Pharmacology Fundamentals

Fundamentals of Pharmacology

• Pharmacology involves understanding the uses, effects, and modes of action of drugs
• A drug is a chemical administered to change body physiology for therapeutic reasons
• Principles of cell and molecular biology, biochemistry, and pharmacodynamics are crucial in pharmacology

What Constitutes a Drug

• Drugs are chemicals affecting bodily functions
• Drugs include therapeutic agents, nutrients, food additives, and pollutants
• A precise definition focuses on substances improving physiology beneficially

The Scope of Pharmacology

• Pharmacology integrates cell biology, biochemistry, physiology, pathophysiology, and medicine
• This broad scope helps understanding drug interactions with biological systems

Examples of Clinical Drugs

• Atropa Belladonna, a plant-sourced drug, is now chemically synthesized for clinical use
• Atropa Belladonna shows the shift from natural to synthetic drug development
• Saquinavir was developed via rational drug design, with knowledge of the target structure

Drug Nomenclature

• Drugs have three names: chemical, generic, and brand
• Chemical names are complex and not for common use
• Generic names are standardized (e.g., Fluoxetine)
• Brand names are proprietary (e.g., Prozac)
• Generic names are important due to regional brand name variations

Classification of Drugs

• Diazepam (Valium), a benzodiazepine, is a drug with classifications based on pharmacological effects, pharmacodynamics, chemistry, and therapeutics

Key Concepts: Pharmacodynamics and Pharmacokinetics

• Pharmacodynamics is what a drug does to the body at molecular, cellular, and tissue levels
• Pharmacokinetics is what the body does to a drug (ADME: absorption, distribution, metabolism, and excretion)
• ADME informs drug bioavailability and action duration

Selectivity and Specificity

• Selectivity is a drug's ability to produce a specific effect
• Selectivity is influenced by a drug's chemical properties, target receptors, administration route, dosage, and patient's individual differences such as age and genetics
• Specificity is a drug's ability to affect a specific function at its target site
• Insulin is highly specific as it acts on specific receptors
• Gaseous anesthetics are non-specific as they affect all cell membranes
• Risk-benefit analysis is essential because few drugs achieve total selectivity

Implications of Pharmacological Principles

• Understanding pharmacological principles helps clinicians choose appropriate therapies and balance efficacy and safety
• The complexity of drug action requires a systematic treatment approach to optimize patient outcomes and minimize adverse effects

Conclusion of Pharmacology

• Pharmacology introduces key terms such as therapeutics, toxicology, bioavailability, and selectivity
• Pharmacology requires skillful management to maximize benefits and reduce risks of intricate tools
• Pharmacology helps healthcare professionals improve patient care and outcomes

Introduction to Fundamentals of Pharmacology

• Focuses on drug classification and nomenclature
• Key concepts are Systematic (IUPAC) name, Generic name, Brand (trade) name, drug class, and clinical indication.
• This vital knowledge allows professionals in the medical and pharmaceutical fields to correlate of how drugs are identified, classified, used, enhances patient safety, and informs healthcare decisions

Drug Classification and Nomenclature

• Drug classification provides a structured approach to categorize medications based on chemical structure, mechanism of action, and therapeutic use
• Deciphering names and classifications helps healthcare professionals prescribe and administer drugs

Key Concepts in Drug Classification

• Systematic (IUPAC) name refers to the International Union of Pure and Applied Chemistry nomenclature for a unique name based on its chemical structure
• Generic name is the official, non-proprietary name of a drug, derived from the IUPAC name and used universally
• Brand (trade) name is the marketing name by a pharmaceutical company, that can vary by country
• Drug class is a categorization based on therapeutic effects or chemical structure
• Clinical indication refers to the specific medical conditions that a drug is approved to treat

Points in Pharmacology- Drug Nomenclature

• The chapter exemplifies various drugs by completing a classification table
• This enhances understanding of drug nomenclature
• 2-acetobenzoic acid (acetylsalicylic acid/Aspirin) is an analgesic and anti-inflammatory

Examples of Drug Classifications

• Fluoxetine's systematic name is 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulfonyl)phenyl]-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
• Fluoxetine is an SSRI (Selective Serotonin Reuptake Inhibitor)
• Fluoxetine treats depression exhibiting its therapeutic utility

Carvedilol Drug Classifications

• Carvedilol's systematic name: (50,6a)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol
• Carvedilol is a vasodilator
• Carvedilol treats high blood pressure and heart failure

Bronchodilator Classification

• Bronchodilators treat breathing troubles in conditions like asthma or COPD
• This shows the significance of therapeutic classification in pharmacology

Supporting Evidence and Arguments

• A comprehensive understanding of drug classifications and nomenclature underpins all areas of pharmacology
• Medical classification enhances the safety and efficacy of pharmacotherapy
• Misclassifications may lead to medical errors, so proper training is important

Real-World Examples

• Aspirin effectively alleviates pain and reduces inflammation
• Fluoxetine is an SSRI for depression-related treatments
• Carvedilol is a vasodilator for chronic health conditions

Summary: Drug Classification

• Understanding drug classification is foundational and aids in classifying drugs by their systematic, generic, and brand names, along with clinical indications
• Expertise and mastery of classifications is indispensable for healthcare professionals, and ensure safe practice and informed patient care

Key Takeaways

• Comprehensive pharmacological knowledge improves drug safety and efficacy
• Accurate drug classification aids in the correct application of pharmacotherapy
• Ongoing study of classifications and their implications will always remain crucial in medical education

Summary: Fundamentals of Pharmacology Introduction

• An understanding of the processes is important to ensure successful outcomes
• Involves the journey of a drug from its formulation to the therapeutic outcome
• Pharmacological aspects apply to both medical professionals and anyone interested in understanding drug action

Pharmaceutical Process

• Determines if the drug successfully reaches the patient after administration
• Propranolol is available in tablets (10 mg), oral solutions (5 mg/5 ml), and injections (1 mg/1 ml)

Key Concepts

• Bioavailability is the extent and rate at which the active ingredient is absorbed and available at the site of action
• Formulation and chemical properties influence propranolol's absorption in the gastrointestinal tract

Pharmacokinetic Process

• Asks the question "Is the drug getting to it's action"

Key Factors

• Propranolol's distribution involves extracellular fluids with approximately 90% bound by plasma protein
• Propranolol undergoes hepatic metabolism, with about 4% excreted unchanged in urine and 10 metabolized

Implications of Drug Binding

• Plasma protein binding affects bioavailability, elimination rate, and duration of action, which can modify therapeutic outcomes

Pharmacodynamic Process

• The primary question is "Is the drug producing the required pharmacological effect"

Mechanisms of Action

• Propranolol acts as an antagonist, targeting specific β1 and β2 adrenoceptors within the heart, kidneys, and central nervous system (CNS)
• Drug effects are intricately linked to plasma concentration

Therapeutic Process

• This phase determines if the pharmacological effect is resulting a therapeutic effect is present

Therapeutic Effects

• Propranolol reduces heart rate and blood pressure, decreasing the risk of cardiovascular events
• Potential Risks: Overdose can cause drowsiness, confusion, and heart failure from extreme reductions in blood pressure

Example: Propranolol

• It has is a well documented treatment of hypertension
• Highlights the complexities and critical factors for drug therapy
• Valuable insight is gives is use for more than learning about Propranolol

Conclusion of Pharmacology

• Illustrates the mechanisms, pharmaceutical formulation, distribution, effects, and efficacy
• Framework cultivates a more profound appreciation for the science of pharmacology and its role in modern medicine
• Includes the recognition of the relation between drug absorption, metabolism, action, tangible health, benefits, and risks
• Guides the safe and effective use of medications like propranolol

How Drugs Exert Their Effects

• Drugs act at four levels: molecular on molecules (e.g., receptors, enzymes), cellular changing cell activity, tissue affecting organ function, and systemic influencing, physiological systems

Site(s) of Action

• Operation occurs from cell to whole body

Examples

• Non specfic drugs such as gaseous anesthetics act on all cell membranes
• Specific drugs like insulin target specific receptiors

Classes of Drug Targets

• Targeted classes include Receptors, Ion Channels, G-Protein Coupled Receptors (GPCRs), Enzymes, and Transporters

Agonist (Activates Receptor)

• Binds to a receptor and triggers a biological response

This can happen in two ways with direct action

• Ion channel opening/closing allows or blocks ion movement
• Enzyme activation/inhibition starts or stops enzyme activity.

Transduction Mechanisms

• Transduction Mechanisms activate intracellular signal pathways
• This leads to Ion channel modulation for indirect ion flow influence
• Also DNA transcription which affects gene expression and protein production

Antagonist (Blocks Receptor)

• Binds to the receptor without activating it
• The prevents the natural molecules from binding

This is a result of no cellular response

• Agonists activate receptors to trigger a response
• Antagonists block receptors to prevent normal molecular function
• Transduction Mechanisms enable long-term effects like gene changes

Types of Receptors

• Type 1 are Ligand-Gated Ion Channels (Ionotropic Receptors)
• Type 2 id G-Protein Coupled Receptors (Metabotropic Receptors)

Ligand-Gated Ion Channels

• Fast-acting receptors open an ion channel when a ligand such as a neurotransmitter binds
• Allows ions to flow directly into cells
• Made of 4 or 5 subunits

The biding

• The binding domain is on the outside (extracellular)
• Once the ligand binds the channel opens instantly

Example

• Nicotinic Acetylcholine Receptor (nAChR) is activated by acetylcholine (Ach)
• GABA-A Receptor is activated by GABA allowing Cl entry

NMDA

• NMDA (Glutamate) Receptor controls Ca entry which is important for learning/memory.
• Easy way to remember
• "Iono" = Ions → Fast direct ion flow when activated

G-Protein Coupled Receptors (Metabotropic Receptors)

• Are slower-acting receptors without a direct ion channel
• Instead, they trigger a signaling cascade inside the cell via G-proteins
• Made of a single subunit that crosses the membrane 7 times

G-protein usage

• The binding domains are on the outside
• The G-protein coupling domain is on the inside (intracellular)
• When activated, signals are sent to second messengers like cAMP, IP3

Example Receptors

• Adrenergic Receptors respond to adrenaline/fight-or-flight
• Dopamine Receptors are important in mood and movement
• Muscarinic Acetylcholine Receptors are Found in the heart, smooth muscle, and brain
• Easy way to remember: "G-protein = Go Signal!"/Slower, but affects many cellular processes

Receptors Key Factors

• Protein pores in cell membranes regulate ion flow (K, Na, Ca, Cl)
• Ions can control resting membrane potential and cell excitability
• Can be open/closed allowing drug control

Example usage

• Nicotinic Acetylcholine Receptor (nAChR) Activated by Ach a neurotransmitter
• Is related to voltage-operated ion channels
• It can also be found in neuromuscular junctions

Example Drug

• Tubocurarine can act as an Antagonist at nAChR
• Competes with Ach to prevent muscle contraction
• Is used in surgery as a muscle relaxant

(GPCRs)

• They do not have ion pores so instead, they can still activate intracellular signaling pathways
• This system relaying it is used a G-protein
• There are 3 G-protein components called, G-protein components: a (alpha) subunit, ẞ (beta) subunit, and y (gamma) subunit

B-Adrenergic Receptors

• Located in heart, lungs, and nervous system
• Agonists like adrenaline/noradrenaline can increase heart rate and force
• B-blockers such as Propranolol blocks B-AR to reduce heart rate

Types of Receptors Linked to Cell Signaling

• Enzyme-linked receptors such as Insulin receptor and or Growth Factor receptors
• Nuclear receptors like Steroid receptors and or Thyroxine receptor
• (GPCRs) Andrenoceptors