pharmacology in ent practices: common drugs

1. Pharmacotherapy in ENT -I
Dr. Raju Kafle
1st year resident
NMCTH, ENT-HNS dept.
1

2. Antimicrobials : Overview
 Antibacterial:
 Cell wall synthesis inhibitors
 Penicillins, cephalosporins, carbapenem,
monobactams
 Protein synthesis inhibitors
 Tetracyclines, macrolides, aminoglycosides,
oxazolidinones (linezolid), chloramphenicol
 Nucleic acid synthesis inhibitors
 Quinolones, folic acid antagonists , sulfa drugs
Antifungals ( topical , systemic)
Antivirals
Antiprotozoal
2

3. Bactericidal and Bacteriostatic agents
3
Primarily bactericidal Primarily bacteriostatic
Penicillins Sulfonamides
Cephalosporins Tetracyclines
Aminoglycosides Chloramphenicol
Ciprofloxacin Erythromycin
Cotrimoxazole Linezolid
Metronidazole Clindamycin
Vancomycin
ATT ( HRZ) ATT( Ethambutol)

4. Penicillins :
• First antibiotic to be used clinically in 1941
• Originally: Fungus Penicillium notatum, presently from P.
chrysogenum.
• They interferes with the last step of bacterial cell wall
synthesis, which is the cross-linking of adjacent
peptidoglycan strands by a process known as
transpeptidation.
Result is formation of weakened cell wall and
ultimately cell death (Bactericidal)
• To be maximally effective, inhibitors of cell wall synthesis
inhibitors require actively proliferating microorganisms.
4

5. Natural penicillins
• Narrow spectrum , activity is limited primarily to gram-
positive bacteria, few gram negative ones and anaerobes.
• Susceptible to β-lactamase , not active against most
staphylococcus species.
 Penicillin G (10 times potent)
 Penicillin V
• Penicillin V- only oral formulation , but not used for
treatment of severe infections due to limited oral
absorption.
• Penicillin V is more acid stable than penicillin G and
is the oral agent employed in the treatment of less
severe infections
5

6. Semi-synthetic penicillins
(Aminopenicillins/ Extended spectrum )
Amoxycillin and ampicillin
Aim
• To overcome the shortcomings of natural penicillins ( Poor
oral efficacy, Susceptibility to penicillinase, Narrow
spectrum of activity, Hypersensitivity reactions
• Widely used in the treatment of respiratory infections.
• Unlike PnG , it Extends activity against gram-negative
bacteria to include H. influenzae, E. coli, and P. mirabilis but
not against pseudomonas species.
• They are more active than PnG in Strep. viridans,
pneumococcus , enterococci and Listeria;.
• Amoxicillin, 250–500 mg three times daily, is equivalent to
the same amount of ampicillin given four times daily.
6
Indications
Bacterial sinusitis,
Otitis media
Lower respiratory tract
infections
Ampicillin and Amoxicillin are
the most active of oral β-
lactam antibiotics against
pneumococci and are the
preferred β-lactam antibiotics
for treating infections
suspected to be caused by these
strains.

7. Ampicillin: Oral ,IM, IV
• Not degraded by gastric acid
• Primarily excretion is kidney, plasma t½ is 1 hr.
Amoxycillin : Oral ,IM, IV
• close congener of ampicillin ,similar in all respects except:
• Oral absorption is better , food does not interfere with absorption
• Higher and more sustained blood levels are produced.
• Incidence of diarrhoea is lower.
• Less active (Shigella and H. influenzae)
• More active against penicillin resistant Strep. Pneumoniae
• Coformulated / augmented with β-lactamase inhibitors
(clavulanic acid or sulbactam) to combat infections caused by β-
lactamase–producing organisms (ex. MSSA)
7

8.  Antistaphylococcal penicillins
(penicillinase-resistant penicillins)
Limited to penicillin resistant staphylococci and
streptococcus, pneumococcus species
Cloxacillin : dependably absorbed from oral route, especially
if taken in empty stomach.
• Plasma t½ : 1 hour.
• Elimination : primarily by kidney , partly by liver.
 Antipseudomonal penicillin
• Piperacillin and ticarcillin : because of its high activity against
Pseudomonas aeruginosa
• Good activity against E.coli ,Klebsiella, many
Enterobacteriaceae and some Bacteroides
• Formulation of piperacillin with tazobactam extends the
antimicrobial spectrum to include penicillinase- producing
organisms (for ex. most Enterobacteriaceae and Bacteroides
species)
8
Penicillinase
resistant
penicillins
Methicillin interstitial
nephritis- no
longer clinically
used
Nafcillin 8-12g/day . 50-
200 mg/kg/day in
children
Oxacillin Same as Nafcillin
Cloxacillin • 0.25-0.5gm,
4-6 hourly
(severe infections
0.25–1 g i.m/ i.v)
• Children :15-
25mg/kg/day
in 4 dd

9. Carbapenems
• Wide spectrum against most Gram-negative rods, including P
aeruginosa, Gram-positive organisms , and anaerobes.
• It is resistant to most β-lactamases
• Administered together with an inhibitor of renal
dehydropeptidase i.e, cilastatin to prevent its breakdown.
Monobactams :Aztreonam
• monocyclic β-lactam ring, limited to aerobic Gram-negative
organisms (including P aeruginosa).
• Unlike other β-lactam antibiotics, they have no activity against Gram-
positive bacteria or anaerobes.
• Used in serious infections (mastoiditis, pneumonia, sepsis,
meningitis) in Penicillin-allergic ,
• Dose : IV , 1–2 g/day every 8 hr , Half-life is 1–2 hr
• skin rashes and elevations of serum aminotransferases. 9
Carbapenem
s
Dose
Imipenem
• half life:
1hr
0.25–0.5 g
IV every 6–8
hours
Meropenem
• half life:
1hr
0.5–1 g IV
every 8
hours.
Ertapenem
• half life :
4hr
once-daily
dose of 1 g
intravenously
or
intramuscular
ly

10. Pharmacokinetics
 Routes of administration:
• Oral : Penicillin V, amoxicillin, ampicillin and dicloxacillin
• IV/IM: Ampicillin + sulbactam, Amoxycillin + clavulanate, piperacillin
+tazobactam, anti-staphylococcal Penicillins ( nafcillin and oxacillin)
• Depot forms: Procaine penicillin G and benzathine penicillin G
Absorption
• Acidic environment: unfavorable for the absorption of penicillins
• Food decreases the absorption of the penicillinase-resistant
penicillins (cloxacillins) so it should be taken on empty stomach.
• Conversely, amoxicillin is stable in acid and is readily absorbed
from the gastrointestinal (GI) tract.
10

11.  Distribution:
• Well distributed throughout the body.
• All crosses the placental barrier, but none have teratogenic effects.
• However, penetration into bone or cerebrospinal fluid (CSF) is insufficient for
therapy unless these sites are inflamed (Note: Inflamed meninges are more
permeable to the penicillins)
 Excretion
• The primary route of excretion is kidney, so dosage regimens adjusted in
patients with impaired kidney function.
• Nafcillin and oxacillin are primarily metabolized in the liver, they do not
require dose adjustment for renal insufficiency.
• The penicillins are also excreted in breast milk.
• Probenacid : competes for penicillin in tubules- decreased secretions and
excretions
11

12. Side effects
12
Pregnancy category :B
 Side effects:
• Hypersensitivity reactions ( 5-8%)
• So used with caution and penicillin skin testing sometimes
• Allergic reactions and anaphylactic shock ( very rare, <
0.05%)
• Serum sickness like reactions
• SJS, TEN
• Interstial nephritis : due to penicillin protrein complex
• Seizures : in renal failure
• Oxacillin : hepatitis
• Ampicillin : pseudomembranous colitis
• Amoxycillin and Ampicillin both: viral illness (EBV- rashes
aggravation 60-65% of cases)

13. Cephalosporins
• Closely related both structurally and functionally
to penicillins, same mode of action as
penicillins, by the same resistance mechanisms.
• Mostly semisynthetic
• However they are more resistant than the
penicillins to certain β-lactamases.
• 1st generation : usually oral and absorbed well
• 2nd generation : usually IV forms
• 3rd generation : usually IV ( Ceftriaxone and
cofotaxime– cross BBB)
• 4th generation : parenteral only
13
Gram +ve
Gram --ve

14. 14

15. Advance generation cephalosporin
• Ceftaroline is a broad-spectrum, advanced-
generation cephalosporin.
• It is the only β-lactam in the United States with
activity against MRSA, and it is indicated
complicated skin and skin structure infections
and community-acquired pneumonia.
• Broad gram-positive activity, plus similar gram-
negative activity as ceftriaxone
Dosage
• Mostly, IV or IM because of their poor oral
absorption.
• Exceptions:
15

16. Important cephalosporins
16

17.  Distribution and elimination
• All cephalosporins distribute very well into body fluids (CSF : ceftriaxone,
cefotaxime)
• Mostly through tubular secretion and /or glomerular filtration (Exception: ceftriaxone
- excreted in bile -so frequently employed in patients with renal insufficiency )
Adverse effects
Pregnancy category : B , excreted very less in breast milk.
Like the penicillins, the cephalosporins are generally well tolerated.
• Cross allergenicity : 10% with penicillin allergic patients
• The highest rate of allergic cross-sensitivity is between penicillin and first-generation
cephalosporins.
• Ceftriaxone : clostridium difficle diarrhoea – commonest .
17

18. Protein synthesis inhibitors
Tetracyclines :
• Broad spectrum bacteriostatic , Mainly against S.
aureus, and some gram –ve organism (H. influenza and
gonococci) and certain anerobes (chlamydiae,
mycoplasma, ricketssiae)
• The drugs bind reversibly to the 30S subunit of the
bacterial ribosome.
• This action prevents binding of tRNA to the mRNA–
ribosome complex, thereby inhibiting bacterial
protein synthesis.
• Avoid in : pregnancy and childhood ( < 8yrs) as
deposited in bones and teeth.
• Side effects : photosensitivity and GI distress
18
Name Dose
Tetracycline 0.25–0.5 g four
times daily
• 25–50 mg/kg/d
for children (8
years of age
and older)
Oxytetracycline
• Less side effect
profile
Doxycycline (
DOC )
Oral or IV
100 mg once or
twice daily
Minocycline
Oral or IV
100 mg twice
daily

19. Tigecycline : semisynthetic
• Derived from minocycline, most resistant of all
• Susceptible organisms :
• coagulase-negative staphylococci and Staphylococcus aureus (including methicillin-resistant,
vancomycin-resistant strains)
• Streptococci, enterococci
• Proteus and P aeruginosa : are intrinsically resistant.
• Tigecycline, formulated for intravenous administration only.
• Given as a 100-mg loading dose, then 50 mg every 12 hours
Pregnancy category and Side effects :
• Pregnancy category : D , can precipitate acute hepatic necrosis (fatal)
• Kidney damage : In renal failure patients ( exception: doxycycline )
• Phototoxicity
19

20. Chloramphenicol
• Synthetic , antibiotics
• Intensely bitter taste ( nitrobenzene moiety )
• Mechanism of action :
• Inhibits bacterial protein synthesis by binding to the 50S ribosome and prevents peptide bond
formation.
• At high doses, it can inhibit mammalian mitochondrial protein synthesis as well. Bone marrow
cells are especially susceptible.
Antimicrobial spectrum
• Primarily bacteriostatic, though high concentrations have been shown to exert cidal
effect on some bacteria, e.g. H. influenzae and N. meningitidis.
• It is a broad-spectrum antibiotic, active against nearly the same range of organisms
(gram-positive and negative cocci and bacilli, rickettsiae, mycoplasma) as
tetracyclines.
• It is more active than tetracyclines against H. influenzae
• Ineffective in Pseudomonas and proteus sp as tetracyclines. 20

21. Preparations and administration:
• The commonest route of administration of chloramphenicol is oral—as capsules;
250–500 mg 6 hourly (max. 100 mg/kg/ day), children 25–50 mg/kg/day.
• Also available as topical eye/ear drops:
• 1% eye oint, 0.5% eye drops, 5% ear drops,
• Of all drugs, chloramphenicol is the most important cause of aplastic anaemia,
agranulocytosis, thrombocytopenia or pancytopenia.
• Hypersensitivity reactions, rashes, fever, atrophic glossitis, angioedema ( infrequent)
• Irritative effects : Nausea, vomiting, diarrhoea, pain on injection.
• Superinfections ( candidial infections) : less common.
21

22. Aminoglycosides
• Hexose ring with various amino sugars attached by glycosidic linkage
Mechanism of action :
• Binds the 30S ribosomal subunit, where they interfere with
assembly of the functional ribosomal apparatus and/or cause the
30S subunit of the completed ribosome to misread the genetic
code.
• Aminoglycosides exhibit concentration dependent killing.
• They also have a significant post-antibiotic effect (antibacterial
activity persists beyond the time during which measurable drug is
present.
• The post-antibiotic effect of aminoglycosides can last several hours. So
has better efficacy when administered as a single large dose than
when administered as multiple smaller doses.
• Also : high interval dosing applied due to this reason
22

23. • When administered with a cell wall-active antibiotic (a β-
lactams, aminoglycosides may exhibit synergistic killing
against certain bacteria.
• Susceptible organisms :
Topical formulation
• Eye/Ear drops
• Framycetin
• Neomycin
• Tobramycin
Systemic formulation
• IV -Tobramycin, Amikacin,
• IM-Streptomycin, Spectinomycin
23

24. Ototoxicity
• Ototoxicity (vestibular and auditory) is directly related to high
peak plasma concentrations and the duration of treatment.
• Aminoglycosides accumulate in the endolymph and perilymph of
the inner ear.
• Deafness may be irreversible and has been known to affect
developing fetuses.
• Patients simultaneously receiving concomitant ototoxic drugs,
such as cisplatin or loop diuretics, are particularly at risk.
• Vertigo (especially in patients receiving streptomycin) may also
occur.
• In menieres disease: gentamicin is purposefully used via injection
through TM , through grommets or via intratympanic or round
window catheter
• Vestibulotoxic and cochlear toxicity( hair cells)
24

25. Macrolides
• Group of antibiotics with a macrocyclic lactone structure to which one or more
deoxy sugars are attached.
• Erythromycin (prototype): was the first of these drugs to have clinical
application, both as a drug of first choice and as an alternative to penicillin in
individuals with an allergy to β-lactam antibiotics.
• Others : clarithromycin , azithromycin and telithromycin
Mechanism of action:
• The macrolides bind irreversibly to a site on the 50S subunit of the bacterial
ribosome, thus inhibiting translocation steps of protein synthesis .
• Primarily bacteriostatic, can be bactericidal at higher doses.
25

26. Erythromycin
• This is effective against many of the same organisms as
penicillin G. therefore, it may be considered as an
alternative in patients with penicillin allergy
Clarithromycin
• Clarithromycin has activity similar to erythromycin, but it
is also effective against Haemophilus influenzae
Azithromycin
• Although less active than erythromycin against
streptococci and staphylococci, azithromycin is far more
active against respiratory pathogens such as H. influenzae
and Moraxella catarrhalis.
• Extensive use of azithromycin has resulted in growing
Streptococcus pneumoniae resistance.
26

27. Clindamycin
• Clindamycin has a mechanism of action that is
similar to that of the macrolides, primarily
bacterostatic
• Clindamycin is used primarily in the treatment of
infections caused by gram-positive organisms,
including MRSA and streptococcus, and anaerobic
bacteria
• penetrates well into abscesses and is actively taken
up and concentrated by phagocytic cells
• Metabolized in liver and excreted in both bile and
urine
• Half life : 2.5 hours
• No dosage adjustment in renal failure .
• Can be given Oral or Iv form 27
Dose • Oral : 0.15–0.3 g
every 8 hours,
(Children: 10–20 mg/kg/day )
• Iv : 600 mg of
clindamycin every 8
hours
Side effects GI upset , clostridum difficle
colitits, hepatotoxicity etc

28. Oxazolidinones: linezolid
• developed to combat gram-positive organisms, including
resistant isolates such as methicillin-resistant
Staphylococcus aureus, VRE, and penicillin-resistant
streptococci
• Linezolid binds to 50S subunit, thereby inhibiting the
translation of bacterial proteins
• Recommended dose : 600 mg oral(100% bioavailability) or,
IV formulations.
• Half life : 4-6 hours
• Principal toxicity : thrombocytopenia ( in 3%, if used greater
than 2 weeks)
• Irreversible peripheral neuropathies and optic neuritis causing
blindness have been associated with greater than 28 days of use,
limiting utility for extended-duration treatments.
• Serottonin syndrome : possess monoamine oxidase activity with large
quantities of tyramine-containing foods,.
28

29. Fluroquinolones
• fluoroquinolones have different targets for gram negative (DNA gyrase) and
gram-positive organisms (topoisomerase IV).
• This interference increases the number of permanent chromosomal breaks,
triggering cell lysis--resulting in rapid cell death
Commonly used :
• Ciprofloxacin
• Levofloxacin
• Ofloxacin
• Gemifloxacin
• Moxifloxacin
• Delafloxacin
29

30. 30
First generation ( narrow spectrum):
Nalidixic acid
Aerobic gram –ve bacilli, mostly
Second generation :
Ciprofloxacin
Broadened coverage, which includes
Enterobacteriaceae, Pseudomonas
aeruginosa, Haemophilus influenzae,
Neisseria spp., Chlamydia spp., and Legionella
spp
Third generation :
levofloxacin
Second gen plus, improved activity against s.
pneumoniae, MSSA, mycobacterium
Fourth generation :
(moxifloxacin, gemifloxacin, and
delafloxacin)
With enhanced gram-positive activity,
including Staphylococcus and Streptococcus
spp. Delafloxacin has activity against
methicillin-resistant Staphylococcus aureus
(MRSA) and Enterococcus
Ciprofloxacin : acts on both stationary and dividing bacteria.
• Drug of choice in MALIGNANT OTITIS EXTERNA ( 1.5g daily for 6-12 weeks)
and also used in treating PERICHONDRITIS due to Pseudomonas aeruginosa

31. Fluoroquinolones
31

32. 32

33. Sulfonamides
• Sulfonamides are synthetic analogs of PABA.
• Because of their structural similarity, sulfonamides compete with
PABA to inhibit dihydropteroate synthetase and the genesis of
bacterial dihydrofolic acid
• Active against most staphylococcus strain ( both methicillin
resistant and susceptibles), respiratory tract pathogens ( H.
influenza, k. pneumoniae)
Oral or IV formulations
 Oral : Trimethoprim( 160mg) + sulfamethoxazole (800mg) 12
hourly
• Otitis media : children – trimethoprim 8mg/kg per day and
sulfamethoxazole 40mg/kg per day in 2 divided dose
IV : used for gram –ve sepsis but replaced by extended spectrum
beta lactams and fluroquionolones.
33

34. Metronidazole
• Nitroimidazole antiprotozoal drug with
• potent antibacterial activity against anaerobes, including Bacteroides and Clostridium species,
Fusobacterium, and anaerobic Streptococci’s.
• It is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up
it is nonenzymatically reduced by reacting with reduced ferredoxin that results in
products that accumulates and are toxic to anaerobic cells.
• Oral or IV formulations.
• Metabolized in the liver and excreted in urine. Plasma half life : 7.5 hours
• The typical dosage is 500 mg three times daily orally ,or IV (30 mg/kg/d).
• Adverse-effects
• Nausea, headache, dry mouth, metallic taste
• Infrequently :Vomiting, diarrhea, insomnia, weakness, dizziness, thrush, rash, dysuria, dark
urine, vertigo, paresthesias, encephalopathy, and neutropenia. peripheral neuropathy with
prolonged use.
• Metronidazole has a disulfiram-like effect, and patients should be instructed to avoid alcohol.34

35. Antifungals : Overview
35
Mainly classified into
• Polyenes (Amphotericin B , Nystatin)
• Antimetabolites: Fluctytosine
• Azoles
• Imidazoles: clotrimazole, miconazole, ketoconazole)
• Triazoles : Fluconazole, Itraconazole, Voriconazole
• Benzofurans: Griseofulvin
• Echinocandins
Theurapeutic uses :
• Fungal otitis externa/ otomycosis
• Adjunct to surgery in allergic fungal rhinosinusitis ,
invasive fungal rhinosinusitis and conventional recurrent
rhinosinusitis
• Oropharyngeal thrush/ mucocutaneous infections Inhibits mitosis : griseofulvin

36. 36
Systemic
antifungals (
systemic
infections)
Oral systemic
antifungals (
mucocutaneous
infections)
Topical
Amphoterin B Griseofulvins Nystatins
Flucytosine Terbinafines Topical azoles
(Clotrimazole and
miconazole )
Azoles Allylamines
(Terbinafine)
Echinocandins
Topical antifungals:
 Nystatin :
• Topical in oropharyngeal thrush, fungal
otitis externa esp by candida sp’s.
• In creams, ointments, suppositories, drops
 Azoles:
• most commonly : clotrimazole and
miconazole
• Effective agaist : Candida, Cyptococcus
neoformans, Aspergillus , etc
 Terbinafines : dermatologic infections

37.  Amphotericin B:
• Amphoteric polyene macrolide
• Wide spectrum against :
• Candida albicans ,Cryptococcus neoformans, Histoplasma
Blastomyces , Coccidioides, Aspergillus , mucormycosis.
• Often limited due to drug-induced renal impairment so ,
lipid formulations ( liposomal activated AMP-B) are used.
• Poorly absorbed from oral formulation, half life : 15 days
• IV: 0.6 mg/kg/day
 Flucytosine : oral or IV
• Systemic candidiasis or cryptococcal infections, often in
combination with amphotericin to prevent resistance.
 Systemic azoles:
• Mostly, Itraconazole and fluconazole
• oral or IV
• Active against aspergillus
• Major side effects : hepatotoxicity
37

38. Antivirals
 Acyclovir :
• Active against herpes virus and prescribed in patients with
ramsay hunt syndrome ( Herpes zoster oticus), Sudden
SNHL, etc
• Acts by inhibiting nucleic acid synthesis
• Oral dosage: 800mg five times a day for 5 days
• If treatment is commenced prior to 72 hours of onset of
rashes, it decreases the rash duration, symptoms and
incidence of post herpetic neuralgia
• Caution in : Pregnancy , breastfeeding, and renal
impairment ,
• Side effects: Nausea, vomiting, Gastointestinal
disturbances, rash , photosensitivity, hepatitis (rare), ARF,
Neurological reactions,etc
38

39.  Interferons :
• Chronic hepatitis B and C infection
• MOA: by inhibition of viral penetration, translation,
transcription, protein processing, maturation, and
release
 Neuraminidase inhibitors :
• Interfere with release of progeny influenza A and B
virus from infected host cells, thus halting the
spread of infection within the respiratory tract
 Zanamivir : used in the form of powder inhalation ,
administered directly to the respiratory tract via
inhalation.
 10 mg twice daily for 5 days for treatment
 10 mg once daily for prevention
39

40. Oseltamivir : safe and well tolerated than zanavir.
• Early administration is crucial as replication of influenza virus peaks at 24–72
hours after the onset of illness,
• 5-day course of therapy within 48 hours after the onset of illness (75 mg twice
daily)
Amantadine : inhibits RNA synthesis
• Effective against influenza-A
Ribavirin : Usually in HCV infection in combination with interferon alfa
• Aerosolized ribavirin : by nebulizer (20 mg/mL for 12–18 hours continuously per
day) to children and infants with severe RSV bronchiolitis or pneumonia
• Systemic absorption is low (<1%).
• Aerosolized form: conjunctival or bronchial irritation and the aerosolized
drug may precipitate on contact lenses.
• Ribavirin is teratogenic and embryotoxic
40

41. Corticosteroids
• The adrenal cortex secretes two types of corticosteroids
• glucocorticoids and mineralocorticoids
• adrenal androgens.
• The adrenal cortex has three zones, and each zone synthesizes a
different type of steroid hormone from cholesterol .
• Secretion by the two inner zones and, to a lesser extent, the outer
zone is controlled by pituitary adrenocorticotropic hormone
(ACTH; also called corticotropin), which is released in response
to hypothalamic corticotropin-releasing hormone (CRH).
• Glucocorticoids serve as feedback inhibitors of ACTH and CRH
secretion
41

42. Corticosteroid: Mechanism of action
• Corticosteroids differ in their metabolic (glucocorticoid) and electrolyte-regulating
(mineralocorticoid) activity.
• The corticosteroids bind to specific intracellular cytoplasmic receptors in target
tissues.
• Glucocorticoid receptors are widely distributed throughout the body, whereas
mineralocorticoid receptors are confined mainly to excretory organs, such as the
kidney, colon, salivary glands, and sweat glands.
• Both types of receptors are found in the brain.
• After dimerizing, the receptor–hormone complex recruits coactivator (or
corepressor) proteins and translocates into the nucleus, where it attaches to gene
promoter elements. There it acts as a transcription factor to turn genes on (when
complexed with coactivators) or off (when complexed with corepressors),
depending on the tissue
• Because of this mechanism, some effects of corticosteroids take hours to days to
occur.
42

43. 1. Promote normal intermediary metabolism:
• Glucocorticoids stimulate hepatic glucose production by enhancing
expression of enzymes involved in gluconeogenesis. They mobilize amino
acids and stimulate lipolysis, thereby providing the building blocks and
energy for glucose synthesis.
2. Increase resistance to stress
• By raising plasma glucose levels, glucocorticoids provide the body with
energy to combat stress caused by trauma, fright, infection, bleeding, or
debilitating disease.
3. Alter blood cell levels in plasma
• Glucocorticoids cause a decrease in eosinophils, basophils, monocytes, and
lymphocytes by redistributing them from the circulation to lymphoid tissue.
Glucocorticoids also increase hemoglobin, erythrocytes, platelets, and
polymorphonuclear leukocytes( neutrophils). 43

44. Anti-inflammatory and immunosuppressive actions: Most
important therapeutic properties of glucocorticoids, mechanism are:
• lowers circulating lymphocytes and inhibit the ability of
leukocytes and macrophages to respond to mitogens and
antigens.
• Decrease the production and release of proinflammatory
cytokines.
• Inhibit phospholipase A2, which blocks the release of
arachidonic acid.
• Lastly, they helps in stabilizing mast cell and basophil
membranes thus decreasing histamine release.
Treatment of allergies
• Beneficial in treatment of allergic rhinitis, as well as drug, serum,
and transfusion allergic reactions.
• Fluticasone and others are inhaled into the respiratory tract from
a metered dose dispenser. This minimizes systemic effects,
reducing or eliminating the use of oral corticosteroids.
44

45. Pharmacokinetics
Formulations (Oral, IV, IM, intraarticular , topical , inhalation or
intranasal)
• All topical and inhaled glucocorticoids are absorbed to some
extent and, therefore, have the potential to suppress the HPA
axis.
• After absorption greater than 90% bound to plasma proteins,
mostly globulin or albumin.
• Metabolized : In liver by microsomal oxidizing enzymes.
• The metabolites are conjugated to glucuronic acid or sulfate and
excreted by the kidney.
• Prednisone is preferred in pregnancy because it minimizes
steroid effects on the fetus. It is a prodrug that is not converted
to the active compound, prednisolone in the fetal liver.
45

46. Dosage
Factors that should be considered in determining the dosage of corticosteroids
include glucocorticoid versus mineralocorticoid activity, duration of action, type of
preparation, and time of day when the drug is administered.
• When large doses of corticosteroids are required for more than 2 weeks,
suppression of the HPA axis occurs.
• Alternate-day administration of corticosteroids may prevent this adverse
effect by allowing the HPA axis to recover/function on days the hormone is
not taken
Discontinuation
• Sudden discontinuation of these drugs can cause serious consequences if the
patient has suppression of the HPA axis.
• In this case, abrupt removal of corticosteroids causes acute adrenal insufficiency
that can be fatal. So dose must be tapered slowly according to individual
tolerance with adequate monitoring. 46

47. 47
4 mg methylprednisolone = 5mg prednisolone=0.75mg beta and dexamethasone = 20mg
hydrocortisone

48. Adverse effects
Often dose related effects:
• Osteoporosis : Most common adverse effect due to the ability of glucocorticoids to
suppress intestinal Ca2+ absorption, inhibit bone formation, and decrease sex hormone
synthesis.
• Patients are advised to take calcium and vitamin D supplements
• Classic Cushing syndrome ( redistribution of body fat, puffy face, hirsutism, and
increased appetite)
• Cataracts: In long-term corticosteroid therapy.
• Hyperglycemia : Diabetes mellitus.
• Diabetic patients should monitor blood glucose and adjust medications accordingly if taking
corticosteroids.
• Topical therapy : skin atrophy, ecchymosis, and purple striae.
48

49. Other side effects
49

50. Intranasal corticosteroids
Aqueous based sprays
• 50% deposited in nostrils and non-ciliated anterior part of nose.
• 50% will reach the ciliated mucus membrane
• Either absorbed or removed by mucociliary clearence within 30 min.
Highly lipophilic molecules : Large tissue distribution, long
elimination time
Fluticasone furoate :Each spray 27.5mcg , OD dosing
• In > 12 years of age : 110mcg /day ( 2 sprays in each )
• In children (2 to 11 Years of Age ) : 55mcg /day ( 1 spray in each )
Mometasone furoate : Each spray 50mcg , OD dosing
• In > 12 years of age : 200mcg /day ( 2sprays in each)
• Once symptoms controlled , maintainence at 100 mcg/day ( 1sprays in each) ,
if not increased upto 400 mcg/day ( 4 sprays in each nostrils)
• In children (2 to 11 Years of Age ): 100mcg/day ( 1 spray in each)
50

51. Less lipophilic molecules: Less distribution locally, quickly
absorbed into circulation, shorter elimination time
Beclomethasone : Each spray : 50mcg, OD dosing
• Adults and Children (6 years and older): 400mcg/day
( 2 sprays each nostrils)
• Less than 6 years : safety not established
Budesonide : Each spray delivers : 100mcg, OD dosing
• Adults and Children (6 years and older) : Initially, 2 sprays
(400mcg) in each nostril then,
For maintenance : one spray (200mcg) in each nostril.
• Polyps : One spray in each nostril, morning and evening, for
up to 3 months, BD dosing
(Not recommended below 6 years of age)
51

52. 52
Side effects:
• If used in recommended dosage (once /day in morning) – minimal side
effects
• In long term therapy : Crusting , dryness of nose, epistaxis (rare)
• If epistaxis : stop temporarily
• If dryness , crusting and blood stained crusts: once daily dosing and apply local neutral
lotion

53. Methods of administering topical nasal
preparations:
• Head down position : best for steroid drops
• Nasal sprays :
1. Blow the nose to cleanse the nostrils
2. Shake the bottle gently
3. Head down position
4. Close 1 nostrils with fingers, insert nozzle upto ½ inch
5. Spray to lateral wall : during spray no inhalation or
gentle breathing
6. Repeat 3-6 steps in other nose
• If 2 sprays are to be administered to each nostrils , one
should spray directing upwards and other to backwards
whilst the patient doesn’t breath.
53

54. Antihistaminics
• Belong to a group of endogenous compounds called
autacoids.
• Being formed by the tissues on which they act and,
therefore, function as local hormones
• Histamine, chemical messenger mostly generated in
mast cells, via multiple receptor systems, mediates a
wide range of cellular responses-
• Allergic and inflammatory reactions, gastric acid secretion,
and neurotransmission in parts of the brain.
54
High
concerntrations
Low
concerntrations
Mast cells and
basophils
Lungs , skin ,
blood vessels and
GIT

55. • The stimuli for release of histamine from tissues may
include destruction of cells as a result of cold, toxins
from organisms, venoms from insects and spiders, and
trauma.
• Allergies and anaphylaxis can also trigger significant
release of histamine
• Histamine released exerts its effects by binding to
various types of histamine receptors
• H1, H2, H3, and H4.
• H1 and H2 receptors are widely expressed and are
the targets of clinically useful drugs.
• Histamine has a wide range of pharmacologic
effects that are mediated by both H1 and H2
receptors.
55

56. Highly sedatives
Diphenhydramine Oral, 25-50mg
Dimenhydrinate Oral , 25-50mg
Promethazine Oral ( 25-50mg)
I.m(1mg/kg)
Hydroxyzine 25-50mg oral, I.m
56
Moderately sedative
Pheniramine Oral, 25-50mg
Cinnarizine
Meclizine 25-50mg , oral
Cyproheptadine 4mg , oral
Mild sedatives
chlorphenaramine Oral, 25-50mg
Dexchlorphenaramine 2mg, oral
Clemastine 1-2mg ,oral
Second generation
anthihistaminics
fexofenadine Oral,120-180 mg
loratidine Oral,10mg
Desloratidine 5mg, oral
Cetrizine 10mg, oral
levocetrizine 5-10mg, oral
Azelastine 4mg,oral
0.28 mg intranasal (topical)
Ebastine
Mizolastine
Rupatadine
10mg ,oral
First generation antihistaminics
Terfenadine and astemizole are the earliest second
generation H1 antihistamines that are now banned

57. Pharmacokinetics
• H1-receptor blockers are well absorbed after oral administration, with
maximum serum levels occurring at 1 to 2 hours.
• Plasma half-life : 4 to 6 hours
• Widely distributed in all tissues, including the CNS.
• All first-generation H1 antihistamines and some second-generation H1
antihistamines (desloratadine and loratadine) are metabolized by the hepatic
cytochrome P450 system.
• Levocetirizine is the active enantiomer of cetirizine.
• Cetirizine and levocetirizine are excreted largely unchanged in urine, and
fexofenadine is excreted largely unchanged in feces.
• After a single oral dose, the onset of action occurs within 1 to 3 hours.
• Azelastine, Olopatadine, Ketotifen, Emedastine are available in ophthalmic
formulations that allow for more targeted tissue delivery
• Azelastine and olopatadine have intranasal formulations, as well.
57

58. Adverse effects
• Sedation
• First-generation H1 antihistamines (chlorpheniramine ,
diphenhydramine, hydroxyzine and promethazine) binds
to central H1 receptors and block the neurotransmitter
effect of histamine in the CNS causing sedation
• Diphenhydramine : paradoxical hyperactivity in young
children.
• Other central actions include fatigue, dizziness, lack of
coordination, and tremors ( more in elderly )
• First-generation antihistamines exert anticholinergic
effects, leading to dryness in the nasal passage and oral
cavity. They also may cause blurred vision and retention
of urine.
• The most common adverse reaction associated with
second-generation antihistamines is headache.
58

59. • Sedation is less common with the second-generation
drugs, since they do not readily enter the CNS, as they
are specific for peripheral H1 receptors
• Among the second-generation agents, desloratadine ,
fexofenadine, and loratadine show the least sedation .
Cetirizine and levocetirizine are partially sedating
second generation agents.
59

60. Other effects
60

61. Sodium cromoglycate
• Act by inhibiting mast cell degranulation
• Available in 2% - 4% aqueous nasal spray
• Also combined with xylometozoline and prophylactically used
in allergic rhinitis
• 4-6times/day depending upon formulations
• Side effects: local irritation (neuronal irritants),
bronchospasms ( transient)
• Can also be used in children but due to frequent dosing : less
compliances
61

62. Decongestants
• Alpha adrenergic agonists causing vasoconstrictions.
• 2 receptors
• First in capacitance vessels in nasal mucosa and another in arterioles that supply the mucosa.
• Rationale: to improve sinus ventilation and drainage
• Radiographically : markedly reduces the size of inferior turbinate and middle
turbinate and improves osteomeatal complex patency .
• Topical : More potent (oxymetazoline and zylometazoline), ephedrine(0.5-1%,
weakest), avoid using more than 10 days.
• Anti-inflammatory action by inhibiting nitric oxide synthetase
• Systemic
• Phenylephrine, pseudoephedrine
• Can be combined with corticosteroids in allergic rhinitis
• C/I : MAOI’s
• Caution : HTN, hyperthyroidism, DM ,closed angle glaucoma, infants < 3 months
62

63. Moffat’s solution
• Provides local anesthesia and vasoconstriction ; used in
nasal preparation for nasal surgery.
• 2ml of 5% cocaine, 1 ml of 1:1000 adrenaline, small
amount of bicarbonate solution
• Preparation of nose immediately after the induction of
anesthesia
• In order to avoid systemic effects , the maximum dose
recommended for application to the nasal mucosa in fit
adults is 1.5mg/kg
• Coloring the cocaine solutions with pink dyes reduces the
risk of being mistaken for other drugs in anesthetic room
63

64. Atrophic rhinitis
• Characterized by dry crusting mucosa, nasal obstruction and a foul smell
• Steam inhalation and humidification : useful
• 25% glucose in glycerine solution: restoration of moisture to nasal mucosa
Preparation:
• 75g glycerine + 25g glucose and mixture stirred until glucose dissolved
• After bottling : lifespan of solution is 3 months
64

65. Hereditiary familial telangiectasia
• Epistaxis a/w HFT is difficult to treat
• Systemic and topical oestrogen : Squamous metaplasia of epithelium and hence
provide protective coat over blood vessels
• Ethinyloestradiol under supervision for HFT in women
• Side effects;
• Nausea , fluid retention, thrombosis
• Gynaecomastia : so not popular in males
65

66. Anticough medicines
66
Groups
Demulcents Lozenges, cough drops, linctuses containing syrup,
glycerine
Expectorants (Mucokinetics) (a) Bronchial secretion enhancers: Sodium or
Potassium citrate/ iodide, Guaiphenesin (Glyceryl
guaiacolate), balsum of Tolu, Vasaka, Ammonium
chloride.
(b) Mucolytics : Bromhexine, Ambroxol, Acetyl
cysteine, Carbocisteine
Antitussives
(a) Opioids:
(b) Nonopioids:
(c) Antihistamines:.
(d) Peripherally acting:
• Codeine, Ethylmorphine, Pholcodeine.
• Noscapine, Dextromethorphan,
• Chlorpheniramine, Diphenhydramine, Promethazine
• Prenoxdiazine.
4. Adjuvant antitussives Bronchodilators: Salbutamol, Terbutalin.

67. • Demulcents:
• sooth the throat and reduce afferent impulses from the inflamed/irritated pharyngeal mucosa -
thus provide symptomatic relief in dry cough arising from throat.
• Expectorants (Mucokinetics)
 Bronchial secretion enhancers : are drugs that increase bronchial secretion or
reduce its viscosity, facilitating its removal by coughing.
• Guaiphenesin, vasaka, tolu balsum : plant products which are supposed to
enhance bronchial secretion .
• Ammonium salts are nauseating—reflexly increase respiratory secretions.
• The US-FDA has stopped marketing of all expectorants, except guaiphenesin.
 Mucolytics :
• Bromhexine : It depolymerises mucopolysaccharides directly as well as by
liberating lysosomal enzymes—network of fibres in tenacious sputum is broken.
• Acetylcysteine: It opens disulfide bonds in mucoproteins present in sputum—
makes it less viscid
67

68. Antitussives :
• These are drugs that act in CNS to raise the threshold of cough centre or act
peripherally in the respiratory tract to reduce tussal impulses.
• Only for dry non-productive cough or if cough is unduly tiring, disturbs sleep or
is hazardous(hernia, organ prolapse)
 H1 antihistaminics:
• Many antihistamines have been conventionally added to antitussive/expectorant
formulations, specially promoted for cough in respiratory allergic states
• They afford relief in cough due to their sedative and anticholinergic actions, but
lack selectivity for the cough centre and has no expectorant property
Commonly used agents:
• Chlorpheniramine : 2–5 mg
• Diphenhydramine :15–25 mg and
• Promethazine (phenargan): 15–25 mg
68

69. Throat lozenges and pastilles
• Both used to deliver medicaments for local effects, either to sooth
or treat infections
 Lozenges: consists of medicaments (for example: antiseptics
like amylmetacresol ,dichlorobenzyl alcohol) in flavoured base
with high compression to ensure slow disintegration in mouth.
• Colouring , flavouring and sweeting agents are incorporated
 Pastilles : medicaments in base containing glycerol or mixture
of acacia( derived from plants to soothe, relieve pain , promotes
wound healing) and sucrose, softer than lozenges
• Sodium benzoate and citric acid are used as preservatives and
antioxidant respectively
• Flavouring with lemon oil may be incorporated .
69

70. Reflux oesophagitis and laryngopharyngeal reflux
• Initial treatment: change in lifestyles( avoid excess alcohol, fatty
foods, wt reduction,stop smoking, raising the head of bed)
 Antacids and alginates : for milder symptoms
 H2 receptor blockers : cimetidine, ranitidine, famotidine
• Blocks action of histamine in parietal cells , decreasing acid secretions
• Caution : in liver or renal disease , pregnancy and lactation
• Side effects :
• Diarrhea, altered liver function, rashes, more rarely (hypersensitivity, AV
block, and blood dyscrasias)
• Cimetidine : gynaecomastia , inhibit cytochrome p-450 reducing hepatic
metabolism of drugs sucha as warfarin
 Proton pump inhibitors:
• Reacts with sulfahydrl group in H+/K+ pump – decrease H=
secretion from parietal cells
• Omeprazole , pantoprazole , rabeprazole, lansoprazole, esomeprazole
70

71. Mouthwashes
• Usually aqueous solution in corncerntrated form of substances with deodorant ,
antiseptic , local anesthesia or astringent properties
 Hydrogen peroxide : Mechanical cleansing action : ( 6% solution) , 15ml is
diluted in half a tumblerful of warm water 2-3 times daily in acute ulcerative
gingivitis ,secondary tonsillectomy hemorrhages.
 Chlorhexidine: Antiseptics- in oral infections, also inhibits plaque formation
• Side effects : tooth discoloration
 Benzydymine: weak base ,locally-acting nonsteroidal anti-inflammatory drug
(NSAID) with local anaesthetic and analgesic properties.
 It is used topically for pain relief and anti-inflammatory treatment of the mouth, throat, apthous
ulcers,etc
71

72.  Povidone iodine : 1-2 % w/v, treatment of Acute Mucosal Infections of the
mouth and pharynx and should not be swallowed .
• Adults, elderly and children over 6 years of age: Use undiluted with an
equal volume of warm water. Gargle or rinse with up to 10mls for up to 30
seconds without swallowing. Repeat up to four times daily upto 14 days.
• Not to be used in children of 6 years and under
• C/I: hypersensivity to iodine , altered thyroid function tests
72

73. Ototopical agents
Acidifying agents ( preventive measures during scuba, swim season and chronic draining ears)
73
Name Indications Dosage Pregnancy/ lactation children
Alcohol- vinegar mix OE 4-5 drops/ 2-4
times/day *10 days
Safe Safe
Acetic acid in
aluminium acetate
Mild fungal/ bacterial
OE
5 drops/ 2-4 times/day
*10 days
unknown Safe
Propylene glycol and
acetic acid solution
Mild fungal/ bacterial
OE
2-4 drops/ 2-4
times/day *10 days
unknown Safe ( > 3 yr)
Hydrocortisone , 1%
propylene glycol,
acetic acid solution
Mild fungal/ bacterial
OE
2-4 drops/ 2-4
times/day *10 days
Cat C Safe ( > 3 yr)
C/I : TM perforations , tubes , hypersensitivity

74. Antibiotics:
74
Name Indications Dosage Pregnancy /
lactation
children
Ofloxacin ( 0.3% ) solution Bacterial OE, otorrhoea
following ear surgery, OM
with tubes
Adults : 10drops , BD * 7-10 days
Childrens( < 13yr : 5drops)
Cat : C ,
unknown
Safe
Ciprofloxacin + hydrocortisone
(0.2 /1%)
Bacterial OE 3 drops , BD * 7 days Cat : C , unkown Safe
Ciprofloxacin + dexamethasone
( 0.3 /1%)
Bacterial OE
OM with tubes
4 drops , BD * 7 days Cat : C , unkown Safe
Neomycin + polymyxin B+
hydrocortisone
Bacterial OE Adults : 4-5 drops , TDS/QID * max-10 days
Childrens ( < 13yr : 3 drops)
Cat : C , unkown Safe
Getamicin Bacterial OE 3-drops , TID* 7days Cat : C , unkown unknown
Tobramycin + dexamethasone Bacterial OE 3-drops , TID* 7days Cat : C , unkown unknown
C/I : TM perforations , tubes , hypersensitivity

75. • Antifungals
75
Name Indications Dosage Pregnancy/ lactation children
Cotrimazole ( 1%)
solution, cream
Fungal OE 3-4 drops, BD * 7days
• 1 application to ext.
canal
Cat : C / probably safe Safe
Miconazole ( 2% cream) Fungal OE 1 application to ext. canal Cat : C /probably safe Safe
Ketoconazole ( 2% cream) Fungal OE 1 application to ext. canal Cat : C / unnknown Safe
Nystatin ( 100,000 units/g
cream)
Fungal OE 1 application to ext. canal Cat : C / safe Safe
Ciclopiroz olamine ( 0.77 %
cream)
Fungal OE 1 application to ext. canal Cat : B / safe Safe , ( > 10 yrs)
Tolnaftate ( 1% cream ) Fungal OE 1 application to ext. canal Cat : C / unknown unknown
Antifungals :
C/I : TM perforations( only nystatin) , hypersensitivity

76. Ceruminolytics
Cerumen impaction is present in 10% of children, 5% of healthy
adults, 57% of older patients, and 36% of patients with
mental retardation
• Oil and aqueous based preparations
• he use of ceruminolytics before irrigation may increase the
success of irrigation by up to 97%.
• Water , sodium chloride 0.9%, sodium bicarbonate 5%, olive or
almond oil
• If impacted: BD dosing for few days prior to syringing
• Use of a ceruminolytic and a water-based agent agent 15 to
30 minutes before irrigation was found to be as effective as
several days of treatment.
• Water or saline based solution was found to be superior to
carbamide peroxide (a non–water-based /non–oil-based
preparation) prior to irrigation 76

77. 77

78. Management of vertigo
• Betahistine
• Dopamine agonists
• Antihistaminics
Betahistine : Antihistaminics with weak agonist ( H1) and strong
antagonist (H3)
• Commonly prescribed , esp when associated with meniere’ disease.
• Reduces endolymphatic pressure through improved microvascular
circulation in stria vascularis of cochlea and by inhibiting vestibular
nuclei
• Caution : patients with asthma ( by H3 effects), h/o PUD, pregnancy
and lactation
• C/I : Phaechromocytoma ( by H3 effect)
• Side effects : GI distress , headache, rashes and pruritus
• Dose : Initially 16 mg 3times /day , and maintanence dose of 24-48
mg/day thereafter.
78

79.  Dopamine agonists
Prochlorperazine - phenothiazines group
• Apart from D2 blocking actions, it also acts centrally by blocking the CTZ and vomiting center ( as it has afferents
from vestibular nuclei)
• Has less sedative effects, fewer antimuscarinic effects but pronounced EPS effects
• Available in : tablets, syrup, injection, suppository and buccal preparations
• Last two preparation are useful as prochlorperazine use cause vomiting and failure to absorb orally ingested form
• Dose : 5 mg three times a day to 30 mg daily.
Antihistamines
• main actions in vomiting centre > CTZ
Commonly used are:
• Cinnarzine : mainly acts via T type –calcium channel antagonism in vestibular type 2 hair cells, H1
antihistaminics, antiserotoninergic plus antidopaminergic effects, 25-75mg TID, half life : mean of 24 hours ,
C/I : hypotension , childrens, parkinsonism.
• Cyclizine : oral or parenterally in acute attack : 50 mg 3times a day
• Promethazine( phenargan) : because of highly sedation action.
79

80. Sodium floride in Otosclerosis
• Autosomal dominant , disease of otic capsule in which new vascular
spongy bone formation causing ankylosis or fixation of footplate of
stapes and progressive CHL and SNHL( if cochlear)
• Used since 35 years in attempt to slow down or arrest SNHL in patients
with stapedial otosclerosis or after stapedectomy, pure cochlear
otosclerosis
• Dose : 20mg PO twice a day for 2 years
• Mechanism of action : Enzyme inhibitors and inhibits osteoclastic
bone resorption
• Fluoride replaces hydroxyl group in bone forming Hydrooxyapatite
• Resistant to resorption
• Increase calcification of new bone
• Causes maturation of active foci
• Side effects: rare , dyspepsia : most common side effects
80

81. ……..Thankyou
81