Pharmacology: Basic Principles and ADME

• Pharmacology is the study of drugs and their effects on living organisms
• It encompasses how drugs are absorbed, distributed, metabolized, and excreted (ADME)
• Pharmacology also covers the mechanisms of drug action and their therapeutic and toxic effects

Basic Principles

• Pharmacokinetics describes what the body does to the drug (ADME)
• Pharmacodynamics describes what the drug does to the body

Pharmacokinetics: Absorption

• Absorption is the process by which a drug enters the bloodstream
• Routes of administration affect absorption
  • Intravenous (IV) administration bypasses absorption (100% bioavailability)
  • Oral administration involves absorption from the gastrointestinal tract
• Factors affecting oral absorption
  • Drug solubility
  • Gastric emptying rate
  • Intestinal motility
  • First-pass metabolism

Pharmacokinetics: Distribution

• Distribution is the process by which a drug reversibly leaves the bloodstream and enters the tissues
• Factors affecting distribution
  • Blood flow
  • Tissue permeability
  • Plasma protein binding
  • Tissue binding
• Volume of distribution (Vd) relates the amount of drug in the body to the plasma concentration
  • Vd = Amount of drug in the body / Plasma drug concentration

Pharmacokinetics: Metabolism

• Metabolism is the process by which a drug is chemically altered in the body, primarily in the liver
• Phase I reactions
  • Oxidation, reduction, hydrolysis
  • Often involve cytochrome P450 enzymes
• Phase II reactions
  • Conjugation (e.g., glucuronidation, sulfation)
  • Increases water solubility for excretion

Pharmacokinetics: Excretion

• Excretion is the process by which a drug is removed from the body
• Primary routes of excretion
  • Renal (kidneys)
  • Biliary (liver and gallbladder)
• Renal excretion involves
  • Glomerular filtration
  • Tubular secretion
  • Tubular reabsorption

Pharmacodynamics: Receptors

• Receptors are proteins that bind drugs and mediate their effects
• Types of receptors
  • Ligand-gated ion channels
  • G protein-coupled receptors (GPCRs)
  • Enzyme-linked receptors
  • Intracellular receptors
• Agonists activate receptors
• Antagonists block receptors

Pharmacodynamics: Dose-Response Relationship

• Dose-response curves illustrate the relationship between drug dose and effect
• Efficacy is the maximum effect a drug can produce
• Potency is the amount of drug needed to produce a given effect
• ED50 is the dose that produces 50% of the maximal effect
• LD50 is the dose that is lethal in 50% of the population
• Therapeutic index (TI) is a measure of drug safety
  • TI = LD50 / ED50

Adverse Drug Reactions

• Adverse drug reactions (ADRs) are unintended and undesirable effects of drugs
• Types of ADRs
  • Side effects (predictable, dose-dependent)
  • Allergic reactions (immune-mediated)
  • Idiosyncratic reactions (unpredictable, rare)
  • Toxic effects (excessive doses or prolonged use)
• Drug interactions can increase the risk of ADRs

Drug Interactions

• Drug interactions occur when one drug affects the action of another drug
• Mechanisms of drug interactions
  • Pharmacokinetic interactions (affecting ADME)
  • Pharmacodynamic interactions (affecting drug action at the receptor)
• Types of drug interactions
  • Additive effects (1 + 1 = 2)
  • Synergistic effects (1 + 1 > 2)
  • Antagonistic effects (1 + 1 < 2)

Autonomic Pharmacology

• The autonomic nervous system (ANS) regulates involuntary functions
• Divisions of the ANS
  • Sympathetic nervous system (SNS)
  • Parasympathetic nervous system (PNS)
• Neurotransmitters
  • Acetylcholine (ACh): primary neurotransmitter in the PNS
  • Norepinephrine (NE): primary neurotransmitter in the SNS
• Receptors
  • Cholinergic receptors (muscarinic and nicotinic)
  • Adrenergic receptors (alpha and beta)

Cardiovascular Pharmacology

• Antihypertensives lower blood pressure
  • Diuretics
  • ACE inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Beta-blockers
  • Calcium channel blockers
• Antianginal drugs relieve chest pain
  • Nitrates
  • Beta-blockers
  • Calcium channel blockers
• Antiarrhythmic drugs treat abnormal heart rhythms
  • Sodium channel blockers
  • Beta-blockers
  • Potassium channel blockers
  • Calcium channel blockers
• Drugs for heart failure
  • ACE inhibitors
  • Beta-blockers
  • Diuretics
  • Digoxin

Central Nervous System Pharmacology

• Anesthetics produce loss of sensation and consciousness
  • General anesthetics (e.g., propofol, isoflurane)
  • Local anesthetics (e.g., lidocaine, bupivacaine)
• Analgesics relieve pain
  • Opioids (e.g., morphine, fentanyl)
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Acetaminophen
• Antidepressants treat depression
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)
• Antipsychotics treat psychosis
  • Typical antipsychotics (e.g., haloperidol)
  • Atypical antipsychotics (e.g., risperidone, olanzapine)

Endocrine Pharmacology

• Drugs for diabetes mellitus
  • Insulin
  • Oral hypoglycemic agents (e.g., metformin, sulfonylureas)
• Thyroid hormones
  • Levothyroxine (T4)
  • Liothyronine (T3)
• Corticosteroids
  • Prednisone
  • Hydrocortisone

Chemotherapy

• Antibiotics treat bacterial infections
  • Penicillins
  • Cephalosporins
  • Macrolides
  • Tetracyclines
  • Fluoroquinolones
• Antiviral drugs treat viral infections
  • Acyclovir (herpes simplex virus)
  • Zidovudine (HIV)
  • Oseltamivir (influenza)
• Antifungal drugs treat fungal infections
  • Azoles (e.g., fluconazole, ketoconazole)
  • Amphotericin B
• Anticancer drugs treat cancer
  • Alkylating agents
  • Antimetabolites
  • Plant alkaloids
  • Targeted therapies