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AFRICAN COLLEGE OF HEALTH (ACH)

BNS YEAR 2 SEMESTER 2; WEEK 5 NOTES:


MONDAY:

Adult Health (pg.2)

TUESDAY: Pharmacology (pg.10)


WEDNESDAY: Adult Health (pg.17)
THURSDAY: Pharmacology (pg.24)
FRIDAY: Adult Health (pg.31)

QUESTIONS? Email: africancollegeofht@nokiamail.com

ADULT HEALTH (MONDAY)


Typhoid (Enteric) Fever:
Definition: Typhoid fever is a systemic infection
characterized by fever and abdominal pain caused by
dissemination of Salmonella typhi and occasionally by
S. paratyphi A and B and S.typhimarium, all of which
are non capsulated, gram negative motile bacteria.

Epidemiology:
Human beings are the only hosts for S. typhi and
S.paratyphi. Thus enteric fever is transmitted only
thorough close contact with acutely infected
individuals or chronic carriers through ingestion of
contaminated food or water.
Chronic carriers are the source of infection
harboring the organisms in their gall bladder
(especially in the presence of gall stones) and rarely
at other sites. It affects people of all ages and both
sexes. Enteric fever is endemic in most developing
countries.
Currently the disease is observed at a great
frequency in AIDS patients than the general population.

Pathogenesis:
Following ingestion of the organism in contaminated
food or drink, Salmonella typhi passes the gastric
barrier and reach the upper small intestine where the
bacilli invade the intestinal epithelium and they are
engulfed by phagosome which reside in the Peyers
patches. The bacilli multiply and enter the blood

stream and cause transient bacteremia. At this stage


the Salmonellae disseminate throughout the body in
macrophages via lymphatic and colonize
reticuloendothelial tissue (liver, spleen, lymph nodes,
and bone marrow).
Patients have relatively fewer or no signs and symptoms
during this initial incubation period. Signs and
symptoms, including fever and abdominal pain result
when a critical number of bacteria have replicated.
During weeks after initial colonization, further
inflammation of the Peyers patches may result
enlargement and necrosis which may result intestinal
hemorrhage and perforation. Infection may become
persistent and invade the gall bladder. The clinical
phase of the disease depends on host defense and
bacterial multiplication.

Clinical Manifestation:
The incubation period varies from 3-60 days. The
manifestation is dependent on inoculums size, state of
host defense and the duration of the disease. The
Severity of the illness may range from mild, brief
illness to acute, severe disease with central nervous
system involvement and death.

First week;
Fever is high grade, with a daily increase in a
step-ladder pattern for the 1st one week and then
becomes persistent.
Headache , malaise , Abdominal pain

Initially diarrhea or loss stole followed by


constipation in adults, diarrhea is dominate feature in
children
Relative bradycardia
Splenomegally /Hepatomegaly
Rose spots not commonly seen in black patients. In
whites it appears as small, pale red, blanching macules
commonly over chest & abdomen, lasting for 2-3 days.
Epistaxis

Second week;
Fever becomes continuous
The patient becomes very ill and withdrawn confused,
delirious and sometimes may be even comatose.

Third Week;
The patient goes to a pattern of typhoidal state"
characterized by extreme toxemia, disorientation, and
pea-soup diarrhea and sometimes may be complicated by
intestinal perforation and hemorrhage.

Fourth Week;
Fever starts to decrease and the patient may
deferveresce with resolution of symptoms. At this
point patient may lose weight.
Relapse may occur in 10% of cases.

Complications of Typhoid fever:


Gastrointestinal perforation and hemorrhage: are
late complications that may occur in the 3rd or 4th
week. May develop despite clinical improvement. These
complications are life threatening and need immediate
medical and surgical interventions.

Other Less common complications;


Hepatitis,Meningitis,Arthritis,Osteomyelitis,Parotitis,
Orchitis,Nephritis,Myocarditis,Bronchitis and
Pneumonia.

N.B these complications can be prevented by prompt


diagnosis and treatment

Chronic Carriers:
Approximately 1- 5 % of patient with Enteric fever
become asymptomatic chronic carriers
They shed S.typhi in either urine or stool for
year

> 1

Incidence of Chronic carriage is high in women and


among patients with biliary abnormality (e.g. gall
stone, carcinoma of gall bladder) and other GI
malignancies.

Diagnosis:

Can be suggested by the presence of Persistent fever


and Relative bradycardia, which was found to occur in
86% of Africans. Rose spots, which occurs in 70% of
whites and 20% of Africans.

Leucopenia; But definitive diagnosis of the disease


requires laboratory tests;
1. Isolation of the organism by blood, stool or urine
culture is diagnostic.
o The yield of recovery of the organism differs
depending on the specimen cultured and the duration of
clinical disease;
o Blood culture -mostly (up to 90%) patients have
positive culture in the 1st week, and only 50% by the
3rd week. The yield is much lower if patient has taken
antibiotics prior to the test.
o Stool culture is negative in the first week and
becomes positive in 75% of patients in the 3rd week.
Urine culture parallels stool culture. Widal test for O
and H antigens
The O (somatic) antigen shows active infection
whereas the H (flagella) antigen could be indicative of
past infection or immunization for typhoid.
Widal test has certain limitations, and to make a
diagnosis of current infection a 4X (fold) rise in
titer on paired sera taken during the acute and
convalescence phases is necessary.

Limitations of Widal test;

It is non-specific and a positive test could be due


to Infection by other salmonellae (as the antigen used
for the test is also shared by other salmonellae)
Recent vaccination for typhoid . Past typhoid (already
treated)
The demonstration of 4- fold rise in titer on paired
sera is not useful for the treatment of acute cases, as
this requires waiting for the convalescence phase of
the disease and at this stage if the patient is lucky
recovery will occur.

Treatment:
Antibiotic therapy is curative. These drugs can be
given either orally or intravenous, depending on
patient condition (able to take orally or not),
severity of the disease. One should note that fever may
persist for 4-6 days despite effective antibiotic
treatment .

Oral drugs:
First Line;
Nowadays 4-amino quinolones are the drugs of choice
because of their effectiveness on multidrug resistant
typhoid, and low relapse and carrier rates.
Ciprofloxacin, norfloxacin, ofloxacin, and pefloxacin
are all equally effective.
Ciprofloxacin: 500mg PO BID for 10 days
Ceftriaxone 1-2 gm IM or IV for 10 -14 days 4- amino
quinolones are not recommended for use in children and
pregnant women because of their observed potential

damaging effect on cartilage of the growing animals.


However, in severe infections especially by MDR
strains, we have to outweigh the benefits and the
potential risks.

Alternatives;
Azithromycin

1 gm PO daily for 5 days

Chloramphenicol

500 mg Po QID for 14 days

Norfloxacin 400mg twice daily


for 10 days.
Chloramphenicol is very cheap and also quite effective
with initial doses of 3 - 4 g/d for adults, with
clinical response observed in 24 - 48hrs after
initiation. Dose should be reduced to 2g/d when fever
starts to decrease (usually after 5 - 6 days), and
continued to complete 2 weeks treatment.

Intravenous drugs are recommended for critically sick


patients who are admitted or for patients who are
unable to take oral drugs;
Ceftriaxone 2-4gm once a day for 3 days and then 12gm IV/IM for a total of 10- 14 days.
Intravenous Chloramphenicol 1gm IV QID for 2-3 days
and then start PO medication as soon as the patient can
take oral medication. This is a drug of choice for
patients that need parenteral therapy.

Problems of antibiotic treatment:


Multidrug resistant (MDR) S.typhi is reported in
different parts of the world, especially Indian

subcontinent and Southeast Asia. Hence if resistance is


suspected in an area, the preferred treatment would be
with quinolones, azithromycin or third generation
cephalosporins
Early use of antibiotics is associated with high rate
of relapse (up to 20%) as compared to untreated cases
(where the relapse rate is 5 - 10%). This is due to
inhibition of adequate development of immune response
by early therapy.
Eradication of chronic carrier state requires
prolonged treatment with Ciprofloxacin for 4 weeks is
effective and much better than the other drugs.
Ampicillin or Amoxicillin 100mg/kg/d taken with
Probenecid 30mg/kg/day for 6 weeks. Co-trimoxazole
(160/800mg twice a day) plus Rifampicin 600mg orally/d
for 6 weeks.

N.B. Drug treatment does not eradicate infection in 40%


of the chronic carriers. Hence surgical resection of
the gall bladder may sometimes be necessary.

Prevention and

control:

Improve environmental sanitation


Identification and treatment of Chronic carriers
Avoid food handling by chronic carriers
Vaccination for travelers to endemic areas;
o Live oral vaccine (TY21a) 3 doses can be given to
those over 6 years. Protective for several years

o Purified Vi polysaccharide vaccine given in a single


dose to those over 2 years and HIV positives, is as
effective as live vaccine.

PHARMACOLOGY (TUESDAY)
Cell membrane phospholipids:

Arachidonic acid 5-Lipooxygenase Leukotrienes


Pharmacological Actions:
a. Smooth muscle: most stimulate myometrium and are
known to be important in the initiation and maintenance
of labor.Prostaglandin E has bronchodilator action.
b. GIT: they increase intestinal motility. PG E
inhibits gastric acid secretion and has cytoprotective
action on the gastroduodenal mucosa. Both PG E and F
produce contraction of the longitudinal muscle of the
gut. They also stimulate intestinal fluid secretion,
resulting in diarrhea.
c. CVS: PGE is peripheral vasodilator and powerful
natriuretic. PGF constricts arterioles and veins.
d. Platelets: Thromobxane causes platelet aggregation
and vasoconstriction. PG I (prostacycline) is found in
the vascular endothelium and is a potent inhibitor of
platelet aggregation and is a vasodilator.
e. Miscellaneous: Prostaglandins are important in pain
generation and perception. PGE and PGI produce
hyperalgesia associated with inflammation.
Therapeutic uses; include cervical ripening and labor
induction, control of postpartum hemorrhage, induction
of abortion, and prophylaxis of NSAID-induced peptic
ulcers.
Adverse Effects; include fever, diarrhea, abdominal
cramps, headache, nausea, and vomiting.
DRUGS ACTING ON THE RESPIRATORY SYSTEM
1.1 Bronchial asthma
Asthma is physiologically characterized by increased
responsiveness of the trachea and bronchi to various
stimuli and by wide spread narrowing of the airways
that changes in severity either spontaneously or as a
result of therapy Impairment of airflow in bronchial
asthma is caused by three bronchial abnormalities.
i. Contraction of airway smooth muscles
ii. Thickening of bronchial mucosa from edema and

cellular infiltration
iii. Inspissations in the airway lumen of abnormally
thick, viscid plugs of excessive mucus.
PHARMACOTHERAPY OF BRONCHIAL ASTHMA
Drug used in the treatment of bronchial asthma can be
grouped into three main categories:
1. Bronchodilators
a. Adrenergic agonists which include: Non selective
agonists e.g. adrenaline, Selective agonists e.g.
salbutamol
b. Methylxanthines; theophylline derivatives
c. Muscranic receptor antagonists e.g. Ipratropium
bromide
2.Mast cell stabilizers, e.g. cromolyn sodium,
nedocromil, ketotifen
3.Antinflammatory agents: corticosteroids
1.ADRENERGIC AGONISTS (SYMPATHOMIMETIC AGENTS)
(a) Non- selective agonists - Epinephrine, ephedrine,
isoprotenerol
(b). Selective agonists - Salbutamol, terbutaline,
metaproterenol, salmeterol, formaterol and etc
Mechanism of Action:
?Agonists stimulate adenyl cyclase and increase
formation of cAMP in the airway tissues. They have got
several pharmacological actions important in the
treatment of asthma. Relax smooth muscles. Inhibit
release of inflammatory mediator or broncho
constricting substances from mast cells. Inhibit
microvasculature leakage Increase mucociliary transport
a. Non-selective ?agonists: Cause more cardiac
stimulation,they should be reserved for special
situation.
Epinephrine: very effective, rapidly acting

bronchodilator especially preferable for the relief of


acute attack of bronchial asthma. Administered by
inhalation or subcutaneously.
Side effects; include arrhythmia and worsening of
angina pectoris, increase blood pressure, tremors etc
Contraindication: - hypertension, arrhythmia,
Ephedrine: compared to epinephrine, it has longer
duration of action but more pronounced central effect
and lower potency. It can be given orally. The drug is
currently infrequently used because of development of
more efficacious and beta2-selective agents.
b. Selective agonists:Largely replaced non selective
agonists, are effective after inhaled or oral
administration and have got longer duration of action.
They are the most widely used sympathomimetics.
Commonly used drugs both by oral and inhalation are
Salbutamol, terbutaline, metaproterenol, pirbuterol and
bitolterol. Salmeterol and formeterol are new
generation, long acting selective agonists (with
duration of action 12 hrs or more). These drugs appear
to interact with inhaled corticosteroids to improve
asthma control. Delivery of adrenoreceptor agonists
through inhalation results in the greatest local effect
on airway smooth muscle with least systemic toxicity.
Side effects: Tremors, anxiety, insomnia, tachycardia,
headache, hypertension and etc.
Contraindications: Sympathomimetics are contraindicated
in patients with known hypersensitivity to the drugs.
Precautions: They should be used cautiously in patients
with hypertension, cardiac dysfunction,
hyperthyroidism, glaucoma, diabetes, pregnancy.

2. METHYLXANTHINES
The three important methylxanthines are theophylline,
theobromine, and caffeine. The theophylline
preparations most commonly used for therapeutic
purposes is aminophylline (theophylline plus
diethylamine).
Mechanism of Action
i. Competitively inhibit phosphodiesterase (PDE) enzyme
leading to increased cAMP level.
ii. They competitively inhibit the action of adenosine
on adenosine (A1 and A2) receptors (adenosine has been
shown to cause contraction of isolated airway smooth
muscle and to provoke histamine release from airway
mast cells.
iii. Inhibit the release of histamines and leukotriens
from the mast cells Of the three natural xanthines,
agents theophylline is most selective in its smooth
muscle effect, while caffeine has the most marked
central effect.
Pharmacokinetics
Only slightly soluble in water so has been administered
as several salts containing varying amounts of
theophylline base. Most preparations are well absorbed
from gastro intestinal tract and metabolized by liver.
Doses should be decreased in cases of liver disease and
heart failure.
Adverse Effects: Anorexia, nausea vomiting, abdominal
discomfort, headache, anxiety, insomnia, seizures,
arrhythmias.
Theophylline is now largely reserved for patients in
whom symptoms remain poorly controlled despite the
combination of regular treatment with an inhaled antiinflammatory agent and as needed use of a agonist.
3. MUSCRANIC RECEPTOR ANTAGONISTS
Mechanism of Action: Muscarinic antagonist

competitively inhibit effect of acetylcholine at


muscarinic receptors, hence block the contraction of
air way smooth muscle and the increase in secretion of
mucus that occurs in response to vagal activity e.g
atropine sulfate Systemic adverse effects as a result
of rapid absorption include urinary retention,
tachycardia, loss of accommodation and agitation and
local effects like excessive dryness of mouth limits
the quantity of atropine used.
Ipratropium bromide is poorly absorbed and does not
readily enter the central nervous system thus permits
the delivery of high doses to muscarinic receptor in
the airways; hence, it can safely be used for bronchial
asthma. Antimuscranic antagonist drugs appear to be
slightly less effective than agonists agents in
reversing asthmatic bronchospasm, The addition of
ipratropium enhances the bronchodilation produced by
nebulized albuterol in acute severe asthma. The
antimuscarinic agents appear to be of significant value
in chronic obstructive pulmonary diseases - perhaps
more than asthma. They are useful as alternative
therapies for patients intolerant of agonists
4. ANTI-INFLAMMATORY AGENTS: CORTICOSTEROIDS
Used both for treatment and prophylactic purposes:
Mechanism of action; They are presumed to act by their
broad anti-inflammatory efficacy mediated in part by
inhibition of production of inflammatory mediators.
They also potentiate the effects of ?receptor agonists
and inhibit the lymphocytic-eosinophilic airway mucosal
inflammation Effects on airway decreases bronchial
reactivity increases airway caliber decreases frequency
of asthma exacerbation and severity of symptoms
The corticosteroids commonly used are hydrocortisone,
predinisolone, beclomethasone, triamcinolone and etc.
The drugs can be taken by inhalation as aerosol, oral,

or an IV administration.
Because of severe adverse effects when given
chronically, oral and parenteral corticosteroids are
reserved for patient who need urgent treatment and
those who have not improved with
Bronchodilator:Aerosol treatment is the most effective
way to decrease the systemic adverse effect of
corticosteroid therapy. Abrupt discontinuation should
be discouraged because of the fear of adrenal
insufficiency. Doses should be decreased after
improvement. Regular or controlled therapy is better
maintained with aerosol corticosteroids.
Clinical uses in bronchial asthma: Urgent treatment of
severe asthma not improved with bronchodilator;IV,
inhalation or oral.
Side effects: Suppression of the hypothalamicpituitary-adrenal axis . Sodium retention and
hypertension. Cataract. Impairment of growth in
children Susceptibility to infection like oral
candidiasis and tuberculosis.
5. MAST CELL STABILIZERS
e.g cromolyn sodium.
Mechanism of action: Stabilize the mast cells so that
release of histamine and other mediators is inhibited
through alteration in the function of delayed chloride
channel in cell membrane. It has no role once mediator
is released and is used for casual prophylaxis.
Clinical uses; Exercise and antigen induced asthma.
Side effects; Poorly absorbed so minimal side effect.
Throat irritation, cough, dryness of mouth, chest
tightness and wheezing.
ADULT HEALTH (WEDNESDAY)

Relapsing Fever:
Definition: Relapsing fever is an acute febrile
illness caused by Borrelia species, presenting with
recurrence of characteristic febrile periods lasting
for days alternating with afebrile periods.

Relapsing fever describes two distinct diseases:


Louse borne (Endemic) relapsing fever (LBRF):transmitted by body louse Pediculus humanis var
corporis
Tick borne (Epidemic) relapsing fever (TBRF)transmitted by tick (Ornithodoros)
Etiology:
Relapsing fever is caused by Borrelia species, which
are spirochetal gram negative helical bacteria.
B. recurrentis is the only species that cause LBRF
B. duttoni is the commonest causes of TBRF in subSaharan Africa. Borrelia demonstrates remarkable
antigenic variation and strain heterogeneity which help
the parasite to escape the immune response of the host
and result in recurrence of febrile episodes.

Transmission:
LBRF: Body lice become infected by B. recurrentis while
feeding on spirochetemic human blood, the only
reservoir of infection. Humans acquire infection when
infected body lice are crushed and their fluids
contaminate mucous membrane or breaks in the skin (such
as abrasions caused by scratching of pruritic louse

bites).LBRF is now an important disease. Some of the


risk factors for LBRF are overcrowding like in military
camps, civilian population disrupted by war and other
disasters.

TBRF: Rodents are the primary hosts and vector ticks


become infected when they feed spirochetemic rodents.
Ticks transmit the Borrelia vertically over several
generations. TBRF is most highly endemic in sub-Saharan
Africa but also is found in Mediterranean and Middle
eastern countries.

Pathophysiology:
In humans, Borrelia after entering the body multiply
in the blood and circulate in great number during
febrile periods. They are also found in the spleen,
liver, central nervous system, bone marrow, and may be
sequestered in these organs during periods of
remission. Severity is related to spirochetal density
in blood but systemic manifestations are related to
release of various cytokines.
The disease is characterized by sub capsular and
parenchymal hemorrhage with infarcts of spleen, liver,
heart and brain is seen. Thus, patients will have
enlarged spleen and liver with variable edema and
swelling of brain, lung and kidneys. Relapsing fever in
pregnancy can result abortion, still birth and fatal
neonatal infection Death from TBRF is rare. In contrast
fatality rate of LBRF may reach up to 20 % during out

beaks mainly among malnourished and stressed


population.

Clinical Features:
The manifestation of both LBRF and TBRF are similar.
Incubation period is 7 days (ranging from 2-18 days).
The onset is sudden with high grade irregular fever,
headache, chills, myalgias, arthralgias, and insomnia.
Patient will be withdrawn, disinterested to food and
other stimuli and thirsty. Patient will have delirium
associated with high grade fever, tachycardia and dry
tongue, injected conjunctiva and photophobia
Summation gallop , occasionally resulting from
myocardial involvement
Upper abdominal tenderness with hepatosplenomegally,
Scattered petechiae over the trunk, extremities and
mucous membrane in 1/3 LBRF and fewer TBRF
Symptoms and signs of meningeal irritation may be
seen in some patients.
Icteric sclera may be found in late stage of the
disease.

Complications:Life threatening complications are unusual in otherwise


healthy persons if the disease is diagnosed and treated
early. Complications are common in late disease in
untreated patients.
Epistaxis, blood streaked sputum
other bleeding tendencies Neurologic manifestations

like iridocyclitis, meningitis, coma, isolated cranial


nerve palsies, Pneumonitis,
Myocarditis and Splenic
rupture etc.
Without treatment, symptoms intensify
over 2-7 days period and subside with spontaneous
crisis during which Borrelia disappear from the
circulation. Such cycles of febrile periods
alternating with afebrile periods may recur several
times.

Basic characteristics of the two types of Borrelia:


Causes

LBRF
B. recurrentis

Parasite in
the vector

Found in
endolymph of lice

Transmission

Contamination of
mucous membrane
or breaks or
abrasions on the
skin by body
fluids of lice,
released during
crushing
- Not transmitted
by the bite of
lice or
inoculation of
louse feces
No

Vertical
transmission
(TransOvarian)

TBRF
B. duttoni + many
others(all zoonotic)
Found in all tissues,
including salivary
glands & ovaries
By bite of tick
during blood meal
(organisms in the
saliva & coaxal fluid
of Borrelia)

Yes

Distribution

East Africa

Occurrence

Epidemics are
frequent in
homeless people
living in
unhygienic
crowded condition
Short life span

Vector
longevity
Jarisch
Herxheimer
Reaction
Eradication

Sub-Saharan Africa,
Mediterranean
littoral, middle
east, Russia, India,
China, USA
Sporadic or in small
often familial
clusters

Lives over 10 Yrs

More severe

Less severe

Easy

Difficult because of:


- the night biting
habit & painless
nature of the bite of
ticks - vertical
transmission/transovarian/ - long life
span.

Diagnosis:
Diagnosis of relapsing fever is made based on
demonstration of the organisms in blood, bone marrow,
CSF etc Blood Film:
Giemsa or Wright stained peripheral blood smear is an
ideal test in the resource limited setting.
Spiral organisms can be demonstrated on peripheral
blood taken during febrile period preceding the crisis.

This is positive in more than 70% of LBRF and in lower


percentage of patients with TBRF.

Other Tests:
Dark field microscopy of unstained blood/CSF
Serologic tests.

Treatment:
Relapsing fever is treated with antibiotics. In LBRF
single dose of erythromycin, tetracycline, doxycycline
or chloramphenicol, produces rapid clearance of
Borrelia from the blood & remission of symptoms. TBRF
is less sensitive to these antibiotics and requires a 7
days course of treatment.

Adult Dosage:
Medication
(Oral)
Erythromycin
Tetracycline
Doxycycline

LBRF (single
dose)
500mg
500mg
100mg

TBRF (7 days
schedule)
500mg every 6 hrs
500mg every 6 hrs
100mg every 12
hrs

Chloramphenicol
Parenteral:
Penicillin G
(procaine)

500mg
600,000 I.M
stat

500mg every 6 hrs


600,000 IM daily

Jarisch- Herxheimer Reaction (JHR):

Rapidly acting antibiotics regularly precipitate


JHR within 1- 4 hrs of 1st dose
More sever in patients with LBRF than TBRF
It is more sever when high numbers of spirochetes are
circulating in the blood
Jarisch- Herxheimer Reaction has three phases;
Chill phase:-

lasts for 10- 30 minutes;

Rigor, hyperventilation, high cardiac output,


High body Temperature ( > or = 41 Co)
, agitation , confusion .

accompanied by

Flush phase:
Fall in body temperature, drenching sweating,
Potential dangerous fall in Systemic blood pressure
( as peripheral vascular resistance falls )
Clinical and ECG evidence of myocarditis may be
seen , S3 gallop and prolonged QT interval
Vital signs must be monitored closely during this
time which usually lasts for <or = 8 hrs.

Recovery (Deferverescence) phase:


Vital signs slowly come to normal
The Patients is exhausted .

Treatment of JHR:
Close monitoring of vital signs

Care full fluid management


Control high body Temperature
Short term digoxin I.V administration in patients
with evidence of myocardial dysfunction.

Prevention and Control of Relapsing Fever:


Avoiding over crowding
Apply hygienic practices that reduce the number of
body lice (washing clothes)
Elimination of ticks
Health education
Early case detection and treatment of infected
persons and close contacts
In out breaks of LBRF, empirical single dose
treatment with doxycycline
Eradication of Rodents to control TBRF:
( Rodenticides ) .

PHARMACOLOGY (THURSDAY)
ANTI-TUSSIVES

Cough is a protective reflex, which serves the purpose


of expelling sputum and other irritant materials from
the respiratory airway.
Anti-tussives are drugs used to suppress the intensity
and frequency of coughing.
Two Types of Anti-tussives:
1. Central anti- tussives Suppress the medullay cough
center and may be divided into two groups: Opoid
antitussive e.g. codeine, hydrocodeine, etc Non opoid
antitussives e.g. dextromethorphan
2. Peripheral antitussives: Decrease the input of
stimuli from the cough receptor in the respiratory
passage. e.g: Demulcents e.g. liquorices lozenges,
honey

DEXTROMETROPHAN
Dextromethorphan is an opoid synthetic antitussive,
essentially free of analgesic and addictive properties
and the main side effects are respiratory depression.
Expectorants are drugs that removes thick tenacious
mucus from respiratory passages, e.g. Ipecac alkaloid,
sodium citrate, saline expectorant, guanfenesin,
potassium salts Mucolytics are agents that liquefy
mucus and facilitate expectoration, e.g.acetylcysteine.
DECONGESTANTS
Decongestants are the drugs that reduce congestion of
nasal passages, which in turn open clogged nasal
passages and enhances drainages of the sinuses.
Clinical uses: Used in congestion associated with
rhinitis, hay fever, allergic rhinitis and to a lesser
extent common cold. Drugs can be administered nasally

or orally for longer duration of action.


Classification:
1. Short acting decongestants administered topically;
phenylepherne and phenylpropanolamine
2. Long acting decongestants administered
orally;ephedrine, pseudoephedrine and naphazoline
3. Long acting topical decongestants;Xylometazoline and
oxymetazoline
Side effects:
1. Rebound nasal congestion
2. Ischemic changes in mucus membranes
3. Nasal burning, stinging, dryness
4. Tachycardia, arrhythmia, nervousness, restlessness,
insomnia, blurred vision
Contraindications : Hypertension and severe coronary
artery disease
DRUGS USED IN GASTROINTESTINAL DISEASES
I. Drugs used in Acid-peptic disease:
Acid-peptic disease includes peptic ulcer (gastric and
duodenal), gastroesophageal reflux and Zollinger
Ellison syndrome. Peptic ulcer disease is thought to
result from an imbalance between cell destructive
effects of hydrochloric acid and pepsin and cellprotective effects of mucus and bicarbonate on the
other side. Pepsin is a proteolyic enzyme activated in
gastric acid, also can digest the stomach wall. A
bacterium, Helicobacter pylori is now accepted to be
involved in the pathogenesis of ulcer. In
gastroesophageal reflux, acidic stomach contents enter
into the esophagus causing a burning sensation in the
region of the heart; hence the common name heartburn,
or other names such as indigestion, dyspepsia, pyrosis,
etc.
Zollinger-Ellison syndrome is caused a tumor of gastrin

secreting cells of pancreas characterized by excessive


secretion of gastrin that stimulates gastric acid
secretion. The disorders can be treated by drugs, which
are able to: Neutralize gastric acid (HCl) e.g.
magnesium hydroxide Reduce gastric acid secretione.g.
cimetidine Enhance mucosal defences e.g sucralfate
Exert antimicrobial action against H.pylori e.g.
clarithromycin
The most commonly used antacids:are mixtures of
aluminium hydroxide and magnesium hydroxide (e.g.
Gelusil, Maalox etc). Antacids act primarily in the
stomach and are used to prevent and treat peptic ulcer.
They are also used in the treatment of Reflux
esophagitis and Gastritis B. Gastric acid secretion
inhibitors (antisecretory drugs): HCl is secreted by
parietal cells of the gastric mucosa which contain
receptors for acetylcholine, histamine and gastrin that
stimulate the secretion.
II. Laxatives and cathartics (purgatives)
Laxatives and cathartics are drugs used orally to
evacuate the bowels or to promote bowel elimination
(defecation). The term laxative implies mild effects,
and eliminative of soft formed stool. The term
cathartic implies strong effects and elimination of
liquid or semi liquid stool. Both terms are used
interchangeably because it is the dose that determines
the effects rather than a particular drug.
Indications for Laxatives and cathartics:
1. To relieve constipation
2. To prevent straining stool softeners
3. To empty the bowel in preparation for bowel surgery
or diagnostic procedures (saline or stimulant)
4. To accelerate elimination of potentially toxic
substances from the GI tract (saline or stimulant)
5. To accelerate excretion of parasite after
anthelmintic drugs (saline or stimulant) have been
administered. Constipation is a common problem in older

adults and laxatives are often used or overused. Non


drug measures to prevent constipation (e.g. increasing
intake of fluid and high fiber foods, exercise) are
much preferred to laxatives.
III. Antidiarrhoeals:
Are used in the treatment of diarrhea, defined as the
frequent expulsion of liquid or semi liquid stools
hinders absorption of fluids and electrolytes. In many
instances, drug intervention is not required because is
a protective mechanism used in an attempt by the body
to flush out the offending pathogen or agent.
Antidiarrheal drugs may be given to relive the symptom
(non-specific therapy) or may be given to treat the
underlying cause of the symptom (specific therapy).For
symptomatic treatment of diarrhoea, opiates and opiate
derivatives are the most effective. They decrease
diarrhea by slowing propulsive movements in small and
large intestine.
Morphine is effective but not used because of serious
potential adverse effects, other synthetic drugs such
as diphenoxylate and loperamide are commonly used
Adsorbent demulcent products such as kaolin pectin
preparation may be included in antidiarrheal
preparations, unfortunately, they may adsornutrient and
other drugs, including the antidiarrheal agents if
given concurrently Anticholinergic agents e.g. atropine
are occasionally used to decrease abdominal cramping
and pain associated with diarrhea.
Specific therapy may include the use of antibacterial,
which are recommended for use in carefully selected
cases of bacterial enteritis. Severe diarrhea by
salmonella, shigella, campylobacter and clostridia.
Species can be treated by antibiotics (ampicillin,
chloramphinicol, colistin, co-trimoxazole etc.
Indications for use:

1. severe or prolonged diarrhea (>2-3 days)


2. when specifice causes have been determined
IV. Antiemetics:
Are drugs used to prevent or treat nausea and vomiting.
Nausea is an unpleasant sensation of abdominal
discomfort accompanied by a desire to vomit. Vomiting
is the expulsion of stomach contents through the mouth
Nausea may occur without vomiting and vomiting may
occur without prior nausea, but the two symptoms most
often occur together.
Vomiting occurs when the vomiting center in the medulla
oblongata is stimulated. Dopamine and acetylcholine
play a major role in stimulating the vomiting center.
To a certain extent, vomiting is a protective mechanism
which can result from various noxious stimuli.
Drugs used in nausea and vomiting: belong to several
different therapeutic classifications. Most antiemetic
agents relieve nausea and vomiting by acting on the
vomiting center, CTZ, cerebral cortex, vestibular
apparatus, or a combination of these. Antiemetic drugs
are generally more effective in prophylaxis than
treatment. Antiemetic drugs include: Phenothiazines
(neuroleptics) such as chlorpromazine Acts on CTZ and
vomiting center Block dopamine receptors Are effective
in prevention or treating nausea and vomiting induced
by drugs, radiation therapy, surgery and most other
stimuli (e.g. pregnancy). Are generally ineffective in
motion sickness.
Antihistamines such as promothazine, dimehydrinate etc.
Are especially effective in prevention and treatment of
motion sickness (but they may cause concurrent
drowsiness, that may be troublesome for travellers) .
Miscellaneous antiemetics: Metoclopramide has both
central and peripheral antiemetic effects. Centrally,
metoclopoamide antagonizes the action of dopamine.
Peripherally metoclopoamide stimulates the release of

acetylcholine, which in turn, increases the rate of


gastric emptying (used in esophapeal reflux)
Indication; as chlorpromazine Scopolamine, an
anticholinergic drug is very effective in reliving
nausea & vomiting associated with motion sickness.
Ondansetron- is serotonin antagonist (5-HT3 receptors)
found on the afferent fibers of the vagus nerve and in
parts of the brain associated with CTZ. Controls
chemical induced vomiting and nausea.
V. Drugs used to induce vomiting
In case of poisoning with noncorrosive agents, and
assuming incomplete absorption of the poison has taken
place, induction of vomiting can be carried out. The
drug used for this purpose is emetine, the active
ingredient of ipecacuanha (syrup of ipecac). Emetine
induces by direct irritation of the upper gut and on
absorption, it also acts on CTZ.
VI. Drugs used in the treatment of haemorrhoids;
Haemorrhoids are varicose veins of the anal canal which
can be very distressing for the sufferer. There is no
pharmacological cure for this disorder, which is often
self-limiting, if not, may require surgical
intervention.
The use of drugs may however, linder the sufferings:
Stool softeners may alleviate constipation; lessen
straining which can worsen the condition. Local
anesthetics (e.g. lignocaine, benzocaine) relieve pain
Corticosteroids (e.g. predniosolone) suppress
inflammation, itching & swelling Vasoconstrictors (e.g.
adrenaline, phenylephine) lessen venous swelling
Astringent compounds (e.g. tannic acid) reduce swelling
by precipitating cell surface proteins.
Antihaemmorhoidal preparations contain one or more of
these agents.

VII. Drugs used in inflammatory bowel disease


(ulcerative colitis and crohns disease)
Ulcerative colitis is an inflammatory condition of the
rectum and colon; crohns disease can involve the whole
intestine. Both diseases can lead to pain and abdominal
discomfort. Two groups of drugs used to treat both
conditions are
1. corticosteroids e.g. prednisolone
2. drugs related to sulphonamides e.g. sulfasalazine.

ADULT HEALTH (FRIDAY)

Rickettsial diseases
Definition: Rickettsiae are small intracellular
bacteria that are spread to man by arthropod vectors,
namely human body lice, fleas, ticks & larval mites.
The organisms inhabit the gastrointestinal tract of
these arthropods & spread to human host by the direct
bite of the vector or the inoculation of the organism
contained in the feces of the vector by bite induced
body itching. These infections are characterized by
persistence in the body, widespread vasculitis
(invading endothelial cells of small blood vessels) &
multi-system involvement. Except in louse borne typhus
humans are accidental hosts in most rickettsial
diseases.

Classification:
Rickettsial diseases are classified into five general
groups;
Tick

and mite borne spotted fever group

Flea and louse borne typhus group Chigger borne


scrub typhus
Ehrlichiosis
Q-fever.

Etiology and Epidemiology of Epidemic and Endemic


Typhus :
Epidemic Typhus (Louse born );
Is caused by R.prowazekii and transmitted by human
body louse (Pediculus humanus corporis). Lice acquire

the rickettsiae while ingesting a blood meal from an


infected patient, the rickettsiae multiply in the
midgut epithelial cells of the louse and are excreted
via louse faeces. The infected louse defecates during a
blood meal and the patient autoinoculates the organisms
by scratching. It is commonly associated with poverty,
cold weather, war and natural disasters. The disease is
prevalent in mountainous areas of Africa, South
America, and Asia.

Endemic Typhus (Flea born) / Murine Typhus;


Is cause by R. thyphi which is transmitted by fleas.
R.typhi is maintained in mammalian host/flea cycles,
with rats. Fleas acquire R.typhi from rikettsemic rats
and carry the organism throughout the rest of their
life span. . Humans and rats are infected when
rickettsiae laden fleas are scratched in to pruritic
bite lesions.

Pathophysiology:
In man rickettsiae multiply in the endothelial cells
of capillaries causing lesions in the skin, brain,
lung, heart, kidneys and skeletal muscles. Endothelial
proliferation coupled with peri-vascular reaction
causes thromboses and small hemorrhages. However,
tissue and organ injury is commonly due to increased
vascular permeability with resulting edema, hypovolemia
and organ ischemia. This leads to multi-system
involvement with complications such as non-cardiogenic
pulmonary edema, cardiac dysrhythemia, encephalitis,
renal and hepatic failure and bleeding.

Clinical Features:
Signs and symptoms;
Incubation period of 1 week
Abrupt onset of illness with prostration, severe
headache and rapidly rising fever of 38.8 to 40.0 C
Cough s seen in 70 % of patients , myalgia may also
occur which may be severe Rash, begins on upper trunk
around 5th day and then becomes generalized, involving
the entire body except face, palms and soles; at first,
rash is macular, becoming maculopapular, petechial and
confluent without treatment, although in black people,
rash may be absent (spotless epidemic typhus)
Photophobia, with conjunctival injection and eye
pain; frequent
Tongue may be dry, brown, furred
The signs of central nervous system involvement,
commonly as meningo-encephalitis, appear towards the
end of the 1st week progressing to seizure and coma.

Brill-Zinsser disease (recrudescent typhus);


This is a mild form of epidemic typhus caused by
reactivation of dormant R. prowazekii in the body (in
the lymph nodes) as a result of Immunosuppression or
old age. Occurs after several years of acute infection.
The manifestation of the disease is similar to acute
epidemic typhus but milder. The organisms may infect
other people in the presence of vectors (body lice).

Endemic typhus (Flea borne typhus);

Epidemic typhus (also known as murine typhus) is a


relatively milder.
The incubation period is 1 - 3 weeks and followed by
sudden onset of fever, rigors, frontal headache, pain
in the back and limbs, constipation and cough (due to
bronchitis).
The fever becomes constant after the third day and
associated with conjunctivitis and orbital pain.
Rash appears on the fifth day initially as blanching
macules at the anterior axillary folds, which
subsequently spread to involve other parts of the body
(sparing the face & the neck) and become purpuric.
During the second week symptoms worsen and additional
manifestations, such as sore lips, dry brown tremulous
tongue, feeble pulse, enlarged spleen & delirium
appear.

Complications of Endemic and Epidemic Typhus:


Skin necrosis, gangrene of digits, Venous
thrombosis, Interstitial pneumonia in severe
cases,Myocarditis,Oliguric renal failure and
Parotitis.
Diagnosis of rickettsial diseases is based on
History, clinical course of the disease and
epidemiologic of the disease may give a clue for
diagnosis.

Laboratory investigations:
Serologic tests;

Indirect fluorescent antibody test


Weil-Felix agglutination test: Not specific or
sensitive. Isolation of the organism by inoculation
into laboratory animals is possible, it is time
consuming and technically demanding.

Treatment of rickettsial diseases:


Endemic Typhus;
*Doxycycline 100mg bid PO for 7-15 days
* Chloramphenicol 500mg QID PO for7-15 days.

Epidemic typhus;
*Doxycycline 200mg as single dose
patient is afebrile for 24 hours.

PO until the

*Delousing louse borne typhus


* Supportive Therapy: Attention to fluid balance,
prevention of bed sores. Treat agitation with diazepam
Steroid treatment (prednisolone 20 mg daily for adults)
in severe cases.

Prognosis:
Untreated disease is fatal in 7 to 40 % of cases,
depending on condition of host. In untreated survivors,
renal insufficiency, multiorgan involvement and
neurologic manifestations (12 %) are common. However,
endemic typhus has better prognosis with a mortality of
only 1 2%. Serious neurological, renal and other
complications are unusual.

Prevention For flea borne typhus:


*Elimination of fleas on clothing & bedding using
insecticides like 1% Malathion powder. Apply residual
insecticide powder on the floor & bedding to kill
hatching fleas. Rodent control using chemicals (e.g.
warfarin).
For louse borne typhus;
*Eradicate all lice on clothing & bedding using
insecticides (1% Malathion powder) including all family
contacts. DDT is not useful as the lice are often
resistant to it
*Wash the patient with soap and water & apply
insecticides all over & disinfect clothing with
insecticides in a bag or sterilize by autoclaving.
*Protective wearing smeared with insect repellents is
recommended for nurses and other attendants.
Chemoprophylaxis: Doxycycline 100mg weekly will
protect those at risk. walesonmd@gmail.com