Pharmacology Chapter: Bioavailability and Drug Properties

The principal pharmacokinetic factors are absorption, distribution, metabolism, and excretion (ADME). These factors influence the concentration of a drug at its site of action and, therefore, determine its bioavailability.

Drug administration methods vary (e.g., oral, intravenous, intramuscular, subcutaneous, inhalation, topical). Each method has its advantages (e.g., ease of use, rapid onset) and disadvantages (e.g., first-pass metabolism, risk of infection) that affect drug bioavailability and onset of action.

Lipid solubility and ionization are the primary determinants. Lipid-soluble (lipophilic), non-ionized drugs are more readily absorbed across cell membranes, whereas ionized (charged) and less lipid-soluble (hydrophilic) drugs are absorbed less efficiently.

<p>The blood-brain barrier (BBB) is a highly selective semipermeable membrane barrier that separates the circulating blood from the brain extracellular fluid in the central nervous system (CNS). It is important in psychopharmacology because it restricts the passage of substances (including drugs) into the brain, affecting drug efficacy and CNS side effects.</p> Signup and view all the answers

<p>Depot binding refers to the binding of drugs to inactive sites in the body, such as plasma proteins, muscle, or fat. This binding reduces the concentration of the drug available to act on its target site, prolonging drug action duration and reducing its intensity.</p> Signup and view all the answers

<p>Synthetic drug metabolism involves phase II reactions (conjugation) that add polar groups to a drug molecule, increasing its water solubility for excretion. Non-synthetic metabolism (phase I reactions) involves oxidation, reduction, or hydrolysis to modify the drug's chemical structure.</p> Signup and view all the answers

<p>Factors influencing drug metabolism and elimination include genetics, age, liver and kidney function, drug interactions (enzyme induction/inhibition), and disease states.</p> Signup and view all the answers

<p>An agonist binds to a receptor and activates it, producing a biological response. An antagonist binds to a receptor but does not activate it, blocking the effects of agonists. A partial agonist activates a receptor but produces a weaker response than a full agonist. An inverse agonist binds to a receptor and produces an effect opposite to that of an agonist.</p> Signup and view all the answers

<p>A dose-response curve is a graph that plots the relationship between the dose of a drug and the magnitude of its effect. It illustrates ED50 (the dose that produces 50% of the maximum effect) and maximum response (the highest effect a drug can produce, regardless of dose).</p> Signup and view all the answers

<p>Potency refers to the amount of drug needed to produce a given effect (e.g., ED50), while efficacy refers to the maximum effect a drug can produce. Graphically, potency is reflected in the position of the dose-response curve along the x-axis (dose), while efficacy is reflected in the maximum height of the curve on the y-axis (effect).</p> Signup and view all the answers

<p>The therapeutic index (TI) is the ratio of the toxic dose (TD50) to the effective dose (ED50) of a drug. It indicates the margin of safety of a drug; a higher TI suggests a safer drug because there is a larger difference between the dose required for therapeutic effect and the dose that produces toxicity.</p> Signup and view all the answers

<p>A competitive antagonist binds reversibly to the same site as the agonist, reducing drug potency by increasing the ED50 (more agonist is needed to achieve the same effect). However, it does not affect drug efficacy because the maximum response can still be achieved with a sufficiently high concentration of the agonist.</p> Signup and view all the answers

<p>Drug tolerance is a state where a person no longer responds to a drug in the way they did at first. The 3 major types of tolerance are metabolic tolerance (increased metabolism of the drug), pharmacodynamic tolerance (changes at the receptor level), and behavioral tolerance (learned adaptation to the drug's effects).</p> Signup and view all the answers

<p>Pharmacogenetics is the study of how genes affect a person's response to drugs. It contributes to personalized medicine by allowing treatments to be tailored to an individual's genetic makeup, optimizing drug efficacy and minimizing adverse effects. For example, variations in genes encoding drug-metabolizing enzymes (e.g., CYP2C19) can affect the metabolism and response to certain antidepressants.</p> Signup and view all the answers

<p>A typical axodendritic synapse consists of a presynaptic axon terminal, a synaptic cleft, and a postsynaptic dendrite. Axosomatic synapses connect an axon to a cell body, axoaxonic synapses connect two axons, and neuromuscular junctions connect a motor neuron to a muscle fiber, differing in location and function compared to axodendritic synapses.</p> Signup and view all the answers

<p>Criteria include: (1) the substance must be synthesized in the neuron, (2) it must be present in the presynaptic terminal and released upon depolarization, and (3) when applied exogenously, it must produce the same effect as the endogenously released neurotransmitter. The demonstration of the same effect might be considered most important.</p> Signup and view all the answers

<p>Neurotransmitter categories include: amino acids (e.g., glutamate), monoamines (e.g., dopamine), peptides (e.g., endorphins), and others (e.g., acetylcholine).</p> Signup and view all the answers

<p>Neuropeptides are synthesized as large precursor proteins in the cell body (soma) and then processed and transported to the nerve terminal via axonal transport. Other neurotransmitters are usually synthesized directly in the nerve terminal.</p> Signup and view all the answers

<p>Neurotransmitters act locally and rapidly at synapses, while neuromodulators act more diffusely and slowly, modulating neuronal activity over a wider area. Neuromodulators utilize volume transmission, affecting multiple neurons simultaneously.</p> Signup and view all the answers

<p>Exocytosis is the process by which neurotransmitters are released from vesicles into the synaptic cleft. It involves the fusion of vesicles with the cell membrane, allowing the neurotransmitters to diffuse and bind to postsynaptic receptors.</p> Signup and view all the answers

<p>Vesicle recycling involves the retrieval of vesicle membrane from the cell surface after exocytosis. Models differ in speed, location (nerve terminal area), and involvement of proteins like clathrin and endosomes. Some models propose rapid recycling at the active zone, while others suggest slower recycling in endosomes.</p> Signup and view all the answers

<p>A retrograde messenger is a chemical signal that travels from the postsynaptic neuron to the presynaptic neuron, influencing neurotransmitter release. Lipid and gaseous transmitters, such as endocannabinoids and nitric oxide (NO), can act as retrograde messengers.</p> Signup and view all the answers

<p>Somatodendritic autoreceptors are located on the cell body and dendrites, while terminal autoreceptors are located on the axon terminal. They control neurotransmitter release by inhibiting neuronal firing (somatodendritic) or directly inhibiting neurotransmitter release (terminal) when activated by the neurotransmitter.</p> Signup and view all the answers

<p>Neurotransmitters are inactivated through reuptake (transport back into the presynaptic neuron), enzymatic degradation (breakdown by enzymes), or diffusion away from the synapse.</p> Signup and view all the answers

<p>The catecholamines are dopamine, norepinephrine, and epinephrine. They all share a catechol nucleus (benzene ring with two hydroxyl groups) and an amine group.</p> Signup and view all the answers

<p>Dopamine synthesis involves tyrosine converted to L-DOPA by tyrosine hydroxylase (rate-limiting step), then L-DOPA converted to dopamine by aromatic L-amino acid decarboxylase. Norepinephrine synthesis involves dopamine converted to norepinephrine by dopamine-β-hydroxylase.</p> Signup and view all the answers

Factors affecting drug absorption, distribution, metabolism, and excretion (ADME).

The proportion of a drug that enters circulation when introduced into the body; directly affects therapeutic efficacy.

Various ways to deliver drugs, e.g., oral, intravenous, intramuscular.

Ability of a drug to dissolve in fats; affects its absorption and distribution in the body.

The process by which a drug gains or loses hydrogen ions; affects its absorption in different pH environments.

A selective permeability barrier between the blood and brain; protects the brain from harmful substances.

Drug binding to tissues that allows for sustained release; affects duration and intensity of drug action.

Synthetic involves chemical alterations (e.g., via enzymes) while non-synthetic involves simple breakdown without modification.

Genetics, age, diet, and organ function affecting how drugs are processed and eliminated.

Substance that activates receptors to produce a biological response.

Substance that blocks or dampens a biological response by binding to receptors.

Graph showing the relationship between drug dose and effect; illustrates potency and efficacy.

The effective dose at which 50% of the population exhibits the intended biological response.

Potency refers to the amount needed for effects, while efficacy refers to the maximum effect achievable.

A ratio that compares the blood concentration at which a drug becomes toxic to its effective level.

A type of antagonist that competes with an agonist for binding to the same receptor.

Decreased response to a drug after repeated use, requiring larger doses to achieve the same effect.

Study of how genes affect a person's response to drugs; contributes to personalized medicine.

The most common type of synapse where the axon of one neuron connects to the dendrite of another.

Set of criteria to define a substance as a neurotransmitter, including presence in the presynaptic neuron, release, and effect on receptors.

Groups based on chemical structure, like amino acids (e.g., glutamate) or monoamines (e.g., serotonin).

The process of releasing neurotransmitters from presynaptic vesicles into the synaptic cleft.

The process by which synaptic vesicles are reused after neurotransmitter release.

Substance that influences activity and effectiveness of neurotransmitters; may not directly activate receptors.

Somatodendritic autoreceptors regulate neuron's overall activity; terminal autoreceptors regulate neurotransmitter release directly at the nerve terminals.

The chemical steps to make serotonin (5-HT), including key enzymes involved.

Drugs that inhibit acetylcholinesterase, increasing acetylcholine levels and improving cholinergic transmission.