Pharmacology: Key Concepts

Pharmacology Assessment

• Lab Portfolio is worth 40% of the total mark
• Examination at the end of Semester 2 is worth 60% of the total module mark

Intro to Pharmacology: Key Topics

• API, Methods, Techniques, and Considerations are key areas of focus
• Factors affecting a drug, like Physicochemical Properties, are important
• Principles of Pharmacokinetics are a topic to be covered
• ADME (Absorption, Distribution, Metabolism, Excretion) is a key concept
• Principles of Pharmacodynamics will be discussed
• Toxicology is included in the curriculum

What is Pharmacology?

• Pharmacology deals with drug names, manufacture, and testing
• Pharmacokinetics and pharmacodynamics are central to pharmacology
• It addresses side effects and uses of drugs
• Pharmacology is defined as a biomedical science
• Pharmacology involves research, discovery, and characterization of chemicals with biological effects
• Elucidation of mechanisms of actions and cellular responses is part of pharmacology

What is a Drug?

• A drug is any chemical substance that modifies a physiological or pathological state
• Drugs can be used for diagnosis, prevention, or treatment of disease

Drugs: Key Aspects

• A drug is a compound interacting with a biological target to produce a biological response
• The biological system can be human, bacteria, or fungi
• The biological response can be desired or undesired
• Molecules are used as medicine to diagnose, cure, or prevent disease
• Medicinal chemistry in drug discovery involves isolating compounds from natural sources or synthesizing new molecules
• Relationships between the chemical structure of compounds and their biological activities are evaluated

The Ideal Drug

• Nontoxic
• Effective and potent
• Selective
• Easily administered
• Cheap
• The 'ideal drug' does not exist in reality

Drug Pharmacology Principles

• Pharmacology principles are divided into pharmacokinetics and pharmacodynamics
• Pharmacokinetics studies what the body does to the drug
• Pharmacodynamics studies what the drug does to the body
• The body absorbs and then uses medicine

The Pharmacokinetic Process (ADME)

• ADME describes the journey of medication through the body.
• A is for Absorption.
• D is for Distribution
• M is for Metabolism
• E is for Excretion

Pharmacodynamics

• Pharmacodynamics is the study of the action of a drug on the body
• This includes receptor interactions, dose-response phenomena, mechanisms of therapeutic and toxic action.

Drug Nomenclature

• Generic names are unique official simple names for specific drugs
• Generic names are easy to remember and used in many circumstances
• Trade names are proprietary or brand names
• A trademark name is assigned by a single manufacturer and used only by that manufacturer
• "Hydrocortisone" is the generic name, while Cortaid, Synacort, Hydrocortone are trade names

Generic Drugs

• A generic drug is bioequivalent to an innovator drug regarding pharmacokinetic and pharmacodynamic properties.
• These drugs must contain the same active ingredient at the same strength as the brand.
• The drugs are bioequivalent and adhere to the same pharmacopeial standards.
• Generic drugs are identical in dose, strength, administration, safety, efficacy, and intended use

Pharmacopia

• A pharmacopia or formulary lists drugs with descriptions and formulas
• The British Pharmacopia (BP) publishes such information
• The United States Pharmacopia (USP) does the same
• The British National Formulary (BNF) is an authorized body that publishes a pharmacopia

Drug Effects

• Therapeutic or desired action is a primary effect
• Stimulating or inhibiting cell function or blocking biochemical effects in tissues, like antihistamine
• Physical or mechanical action, like a laxative

Unwanted effects on the body

• Mild side effects include dry mouth
• Dangerous effects can be life threatening, adverse, or toxic

Interactions

• A drug's effect can be modified by combining it with other drugs, food, or ingested substances
• This includes aspirin, antacids, and alcohol
• Synergism is when the combination increases the effects
• Synergism is life threatening
• Antagonism decreases the effects

Drug Administration: Dosage

• Dosage is the amount of drug to produce the specific desired effect in an adult
• Measured by weight or measure, plus a time factor (frequency per day)
• Administration of drugs involves different routes
• A loading dose is a large first dose to reach effective drug levels quickly.
• Maintaining effective blood levels is important

Drug Administration Factors

• Absorption
• Transport in the blood
• Half-life of the drug

Placebo

• A placebo is is something used in clinical trials
• Placebos are given to the control group
• Placebos lack the active ingredient (API)

Active Pharmaceutical Ingredient (API)

• Active Pharmaceutical Ingredient (API) is a substance used in a finished pharmaceutical product (FPP)
• APIs furnish pharmacological activity, have a direct effect in diagnosis, cure, mitigation, treatment, or prevention of disease
• APIs restore, correct, or modify physiological function to human beings
• APIs are active chemicals and may be toxic (steroids, cytotoxic)
• APIs may be highly pharmacological or sensitizing agents

The World of Drugs: API

• Begins with the Active Pharmaceutical Ingredient (API)
• APIs are chemicals shown through clinical studies to have desirable properties
• These are extracts from natural products or chemically/biologically synthesized
• The Safety and Efficacy (S&E) of APIs are established almost universally
• ICH guidelines are adopted into the laws and regulations of the ICH countries
• ICH countries (European Union, Japan and United States) conduct 100% of drug research
• ICH countries constitute over 85% of the world drug market

API Market

• The global Active Pharmaceutical Ingredient (API) market size was valued at USD 134.2 billion in 2015
• The global Active Pharmaceutical Ingredient (API) market size is estimated to reach USD 239.8 billion by 2025
• The global Active Pharmaceutical Ingredient (API) market size has compound annual growth rate (CAGR) of 6.0 %
• Market growth links to rising prevalence of chronic diseases, like cancer and cardiovascular diseases
• Increasing demand for efficient drugs and innovative manufacturing facilities drives growth
• Major pharmaceutical players are outsourcing API from China, India, and Brazil
• API outsourcing developing regions provides potential growth platform

Branding and Patents Process

• Pharmaceutical companies initially sell new drugs under a brand name.
• The drug is covered under patent protection
• Only the company with the patent can manufacture, market, and profit from it.
• The drug patent generally awarded for twenty years in the United States
• Patents vary between countries and drugs
• After the patent expires, other companies manufacture/sell the drug as a generic drug.
• Generic drugs must be identical to the branded drug in efficacy, safety, usage, route of administration, pharmacokinetics and pharmacodynamics

Branding and Patents Criteria

• A drug can be manufactured as a generic drug when the patent has expired
• A drug can be manufactured as a generic drug when there has never been any patents on it before
• A drug can be manufactured as a generic drug in countries where the drug has no patent protection
• Generic drugs on the market removes monopolies and encourages competition
• Generics provide significant drop in drug costs and ensures access to life-saving drugs.
• Initial patent holders may renew it by forming a new, significantly changed version of the drug
• The new version may need new clinical trials and re-application of the patent.
• The new compound may have to compete with the original generic molecule

Branding and Patents Effects

• Patent expirations are responsible for tremendous loss for pharmaceutical companies in terms of revenue.
• Patent expirations of blockbuster drugs give rise to generic versions
• R&D investments are no longer beneficial after a patent expires.
• A trend of outsourcing APIs is consistently increasing in the industry.

Synthesis Type Insights

• The market is categorized into biotech and synthetic drugs
• Synthetic APIs are produced with an organic chemistry base
• Biotech APIs are manufactured using molecular techniques such as monoclonal antibodies or recombinant proteins
• Biotech APIs are manufactured using molecular techniques such as vaccines
• The Synthetic segment held the largest market share in 2015
• Extensive R&D for biosimilar drugs, rising demand for protein-based therapeutics fuels a lucrative growth of biotech APIs

Application Insights

• Major applications of API are cardiovascular diseases, cancer, CNS & neurological disorders, and endocrinal disorders
• cardiovascular disease dominate in 2015 due to high prevalence and product availability
• Heart diseases are the leading cause of death in the U.S
• Oncology is projected to be a high number of products waiting for market approval

Regulatory Affairs

• Pharmaceutical products are regulated in essentially every country
• Regulations apply to the investigation and marketing of compounds

Regulatory Affairs Profession

• Regulatory Affairs is a specialized profession within the pharmaceutical/biotechnology sector.
• Regulatory Affairs oversees company compliance with regulations and laws pertaining to manufacturing, marketing and development.
• It interacts with worldwide, federal, state, and local regulatory agencies Regulatory Affairs assures:
• licensing
• registration
• development
• manufacturing
• marketing
• labeling

Regulatory Framework: Why Regulate?

• It takes 8 to 15 years min to develop a new drug/biologic product
• Costs up to $ 800 million.
• Attention to early development, successfully execution of significant clinical studies helps to reduce number of development failures
• Regulatory affairs provides insight/guidance into development through agency wisdom
• Compliance with Regulator expectations equates with developing successfully.
• Patient Protection is of greatest importance

Chemistry and Manufacturing

• Drug substance (API) is the material exerting the pharmacological action
• The drug substance, along with other ingredients is used to formulate the drug product
• A drug substance can be composed of :
  • the desired active material
  • product-related substances
  • product-or process related impurities
• Drug substances can contain other components, vehicles, or buffers
• These are for the Biologics and biotechnology industry

Drug Product

• The drug product is the dosage form or finished product
• It contains active pharmaceutical ingredients
• It contains active pharmaceutical ingredients with excipients

Roles of Excipients

• Excipients are to formulate APIs into products are generally food grade chemicals & Bulk Commodities.
• Excipients facilitate manufacture, enhance stability, control API release, assist in product identification, and enhance characteristics For Example:
• 325 mg Tylenol Excipients are cellulose, corn starch, magnesium stearate, sodium starch glycolate
• Excipients vary according to dosage form

Impurity Definition

• Impurity is any component present in the excipient, drug substance, or drug product that is not:
  • the desired product,
  • a product-related substance,
  • or excipient, (including buffer components)
• Impurities may either be process- or product-related
• Impurities may be the result of active principle degradation during holding/processing

Chemistry Manufacturing to control

• Analytical Method
• Degradation Products
• Specifications
• In-process controls
• Methods Validation
• Process Validation
• Container / Closure System
• Characterisation
• Stability