MSOP 1002 Ear, Nose, Throat Pharmacology, University of Greenwich

Medway School of Pharmacy

Learning Objectives

• Understand basic pharmacological concepts (ADME, pharmacokinetics vs pharmacodynamics)
• Describe pharmacological management (types of drugs used, mechanism of action) of:
  Ear conditions:
  Nose conditions
  Throat conditions

Foundations of Pharmacology

Disclaimer: all medications mentioned in this lecture are for example purposes only. Refer to specific Pharmacy Practice lectures and BNF on the medicines and dosages that patients should use

What is Pharmacology?

Definition: the branch of medicine concerned with the uses, effects, and modes of action of drugs.

Drugs are classified by:

• Therapeutic
  use
• Chemical
  structure
• Mechanism
  of action

How the body affects the drug - Pharmacokinetics

ADME - Absorption, Distribution, Metabolism, Excretion

PK involves all of the kinetic processes from:
- the drug released from its dosage form (e.g., oral, intravenous, subcutaneous)
- to the delivery of drug to its site or tissue responsible for initiating the translation of
drug concentration/exposure into a response

Taken from: Luu, B. Q., & Kayingo, G. (2021). Advanced Pharmacology for Prescribers. Springer Publishing Company.

Absorption Methods

• Inhalation or
  nebulization
  . Breathed into the lungs
  through the mouth;
  absorbed by lungs
• Intramuscular
  · Inserted into muscle of
  upper arm, thigh, or
  buttock
• Intranasal
  · Breathed into nose;
  absorbed through thin
  mucous membrane that
  lines the nasal passages
• Intraocular
  · Applied to or inserted
  onto affected eye
• Intrathecal
  · Injected into the spinal
  canal
• Intravenous
  · Inserted into a vein
• Ocular
  · Placed in the eye
• Oral
  · Taken by mouth; absorbed
  by mouth, stomach, or
  small intestine
• Otic
  · Applied to affected ear
• Rectal
  · Inserted into rectum;
  absorbed through rectal
  wall
• Subcutaneous
  · Injected into fatty tissue
  just beneath the skin
• Sublingual or buccal
  . Placed under the tongue
  (sublingual) or between
  the gums and teeth
  (buccal);
• Transdermal
  · Delivered through a patch
  on the skin
• Vaginal
  · Inserted into vagina;
  absorbed through vaginal
  wall

Drug Absorption: Overview - Concept

Pharmacokinetics and
Pharmacodynamics
JoVe
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Factors Influencing Drug Absorption

· Factors Influencing Drug Absorption: Disease States and Pharmacology -
Concept
Pharmacokinetics and Pharmacodynamics
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Distribution

· What happens when the drug enters systemic circulation?
. How can the drug enter the cells?
Passive diffusions, presence of transport proteins, hemodynamics, and the
physicochemical properties of the drug influence the extent of distribution
of the drug.

Protein Binding

. Only unbound fraction of drugs can distribute into the tissue, undergo
metabolism and excretion, and exert its pharmacological and toxicological
effects.

Factors Influencing Drug Binding

• Drug
  · Physicochemical
  properties
  · Total drug
  concentration
• Plasma protein
  · Total
  concentration of
  available plasma
  protein
• Binding affinity
  · Binding affinity
  of a drug to a
  plasma protein
  is determined
  by both the
  physicochemical
  properties of
  the drug and
  protein
• Comorbid
  conditions
  · Diseases may
  alter plasma
  protein levels or
  binding affinity
• Drug interactions
  · Competitive
  binding by two
  drugs for same
  plasma protein
  · Alterations in
  binding affinity
  by one drug
  affecting
  another drug

Drug Metabolism

· Drug metabolism is the process by which the body
chemically modifies drugs to make them easier to
excrete.
· The goal of drug metabolism is to inactivate drugs
BUT some metabolites can still be pharmacologically
active.
· >75% of drugs are metabolised (primarily in the liver)
. Other metabolism sites - gastrointestinal wall,
kidneys, lungs, blood plasma
· The rate at which a patient metabolizes a drug can
impact the drug's efficacy and toxicity.

Drug Excretion

Excretion refers
to the irreversible
loss of an intact
drug.
Typically occurs
through the
kidneys.
Other routes:
bile, breast milk,
saliva, sweat,
stool, tears.

ADME summary:
Absorption (how it enters the body),
Distribution (how it travels through the bloodstream),
Metabolism (how the liver breaks it down), and
Excretion (how it's removed, often through urine).

Principles of Pharmacokinetics

Oral administration
Intravenous administration
Absorption
(intestine)
Bloodstream
Plasma
protein
Drug
Release
First-pass
effect
Metabolism
(liver)
Drug
Metabolites
Tissue
Distribution
Elimination
(gallbladder)
Elimination
(Kidney - urine)
Drug
Pharmacological
effect at site of action

Key Clinical Considerations

• Medications administered through depot delivery systems (intramuscular
  injections, pills, ointments, and sprays) are absorbed more slowly and require
  more time to achieve steady-state blood levels.
• Changes in a patient's physiological status (age, lean body mass,
  inflammation, fever, dehydration, malnutrition) may profoundly affect the
  pharmacokinetics and pharmacodynamics of a drug.
• Drugs that are highly protein-bound or fat soluble require a longer time to
  achieve steady state or to be eliminated from the body.
• Drug-drug interactions can significantly affect the bioavailability of an agent
  through changes in hepatic metabolism and renal excretion.

How the drug affects the body - Pharmacodynamics

Where PK ends, PD begins!
The therapeutic goal is to understand how
changes in dose alter the patient's response to
that dosing change.

Taken from: Luu, B. O., & Kayingo, G. (2021). Advanced Pharmacology for Prescribers. Springer Publishing Company.

Ear Pharmacology

Otitis Media & Externa

Common ear conditions
· Otitis Media - Inflammation/infection of the middle ear, common in children.
· Otitis Externa - Also called "swimmer's ear," inflammation of the external ear
canal.

Medications:
Antibiotics (for bacterial infections)
** Anti-inflammatory agents (for reducing
inflammation)
** Analgesics (for pain relief)

OTITIS MEDIA is typically caused
by an allergic reaction,
a viral infection or a bacterial infection

Antibiotics in Ear Pharmacology

Examples of Common Antibiotics for Ear Infections:
. Amoxicillin - A B-lactam antibiotic used for otitis media.
. Ciprofloxacin - A fluoroquinolone used for otitis externa (typically in ear drops).
. Neomycin - An aminoglycoside often used in combination with other agents for
otitis externa.

Mechanism of Action:
. Amoxicillin: Inhibits bacterial cell wall synthesis by binding to penicillin-binding
proteins, leading to bacterial lysis and death.
. Ciprofloxacin: Inhibits bacterial DNA gyrase and topoisomerase IV, preventing
DNA replication and transcription, leading to bacterial death.
. Neomycin: Binds to bacterial ribosomes and interferes with protein synthesis,
causing bacterial cell death.

Pharmacokinetics of Ear Antibiotics

• Absorption:
  · Oral amoxicillin
  rapidly absorbed in
  the GI tract
  · Ciprofloxacin can be
  given orally or
  topically in ear drops
  for otitis externa.
• Distribution:
  · Amoxicillin
  distributes well into
  most body tissues,
  including the middle
  ear where
  inflammation is
  present.
  · 17% is bound to
  blood proteins.
  What could this mean?
• Metabolism and
  Excretion:
  · Amoxicillin is
  primarily excreted
  unchanged in the
  urine.
  · Ciprofloxacin
  undergoes some
  hepatic metabolism
  but is mostly excreted
  in urine as well.

More information: Amoxicillin: Uses, Interactions, Mechanism of Action | DrugBank Online

Anti-inflammatory Agents in Ear Treatment

· Corticosteroids (e.g., hydrocortisone or dexamethasone) are often included in
ear drop formulations to reduce inflammation.
· Mechanism of Action:
· Corticosteroids act by suppressing the immune response and decreasing
inflammation by inhibiting the release of inflammatory mediators such as
prostaglandins and leukotrienes.
Result - Reduced capillary permeability, decreases vasodilation, and limits
inflammatory cell migration, which helps alleviate swelling and discomfort in ear
infections.

Anti-inflammatory Agent Pharmacokinetics

• Absorption:
  · When applied
  as ear drops,
  corticosteroids
  have minimal
  systemic
  absorption,
  reducing the
  risk of side
  effects.
• Distribution:
  . Act locally in
  the ear,
  decreasing
  inflammation
  directly at the
  site of infection.
• Metabolism:
  . Systemically
  absorbed
  corticosteroids
  are metabolised
  in the liver, but
  for ear
  treatments,
  local absorption
  is minimal.
• Excretion:
  . Any systemically
  absorbed
  corticosteroids
  are excreted via
  urine.