Drug Administration Routes and Formulations

Introduction to Pharmacology - Week 3: Pharmacokinetics

• Pharmacokinetics is the study of how the body handles a drug
• It involves the movement of drugs within the body
• Key processes include: absorption, distribution, metabolism, and excretion
• Understanding these processes is crucial for determining appropriate dosage, route of administration, and dosing frequency for effective drug treatment

Pharmaceutical Preparations

• Pharmaceutical preparations are different dosage forms designed to deliver a specific dose of a drug
• Drugs can be administered via local or systemic routes
• Local routes target a specific site for action, minimizing side effects (e.g., topical application)
• Systemic routes deliver the drug to the bloodstream for systemic effects throughout the body (e.g., enteral or parenteral administration)

Summary of Medicine Preparations

• Medications come in various forms (tablets, capsules, powders, liquids)
• Enteral administration involves the gastrointestinal tract
• Parenteral administration avoids the GI tract (e.g., IV, IM)

Stages of Drug Action

• The process of drug action has several stages
• First, the pharmaceutical stage involves the dissolution and preparation of the drug
• Then, pharmacokinetic processes determine how the body absorbs, distributes, metabolizes, and excretes the drug
• Finally, pharmacodynamic actions of the drug involve the drug's interaction with its target sites.

Routes of Administration

• The choice of route depends on patient factors, drug characteristics, type of use, etc.
• The presentation and delivery methods of the drug can significantly impact the effect

Factors Determining Route

• Key factors influencing the chosen route include:
• Drug characteristics (e.g., nature, stability)
• Patient condition (e.g., conscious/unconscious)
• Patient's age and other co-morbid diseases
• Patient/doctor preference

Local Administration - Topical

• Topical administration applies medication directly to the skin/mucous membrane for local action.
• A wide variety of preparations is available, including creams, gels, lotions, and patches
• Numerous application sites exist, including oral cavity, GI tract, rectum/anal canal, eye/ear/nose, bronchi, vagina, urethra.

Systemic Routes - Enteral vs Parenteral

• Enteral (GI tract) administration includes oral, sublingual, and rectal routes.
• Parenteral administration bypasses the GI tract and includes injection, inhalation and transdermal routes

Enteral Route - Oral

• Oral administration is common and accepted, using tablets, capsules, syrups, etc.
• Advantages:
  • Cheap, self-administered, convenient, relatively safe, and pain-free
• Disadvantages:
  • Slow onset, unsuitable for emergencies, unpalatable drugs, effects can be altered by stomach acid, unsuitable for unconscious patients, nausea or vomiting.

Hepatic First-Pass Effect

• Drugs administered orally first pass through the liver where they undergo metabolism
• This can lead to a decrease in bioavailability with some drugs
• It involves active transport from the gut to the liver in the portal vein and metabolism in the liver, which significantly reduce the drug's bioavailability

Oral Route - Enteric Coating of Tablets

• Enteric coatings prevent gastric irritation, protects the drug from gastric acid, and prolong the duration of action.
• Enteric-coated tablets deliver medication to the intestines to avoid stomach acid.
• These modified tablets are widely used in chronic conditions.

Enteral Route - Sublingual/Buccal

• Drugs are placed under the tongue or in the cheek for absorption
• Advantages: rapid onset, bypasses the first-pass metabolism
• Disadvantages: unsuitable for drugs that are irritating, lipid insoluble, patients who cannot swallow tablets.

Enteral Route - Rectal

• Solid or liquid forms can be administered rectally for local or systemic effects
• Advantages: local effect, suitable for unconscious or vomiting patients, bypass first-pass metabolism
• Disadvantages: potential irritation, susceptibility to first pass effect. Uncomfortable

Parenteral Routes

• Routes of administration that do not involve the GI tract
• Examples include injection (intradermal, subcutaneous, intramuscular, intravenous), inhalation, and transdermal
• Advantages: rapid onset, suitability for unconscious or vomiting patients, administration to specific areas of the body. Administration of irritant drugs and drugs that are destroyed by digestive juices.
• Disadvantages: requires sterile conditions, invasive techniques, potential for complications—tissue damage, pain, infection.

Parenteral Route - Inhalation

• Suitable for volatile liquids and gases, like general anaesthetics.
• Advantages: rapid onset, localized delivery to respiratory system
• Disadvantages: potential for local irritation, rapid termination of effect.

Parenteral Route - Transdermal

• Drug delivery system through a patch applied to the skin
• Advantages: Self-administered, good patient compliance, prolonged action, minimal side effects, constant plasma concentration
• Disadvantages: Expensive, potential for patch dislodgement, local irritation.

Parenteral Route - Injection Types

• Different types of injections target various areas
• Injection sites include intradermal, subcutaneous, intramuscular, intravenous, intra-arterial, intrathecal/epidural, intra-articular, intra-osseous

What Determines Type of Injection?

• Factors affecting injection type:
• Drug properties
• Desired speed of action
• Drug volume
• Patient factors (age, size, condition)
• Site of action
• Duration of effect, formulation requirements

Intradermal Route - Injections

• Injected into the dermal layer (skin)
• Examples: vaccinations, allergy testing

Subcutaneous Route – Injections

• Injected into the subcutaneous tissue
• Advantages: self-administered, suitable for depot medications, slow release
• Disadvantages: unsuitable for irritants

Intramuscular Route – Injections

• Injected into the muscle tissue
• Advantages: faster onset compared to other routes, suitable for vaccines and hormonal medications, gradual absorption.
• Disadvantages: requires sterile conditions, painful, potential for complications

Intravenous Route – Injections

• Injected directly into the bloodstream
• Advantages: rapid onset, large volume administration, maintained drug concentration.
• Disadvantages: higher risk of infection, potential for severe complications, the ability to administer drugs immediately.

Intra-arterial Route – Injections

• Injected directly into the artery
• Advantages: targeted delivery to specific areas
• Disadvantages: invasive procedure.

Intrathecal/Epidural Route – Injections

• Injected into the spine
• Advantages: bypasses the blood-brain barrier, can be effective in administering pain medications
• Disadvantages: invasive

Intra-articular Route – Injections

• Injected into the joint space
• Advantages: Local treatment

Intra-osseous Route – Injections

• Injected into the bone marrow
• Advantages: useful when intravenous access is difficult
• Disadvantages: can be challenging.

Pharmacokinetics

• Absorption
• Distribution
• Metabolism
• Excretion

Drug Absorption

• Movement of drugs across biological membranes
• Methods: passive diffusion, filtration, specialized transport
• Factors affecting absorption: physical state, particle size, disintegration time, dissolution time, lipid solubility, pH, ionisation (and also gastrointestinal motility, blood flow, and presence of food).

Drug Distribution

• Drug movement from the blood to the tissues
• Factors affecting distribution (include): - Lipid solubility, vascularity, ionisation, binding proteins (plasma and cellular)
• Uneven distribution due to variations in blood flow, binding to tissues, and regional pH. - Plasma protein binding, and significant clinical relevance.

Drug Metabolism (Biotransformation)

• Chemical alteration of drugs in the body
• Primary site is the liver
• Metabolites can be active or inactive, and some can be toxic.
• Various factors modify drug metabolism: age, diet, diseases, genetic factors or external factors

Phases of Drug Metabolism

• Drug metabolism occurs in two main phases:
  • Phase I – initial chemical transformation (oxidation, reduction, hydrolysis)
  • Phase II– conjugation with more polar molecules, enhancing excretion
• Multiple factors may affect drug metabolism
• The combination of both phases determines the final, active metabolite form in the body

Drug Excretion

• Removal of the drug from the body
• Major route: Kidneys
• Minor routes: lungs, bile, faeces, sweat, saliva, milk
• Clearance: rate of elimination divided by the concentration of the drug.

Drug Half-Life

• Time for plasma drug concentration to reduce by half
• Important for determining duration of drug action and dosing frequency
• Relationship between half-life and steady state concentration

Why is Half-Life Important?

• Useful for determining dosing intervals to maintain therapeutic levels
• Essential for maintaining a chronic disease treatment regimen

What Happens If You Miss a Dose?

• Drug concentration in the body decreases, potentially below the therapeutic range.
• Impact depends greatly on the drug's half-life
  • Short half-life will rapidly decrease drug levels (substantial drop below effective levels possible if a single dose is missed) to cause a return to symptoms
  • Long half-life will have a less rapid drop to steady state, but long enough that accumulation is crucial to avoid harmful levels

Decision to Double the Next Dose

• Doubling the next dose is dangerous for drugs with a narrow therapeutic index
• This could lead to toxicity
• This can be a particularly risky factor in drugs with a long half-life.

Why is Steady-State Concentration Important?

• When the rate of drug absorbed is equal to the rate of drug eliminated.
• This is crucial to maintain a constant therapeutic level.

Development of Steady State Concentration

• To achieve steady state, multiple doses of a drug are given at regular intervals.
• After several doses, roughly 97% of steady state is reached

Effects of Circumstances on Drug Therapy

• Changes in circumstances may influence drug response (e.g., decreased plasma proteins, liver disease)

Question - Factors Increasing Metabolism Rate

• Factors influencing drug metabolism rate
  • Exposure to chemicals (can induce microsomal enzymes)
  • Drug-drug interactions (can increase expression/activity of enzymes involved)
  • Decreased levels of plasma proteins (may increase rate of drug metabolism) .

Case Studies

•  Case studies on various drug-related situations (renal failure, pesticide exposure, diet impact on drug metabolism).
•  Case studies provide specific scenarios and highlight how pharmacokinetic factors affect drug efficacy, including the need for modification of drug treatment in various situations.

Explore drug administration routes and formulations, including enteric-coated tablets for rheumatoid arthritis and topical vs. systemic applications. Learn about factors influencing route selection and the effects of different administration methods on drug action.