ANTIHISTAMINES

DESCRIPTION Acts on receptors

Competes with histamine for histamine receptors
Pharmacologic antagonism

Histamine Receptor Agonist

H1 receptors H2 receptors H3 receptors H4 receptors
- Main concern of ENT drugs - Mediate gastric acid secretion - Presynaptic autoreceptors and - Eosinophils, neutrophils, CD4 T cells
- Mediate bronchial & gastrointestinal smooth muscle - Lack the action of H1 receptors heteroreceptors: brain,
contraction, venular and arteriolar vasodilatation, stimulation - Histamine release is associated with allergy myenteric plexus, other neurons
of sensory nerve endings VASODILATATION (as physiologic activity). Thats
- Classified before as Autacoids (stimulates to the non-vascular why our remedy is VASOCONSTRICTOR. Either it
smooth muscles and inhibits vascular smooth muscles) would be a drug that will compete with histamine
- When we say stimulate we mean contraction or constriction for the receptor or a drug that would act on
and when we say inhibit we mean relaxation or dilation another receptor yet have an opposite
- Associated with pain and itch physiologic effect.

Respiratory and GI: contracts bronchial and intestinal smooth Cardiac: Increases heart rate and contractility Neural autoreceptors which Mediates mast cell chemotaxis and WBC
muscle modulate histamine synthesis and
GI: increases gastric secretions release in CNS
Neurological: acts on sensory nerve endings to cause pain and
itching

MECHANISM OF Acts as a COMPETITIVE ANTAGONIST of histamine at receptors or NONSURMOUNTABLE MANNER

ACTION
Physiologic antagonists: especially epinephrine, have smooth muscle actions opposite to those of histamine, but they act at different receptors. This is important clinically because injection of epinephrine can be lifesaving in
systemic anaphylaxis and in other conditions in which massive release of histamineand other more important mediatorsoccurs.

Release inhibitors reduce the degranulation of mast cells that results from immunologic triggering by antigen-IgE interaction.
Histamine receptor antagonists represent a third approach to the reduction of histamine-mediated responses.

HISTAMINE RECEPTOR ANTAGONISTS

Classical H1- Antagonists
1st Generation
May cause either central nervous system
depression or stimulation
Prototype: Diphenhydramine (Benadryl)
Can cross the BBB (Blood Brain Barrier) cause
CNS depression cause sedation so tell patient
to refrain from driving or operating machinery
Compounds that competitively block histamine
or act as inverse agonists at H 1 receptors have
been used in the treatment of allergic
conditions for many years.
Newly Developed Non-Sedating H1 Blockers Certain H1-blockers suppress motion sickness
(Terfenadine & Astemizole)
Newer Non-sedating Antihistamines act in a Dimenhydrinate
nonsurmountable manner Diphenhydramine
Promethazine
Nonsurmountable manner when an agonist is Piperazine derivatives
administered it cant hardly bring back the effect. Although less effective in suppressing motion
sickness than anticholinergic drug
Surmountable there is a continuous competition between Scopolamine
the agonist and antagonist
o have a more permanent action or a longer duration of Scopolamine
action whereas a competitive antagonist continuously - An anticholinergic
competes with each other with the histamine receptor
meaning histamine can easily displace them
- superstar for anti-motion sickness
H3 and H4 Antagonist
Although no selective H 3 or H 4 ligands
are presently available for general
clinical use, there is great interest in
their therapeutic potential. H 3 -
selective ligands may be of value in
sleep disorders, narcolepsy, obesity,
and cognitive and psychiatric disorders.
Because of the homology between the
H 3 and H 4 receptors, many H 3
ligands also have affinity for the H 4
receptor. H 4 blockers have potential in

The H 1 antagonists are conveniently divided into:
first-generation and
second-generation agents
These groups are distinguished by the relatively
strong sedative effects of most of the first-
generation drugs. The first-generation agents are
also more likely to block autonomic receptors.
Second-generation H 1 blockers are less sedating,
owing in part to their less complete distribution
into the central nervous system.
- 1st cousin of Atropine chronic inflammatory conditions such
o In the case of newer non-sedating antihistaminics, they - act by competing with acetylcholine for as asthma, in which eosinophils and
(histamine) cannot easily displace your drug from the the cholinergic receptor mast cells play a prominent role.
receptor because usually their site of action in the
receptor is different and the combination of your drug
- Most effective drug against motion
sickness
with the receptor is more permanent. The bonding of
your drug with the receptor is a more permanent
manner. Thats why your histamine or agonist cannot
easily displace the drug from the receptor. That is why
non surmountable.
o Unable to cross the blood brain barrier so they are non-
sedating

CLINICAL USES A. H1 Antagonists

Allergic reactions
o Drug of choice for urticaria
o Second line drugs in allergic rhinitis (hay fever)
Motion sickness and vestibular disturbances
o Diphenhydramine and Promethazine for motion sickness
o Piperazines (Cyclizine & Meclizine)

B. H3 and H4 Antagonists
None presently available for clinical use
Potential of H3 in sleep disorders, narcolepsy, obesity, cognitive and psych disorder
H4 may be useful in pruritus, asthma, allergic rhinitis and pain conditions
ADVERSE EFFECTS Anticholinergic effects
o Classical antihistaminics have anticholinergic effects
o Xerostomia
- Drying of the mouth and perspiration
o Micturition difficulty
- Because anticholinergics will close the sphincter or stimulates the sphincter to close, thus there will be urinary retention as well
o Impotence
- Because of the drying effect, used to treat Allergic Rhinitis

TERFENADINE & ASTEMIZOLE OVERDOSAGE

o Newer antihistaminics
o QT interval prolongation
o Torsades de pointes (polymorphic ventricular tachycardia)
o An uncommon and distinctive form of polymorphic ventricular tachycardia (VT) characterized by a gradual change in the amplitude and twisting of the QRS complexes around the isoelectric line. Torsade de
pointes, often referred to as torsade, is associated with a prolonged QT interval, which may be congenital or acquired (Group IA Antidysrhythmic drugs, erythromycin). Torsade usually terminates
spontaneously but frequently recurs and may degenerate into ventricular fibrillation
o Newer non-sedating antihistamines - has adverse effect on the heart
 ANTICHOLINERGICS
Description Peripheral and Central Effects Drugs Adverse Effects
Most effective drugs for the prevention & treatment Parasympatholytic, smooth muscle inhibition, A. Atropine Xerostomia, Tachycardia, Drowsiness, Headache, GI,
of motion sickness depression of cerebral and medullary centers prototype of anticholinergic drugs Upset, Nightmares, etc.
Acts by competitive antagonism of acetylcholine at Experimental evidence suggests that comes from the plant Atropa Belladona Similar to flight or fight/ adrenergic effects
muscarinic receptor sites vestibular receptors are cholinergic with Atropa from the Greek God Atropus
cortical action contributing to the effect on because of toxic effects
vestibular function Bella Donna beautiful woman because
it is used before to dilate the pupils to
make woman beautiful
REMEMBER: PUPIL DILATATION

B. Scopolamine
Most effective drug for motion sickness
with fewer side effects
Scopolamine has more CNS effects than
Atropine.

C. Glycopyrrolate

PHENOTIAZINE
Description Mechanism of Action Drugs
Antipsychotic agent Most older typical antipsychotic drugs, with the exception of A. Prochlorperazine (Compazine)
As far as ENT is concerned these drugs are used as antiemetic thioridazine, have a strong antiemetic effect. B. Promethazine (Phenergan)
drugs Both drugs are commonly used in the treatment of postoperative
This action is due to DOPAMINE-RECEPTOR BLOCKADE, both nausea and vomiting
centrally (in the chemoreceptor trigger zone of the medulla) and
peripherally (on receptors in the stomach). Some drugs, such as C. Meclizine (Bonamine)
prochlorperazine and benzquinamide, are promoted solely as Most popular
antiemetics. Used as antiemetic agents
Taken 30min before you board an airplane or a boat
Phenothiazines with shorter side chains have considerable
H 1 - receptor-blocking action and have been used for relief of
pruritus or, in the case of promethazine, as preoperative sedatives.

Decongest the nasal mucosa
Always check the BP since it can trigger HPN.
DRUGS
Epinephrine Ephedrine
Sympathomimetic Non-catecholamine
sympathomimetic, oral & topical
onset within minutes of topical application or preparations available
subcutaneous injection, may be irritating to nasal
mucosa, no oral preparation available Same pharmacologic effect with
Epinephrine
Not absorbed from the GIT. Given topically or
parenteral, which is usually subcutaneously Difference from epinephrine:
- absorbed from the GIT
If given systemically. Has short duration - can be given orally
- has longer duration
Used to counteract the effect of histamine
Used as maintenance
Drug of choice for anaphylactic shock where histamine
is the culprit Central stimulation may produce
insomnia, palpitation and
Nasal vasoconstrictor nervousness (side effects)
VASCONSTRICTORS
TOPICAL
Phenylopropanolamine
Administered orally and topically to relieve nasal A. Cocaine
congestion A prohibited drug
- It relieves congestion by vasoconstriction Potent vasoconstrictor
since this drug is an alpha agonist Administered by sniffing. It can cause nasal septum
Associated w/ hypertension & risk of stroke & perforation because of powerful vasoconstrictor
myocardial damage when taken in large doses effect.
- Important to ask history of hypertension B. Oxymetazoline
Constrict vessels in the nose to relieve nasal C. Ephedrine
stuffiness D. Phenylephrine alpha agonist
E. Propylhexedrine
F. Naphazoline
G. Tetrahydrozoline
H. Xylometazoline
PROBLEM: CAN CAUSE REBOUND NASAL CONGESTION

CORTICOSTEROIDS
DESCRIPTION MECHANISM OF ACTIONS ADVERSE EFFECTS
A few days of therapy in the absence of specific contraindications is Increase gluconeogenesis - Increase blood sugar Delay wound healing
without harmful effects Decrease the sensitivity of tissues to the action of insulin Retard osseous growth centers
- Thats why in asthma given only for few day Increase protein catabolism Inhibit fibroblast collagen formation & tissue nonvascularization
- Limit the number of days in giving steroids Cause diuresis of free water Cause immunosuppression
- Taper drugs when withdrawn - Even if we give these drugs topically still it will produce Increase histamine oxidase
systemic effects Cause anterior pituitary ACTH suppression
Given perioperatively in selected otolaryngological & oral surgical
procedures to limit edema & pain
- Since it has anti-inflammatory effects
If used for longer period, reduce dose gradually before we withdrawal them
to avoid adrenal crisis
 OTOTOXIC DRUGS
SALICYLATES Cause reversible hearing loss & tinnitus
Mechanism of action: UNCOUPLING OF OXIDATIVE PHOSPHORYLATION; 6-8 g/day to produce toxicity
Salicylism (ringing of the ears and deafness)
Ordinary dose: 300-600 mg/dose (325 mg old notes)

Aspirin in overdose may induce tinnitus and a flat pure tone hearing loss of up to 60 dB
This is usually reversible on withdrawing the drug
The vestibular apparatus is undisturbed and recent work has suggested a direct effect of salicylates on the outer hair cells of the cochlea.
Aspirin is cleared rapidly by the kidney so that treatment comprises adequate hydration and the use of an H2 antagonist e.g. cimetidine or a proton pump
inhibitor e.g. omeprazole to prevent upper GI complications
QUININE Reversible hearing loss & tinnitus
Cinchonism
o A condition resulting from excessive ingestion of cinchona bark or its alkaloid derivatives (quinine or quinidine). Cinchonism is characterized by hearing loss, headache, tinnitus, and signs of cerebral congestion

Formerly used in the treatment of malaria and still used today to control night leg cramps
quinine has cochleotoxic effects similar to aspirin except hearing loss may progress after withdrawing therapy and is more likely to be permanent.
In a minority, hypersensitivity occurs whereby cochleotoxicity develops at therapeutic plasma levels
As most of the drug is bound to plasma proteins, plasmaphoresis is an effective therapy in massive overdose.
CHEMOTHERAPEUTIC DRUGS CISPLATIN/CARBOPLATIN NITROGEN MUSTARDS MESONIDAZOLE OTHERS
May produce high frequency hearing loss with loss of the outer hair cells of Produces sensorineural hearing loss Used with adjuvant Polymyxin B
the basal cochlear turns through destruction of hair cells radiotherapy may o Combined with Neomycin given topically
Platinum coordination compound that inhibits DNA synthesis; cross-links Inhibits DNA & RNA synthesis, via produce sensorineural o They act on the cell membrane
and denatures strands of DNA; disrupts DNA function by covanlantly formation of carbonium ions; cross links hearing loss of cochlear Colistin
binding to DNA bases; can also produce DNA intrastrand cross-linking and DNA strands causing miscoding breakage origin Vancomycin
breakage and DNA replication failure o These drugs are not given systemically but they
The ototoxic effects is directed mainly against the hair cells are incorporated to minimize toxic effect
The hearing loss associated with cisplatin use is a typical COCHLEAR HIGH- Iodoform
TONE LOSS which maybe reversible to some degree Alkaloids
DIURETICS Also cause hearing loss
When you urinate excessively, you became deaf
High-ceiling loop diuretics are especially associated
The stronger the diuretic the more it can cause hearing loss
Loop diuretics can cause dose-related hearing loss that is usually reversible. It is most common in patients who have diminished renal function or who are also receiving other ototoxic agents such as aminoglycoside
antibiotics
Frusemide, bumetamide and ethacrynic acid in high doses may produce a reversible high tone sensorineural hearing loss.
Light microscopy shows the stria vascularis to be grossly oedematous but the organ of Corti remains essentially normal.
A permanent hearing loss is unusual but has been described in renal dialysis and transplant patients
Since 5% of this group become deaf purely as a result of their disease the contribution of the diuretic to the deafness is, in many cases, uncertain.
ETHACRYNIC ACID FUROSEMIDE

Causes destruction of the intermediate layer of the striavascularis & outer hair cells of the organ Widely used than ethacrynic acid
of corti, most severe in the basal turn. Hearing loss, tinnitus & vertigo Should be administered over several minutes to minimize hearing loss
Should not be used in pregnant women Drug-induced changes in the electrolyte composition of the endolympathic fluid
Should not be used with another ototoxic drug
Ethacrynic acid and furosemide are loop diuretics
AMINOGLYCOSIDES Not absorbed GIT. Given parenterally
3 adverse effects:
o Ototoxicity
o Nephrotoxicity
o Neuromuscular blockade

Mode of Action: Aminoglycosides are irreversible inhibitors of protein synthesis, but the precise mechanism for bactericidal activity is not known. Inside the cell, aminoglycosides bind to specific 30S-subunit ribosomal
proteins (S12 in the case of streptomycin)
STREPTOMYCIN DIHYDROSTREPTOMYCIN NEOMYCIN GENTAMICIN KANAMYCIN TOBRAMYCIN
Causes vertigo before the onset of tinnitus A variant of streptomycin; Repeated use in inflamed Most widely used because it Not as ototoxic as neomycin; Similar to kanamycin in
& hearing loss has more tendency to tissue can cause preferentially affects the 15 mg/k/d will cause mild to pharmacology
The most serious toxic effect with produce hearing loss irreversible hearing loss vestibular rather than the no hearing loss (good renal
streptomycin is disturbance of May cause severe & erratic Not encourage for auditory system function)
VESTIBULAR FUNCTIONVERTIGO AND hearing loss even as long as systemic use because of Given systematically If renal function is impaired it
LOSS OF BALANCE 2 months after toxicity Widely used for gram could lead to drug
The frequency and severity of this discontinuation We usually we do not negative infections accumulation and ototoxicity
disturbance are in proportion to the age of Will cause hearing loss administer parenterally Usually combined with Used systematically
the patient, the blood levels of the drug, Used in combination penicillin synergistic effect Can be combined with
and the duration of administration with topical agents (such Gentamicin: inhibit protein penicillin
Damage to the vestibular apparatus as dermatologic agents). synthesis (30S subunit)
Can be compensated if patient is able to Cleaning GIT-local effect Penicillin: inhibit cell wall
see synthesis
Better choice
TB drug: Dilemma posed between
Streptomycin and Dihydrostreptomycin
- Streptomycin may cause vertigo in
contrast with Dihydrostreptomycin that
can cause hearing loss more
- Streptomycin was chosen since the eyes
are able to assist or compensate with
coordination of balance and gait in
response to vertigo

HISTOLOGIC FINDINGS:
Adverse effects on Hearing
Minimal scattered loss of outer hair
cells in the upper basal turn of the
cochlea. Normal supporting cells
Severe damage to the sensory
epithelium of the cristae of all canals.
Severe hair cell loss and flattening of
the sensory epithelium of the cristae
and saccule
Stereocilia in the canal ampullae
swollen & twice their normal diameter
 NEUROLOGIC MEDICATIONS Diphenylhydantoin
(Dilantin or Phenytoin)
Stabilizes and prevents the spread of seizure activity
GINGIVAL HYPERPLASIA
o occurs in 25% of chronically treated patients
probably due to altered collagen metabolism
o Good oral hygiene to minimize
Class: Anticonvulsant agent
Promoted Na+ efflux or decreases Na+ influx from
membranes in motor cortex neurons; stabilizes neuronal
membrane; slows conduction velocity
Carisoprodol
Blocks interneuronal activity in the
descending reticular formation & spinal cord
(internuncial neuron)
Blocks transmission of impulse from pre to
post ganglionic neuron
Class: Centrally acting skeletal muscle
relaxant
Ergotamine Sumatripan
Selectively produces cerebral Selective 5HT1 serotoninergic agonist for migraine
vasoconstriction
The drug given after delivery of Selective 5-HT1B and 5-HT1D receptor agonist in cranial
placenta to contract the uterus arteries; elicits vasocontrictive and anti-inflammatory
From ergot which is a vasoconstrictor effects; associated with antidromic neuronal transmission
and relief of migraine headache
Stimulates alpha receptors to constrict
vessels with low vascular tone; vasodilates
hypertonic vessels; at higher doses compete
for alpha receptor to block it

ANTI-EMETICS
Used during surgery because of:
o Nausea and vomiting due to anesthetic drugs
o Nausea and vomiting in the chemotherapeutic treatment of head & neck cancer
o Input from Chemoreceptor Trigger Zone (CTZ) converges in emetic center (EC) vomiting
Dopamine Antagonist Phenothiazines and H1-Antihistamines Combination regimens Adjunctive Agents Selective 5HT3
(Metoclopramide) Butyrophenones (Diphenyhydramine)
Anti-emetic Antipsychotic Also effective anti-emetics Metoclopramide-Dopamine Antagonist Benzodiazepines are most effective in the
Acts by propelling the food from Act by inhibiting + Diphenhydramine-H1 Antagonist - Valium, hypnotic agent, prevention and treatment
the upper portion of the GIT dopaminergic receptors in Histamine H1-receptor antagonist Recommended together beccause they an adjunct for nausea of chemotherapy-induced
downwards the chemoreceptor trigger of effector cells in respiratory tract, have better effects and vomiting nausea and vomiting (CINV),
zone (CTZ) blood vessels, and GI smooth Corticosteroids especially that caused by
Increases upper GI motility but not muscle; Moderate to high Cannabinoids highly emetogenic drugs such
secretions; increases lower Antagonizes dopamine D2 anticholinergic and antiemetic - Relatives of marijuana as cisplatin
esophageal sphincter tone receptors in brain, depresses properties
release of hypothalamic and also indicated in the prevention
hypophyseal hormones; may and treatment of radiation-
also depress reticular activating induced nausea and vomiting
system (RINV), when needed,
and postoperative nausea and
vomiting (PONV)
 MISCELLANEOUS DRUGS
CROMOLYN SODIUM Prophylactic drug for Bronchial Asthma
Liquid nasal spray for allergic rhinitis
MOA: prevention of antigen-triggered release of autacoid substances
- Inhibits release of histamine from mast cells (mast cell degranulation)
- More effective when given before exposure to agent
Most effective before exposure to allergen
Onset may take 4 weeks
AE: Stinging, burning, irritation, sneezing

An alteration in the function of delayed chloride channels in the cell membrane, inhibiting cellular activation. This action on airway nerves is thought to be responsible for nedocromil's
inhibition of cough; on mast cells, for inhibition of the early response to antigen challenge; and on eosinophils, for inhibition of the inflammatory response to inhalation of allergens.
MUCOLYTICS Iodinated glycerol Gualafenesin Haluronidase
Increase output of secretions - clearance of sinus disease Alone or with phenylpropanolamine or Added to injectable local anesthetic to enhance
Reduces viscosity of secretions by pseudoephedrine dispersion & absorption. May facilitate form of
increasing amount of respiratory tract
Additional drugs are vasoconstrictors hematomas (side effect)
fluid and irritates gastric mucosa
Water - cheapest and best available mucolytic
NICOTINE Polyacrilex gum Nicotine Patches
Sugar-free chewing gum containing 2 mg of nicotine Transdermal: shorter-term delivery
Lower peak & slower onset Failure to prevent early morning craving (disadvantage)
Stimulates central autonomic ganglia producing rel. of catecholamines Typical course involves 12 weeks decrease dose at a cost of $350
Does not produce the same sensation of pleasure (disadvantage) SE: Cutaneous hypersensitivity
Used to wean patients who are addicted to smoking Binds to nicotine receptors; reduces withdrawal symptoms, including nicotine craving, associated with
smoking cessation
GERD TREATMENT Antacids Sucralfate Metoclopramide Omperazole
Mg (OH)2, Al(OH)3,CaCO3,NaHCO3 Complex sulfated sucrose &AlOH - Promote gastric emptying Proton Pump Inhibitor
Mg (OH)2&Al(OH)3 protective coating MOA: Enhance the contraction of Binds to H+/K+ - exchanging ATPase
- Favor local antacids MOA: to coat GIT mucosa GIT to propel the food from the (proton pump) in gastric parietal cells,
- Easily excreted in GIT UGIT to LGIT resulting in suppression of basal and
NaHCO3 Forms ulcer-adherant complex; protects ulcer stimulated acid secretion
- Systemic antacid from acid, pepsin, and bile salts, thus allowing it
- Can affect acid-base balance to heal
- Discouraged
- Metabolic Alkalosis
AE:
- Mg (OH)2 diarrhea
- Al(OH)3 constipation
- Mg (OH)2 + Al(OH)3 to offset each
adverse effect

The choice of antacid should favor the ones which

are non systemic or those with local effect
APHTHOUS STOMATITIS TREATMENT ZILACTIN ACYCLOVIR

Film-forming medicine Interferes w/ herpes virus DNA replication & reduce duration of acute infection
Providing pain relief & mucosal protection Interferes with DNA polymerase to inhibit DNA replication via chain termnation
Anti-inflammatory, antiviral,antifungal
TOPICAL ORAL ANTIBIOTIC MOUTH Not advisable to use mouth rinse because it destroy normal flora of the oral cavity
RINSE Decrease polymicrobial aerobic & anaerobic bacteria by 95%
Drugs:
- Clindamycin
- Sanguinaria
- Chlorhexidine
- Neomycin
- Erythromycin
- Vancomycin
Disadvantage:
- Some only kill Gram-positive bacteria. Gram-negative bacteria will dominate and may empower the gram negative and cause infection.
XEROSTOMIA TREATMENT Dryness of the mouth
- cause by anticholinergic effect
Treatment:
- Cholinergic agonists pilocarpine
- Frequent sips and ice chips
- Sugarless or xylitol-based candy or gum may help
- Commercial nonprescription saliva substitutes

HEMOSTATICS Amicar, EACA, Tranexamic acid Topical gelatin and collagen foam
Antifibrinolytic agents used in the perioperative treatment of patients with bleeding problems Are available adjuncts to hemostasis
Inhibits fibrinolysis through inhibition of plasminogen activator substances; exhibits antiplasmin Applied locally to the bleeding area
activity
AESTHETIC DRUGS Minoxidil Botulinum
2% topical for treatment of male-pattern baldness a toxin produces an irreversible blockade of cholinergic synapses at
Used to be an Antihypertensive neuromuscular junction denervating muscle
Side Effect: HAIR GROWTH/ Hirsutism Treatment of facial dystonias
Direct vasodilator; dilate arterioles with little effect on veins, decreases systemic resistance Block Acetylcholine to inhibit the muscle

Neurotoxin from Clostridium botulinum; prevents Ach release from presynaptic

membrane, causing temporary calming of muscle contractions by blocking the
transmission of nerve impulses