Pharmacology: Basic Principles & Absorption

• Pharmacology is the study of drugs and their effects on living organisms.

Basic Principles

• Pharmacokinetics describes what the body does to a drug (absorption, distribution, metabolism, excretion).
• Pharmacodynamics describes what a drug does to the body (mechanism of action, therapeutic and toxic effects).
• Drugs can be synthesized in a lab, or purified from natural sources.
• Many drugs are designed to interact with specific molecular targets in the body.

Pharmacokinetics: Absorption

• Absorption is the process by which a drug enters the bloodstream from the site of administration.
• Routes of administration include oral, intravenous, subcutaneous, intramuscular, transdermal, inhalation, and rectal.
• Bioavailability refers to the fraction of the administered dose that reaches systemic circulation.
• Intravenous administration has 100% bioavailability.
• Oral administration bioavailability can be affected by factors such as first-pass metabolism in the liver.
• Factors affecting absorption include drug solubility, ionization, and blood flow to the absorption site.

Pharmacokinetics: Distribution

• Distribution is the process by which a drug moves from the bloodstream to various tissues and organs in the body.
• Factors affecting distribution include blood flow, tissue permeability, and binding to plasma proteins.
• The volume of distribution (Vd) is a measure of the apparent space in the body available to contain the drug.
• A high Vd indicates that the drug is widely distributed throughout the body.
• The blood-brain barrier restricts the passage of many drugs into the central nervous system.

Pharmacokinetics: Metabolism

• Metabolism (biotransformation) is the process by which the body chemically modifies a drug.
• The liver is the primary site of drug metabolism.
• Phase I reactions (e.g., oxidation, reduction, hydrolysis) introduce or expose a functional group on the drug molecule.
• Phase II reactions (e.g., glucuronidation, sulfation) involve conjugation of the drug molecule with a polar molecule to increase its water solubility.
• Cytochrome P450 (CYP) enzymes are a major family of enzymes involved in drug metabolism.
• Some drugs can induce or inhibit CYP enzymes, leading to drug-drug interactions.
• Prodrugs are inactive compounds that are metabolized into active drugs in the body.

Pharmacokinetics: Excretion

• Excretion is the process by which the body eliminates a drug or its metabolites.
• The kidneys are the primary site of drug excretion.
• Other routes of excretion include the bile, feces, lungs, and breast milk.
• Renal excretion involves glomerular filtration, tubular secretion, and tubular reabsorption.
• Clearance is a measure of the rate at which a drug is removed from the body.
• Half-life (t1/2) is the time it takes for the plasma concentration of a drug to decrease by 50%.

Pharmacodynamics: Drug-Receptor Interactions

• Receptors are proteins that bind to drugs (ligands) and mediate their effects.
• Drug-receptor interactions are typically reversible and based on chemical bonds.
• Affinity is the measure of how tightly a drug binds to its receptor.
• Efficacy (intrinsic activity) is the measure of a drug's ability to produce a response once bound to the receptor.
• Agonists are drugs that bind to a receptor and activate it, producing a response.
• Antagonists are drugs that bind to a receptor but do not activate it, instead blocking the binding of agonists.
• Competitive antagonists bind to the same site on the receptor as the agonist, while non-competitive antagonists bind to a different site.
• Partial agonists produce a submaximal response, even when occupying all available receptors.
• Inverse agonists bind to a receptor and produce an effect opposite to that of an agonist.

Pharmacodynamics: Dose-Response Relationships

• The dose-response relationship describes the relationship between the dose of a drug and the magnitude of its effect.
• The potency of a drug is a measure of the amount of drug required to produce a given effect.
• The effective dose (ED50) is the dose that produces a specified effect in 50% of the population.
• The lethal dose (LD50) is the dose that causes death in 50% of the population.
• The therapeutic index (TI) is the ratio of the LD50 to the ED50, and is a measure of drug safety.
• A higher therapeutic index indicates a safer drug.

Drug Safety and Toxicity

• Adverse drug reactions (ADRs) are unwanted or unexpected effects caused by a drug.
• Side effects are predictable and often unavoidable ADRs.
• Allergic reactions are immune-mediated ADRs.
• Idiosyncratic reactions are unpredictable and rare ADRs.
• Drug interactions can occur when one drug affects the pharmacokinetics or pharmacodynamics of another drug.
• Contraindications are specific situations in which a drug should not be used.
• Tolerance is a decrease in response to a drug over time.
• Dependence is a state in which the body has adapted to the presence of a drug, and withdrawal symptoms occur if the drug is discontinued.

Autonomic Pharmacology

• The autonomic nervous system (ANS) regulates involuntary functions such as heart rate, blood pressure, and digestion.
• The ANS has two main divisions: the sympathetic and parasympathetic nervous systems.
• Sympathetic nervous system activation is associated with the "fight-or-flight" response.
• Parasympathetic nervous system activation is associated with the "rest-and-digest" response.
• Neurotransmitters in the ANS include acetylcholine (ACh) and norepinephrine (NE).
• Cholinergic receptors bind ACh, while adrenergic receptors bind NE and epinephrine.
• Cholinergic receptors are divided into nicotinic and muscarinic receptors.
• Adrenergic receptors are divided into alpha and beta receptors.
• Drugs that affect the ANS can be used to treat a variety of conditions, such as hypertension, asthma, and glaucoma.

Central Nervous System Pharmacology

• The central nervous system (CNS) consists of the brain and spinal cord.
• Neurotransmitters in the CNS include glutamate, GABA, dopamine, serotonin, and norepinephrine.
• Glutamate is the primary excitatory neurotransmitter in the CNS.
• GABA is the primary inhibitory neurotransmitter in the CNS.
• Drugs that affect the CNS can be used to treat a variety of conditions, such as depression, anxiety, schizophrenia, and Parkinson's disease.
• Anesthetics are drugs that reduce or eliminate sensation.
• Analgesics are drugs that relieve pain.
• Sedatives and hypnotics are drugs that promote relaxation and sleep.
• Antidepressants are drugs that treat depression.
• Antipsychotics are drugs that treat psychosis.
• Neurodegenerative diseases are characterized by the progressive loss of neurons.

Cardiovascular Pharmacology

• Cardiovascular drugs are used to treat conditions such as hypertension, heart failure, and arrhythmias.
• Antihypertensive drugs lower blood pressure.
• Diuretics increase urine output and reduce blood volume.
• Beta-blockers block the effects of norepinephrine on the heart.
• ACE inhibitors block the production of angiotensin II, a vasoconstrictor.
• Calcium channel blockers block the entry of calcium into smooth muscle cells, causing vasodilation.
• Vasodilators widen blood vessels, lowering blood pressure.
• Antiarrhythmic drugs restore normal heart rhythm.
• Positive inotropic drugs increase the force of heart muscle contraction.

Endocrine Pharmacology

• Endocrine drugs are used to treat conditions related to hormone imbalances.
• Insulin is used to treat diabetes mellitus.
• Oral hypoglycemic agents lower blood glucose levels.
• Thyroid hormones are used to treat hypothyroidism.
• Corticosteroids are used to treat inflammation and immunosuppression.
• Sex hormones (e.g., estrogen, testosterone) are used to treat hormone deficiencies and certain cancers.

Anti-inflammatory and Immunomodulating Drugs

• Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation and pain by inhibiting cyclooxygenase (COX) enzymes.
• Corticosteroids are potent anti-inflammatory drugs that suppress the immune system.
• Immunosuppressants are used to prevent organ rejection after transplantation and to treat autoimmune diseases.
• Biologic therapies target specific components of the immune system.

Antimicrobial Pharmacology

• Antibiotics are used to treat bacterial infections.
• Antivirals are used to treat viral infections.
• Antifungals are used to treat fungal infections.
• Antimicrobial resistance is a growing problem.
• Appropriate use of antimicrobials is essential to prevent the development of resistance.