Pharmacology Quiz: Drug Actions and Bioavailability

The principal pharmacokinetic factors—absorption, distribution, metabolism, and excretion—determine bioavailability by influencing the concentration of a drug at its site of action.

Drug administration methods vary in terms of onset, bioavailability, and convenience, each having specific advantages and disadvantages.

Increased lipid solubility enhances drug absorption, while ionization typically decreases it, as ionized drugs are less able to cross lipid membranes.

<p>The blood-brain barrier is a protective layer of cells that restricts the passage of substances from the bloodstream into the brain, which is crucial in psychopharmacology because it affects drug access to the brain.</p> Signup and view all the answers

<p>Depot binding is the attachment of drugs to inactive sites in the body, reducing the amount of drug available to reach the target site, which affects drug action duration and intensity.</p> Signup and view all the answers

<p>Synthetic drug metabolism involves phase II reactions like glucuronidation, which conjugate drugs with polar molecules to enhance excretion, while non-synthetic (phase I) metabolism involves oxidation, reduction, or hydrolysis to modify the drug's structure.</p> Signup and view all the answers

<p>Factors influencing drug metabolism and elimination include genetics, liver function, age, and interactions with other drugs, which can alter enzyme activity.</p> Signup and view all the answers

<p>An <em>agonist</em> activates a receptor; an <em>antagonist</em> blocks a receptor; a <em>partial agonist</em> partially activates a receptor; and an <em>inverse agonist</em> causes an opposite effect to that of an agonist.</p> Signup and view all the answers

<p>A dose-response curve shows the relationship between drug dose and effect, illustrating ED50 as the dose producing 50% of the maximum effect and the maximum response as the greatest effect a drug can achieve.</p> Signup and view all the answers

<p><strong>Potency</strong> refers to the amount of drug needed to produce an effect, while <strong>efficacy</strong> is the maximum effect a drug can produce. Graphically, potency is shown by the position of the curve along the x-axis, and efficacy is shown by the height of the curve.</p> Signup and view all the answers

<p>The therapeutic index (TI) is crucial in drug safety evaluation, as it indicates the margin between effective and toxic doses, helping to determine the safety of a drug.</p> Signup and view all the answers

<p>A competitive antagonist reduces drug potency by requiring a higher concentration of the agonist to achieve the same effect, but it does not affect the drug's efficacy if sufficient agonist is present.</p> Signup and view all the answers

<p>Drug tolerance is the decreased response to a drug after repeated use. The three major types are metabolic tolerance, pharmacodynamic tolerance, and behavioral tolerance.</p> Signup and view all the answers

<p>Pharmacogenetics is the study of how genes affect a person's response to drugs, contributing to personalized medicine by predicting drug efficacy and adverse effects. An example is testing for CYP2C19 variants before prescribing clopidogrel.</p> Signup and view all the answers

<p>A typical axodendritic synapse includes a presynaptic axon terminal and a postsynaptic dendrite. Axosomatic synapses connect axons to cell bodies, axoaxonic synapses connect axons to other axons, and neuromuscular junctions connect motor neurons to muscle fibers, differing structurally and functionally from axodendritic synapses.</p> Signup and view all the answers

<p>Criteria for a neurotransmitter include synthesis within the neuron, release upon stimulation, receptor binding, and a mechanism for inactivation. Release upon stimulation is arguably the 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 in the cell body and transported to the nerve terminal, unlike other neurotransmitters, which are often synthesized directly in the nerve terminal.</p> Signup and view all the answers

<p>A neurotransmitter acts directly on postsynaptic receptors at a synapse, while a neuromodulator affects neuronal activity more diffusely. Neuromodulators are linked to volume transmission as they can affect multiple neurons over a wider area.</p> Signup and view all the answers

<p>Exocytosis is the process by which vesicles fuse with the presynaptic membrane to release neurotransmitters into the synaptic cleft.</p> Signup and view all the answers

<p>Vesicle recycling involves the retrieval of vesicle membranes from the presynaptic terminal after exocytosis. Models vary in speed, area of retrieval (directly from the membrane or via endosomes), and clathrin involvement. Some propose rapid 'kiss-and-run' recycling, while others involve endocytosis and clathrin-mediated retrieval.</p> Signup and view all the answers

<p>A retrograde messenger is released by the postsynaptic neuron to affect the presynaptic neuron. Lipid (e.g., endocannabinoids) and gaseous (e.g., nitric oxide) transmitters can act as retrograde messengers, influencing presynaptic neurotransmitter release.</p> Signup and view all the answers

<p>Somatodendritic autoreceptors are located on the cell body and dendrites, while terminal autoreceptors are found on the axon terminal. Both control neurotransmitter release by inhibiting further release when activated by the neurotransmitter itself.</p> Signup and view all the answers

<p>Neurotransmitters are inactivated by reuptake into the presynaptic neuron, enzymatic degradation in the synaptic cleft, or diffusion away from the synapse.</p> Signup and view all the answers

<p>Catecholamines include dopamine, norepinephrine, and epinephrine. They are characterized by 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 being converted to L-DOPA by tyrosine hydroxylase (the rate-limiting step), then to dopamine by DOPA decarboxylase. Norepinephrine synthesis involves dopamine being converted to norepinephrine by dopamine beta-hydroxylase.</p> Signup and view all the answers

<p>The rate of catecholamine synthesis is regulated by the availability of precursor amino acids (tyrosine), the activity of tyrosine hydroxylase, and feedback inhibition from dopamine and norepinephrine.</p> Signup and view all the answers

<p>The vesicular monoamine transporters (VMATs) transport catecholamines into synaptic vesicles. VMAT2 is expressed in the brain, and VMAT1 is primarily expressed in the adrenal medulla.</p> Signup and view all the answers

<p>Single-spiking refers to regular, isolated action potentials, while burst firing involves clusters of action potentials. Burst firing results in greater dopamine release at the nerve terminal.</p> Signup and view all the answers

<p>Catecholamine release is regulated by autoreceptors, which inhibit further release when activated. Terminal autoreceptors are on axon terminals and reduce exocytosis, while somatodendritic autoreceptors on cell bodies slow firing. Alpha-2 adrenergic receptors function as noradrenergic autoreceptors. Clonidine is an agonist (reduces cell firing), and yohimbine is an antagonist (increases cell firing).</p> Signup and view all the answers

<p>Catecholamine transmission is terminated by reuptake into the presynaptic neuron via transporters and enzymatic degradation by enzymes like MAO and COMT.</p> Signup and view all the answers

<p>The major metabolites of dopamine (DA) are DOPAC and HVA. The major metabolites of norepinephrine (NE) are MHPG and VMA.</p> Signup and view all the answers

<p>Drugs that alter catecholamine reuptake (e.g., cocaine, amphetamine) are used to treat ADHD and narcolepsy by increasing DA and NE levels. Drugs that alter catecholamine metabolism (e.g., MAO inhibitors) are used to treat depression by preventing the breakdown of DA, NE, and 5-HT.</p> Signup and view all the answers

<p>The two major dopaminergic pathways are the mesolimbic pathway (VTA to nucleus accumbens, involved in reward) and the mesocortical pathway (VTA to prefrontal cortex, involved in cognition). 'Meso' refers to the midbrain origin, 'limbic' to the limbic system target, and 'cortical' to the cortical target.</p> Signup and view all the answers

<p>Neurotoxins (like 6-OHDA) cause cell death, leading to rapid DA depletion, but can affect other cell types. Genetic engineering (like DD mice) creates specific DA deficiencies, allowing for chronic study but can activate compensatory mechanisms. Neurotoxin-lesioned animals show severe motor deficits; DD mice might show more subtle cognitive or motivational impairments.</p> Signup and view all the answers

<p>(a) The mesolimbic pathway is involved in reward and motivation, while the mesocortical pathway is involved in cognition and executive functions. (b) Different VTA DA neuron subsets respond to rewarding stimuli (increasing firing) or aversive stimuli (decreasing firing).</p> Signup and view all the answers

<p>There are five subtypes of dopamine (DA) receptors which are grouped into two families: D1-like (D1 and D5) and D2-like (D2, D3, and D4). D1 receptors activate adenylyl cyclase and increase cAMP, while D2 receptors inhibit adenylyl cyclase and decrease cAMP. The D1 receptors typically have a lower affinity for DA than D2 receptors.</p> Signup and view all the answers

<p>Behavioral supersensitivity is an enhanced response to a drug after repeated exposure or withdrawal. D2 receptor supersensitivity can be induced by chronic antagonist treatment; the proposed mechanism involves receptor upregulation or increased receptor sensitivity.</p> Signup and view all the answers

<p>In the forebrain, NE is mainly from the locus coeruleus. In the peripheral nervous system, NE is from sympathetic neurons and the adrenal medulla. The &quot;fight-or-flight” response is mediated by EPI and NE, leading to increased heart rate, blood pressure, and alertness in response to stress.</p> Signup and view all the answers

<p>Adrenergic receptors are divided into alpha (α1, α2) and beta (β1, β2, β3) subtypes. α1 receptors increase intracellular calcium, α2 receptors inhibit adenylyl cyclase, and beta receptors stimulate adenylyl cyclase.</p> Signup and view all the answers

<p>The central noradrenergic system is involved in arousal, attention, and cognition. Pharmacological activation (e.g., amphetamine) enhances alertness, while blockade (e.g., clonidine) reduces it. α2 agonists can improve attention, while β-blockers can impair cognitive functions.</p> Signup and view all the answers

<p>Peripheral EPI enhances consolidation of emotional memories; evidence comes from studies where EPI administration after a learning experience improves later recall. Mechanisms involve activation of peripheral β-adrenergic receptors, leading to increased amygdala activity via vagal nerve stimulation.</p> Signup and view all the answers

<p>Medications stimulating peripheral adrenergic receptors (e.g., pseudoephedrine) are used as decongestants. Medications blocking peripheral adrenergic receptors (e.g., beta-blockers) are used to treat hypertension and anxiety.</p> Signup and view all the answers

<p>Serotonin (5-HT) synthesis involves tryptophan being converted to 5-hydroxytryptophan by tryptophan hydroxylase (the rate-limiting step), then to 5-HT by aromatic L-amino acid decarboxylase.</p> Signup and view all the answers

<p>Pharmacological methods to increase 5-HT include SSRIs (selective serotonin reuptake inhibitors) which prevent the reuptake of serotonin, and MAO inhibitors, which prevent serotonin breakdown. Dietary methods include increasing tryptophan intake by eating protein-rich foods, which can modestly boost serotonin synthesis but is less reliable.</p> Signup and view all the answers

<p>Increasing brain 5-HT (e.g., via SSRIs) generally improves mood and reduces anxiety. Decreasing brain 5-HT can worsen mood and impair cognitive functions such as attention and memory.</p> Signup and view all the answers

<p>5-HT is stored in vesicles, released via exocytosis, and inactivated by reuptake (via SERT) or enzymatic degradation (by MAO). SSRIs block reuptake, increasing 5-HT; MAO inhibitors block degradation also increasing 5-HT; MDMA triggers release.</p> Signup and view all the answers

<p>Serotonergic neurons synthesize 5-HT in the brain. The two specific cell groups that are responsible for most of the serotonergic projections to the forebrain are the dorsal raphe nucleus and the median raphe nucleus. Major forebrain areas receiving these projections include the cortex, hippocampus, amygdala, and hypothalamus.</p> Signup and view all the answers

<p>Dorsal raphe serotonergic neurons firing varies with behavioral state, showing increased activity during active wakefulness and decreased activity during sleep. Firing rates also tend to decrease in response to both rewards and punishments, often signaling changes in reinforcement value rather than pure reward or aversion.</p> Signup and view all the answers

<p>Serotonergic receptor subtypes include 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A, 5-HT5B, 5-HT6, and 5-HT7. All are metabotropic (GPCRs) except 5-HT3, which is ionotropic (ligand-gated ion channel).</p> Signup and view all the answers

<p>5-HT1A receptors primarily signal via Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP levels, which hyperpolarizes the cells. 5-HT2A receptors signal via Gq proteins, activating phospholipase C and increasing IP3 and DAG, which depolarizes the cells.</p> Signup and view all the answers

<p>Tph2-knockout mice (lacking brain serotonin synthesis) and mice without central serotonergic neurons show increased aggression, anxiety, and altered feeding behaviors. Physiologically, they may exhibit altered sleep patterns, reduced stress responses, and changes in pain sensitivity.</p> Signup and view all the answers

<p>The 5-HT1A receptor subtype has been strongly implicated in anxiety control. Drugs that act as 5-HT1A receptor agonists, like buspirone, have been shown to reduce anxiety in both animal models and clinical trials. Decreased 5-HT1A receptor binding in certain brain regions is associated with increased anxiety.</p> Signup and view all the answers

<p>5-HT is involved in pain regulation through descending pathways that modulate nociceptive transmission in the spinal cord. Serotonergic medications, particularly SNRIs (serotonin-norepinephrine reuptake inhibitors), can be used to treat chronic pain conditions like fibromyalgia and neuropathic pain by enhancing the activity of these descending inhibitory pathways.</p> Signup and view all the answers

<p>5-HT1A receptors in the hippocampus and prefrontal cortex are involved in spatial and working memory; activation of these receptors can improve performance in memory tasks. 5-HT4 receptors in the hippocampus enhance long-term potentiation (LTP) and improve memory consolidation. 5-HT6 receptors, also in the hippocampus and cortex, modulate neurotransmitter release and synaptic plasticity, and their blockade can enhance cognitive function.</p> Signup and view all the answers

<p>The primary source of 5-HT in the GI tract is enterochromaffin cells. Pharmacologists are interested in gut 5-HT because it regulates gut motility, secretion, and sensation. Serotonergic medications such as 5-HT3 receptor antagonists (e.g., ondansetron) are used to treat nausea and vomiting, while 5-HT4 receptor agonists (e.g., prucalopride) are used to treat constipation.</p> Signup and view all the answers

The study of how drugs move through the body affecting their bioavailability.

Different ways drugs can be given to patients, each with pros and cons.

A measure of how well a drug can pass through cell membranes, impacting absorption.

A selective barrier that protects the brain by blocking harmful substances.

The process where drugs bind to inactive sites, affecting their duration and intensity.

Synthetic drugs are made artificially, while non-synthetic are naturally occurring.

Factors like age, genetics, and health that influence how drugs are processed.

Substances that activate receptors to produce a response.

Substances that block or dampen the action of agonists.

A graph that represents the relationship between drug dose and its pharmacological effect.

Potency refers to the strength of a drug at a certain dose; efficacy is the maximum effect achievable.

The ratio between the toxic and therapeutic doses of a drug, indicating safety.

Drugs that bind to the same receptor as the agonist but do not activate it, reducing agonist efficacy.

The reduced reaction to a drug after repeated use, requiring higher doses.

The study of how genes affect individual responses to drugs, aiding personalized medicine.

Conditions that a substance must fulfill to be classified as a neurotransmitter.

Groups based on chemical structure, e.g., amino acids and peptides.

The process where neurotransmitters are released from vesicles into the synaptic cleft.

The process of reusing vesicles after neurotransmitter release.

Receptors on the cell body that regulate neurotransmitter release.

A group of neurotransmitters including dopamine, norepinephrine, and epinephrine.

The biochemical steps and enzymes required to produce dopamine.

Processes that terminate neurotransmitter action by absorbing them back into neurons.

The sequential reactions to produce serotonin, including rate-limiting steps.

Changes in serotonin levels influence mood and cognitions in individuals.

The process of how acetylcholine is synthesized, released, and broken down in the nervous system.

Drugs that mimic the effects of the parasympathetic nervous system.