Pharmacology for Respiratory Care — Drug Action and Administration

Introduction to Respiratory Care Pharmacology

• Pharmacology: study of drugs, including their origin, properties, and interactions with living organisms.

• Respiratory Care: application of pharmacology to the treatment of cardiopulmonary disease and critical care.

Define Drugs

• Medicinal drugs are substances that treat, prevent, or diagnose disease.

• They can also be used to modify physiological functions.

Naming Drugs

• Chemical name: based on chemical structure.

• Code name: given by manufacturer, usually experimental.

• Generic name (non-proprietary): ready-to-market drug; loosely based on chemical structure.

• Official name: fully approved; usually adopts the generic name.

• Trade name (proprietary): by different manufacturers.

Sources of Drugs

• Animal sources

• Plant sources

• Mineral sources

• Elements and minerals (examples listed): Zn, P, Mn, Fe, Ca.

Approval process

• Chemical identification.

• Animal studies.

• Investigational New Drug (IND) Approval.

• Phases of human testing:

  • Phase 1: small number, healthy volunteers.

  • Phase 2: small number with disease.

  • Phase 3: large multicenter study.

• New Drug Application (NDA).

The Prescription

• Required elements: patient name, address, date.

• Rx: order to the pharmacist to prepare the drug; superscription.

• Inscription: name and quantity of drug.

• Subscription: prescription for the pharmacist.

• Sig (signa): instructions to the patient.

• Name of prescriber: doctor’s name.

The prescription (sample components)

• Superscription (recipe): patient and prescriber information.

• Inscription: medication name and quantity.

• Subscription: instructions for preparation by pharmacist.

• Sig (signa): directions for the patient.

• Prescriber information: name, address, contact.

• Note: actual sample text includes complex handwritten details; core concepts are the four elements above.

Other terms

• Over-the-counter (OTC) drugs: medicines purchasable without a prescription; also called nonprescription medicines.

• Generic substitutions.

• Orphan drugs: designated for < 200,000 patients or those not able to recover development costs.

Over-the-counter (OTC) drugs (summary)

• OTC (nonprescription) status allows purchase without a prescription.

• Role in therapy: often used for symptom relief and minor conditions.

Respiratory Drugs (categories)

• Adrenergic

• Anticholinergic

• Corticosteroids

• Antiasthmatic

• Anti-infective

• Surfactants

Principles of Drug Action (Pharmacokinetics)

• Absorption: routes of administration; factors affecting absorption.

• Distribution: plasma protein binding; tissue distribution.

• Metabolism: drug biotransformation; role of cytochrome P450 enzymes.

• Excretion: renal and biliary excretion.

Principles of Drug Action (Phases)

• Pharmacokinetic phase: from dose to effect via absorption, distribution, metabolism, elimination.

• Pharmacodynamic phase: drug + receptor leading to effect; includes receptor interactions and signaling.

• Dose-to-effect pathway components:

  • Drug administration → dose → dosage form → route of administration → course of drug action → PK phase → PD phase → EFFECT.

Drug Administration Phase

• Definition: how a drug dose is made available to the body.

• Drug dosage forms and excipients (gelatin, fillers, coatings, propellants, preservatives).

• Compatibility with route of administration.

Routes of Administration

• Enteral: via GI tract (capsules, tablets, suppositories, elixirs, suspensions).

• Parenteral: by injection (IV, IM, SC).

• Transdermal: skin application for systemic effect; long-term delivery.

• Inhalation: systemic or local effect; devices include SVN, MDI, DPI, USN, atomizer, vaporizer.

• Other routes: topical, sublingual, rectal, etc.

Most common routes for medication administration

• Oral (per os, PO)

• IV (intravenous)

• IM (intramuscular)

• SC (subcutaneous)

• Topical

• Inhalation

• Ointment

• Sublingual

• Rectal

• Otic

• Ophthalmic

IV cannulation

• Brief procedural concept referenced in the material.

Topical administration

• Applied directly to skin for local effect; minimizes systemic absorption.

• Example: topical excipients and formulations.

The Pharmacokinetic Phase (definition)

• Describes time course and disposition of a drug in the body based on absorption, distribution, metabolism, and elimination.

• Key processes: Absorption, Distribution, Metabolism, Elimination.

The Pharmacokinetic Phase (ADME overview)

• Absorption: how the drug gets into circulation.

• Distribution: how the drug travels to tissues.

• Metabolism: biotransformation to more water-soluble forms.

• Excretion: elimination from the body.

Absorption (detailed)

• Systemic absorption: passes through multiple layers to reach circulation.

• For inhaled drugs: airway surface liquid, epithelial cells, basement membrane, interstitium, capillary network.

Diffusion mechanisms

• Aqueous diffusion: occurs in aqueous compartments; usually via concentration gradients.

• Lipid diffusion: requires lipid-soluble drugs to diffuse through lipid membranes.

• Diffusion barriers include cellular membranes and transporters.

Ionization and pKa (drug ionization)

• Degree of ionization depends on whether the drug is a weak acid or weak base, the ambient pH, and its pKa.

• pKa: pH at which a drug is 50% ionized and 50% nonionized.

• For weak acids: protonation in acidic environments can increase nonionized, lipid-soluble form.

• For weak bases: protonation in acidic environments increases ionization, reducing lipid solubility.";

• Henderson–Hasselbalch relations (conceptual):

  • For acids: ext{pH} = ext{p}K_a + \log\left(\frac{[A^-]}{[HA]}\right)

  • For bases: ext{pH} = ext{p}K_a + \log\left(\frac{[BH^+]}{[B]}\right)

Carrier-mediated transport and pinocytosis

• Carrier-mediated transport: carriers resemble amino acids, sugars, or peptides; possible competition with endogenous substances.

• Pinocytosis: membrane engulfment and uptake.

Factors affecting absorption (summary)

• Route of administration (PO vs IV) and local factors.

• Blood flow to the site of absorption.

Distribution ( Compartments and volumes )

• Drug distribution requires reaching the site of action.

• Volume of distribution by compartment (typical example values):

  • Vascular (blood): V_{ ext{blood}} = 5\ \text{L}

  • Interstitial fluid: V_{ ext{interstitial}} = 10\ \text{L}

  • Intracellular fluid: V_{ ext{intracellular}} = 20\ \text{L}

  • Fat (adipose tissue): V_{ ext{fat}} = 14\text{–}25\ \text{L}

Metabolism

• Primary site: liver.

• Primary enzyme: cytochrome P450.

• Role: turns lipid-soluble drugs into water-soluble drugs to facilitate excretion.

• Other sites: intestinal wall, lung.

Enzyme induction and inhibition; First Pass effect

• Enzyme induction: chronic drug administration increases enzyme amount; leads to tolerance.

  • Example: nicotine induces enzymes that metabolize theophylline, increasing its clearance.

• First Pass effect: oral drugs undergo extensive hepatic metabolism before reaching systemic circulation; reduces bioavailability.

• Drugs with high first-pass effect are often given via injection, sublingual, transdermal, rectal, or inhalation routes.

Liver (anatomical note)

• Diagrammatic anatomy showing hepatic veins, portal vein, gallbladder, stomach, esophagus, pancreas, etc. (conceptual reference)

Elimination

• Primary site: kidney.

• Processes: elimination of drug metabolites and non-metabolized drug.

• Plasma clearance: Cl_p ext{ (L/h)}.

• Volume of plasma cleared of drug over time; role in maintaining drug concentration.

• Maintenance dose: ext{Dosing rate} = Clp imes C{ ext{plasma}}.

• Plasma half-life: (conceptual) time for concentration to decrease by half.

Pharmacokinetics of Inhaled Aerosol Drugs

• Local vs systemic effects.

• Inhaled drugs can act topically (local in lungs) or systemically (e.g., inhaled insulin).

• Aimed to maximize lung deposition and minimize systemic exposure.

• Distribution of inhaled aerosols:

  • Oral portion: approximately [0.70, 0.90] (70–90%)

  • Inhaled portion: approximately [0.10, 0.30] (10–30%)

• Lung availability relative to total availability: context-dependent.

Inhaled deposition and systemic availability (example data)

• Airway absorption for metered-dose inhaler (MDI): around 30\% absorbed in the airway; 70\% swallowed (oral portion).

• For dry powder inhaler (DPI): airway absorption around 13\%; oral portion around 87\%.

• Inhalation products yield both local lung effects and potential systemic absorption depending on formulation and deposition.

• Relative distribution: airway absorption vs systemic absorption can be quantified by lung-to-total absorption ratios (L/T).

• Example ratio calculations (illustrative): L/T ≈ \frac{30}{65} ≈ 0.46 for one system; L/T ≈ \frac{13}{57} ≈ 0.23 for another.

The Pharmacodynamic Phase

• Definition: describes mechanisms of drug action by which a drug causes its effect in the body.

• Drugs act by binding to and modulating the function of proteins, inducing physiological changes.

• Targets include: receptors, enzymes, ion channels, carrier molecules, and interactions with DNA (e.g., antivirals, chemotherapeutics).

Structure–Activity Relations

• Structural similarities between drug molecules and binding sites influence binding affinity and response.

• Example concept: some bronchodilators resemble endogenous neurotransmitters in structure.

Example structures and pharmacokinetics (illustrative)

• Isoproterenol vs Albuterol: structural comparisons show differences in pharmacokinetics and side effects.

• Isoproterenol (catecholamine analogue) vs Albuterol (sulfur-free derivative) show different peak effects and durations, illustrating structure–function relationships.

Nature and Types of Drug Receptors

• Receptors are proteins or polypeptides whose 3D shape and charge match the drug.

• Receptors may be on the cell surface or intracellular.

• Attachment initiates intracellular signaling cascades (transduction) that control cell function.

• Receptor signaling can involve transcriptional effects, enzyme activity changes, or ion channel modulation.

Mechanisms of Transmembrane Signaling (4)

• Lipid-soluble drugs cross the cell membrane to act on intracellular receptors (e.g., corticosteroids).

• Extracellular binding to a receptor that activates intracellular enzyme systems (e.g., insulin via a surface receptor).

• Surface receptor binding that regulates opening of ion channels (e.g., GABA receptors).

• Transmembrane receptor coupled to a G protein that modulates intracellular enzymes (e.g., adrenergic drugs).

Receptors Linked to G Proteins

• G protein–coupled receptors (GPCRs) mediate many airway responses: bronchodilation (via norepinephrine) and bronchoconstriction (via acetylcholine).

• Three components required for signaling:

  • Drug receptor

  • G protein

  • Effector system

• When drug binds receptor, these components interact to elicit a cellular response.

GPCR Signaling Pathway (example)

• Drug binds extracellular receptor.

• Receptor activates G protein on the inner cell membrane surface.

• G protein (composed of α, β, γ subunits) modulates an effector system.

• Effector can be:

  • An enzyme that catalyzes a second messenger (e.g., cyclic AMP).

  • An ion channel that alters ion flow (e.g., K^+ efflux).

• Example: B-adrenergic bronchodilator activates Gs → adenylyl cyclase → cyclic 3',5'-AMP (cAMP).

Example of G protein signaling for bronchodilation

• Example drug: Albuterol (B-adrenergic agonist) stimulates Gs protein, which activates adenylyl cyclase to increase cAMP.

• Result: relaxation of airway smooth muscle (bronchodilation).

Dose–Response Relationships

• Response is proportional to receptor occupancy up to a maximum.

• Potency: EC50 = concentration at which 50% of the maximal response is achieved.

• Dose that produces 50% of the maximal effect: ED50.

• Maximal effect: the plateau beyond which increasing dose does not increase response.

Therapeutic Index

• TI =
  LD{50} / ED{50}

• LD50: dose lethal for 50% of test population.

• ED50: dose effective for 50% of population.

• Interpretation: higher TI indicates a safer drug.

• Examples:

  • If LD50 = 5 mg and ED50 = 2.5 mg, TI = 5/2.5 = 2.

  • If LD50 = 50 mg and ED50 = 2.5 mg, TI = 50/2.5 = 20.

Agonists and Antagonists

• Agonists: bind to a receptor, have affinity, and elicit a cellular response (efficacy).

• Antagonists: bind to a receptor with affinity but have no efficacy; block or inhibit agonists from receptor.

Other definitions

• Synergism: combined effect greater than the sum of individual effects: (1 + 1 = 3).

• Additivity: simple sum of individual effects: (1 + 1 = 2).

• Potentiation: one drug increases the effect of another (1 + 0 = 2).

• Idiosyncratic effect: unusual or opposite reaction to a drug.

• Hypersensitivity: immune-mediated drug reaction.

• Tolerance: increased enzyme production reducing drug effect.

• Tachyphylaxis: rapid decrease in responsiveness to a drug.