstrate improvement in the
cough with appropriate therapy for asthma (eg, two to four weeks of inhaled glucocorticoids.
- Patients with active asthma typically have eosinophilic bronchitis. The diagnosis of nonasthmatic
eosinophilic bronchitis should be considered in atopic patients with an idiopathic chronic cough
and sputum eosinophilia in the absence of airway hyperreactivity.
o Exhaled nitric oxide (NO) has been studied as a predictor of response to inhaled
glucocorticoids in both asthma and in nonasthmatic eosinophilic bronchitis. Exhaled NO and
sputum eosinophilia are correlated in these conditions. However, some studies have shown
exhaled NO to be a good predictor of response of chronic cough to inhaled steroids [33],
while other studies have not. The explanation for this discrepancy may in part be related to
what value is chosen to reflect an abnormally elevated exhaled NO.
- Treatment for cough variant asthma :
o Regular use of inhaled glucocorticoids (GC) and as-needed use of inhaled bronchodilators
o Leukotriene receptor antagonists (LTRA) have also been shown to improve cough in patients
with cough variant asthma. LTRAs are an alternative among patients who wish to avoid or
who have not responded to glucocorticoids.
o For patients who are disabled by their cough, a short (one to two week) course of
oral prednisone can be given, generally with excellent results. Once the patient has
improved, prednisone is discontinued and maintenance therapy with inhaled GCs is
continued.
o Sputum eosinophil cell count and exhaled nitric oxide measurement have been used in
patients with asthma as measures of airway inflammation. This has led some to suggest that
such tests can be used by the clinician in evaluating whether patients with a suboptimal
response to therapy for cough variant asthma would benefit from an escalation in their anti-
inflammatory asthma treatment. Further study of this approach is needed before widespread
implementation.
4) Gastroesophageal reflux
- Often reported to be the second or third most common cause of persistent cough
- Symptoms: heartburn or a sour taste in the mouth; however, these symptoms are absent in
more than 40 percent of patients in whom cough is due to reflux
- Esophageal dysmotility, with or without evidence of GERD, appears to be common in
patients with chronic cough. However the role of esophageal manometry in the evaluation
remains to be defined.
- Gastroesophageal reflux can also contribute to asthma symptoms.
- Factors are potentially responsible for the cough associated with gastroesophageal reflux:
o Stimulation of receptors in the upper respiratory tract (eg, in the larynx).
o Aspiration of gastric contents, leading to stimulation of receptors in the lower respiratory
tract.
o An esophageal-tracheobronchial cough reflex induced by reflux of acid into the distal
esophagus.
 In one study of patients with chronic cough and reflux, infusion of acid into the distal
esophagus significantly increased cough frequency. This effect was absent in
control subjects without chronic cough.
 Treatment: The acid-induced cough was significantly decreased by pretreatment
with either inhaled ipratropium or a topical anesthetic (lignocaine) instilled into the
esophagus.
- Diagnostics:
o The presence of cough induced by gastroesophageal reflux may be suggested by an
abnormal barium swallow, but this study is negative in the majority of patients and many
patients with reflux do not have cough.
o Prolonged (24 hour) esophageal pH monitoring, ideally performed with event markers to allow
correlation of cough with esophageal pH, is generally considered the optimal diagnostic
study, with a sensitivity exceeding 90 percent.
 However, even with maximal antireflux therapy, some patients with positive results on
esophageal pH monitoring continue to cough.
- Treatment / Lifestyle Modification:
o The evidence in favor of lifestyle modifications to reduce or prevent GERD and thereby treat cough
is limited. The following interventions are based on the lifestyle modifications that are suggested for
the routine management of GERD:
 Weight loss for patients who are overweight
 Elevation of the head of the bed three to four inches
 Cessation of smoking
 Avoidance of reflux-inducing foods (eg, fatty foods, chocolate, excess alcohol)
 Avoidance of very acidic beverages (eg, colas, red wine, orange juice)
 Avoidance of meals for two to three hours before lying down (except for medications)
o Acid-suppression medication — key component to the treatment of cough due to GERD in
combination with lifestyle modifications. However, regimens proven effective in the management
of GERD may not necessarily be the optimum regimen for cough due to GERD. A meta-analysis of
randomized trials of medical GERD interventions for cough showed that while such therapy indeed
has some effect in adults, the effect is less universal than often suggested in consensus guidelines.
A possible explanation for failure to improve despite acid suppression is that of nonacidic reflux.
 Empiric trial of a proton pump inhibitor at a moderate dose (eg, omeprazole 40 mg once daily
in the morning). This is based on the evidence that therapy with a PPI is more effective than
H2 antagonist treatment. In addition, as it may take up to eight weeks, and sometimes several
months, to yield optimal improvement in cough, it seems reasonable to start with the more
effective choice.
o For patients whose cough does not improve after one to two months of empiric therapy:
 24 hour esophageal pH probe monitoring - results suggestive of cough due to GERD include
an abnormal amount of time with an esophageal pH less than four and cough occurring within
a few minutes of reflux events.
 Multichannel intraluminal impedance (MII) monitoring, which is increasingly available, may
help identify patients with cough from nonacidic reflux.
o Other therapies — The addition of prokinetic therapy such as metoclopramide may be beneficial
in patients with nonacidic reflux or may add to the effectiveness of acid suppression therapy in
cough due to acidic reflux. However, supportive data are weak and patients placed on
metoclopramide should be followed for the possible development of extrapyramidal side effects
(eg, rigidity, bradykinesia, tremor, and restlessness).The role of anti-reflux surgery to relieve extra-
esophageal symptoms related to GERD is unclear.
o We reserve laparoscopic or open Nissen fundoplication for the small number of patients with
chronic cough who have objectively documented gastroesophageal or laryngopharyngeal reflux
disease that is refractory to medical measures.
5) Laryngopharyngeal reflux - is the retrograde movement of gastric contents (acid and enzymes such as
pepsin) into the laryngopharynx leading to symptoms referable to the larynx/hypopharynx. Most
patients are relatively unaware of LPR with only 35 percent reporting heartburn.
- Typical LPR symptoms: dysphonia/hoarseness, chronic cough, mild dysphagia and nonproductive
throat clearing.
 - Seen as primarily an upper esophageal sphincter (UES) problem that mainly occurs in the upright
position during periods of physical exertion (eg, bending over, Valsalva, exercise).
o In contrast, GERD is felt to be a problem of the lower esophageal sphincter and mainly
occurs in a recumbent position. There appears to be a lower incidence of esophageal
dysmotility in LPR versus GERD.
- Diagnostics:
o Direct laryngoscopic evaluation can assist in the diagnosis of cough from reflux.
 Arytenoid erythema and edema and pharyngeal inflammation often suggest laryngeal
and pharyngeal reflux, and when seen, suggest that a course of treatment for reflux is
indicated with monitoring of the cough on such therapy.
o Multichannel intraluminal impedance (MII) - used to assess laryngopharyngeal and high
esophageal reflux in patients with chronic cough. Among 49 patients with unexplained
chronic cough who underwent MII, 73 percent had nonacid proximal esophageal events.
Furthermore, in the nearly half of these who went on to anti-reflux surgery, 100 percent had
either total or significant resolution of cough. The authors concluded that a “pH-centric”
approach may well be inadequate to evaluate cough related to reflux, which may explain
the debate still present in some circles on the relationship between GERD and cough.
6) Respiratory tract infection — Cough following viral or other upper respiratory tract infection can persist
for more than eight weeks after the acute infection. Such cases increase in frequency during outbreaks
of Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis.
- Possible mechanisms responsible for cough in this setting:
o Secretions from a postnasal drip may stimulate receptors in the upper respiratory tract.
 Tx: Antihistamine-decongestant therapy may be effective in reducing nasal discharge,
nasal obstruction, throat clearing, and cough.
o Enhanced sensitivity of airway nerves, assessed experimentally by the concentration of
inhaled capsaicin required to elicit cough, may be present after upper respiratory tract
infections, particularly in those patients who develop a nonproductive cough.
 A possible explanation for this response is exposure of afferent nerves, located
immediately below epithelial tight junctions, as a consequence of viral-induced epithelial
necrosis.
o Airway inflammation following acute viral respiratory infections is associated with airway
hyperresponsiveness and the potential for cough as well as airway constriction.
- Pertussis is a common, but under recognized, cause of persistent cough in adolescents and adults.
o In one series of 75 adults with cough lasting more than two weeks, 21 percent met serologic
criteria for pertussis infection despite a negative culture for Bordetella pertussis. However,
accurate serologic studies are infrequently available and may be difficult to interpret, further
complicating confirmation of this diagnosis.
- Some patients appear to have unsuspected bacterial suppurative disease of the large airways, in
the absence of bronchiectasis, as a cause of chronic cough.
- Diagnostics:
o Bronchoscopic evaluation and microbiologic sampling of the airways led to this diagnosis in a
series of 15 patients undergoing evaluation at a single center for cough that remained
unexplained after extensive evaluation. While four of these patients had underlying systemic
disease, the remainder had no evidence of immune compromise.
- Treatment: Aggressive antibiotic therapy, based upon the results of bronchoscopic culture, led to
improvement or elimination of the cough in all patients.
- For postviral cough without upper airway cough syndrome: the agents described above for cough
variant asthma are used. These patients often have transient bronchial hyperreactivity and a
positive methacholine challenge test.
- For postviral cough who have no evidence of airway hyperreactivity: Inhaled ipratropium bromide
has been reported to produce improvement in the cough.
- For Infection due to Bordetella pertussis (whooping cough): may be responsible for approximately
20 percent of cases of prolonged cough in adolescents and adults. It is therefore important to
consider this diagnosis in the patient with an apparent postinfectious cough, especially if post-
tussive vomiting is present. Patients are treated with a macrolide antibiotic, or trimethoprim-
sulfamethoxazole, if a macrolide cannot be given. However, there is limited evidence for efficacy
when these medications are administered beyond the first two weeks of the illness.
7) ACE inhibitors — A nonproductive cough is a well-recognized complication of treatment with
angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15 percent of patients treated with
these agents.
- Although the pathogenesis of the cough is not known with certainty, it has commonly been
hypothesized that accumulation of bradykinin, which is normally degraded in part by ACE, may
stimulate afferent C-fibers in the airway.
o The important observation that cough does not appear to occur with increased frequency in
patients treated with angiotensin II receptor antagonists (which do not increase kinin levels) is
consistent with the kinin hypothesis.
- The cough usually begins within one to two weeks of starting therapy, but may be delayed for as
long as six months.
- ACE inhibitor-induced cough has the following general features:
o It usually begins within one week of instituting therapy, but the onset can be delayed up to six
months.
o Symptoms: It often presents with a tickling, scratchy, or itchy sensation in the throat
o It typically resolves within one to four days of discontinuing therapy, but can take up to four
weeks.
o It generally recurs with rechallenge, either with the same or a different ACE inhibitor.
o It is a more common complication in women than in men, and is also more common in those
of Chinese ancestry.
o It does not occur more frequently in asthmatics than in non-asthmatics.
o It is generally not accompanied by airflow obstruction.
- Treatment: Discontinuing the ACE inhibitor and, if necessary, switching the patient to losartan or
another angiotensin II receptor antagonist
o Although theophylline, inhaled sodium cromoglycate, and a thromboxane antagonist
(picotamide) may partially alleviate this cough, the treatment of choice is withdrawal of
the ACE inhibitor. The cough will typically resolve within one to four weeks after stopping
the ACE inhibitor, but occasionally will last up to three months.
8) Chronic bronchitis — presence of cough and sputum production on most days over at least a three-
month period for more than two consecutive years in a patient without other explanations for cough.
- Almost all patients are smokers, except a small number who have chronic exposure to and airway
inflammation due to other fumes or dusts
- Signs: The sputum produced is usually clear or white.
o A purulent appearance to sputum often suggests a concomitant upper or lower respiratory
infection, such as acute bronchitis, bronchiectasis, or sinusitis. In any smoker who presents for
evaluation of cough, one must ensure that the symptoms do not represent a change in a
chronic cough that is suggestive of a neoplasm.
9) Bronchiectasis — results from severe, repeated, or persistent airway inflammation that leads to
progressive airway damage.
- Bronchi become dilated and cystic, leading to poor mucus clearance, secretion pooling, and
chronic infection of the lower respiratory tract. This, in turn, serves to worsen airway inflammation
and bronchial destruction.
- Symptom: Cough is a major symptom of bronchiectasis, and in some studies, bronchiectasis is the
cause of chronic cough in 4 percent of patients.
o While some patients with bronchiectasis have only a dry cough, most produce chronic sputum
that is mucopurulent, and which becomes frankly purulent during an exacerbation.
- PE: The lung examination may be surprisingly normal, but more often reveals focal or bilateral
rhonchi, crackles, or wheezes.
- Diagnostics:
o Chest radiograph may suggest the disease by demonstrating crowded lung markings,
thickened bronchial walls, or small fluid-filled cystic structures. However, these findings are
insensitive and nonspecific
o Chest CT with high resolution imaging is the optimal method of securing the diagnosis.
- Once bronchiectasis is diagnosed, one should attempt to define its cause.
o Focal bronchiectasis is often the result of a prolonged or severe remote lower respiratory
infection.
o Multifocal bronchiectasis, especially in a middle aged woman, is often due to chronic lower
airway infection with Mycobacterium avium complex (MAC).
o More diffuse bronchiectasis, especially in a younger individual, raises the possibility of cystic
fibrosis or an immunoglobulin deficiency state.
10) Lung cancer — Bronchogenic carcinoma is a feared diagnosis in which cough is present in a
significant number of cases.
- However, lung cancer is the etiology in less than 2 percent of the cases of chronic cough.
- Most cases of lung cancer that manifest with cough are due to neoplasms originating in the large
central airways, where cough receptors are common.
- PE: Focal wheezing or diminished breath sounds, indicative of focal airway obstruction from tumor.
- Pulmonary lymphangitic carcinomatosis from extrapulmonary malignancies can also present as
cough, but is generally accompanied by dyspnea.
- Bronchogenic cancer - possible etiology of cough in any current or former smoker, and should be
particularly suspected in those with:
o A new cough or a recent change in chronic "smoker's cough"
o A cough that persists more than one month following smoking cessation
o Hemoptysis that does not occur in the setting of an airway infection
specialized clinic noted tonsillar enlargement in the absence of other known causes of chronic
cough in eight individuals (3.4 percent). Following tonsillectomy, these patients had decreased
cough sensitivity and significantly improved symptom control. These intriguing preliminary
observations require further investigation before this approach can be recommended.
- Irritation of the external auditory canal by impacted foreign bodies or cerumen is another unusual
cause of chronic dry cough.
o The etiology of the "ear-cough" (or oto-respiratory) reflex is related to stimulation of the
auricular branch of the vagus nerve (Arnold's nerve).
o PE: Otoscopic examination should be performed in patients with an undiagnosed chronic
cough.
- Premature ventricular contractions (PVCs) may rarely cause a chronic cough. In a series of 120
patients referred to an electrophysiology center for evaluation of PVCs, six had a chronic cough
that either disappeared upon spontaneous resolution of the PVCs or markedly improved with
treatment of the arrhythmia.
- Another rare cause of chronic cough is Holmes-Adie syndrome due to autonomic dysfunction
affecting the vagus nerve.
o PE: Patients present with anisocoria, abnormal deep tendon reflexes, and patchy areas of
hyperhidrosis or anhidrosis.
o In adults, somatic cough syndrome and tic cough (also known as "psychogenic" or habit
cough) may rarely be the cause of a chronic cough that remains troublesome despite a
thorough evaluation, including ruling out tic disorders
 No particular clinical manifestations or associated conditions have been confirmed,
although patients should be evaluated for common problems such as anxiety,
depression, and domestic violence. The diagnostic features are the lack of a diagnosis
following a complete evaluation and improvement with behavior modification or
psychiatric therapy.

11) Nonasthmatic eosinophilic bronchitis — for patients who lack any of the risk factors described Diagnostics:
above. Chest radiograph
- Patients with this disorder demonstrate atopic tendencies, with elevated sputum eosinophils and Examination of expectorated sputum
active airway inflammation in the absence of airway hyperresponsiveness. Cytologic examination of mucoid sputum may be useful to assess for
o These same findings with evidence of hyperresponsiveness are consistent with the diagnosis of malignancy and to distinguish neutrophilic from eosinophilic bronchitis.
cough-variant asthma.
- Diagnostics: ALGORITHM FOR SUBACUTE AND CHRONIC COUGH IN ADULTS
o Although bronchial mucosal biopsies are required to definitively diagnose eosinophilic
bronchitis, a trial of therapy is usually performed without biopsy, since most patients respond
well to inhaled glucocorticoids.
 Airway eosinophils and basement membrane thickening are present in both asthma and
eosinophilic bronchitis, but mast cell infiltration is noted only in asthmatics, which may
explain the differences in airway reactivity.
12) Rare causes — In the elderly or infirm, swallowing dysfunction may lead to recurrent aspiration and
chronic cough. Formal assessment by a speech pathologist may be needed for clinically silent
aspiration.
- Lesions that compress the upper airway, including arteriovenous malformations and retrotracheal
masses, may present with chronic cough.
o Can be a symptom of tracheobronchomalacia, which results from loss of rigid support of
the large airways and inspiratory collapse, and is usually seen in conjunction with
obstructive lung disease in patients with a history of cigarette smoking.
o Tracheal diverticuli have also been noted in association with chronic cough.
- Laryngeal sensory neuropathy has been identified as the cause of chronic cough in 18 of 26
patients with acute onset of cough that was often associated with laryngospasm or throat clearing.
o Diagnostics: Laryngeal electromyography or videostroboscopy, usually after exclusion or
treatment of other causes of chronic cough.
- Chronic tonsillar enlargement has been proposed as a cause of chronic cough, but clinical
evidence of this association is limited. One series of 236 patients referred for evaluation in a
 disease as the cause of their cough. More often, however, they have what many now term
“unexplained chronic cough”, “chronic idiopathic cough”, or “cough hypersensitivity syndrome”.
This disorder may in part be due to an abnormally sensitive cough reflex, perhaps in the form of
heightened sensory nerve receptor sensitivity due to alterations in receptor ion channels, such as
transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1).
- Until cough receptor antagonists are developed and tested, the currently available nonspecific
cough remedies described below are reasonable for the management of disabling chronic cough
that has not responded to specific therapy.

1) Centrally acting antitussive agents — A number of agents, both opioid and non-opioid, are
thought to suppress cough via an action on the central cough center. The data are limited
regarding efficacy despite widespread use. We usually start with dextromethorphan, due to its
better side effect profile. If that is ineffective, then codeine or long-acting morphine are tried,
recognizing the risk of addiction and other narcotic-related adverse effects. Use of gabapentin for
cough is “off-label”, but may be tried for cough refractory to other measures, as described below.

a. Dextromethorphan — Dextromethorphan is probably the most common non-opioid

agent used for cough. Studies that have compared
codeine and dextromethorphan have shown variable results, but the number of subjects
in each study is small.
i. In a cross-over study of 16 patients with chronic, stable cough, codeine (20 mg)
and dextromethorphan (20 mg) were equally effective in reducing cough
frequency. However, because cough intensity was lowered more by
dextromethorphan than by codeine, the majority of patients preferred the use
of dextromethorphan.

b. Codeine — traditional opiate used for cough, although evidence regarding its efficacy
for chronic cough is limited. In a systematic review, codeine was more effective than
placebo in reducing the severity and frequency of cough, although the quality of the
available studies was judged to be fair or poor. Codeine reduced cough counts relative
to placebo, but the effect was not statistically significant. However, the dose of codeine
was low, as the usual dosing in adults is 30 to 60 mg every 4 hours. In our practice, when
prescribing codeine, we start at 30 mg every 4 to 6 hours as needed and increase to 60
mg, if the lower dose is insufficient. We caution patients about potential adverse effects
such as somnolence and constipation.

c. Morphine — Morphine and other agents in the phenanthrene alkaloid group are
effective in some but not all patients. In a double-blind crossover trial, 27 patients who
had a persistent cough of greater than three months duration and failed specific
treatment were randomly assigned to receive slow-release morphine (5 mg twice daily)
or placebo for four weeks. Morphine improved daily cough severity scores, although the
cough reflex was unaltered. Among those patients who did not respond to 5 mg twice
daily, improvement was detected when the dose was increased to 10 mg twice daily.
Patients should be warned about potential somnolence and constipation.

2)
Other Non specific Treatment
- Nonspecific therapy should be reserved for those patients who do not respond to the algorithm
described above. Rarely, these patients may have another underlying airway or parenchymal
Gabapentin and pregabalin — Gamma aminobutyric acid (GABA) analogs that bind to the
voltage-gated calcium channels and inhibit neurotransmitter release, are thought to ameliorate
chronic neuropathic pain via a central mechanism. It is hypothesized that these agents may also
act to reduce chronic cough via a central mechanism. Neither medication is approved for use in
chronic cough, although gabapentin is recommended for unexplained chronic cough in the
American College of Chest Physicians (ACCP) guidelines. The supportive data for the use of
pregabalin were published after the ACCP guidelines were prepared.
 a. Gabapentin – To reduce adverse effects of sedation and dizziness, gabapentin is initiated
at low dosage (300 mg once a day) with gradual increases until cough relief, dose-limiting
adverse effects, or a dose of 1800 mg a day in two divided doses is achieved
i. Adverse effects may include diarrhea, nausea, emotional lability, somnolence,
nystagmus, tremor, weakness, and peripheral edema. After six months, therapy
should be reassessed to determine whether gabapentin is still needed to control
cough.
ii. Side effects, chiefly nausea and fatigue, occurred in over 30 percent of those
receiving gabapentin and were often managed by dose reduction.
b. Pregabalin – initiated at a low dose and gradually increased over a week to
300 mg/day to minimize sedation and dizziness.
i. Adverse effects in the pregabalin group included dizziness in 45 percent and
cognitive changes in 30 percent, although these did not lead to discontinuation
of the study drug. Four weeks after withdrawal of study medication, there was
no deterioration in symptom control.
3) Peripherally acting antitussive agents — Benzonatate is a peripherally acting antitussive agent that
presumably acts by anesthetizing stretch receptors in the lungs and pleura. It has been used as a
nonspecific treatment for cough since 1958. While there are few good controlled studies of its use,
one report showed that a combination of 200 mg of benzonatate and 600 mg
of guaifenesin significantly suppressed capsaicin-induced cough compared to guaifenesin alone.
There are case reports of effective use of benzonatate in the palliative treatment of cough in
advanced cancer. It may be tried as an adjunctive treatment to narcotics in such cases.
Accidental ingestion of benzonatate and fatal overdoses have been reported in children <10 years
of age. Signs and symptoms of overdose (restlessness, tremors, convulsion, coma, cardiac arrest)
may occur within 15 to 20 minutes after ingestion.
a. Thalidomide has been evaluated as an antitussive agent for patients with cough due to
idiopathic pulmonary fibrosis (IPF). The mechanism by which thalidomide might suppress
cough in IPF is not known, but it is speculated to be due to its anti-inflammatory or
antifibrotic properties or to its inhibition of pulmonary sensory nerve fibers. In a randomized
cross over trial, participants were randomly assigned to receive either thalidomide (in
doses up to 100 mg daily) or placebo for 12 weeks. Cough was significantly decreased in
the thalidomide group compared to placebo, although patients in the thalidomide
group had more adverse events, chiefly constipation, dizziness, and viral upper respiratory
infections. Additional study of thalidomide is needed before widespread implementation
for chronic cough, because of its serious adverse effect profile, including teratogenicity.
b. Nebulized lidocaine may be helpful in a minority of patients with refractory chronic
cough. In an observational study, nebulized lidocaine (3 mL of 4 percent lidocaine [120
mg]) was prescribed two or three times daily to patients with chronic cough with the
option to increase to 5 mL (200 mg) if numbness of the throat lasted less than 20 minutes.
Among 99 patients who responded to a follow-up questionnaire, cough severity scores
significantly decreased, generally by two weeks. Only 34 percent of patients reported
being satisfied with the treatment and less than 30 percent chose to continue it beyond
three months. Adverse events, such as unpleasant taste, throat irritation, and choking on
water or food, were reported by 43 percent.
4) Inhaled glucocorticoids — the observation that chronic cough is associated with airway
inflammation even in nonasthmatic patients, has prompted use of inhaled glucocorticoids (GCs)
for nonspecific management of chronic cough. However, studies of inhaled glucocorticoids for the
treatment of cough in the absence of asthma have yielded conflicting results.
a. These differences in observed efficacy may be due to the presence of patients with
eosinophilic bronchitis in some studies. These patients would not have physiologic
evidence of asthma, but would likely respond to inhaled GCs.
5) Ipratropium bromide — The anticholinergic agent, inhaled ipratropium bromide, has been
proposed to have at least two potential mechanisms by which it may alleviate cough:
a. Blocking the efferent limb of the cough reflex
b. Decreasing stimulation of cough receptors by alteration of mucociliary factors
c. The usual dose of ipratropium is 2 inhalations by metered dose inhaler, four times a day.
6) Macrolide antibiotics — Patients with chronic cough tend to have increased levels of neutrophils
in their induced sputum, which led to the hypothesis that macrolide antibiotics, which have
antineutrophil effects independent of antimicrobial effects, might be efficacious in treating chronic
cough. However, trials with azithromycin and erythromycin have not demonstrated benefit.
a. The effect of azithromycin was examined in a trial that randomly assigned 44 patients with
refractory cough to take low dose azithromycin (250 mg) or placebo three times a week
for eight weeks [72]. Azithromycin did not significantly improve the Leicester Cough
Questionnaire score compared with placebo.
7) Non-pharmacologic interventions — Modalities such as speech therapy, breathing exercises,
cough suppression techniques, and patient counseling have been tried in the management of
chronic cough.
Pathophysiology of cough
1) COUGH REFLEX ARC — Each cough occurs through the stimulation of a complex reflex arc. This is
initiated by the irritation of cough receptors that exist not only in the epithelium of the upper and
lower respiratory tracts, but also in the pericardium, esophagus, diaphragm, and stomach.
o Chemical receptors sensitive to acid, cold, heat, capsaicin-like compounds, and other
chemical irritants trigger the cough reflex via activation of ion channels of the transient
receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type
1 (TRPA1).
o Mechanical cough receptors can be stimulated by triggers such as touch or
displacement. Laryngeal and tracheobronchial receptors respond to both mechanical
and chemical stimuli. Impulses from stimulated cough receptors traverse an afferent
pathway via the vagus nerve to a "cough center" in the medulla, which itself may be
under some control by higher cortical centers.
Sex-related differences in cough reflex sensitivity explain the observation that women are more likely than
men to develop chronic cough. The cough center generates an efferent signal that travels down the vagus,
phrenic, and spinal motor nerves to expiratory musculature to produce the cough.
HYPERTENSION
- The following definitions were suggested in 2003 by the seventh report of the Joint National Committee
(JNC 7) and are based upon the average of two or more properly measured readings at each of two or
more office visits after an initial screening:
- Normal blood pressure: systolic <120 mmHg and diastolic <80 mmHg
- Prehypertension: systolic 120 to 139 mmHg or diastolic 80 to 89 mmHg
- Hypertension:
o Stage 1: systolic 140 to 159 mmHg or diastolic 90 to 99 mmHg
o Stage 2: systolic ≥160 mmHg or diastolic ≥100 mmHg
- Isolated systolic hypertension- is considered to be present when the blood pressure
is ≥140/<90 mmHg, and isolated diastolic hypertension is considered to be present when the blood
pressure is <140/≥90 mmHg. Patients with blood pressure ≥140/≥90 mmHg are considered to have
mixed systolic/diastolic hypertension.
 o These definitions apply to adults on no antihypertensive medication and who are not
acutely ill. If there is a disparity in category between the systolic and diastolic pressures,
the higher value determines the severity of the hypertension.
- The prognostic significance of blood pressure as a cardiovascular risk factor appears to be age
dependent. The systolic pressure is the greater predictor of risk in patients over the age of 50 to 60
years. Under age 50 years, diastolic blood pressure is a better predictor of mortality than systolic
readings.
- White coat hypertension — blood pressure that is consistently elevated by office readings but does
not meet diagnostic criteria for hypertension based upon out-of-office readings.
- Masked hypertension — blood pressure that is consistently elevated by out-of-office
measurements but does not meet the criteria for hypertension based upon office readings.
- Moderate to severe hypertensive retinopathy (formerly called "malignant
hypertension") — Moderate to severe hypertensive retinopathy, corresponding to grades III and IV
hypertensive retinopathy, refers to specific pathophysiological changes that may be associated
with marked hypertension, including retinal hemorrhages, exudates, or papilledema.
PRIMARY / ESSENTIAL HYPERTENSION
A.
- Blood pressure reacts to changes in the environment to maintain organ perfusion over a wide variety
- The pathogenesis of primary hypertension (formerly called "essential" hypertension) is poorly
B.
(A) Mild hypertensive retinopathy is indicated by the presence of generalized arteriolar narrowing,
arteriovenous (AV) nicking, and opacification of the arteriolar wall ("copper wiring").
(B) Mild hypertensive retinopathy with focal arteriolar narrowing.
(C,D) Moderate hypertensive retinopathy with multiple retinal hemorrhages and cotton wool patches.
(E,F) Severe hypertensive retinopathy with swelling of the optic disk, retinal hemorrhages, hard exudates,
and cotton wool patches.
- These findings may be associated with hypertensive encephalopathy and acute hypertensive
nephrosclerosis (formerly called "malignant nephrosclerosis").
o Malignant hypertension is usually associated with diastolic pressures above 120 mmHg.
However, it can occur at diastolic pressures as low as 100 mmHg in previously
normotensive patients with acute hypertension due to preeclampsia or acute
glomerulonephritis.
- Hypertensive emergency — Severe hypertension (usually a diastolic blood pressure above 120
mmHg) with evidence of acute end-organ damage. A hypertensive emergency can be life
threatening and requires immediate treatment, usually with parenteral medications in a monitored
setting.
- Hypertensive urgency — Severe hypertension (usually a diastolic blood pressure above 120 mmHg)
in asymptomatic patients is referred to as hypertensive urgency. There is no proven benefit from
rapid reduction in blood pressure in asymptomatic patients who have no evidence of acute end-
organ damage and are at little short-term risk.
Pathogenesis — Maintenance of arterial blood pressure is necessary for organ perfusion. In general,
the arterial blood pressure is determined by the following equation:
Blood Pressure (BP) = Cardiac Output (CO) x Systemic Vascular Resistance (SVR)
of conditions. The primary factors determining the blood pressure are the sympathetic nervous system,
the renin-angiotensin-aldosterone system, and the plasma volume (largely mediated by the kidneys).
understood but is most likely the result of numerous genetic and environmental factors that have
multiple compounding effects on cardiovascular and renal structure and function. Some of these
factors are discussed in the ensuing section.
Risk factors for primary (essential) hypertension — Although the exact etiology of primary hypertension
remains unclear, a number of risk factors are strongly and independently associated with its
development, including:
o Age – Advancing age is associated with increased blood pressure, particularly systolic blood
pressure, and an increased incidence of hypertension.
o Obesity – Obesity and weight gain are major risk factors for hypertension and are also
determinants of the rise in blood pressure that is commonly observed with aging.
o Family history – Hypertension is about twice as common in subjects who have one or two
hypertensive parents, and multiple epidemiologic studies suggest that genetic factors account
for approximately 30 percent of the variation in blood pressure in various populations.
o Race – Hypertension tends to be more common, be more severe, occur earlier in life, and be
associated with greater target-organ damage in blacks.
o Reduced nephron number – Reduced adult nephron mass may predispose to hypertension,
which may be related to genetic factors, intrauterine developmental disturbance (eg, hypoxia,
drugs, nutritional deficiency), premature birth, and postnatal environment (eg, malnutrition,
infections).
o High-sodium diet – Excess sodium intake (eg, >3000 mg/day) increases the risk for hypertension,
and sodium restriction lowers blood pressure.
o Excessive alcohol consumption – Excess alcohol intake is associated with the development of
hypertension.
o Inactivity increases the risk for hypertension, and exercise is an effective means of lowering blood
pressure.
 o Diabetes and dyslipidemia – The presence of other cardiovascular risk factors, including diabetes
and dyslipidemia, appear to be associated with an increased risk of developing hypertension
o Personality traits and depression – Hypertension may be more common among those with certain
personality traits, such as hostile attitudes and time urgency/impatience, as well as among those
with depression.
SECONDARY OR CONTRIBUTING CAUSES OF HYPERTENSION
— A number of common and uncommon medical conditions may increase blood pressure and lead
to secondary hypertension. In many cases, these causes may coexist with risk factors for primary
hypertension (formerly called "essential" hypertension) and are significant barriers to achieving
adequate blood pressure control.
- Major causes of secondary hypertension include:
o Prescription or over-the-counter medications:
 Oral contraceptives, particularly those containing higher doses of estrogen, which can
often raise the blood pressure within the normal range but can also induce overt
hypertension
 Nonsteroidal anti-inflammatory agents, particularly chronic use
 Antidepressants, including tricyclic antidepressants and selective serotonin reuptake
inhibitors
 Glucocorticoids
 Decongestants, such as pseudoephedrine
 Weight loss medications
 Erythropoietin
 Cyclosporine
 Stimulants, including methylphenidate and amphetamines
o Illicit drug use – Drugs such as methamphetamines and cocaine can raise blood pressure.
o Primary renal disease – Both acute and chronic kidney disease, particularly with glomerular
or vascular disorders, can lead to hypertension.
o Primary aldosteronism – The presence of primary mineralocorticoid excess, primarily
aldosterone, should be suspected in any patient with the triad of hypertension, unexplained
hypokalemia, and metabolic alkalosis. However, up to 50 percent of patients will have a
normal plasma potassium concentration. The presence of primary aldosteronism should also
be considered in patients with resistant hypertension.
o Renovascular hypertension – is more often due to fibromuscular dysplasia in younger
patients and more often due to atherosclerosis in older patients.
o Obstructive sleep apnea – Disordered breathing during sleep appears to be an independent
risk factor for systemic hypertension.
o Pheochromocytoma –is a rare cause of secondary hypertension. About one-half of patients
with pheochromocytoma have paroxysmal hypertension; most of the rest have what
appears to be primary hypertension.
o Cushing's syndrome – is a rare cause of secondary hypertension, but hypertension is a major
cause of morbidity and death in patients with Cushing's syndrome. Other endocrine disorders
– Hypothyroidism, hyperthyroidism, and hyperparathyroidism may also induce hypertension.
o Coarctation of the aorta – is one of the major causes of secondary hypertension in young
children, but it may also be diagnosed in adulthood.
COMPLICATIONS OF HYPERTENSION
— Hypertension is associated with a number of serious adverse effects. The likelihood of developing these
complications is increased with higher levels of blood pressure. The increase in risk begins as the blood
pressure rises above 115/75 mmHg in all age groups. However, this relationship does not prove causality,
which can only be demonstrated by randomized trials showing benefit from blood pressure reduction.
- Hypertension is quantitatively the major modifiable risk factor for premature cardiovascular
disease, being more common than cigarette smoking, dyslipidemia, or diabetes, which are the
other major risk factor. In older patients, systolic pressure and pulse pressure are more powerful
determinants of risk than diastolic pressure. Importantly, the increase in cardiovascular risk
associated with hypertension is affected by the presence or absence of other risk factors.
Each of the following complications is closely associated with the presence of hypertension:
o Left ventricular hypertrophy (LVH) is a common and early finding in patients with hypertension. LVH
is associated with a higher incidence of subsequent heart failure, myocardial infarction, sudden
death, and stroke.
o The risk of heart failure, both systolic (reduced ejection fraction) and diastolic (preserved ejection
fraction), increases with the degree of blood pressure elevation. The pathogenesis of heart failure
in patients with hypertension is both ischemic and nonischemic.
o Hypertension is the most common and most important risk factor for ischemic stroke, the incidence
of which can be markedly reduced by effective antihypertensive therapy.
o Hypertension is the most important risk factor for the development of intracerebral haemorrhage.
o Hypertension is a leading risk factor for ischemic heart disease, including myocardial infarction and
coronary interventions.
o Hypertension is a risk factor for chronic kidney disease and end-stage renal disease. It can both
directly cause kidney disease, which is called hypertensive nephrosclerosis, and accelerate the
progression of a variety of other renal diseases. The relationship between blood pressure and renal
disease is stronger among blacks.
DIAGNOSIS OF HYPERTENSION
— All adults should be screened for hypertension. An elevated screening blood pressure, which is typically
obtained in the clinician's office, should be confirmed using out-of-office measurements, if possible:
Screening — We agree with the 2015 United States Preventive Services Task Force (USPSTF) guidelines that
all individuals 18 years or older should be screened for elevated blood pressure [35]. In practice, blood
pressure measurement is simple and quick and is performed at most office visits.
However, at a minimum, the frequency of screening should be as follows:
●Adults 40 years or older should have their blood pressure measured at least annually
●Adults between 18 and 39 years should also be screened at least annually if they have risk factors
for hypertension (eg, obesity) or if their previously measured blood pressure was 130-139/85-89 mmHg
●Adults between 18 and 39 years whose latest blood pressure was <130/80 mmHg and have no risk
factors for hypertension should be screened at least every three years.
In all other patients who have an elevated screening blood pressure, the diagnosis of hypertension should
be confirmed using out-of-office blood pressure measurement, preferably ambulatory blood pressure
monitoring (ABPM). Home blood pressure monitoring is an acceptable alternative to ABPM if ABPM is not
possible.
ABPM — ABPM is the preferred method for confirming the diagnosis of hypertension. High-quality data
suggest that ABPM predicts target-organ damage and cardiovascular events better than office blood
pressure readings. ABPM records the blood pressure at preset intervals (usually every 15 to 20 minutes during
the day and every 30 to 60 minutes during sleep). ABPM can identify white coat and masked hypertension
and can also be used to confirm normal blood pressure readings obtained by self-monitoring at home. It is
also the only method of blood pressure measurement that can reliably obtain nocturnal readings, which
may have important prognostic implications.
* If the blood pressure is this elevated, or if there are signs and symptoms of hypertensive emergency at any
point later in the algorithm, a diagnosis of hypertension can be made. Signs and symptoms of a hypertensive
emergency include headache, altered mental status, nausea, vomiting, chest pain, among others

In addition to patients with suspected white coat hypertension, ABPM could be considered in the following
circumstances:
o Suspected episodic hypertension (eg, pheochromocytoma)
o Determining therapeutic response (ie, blood pressure control) in patients who are known to have
a substantial white coat effect)
o Hypotensive symptoms while taking antihypertensive medications
o Resistant hypertension
o Autonomic dysfunction

EVALUATION — Once it has been determined that the patient has persistent hypertension, an evaluation
should be performed to ascertain the following information:
o To determine the extent of target-organ damage and/or established cardiovascular disease.
o To assess other cardiovascular risk factors.
o To identify lifestyle factors that could potentially contribute to hypertension.
o To identify interfering substances (eg, chronic use of nonsteroidal anti-inflammatory drugs, oral
contraceptives) and potentially curable causes of secondary hypertension.
Most patients with presumed primary hypertension (formerly called "essential" hypertension) should
undergo a relatively limited work-up for secondary causes utilizing information gained from the
history, physical examination, and routine laboratory tests. (See 'History' below and 'Physical
examination' below and 'Laboratory testing' below.)

HISTORY OF HYPERTENSION
History — The history should search for those facts that help to determine the presence of precipitating or
aggravating factors (including prescription medications, nonprescription nonsteroidal anti-inflammatory
agents, and alcohol consumption), the duration of hypertension, previous attempts at treatment, the
extent of target-organ damage, and the presence of other known risk factors for cardiovascular disease.
 TESTING FOR SECONDARY HYPERTENSION
- Secondary causes of hypertension are relatively uncommon, and testing for secondary hypertension may
produce false positive results. Thus, screening for secondary causes is not recommended for all patients
with primary hypertension. Instead, a targeted approach is indicated whereby screening for secondary
causes should be performed only in patients with an unusual presentation of hypertension (new onset at
an especially young or especially old age, presentation with stage 2 hypertension, abrupt onset of
hypertension in a patient with previously normal blood pressure, resistant hypertension) or in those with a
clinical clue for a specific cause of hypertension, such as an abdominal bruit.

Clinical features of the different causes of secondary hypertension

Disorder Suggestive clinical features
General Severe or resistant hypertension
An acute rise in blood pressure over a previously stable value
Proven age of onset before puberty
Age less than 30 years with no family history of hypertension and no obesity
Renovascular disease An acute elevation in serum creatinine of at least 30% after administration
of angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor
blocker (ARB)
Moderate to severe hypertension in a patient with diffuse atherosclerosis, a
unilateral small kidney, or asymmetry in renal size of more than 1.5 cm that
cannot be explained by another reason
Moderate to severe hypertension in patients with recurrent episodes of flash
pulmonary edema
Onset of stage II hypertension after age 55 years
Systolic or diastolic abdominal bruit (not very sensitive)
Primary renal disease Elevated serum creatinine concentration
Abnormal urinalysis
PHYSICAL EXAMINATION Oral contraceptives New elevation in blood pressure temporally related to use
Physical examination — The main goals of the physical examination are to evaluate for signs of end-organ NSAIDs
damage, for established cardiovascular disease, and for evidence of potential causes of secondary
Stimulants (eg, cocaine,
hypertension. The physical examination should include the underutilized but important funduscopic
methylphenidate)
examination to evaluate for hypertensive retinopathy (table 6).
Calcineurin inhibitors
LABORATORY TESTING Antidepressants
— The following tests should be performed in all patients with newly diagnosed hypertension Pheochromocytoma Paroxysmal elevations in blood pressure
o Electrolytes and serum creatinine (to calculate the estimated glomerular filtration rate) Triad of headache (usually pounding), palpitations, and sweating
o Fasting glucose Primary aldosteronism Unexplained hypokalemia with urinary potassium wasting; however, more
o Urinalysis than one-half of patients are normokalemic
o Lipid profile (total and HDL-cholesterol, triglycerides) Cushing's syndrome Cushingoid facies, central obesity, proximal muscle weakness, and
o Electrocardiogram ecchymoses
May have a history of glucocorticoid use
Additional tests — Additional tests may be indicated in certain settings: Sleep apnea syndrome Common in patients with resistant hypertension, particularly if overweight or
o Increased albuminuria is increasingly recognized as an independent risk factor for cardiovascular obese
disease Loud snoring or witnessed apneic episodes
o Echocardiography is a more sensitive means of identifying the presence of left ventricular Daytime somnolence, fatigue, and morning confusion
hypertrophy (LVH) than an electrocardiogram. It is indicated in patients with clinically evident Coarctation of the aorta Hypertension in the arms with diminished or delayed femoral pulses and low
heart failure or if left ventricular dysfunction or coronary artery disease is suspected or unobtainable blood pressures in the legs
Left brachial pulse is diminished and equal to the femoral pulse if origin of
the left subclavian artery is distal to the coarct
Hypothyroidism Symptoms of hypothyroidism
 Elevated serum thyroid stimulating hormone
Primary Elevated serum calcium
hyperparathyroidism
TREATMENT
A. Nonpharmacologic therapy — Treatment of hypertension should involve nonpharmacologic therapy
(also called lifestyle modification) alone or in concert with antihypertensive drug therapy:
o Dietary salt restriction – In well-controlled randomized trials, the overall impact of moderate sodium
reduction is a fall in blood pressure in hypertensive and normotensive individuals of 4.8/2.5 and 1.9/1.1
mmHg, respectively.
o Weight loss – Weight loss in overweight or obese individuals can lead to a significant fall in blood
pressure independent of exercise. The decline in blood pressure induced by weight loss can also occur
in the absence of dietary sodium restriction, but even modest sodium restriction may produce an
additive antihypertensive effect. The weight loss-induced decline in blood pressure generally ranges
from 0.5 to 2 mmHg for every 1 kg of weight lost, or about 1 mmHg for every 1 pound lost.
o Dietary Approaches to Stop Hypertension (DASH) diet – The DASH dietary pattern is high in vegetables,
fruits, low-fat dairy products, whole grains, poultry, fish, and nuts; and low in sweets, sugar-sweetened
beverages, and red meats. The DASH dietary pattern is consequently rich in potassium, magnesium,
calcium, protein, and fiber, but low in saturated fat, total fat, and cholesterol. A trial in which all food
was supplied to normotensive or mildly hypertensive adults found that the DASH dietary pattern
reduced blood pressure by 6/4 mmHg compared with typical American-style diet that contained the
same amount of sodium and the same number of calories. Combining the DASH dietary pattern with
modest sodium restriction produced an additive antihypertensive effect.
o Exercise – Aerobic exercise, and possibly resistance training, can decrease systolic and diastolic
pressure by, on average, 4 to 6 mmHg and 3 mmHg, respectively, independent of weight loss. Most
studies demonstrating a reduction in blood pressure have employed three to four sessions per week of
moderate-intensity aerobic exercise lasting approximately 40 minutes for a period of 12 weeks.
o Limited alcohol intake – Women who consume two or more alcoholic beverages per day and men
who have three or more drinks per day have a significantly increased incidence of hypertension
compared with nondrinkers; this effect is dose related and is most prominent when intake exceeds five
drinks per day. On the other hand, decreasing alcohol intake in individuals who drink excessively
significantly lowers blood pressure. Moderate alcohol use (one drink per day for women and one to
two drinks per day for men) has a limited effect on blood pressure, associated with a modest decrease
in cardiovascular risk as compared with no alcohol consumption.
o Comprehensive intervention – The benefits of comprehensive lifestyle modification, including the DASH
diet and increased exercise, were tested in the PREMIER trial. At 18 months, there was a lower
prevalence of hypertension (22 versus 32 percent), and less use of antihypertensive medications (10
to 14 versus 19 percent), although the difference was not statistically significant.
o Patient education – Patient education has been demonstrated to result in improved blood pressure
control. In addition to education of patients by their clinicians, blood pressure control may be
improved when patients with hypertension hear the personal stories of their peers with hypertension.
B. Drug treatment
General efficacy — Multiple guidelines and meta-analyses conclude that the degree of blood pressure
reduction, not the choice of antihypertensive medication, is the major determinant of reduction in
cardiovascular risk in patients with hypertension. Recommendations for the use of specific classes of
antihypertensive medications are based upon clinical trial evidence of decreased cardiovascular risk, blood
pressure-lowering efficacy, safety, and tolerability. Most patients with hypertension will require more than
one blood pressure medication to reach goal blood pressure. Having multiple available classes of blood
pressure medication permits clinicians to individualize therapy based upon individual patient characteristics
and preferences.
o Initial monotherapy in uncomplicated hypertension — In the absence of a specific indication,
there are four main classes of drugs that are recommended for use as initial monotherapy:
 Thiazide diuretics
 Long-acting calcium channel blockers (most often a dihydropyridine such as amlodipine)
 Angiotensin-converting enzyme (ACE) inhibitors
 Angiotensin II receptor blockers (ARBs)
- Most guidelines and recommendations, including those made by panel members from JNC 8
and ESH/ESC, support the use of any of these classes as initial therapy in many patients.
- However, a thiazide diuretic or long-acting calcium channel blocker should be used as initial
monotherapy in black patients, and an ACE inhibitor or ARB should be used for initial monotherapy
in patients who have diabetic nephropathy or nondiabetic chronic kidney disease complicated
by proteinuria.
- Beta blockers are no longer recommended as initial monotherapy in the absence of a specific
(compelling) indication for their use, such as ischemic heart disease or heart failure with decreased
ejection fraction
Combination therapy — In most cases, single-agent therapy will not adequately control blood pressure,
particularly in those whose blood pressure is more than 20/10 mmHg above goal. Combination therapy with
drugs from different classes has a substantially greater blood pressure-lowering effect than doubling the
dose of a single agent . When more than one agent is needed to control the blood pressure, we recommend
therapy with a long-acting ACE inhibitor or ARB in concert with a long-acting dihydropyridine calcium
channel blocker. Combination of an ACE inhibitor or ARB with a thiazide diuretic can also be used but may
be less beneficial. ACE inhibitors and ARBs should not be used together. The supportive data for these
recommendations are presented elsewhere.
Fixed-dose, single-pill combination medications should be used whenever feasible to reduce the burden on
patients and improve medication adherence.
… More for drug please
Hyperthyroidism
APPROACH TO PATIENTS WITH FEVER
- Body temperature is controlled by the hypothalamus.
- Neurons in both the preoptic anterior hypothalamus and the posterior hypothalamus receive two kinds
of signals: one from peripheral nerves that transmit information from warmth/cold receptors in the skin
and the other from the temperature of the blood bathing the region.
o These two types of signals are integrated by the thermoregulatory center of the hypothalamus to
maintain normal temperature.
- In a neutral temperature environment, the human metabolic rate produces more heat than is necessary
to maintain the core body temperature in the range of 36.5–37.5°C (97.7–99.5°F).
- A normal body temperature is ordinarily maintained despite environmental variations because the
hypothalamic thermoregulatory center balances the excess heat production derived from metabolic
activity in muscle and the liver with heat dissipation from the skin and lungs.
- According to studies of healthy individuals 18–40 years of age, the mean oral temperature is 36.8° ±
0.4°C (98.2° ± 0.7°F), with low levels at 6 a.m. and higher levels at 4–6 p.m. The maximal normal oral
temperature is 37.2°C (98.9°F) at 6 a.m. and 37.7°C (99.9°F) at 4 p.m.
- In light of these studies, an a.m. temperature of >37.2°C (>98.9°F) or a p.m. temperature of >37.7°C
(>99.9°F) would define a fever. The normal daily temperature variation is typically 0.5°C (0.9°F). However,
in some individuals recovering from a febrile illness, this daily variation can be as great as 1.0°C. During
a febrile illness, the diurnal variation is usually maintained, but at higher, febrile levels.
- Rectal temperatures are generally 0.4°C (0.7°F) higher than oral readings. The lower oral readings are
probably attributable to mouth breathing, which is a factor in patients with respiratory infections and
rapid breathing.
- Lower-esophageal temperatures closely reflect core temperature.
- Tympanic membrane thermometers measure radiant heat from the tympanic membrane and nearby
ear canal and display that absolute value (unadjusted mode) or a value automatically calculated from
the absolute reading on the basis of nomograms relating the radiant temperature measured to actual
core temperatures obtained in clinical studies (adjusted mode).

Pending:
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