Pharmacokinetics and Reaction Rates

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Questions and Answers

What is the primary characteristic that defines ion channels?

Size of ions

Molecular structure

Selectivity for a particular ion (correct)

Gating properties

What triggers ligand-gated ion channels to open?

Increase in membrane potential

Binding of an agonist (correct)

Presence of toxins

Changes in temperature

Which type of ion channel is gated by changes in transmembrane potential?

Voltage-gated ion channels (correct)

Gap junctions

Ligand-gated ion channels

Mechanically-gated channels

What is the primary role of G-proteins in cellular signaling?

To recognize activated GPCRs and relay messages to effector systems Signup and view all the answers

Which of the following represents the mechanism of action for many drugs and toxins related to ion channels?

Altering the behavior of ion channels indirectly or directly Signup and view all the answers

Which type of neurotransmission provides the fastest synaptic events in the nervous system?

Ligand-gated ion channel signaling Signup and view all the answers

How does G-protein activation result in signal amplification?

Through the dissociation of G-protein from the activated receptor Signup and view all the answers

Which type of ligands binds to the ligand binding domain of GPCRs?

Small molecules buried in clefts Signup and view all the answers

What do Type B adverse drug reactions (ADRs) characterize?

Bizarre and unexpected responses unrelated to dosage Signup and view all the answers

Which mechanism can cause oxidative destruction in cells?

Lipid peroxidation Signup and view all the answers

What limits the detection of delayed adverse drug reactions during clinical trials?

Short trial duration Signup and view all the answers

What type of reactions does Type C ADR encompass?

Chronic toxic effects Signup and view all the answers

What is the primary challenge in linking ADRs to specific drugs?

Concurrent drug use Signup and view all the answers

Which process describes genetic mutations related to DNA?

Mutagenesis Signup and view all the answers

What can occur during pharmaceutical interactions prior to administration?

Inactivation due to mixing Signup and view all the answers

Which term best describes the multi-step process leading to cancer formation?

Carcinogenesis Signup and view all the answers

Which statement accurately describes the rate of a zero order reaction?

The rate is constant and does not depend on the concentration of reactants. Signup and view all the answers

In first order reactions, how does the half-life behave over time?

The half-life remains constant regardless of the reactant concentration. Signup and view all the answers

What effect do liver or kidney diseases have on drug clearance?

They slow drug clearance, increasing the risk of drug accumulation. Signup and view all the answers

How does age affect drug metabolism in elderly patients?

Elderly patients may have slower drug metabolism and altered drug clearance. Signup and view all the answers

What is a primary characteristic of enteric-coated capsules?

They protect drugs from stomach acid and release them in the intestines. Signup and view all the answers

How can food impact drug absorption?

Food can enhance, delay, or reduce drug absorption depending on the drug and meal composition. Signup and view all the answers

In relation to drug absorption, how does a fatty meal affect lipophilic drugs?

It enhances the absorption of lipophilic drugs. Signup and view all the answers

What is the implication of immature renal function in children on drug clearance?

Immature renal function leads to slower drug clearance and may require dose adjustments. Signup and view all the answers

What does the acronym SLUDDE represent in relation to muscarinic agonists?

Salivation, Lacrimation, Urination, Defecation, Diarrhea, Emesis Signup and view all the answers

Which effects are associated with muscarinic antagonists?

Decreased gastrointestinal motility Signup and view all the answers

What is a method by which indirect agonists enhance acetylcholine activity?

Inhibiting the breakdown of acetylcholine Signup and view all the answers

What is the primary neurotransmitter released from adrenergic neurons?

Norepinephrine Signup and view all the answers

How is norepinephrine release regulated?

Via presynaptic alpha-2 receptors feedback Signup and view all the answers

Which type of cholinesterase primarily breaks down acetylcholine in the synapse?

Acetylcholinesterase Signup and view all the answers

What effect does adenylate cyclase have on neurotransmitter release?

It promotes cAMP production and norepinephrine exocytosis Signup and view all the answers

Which of the following actions would decrease acetylcholine release at the synapse?

Inhibiting calcium entry into the presynaptic neuron Signup and view all the answers

What effect do a2 adrenergic receptors have when activated?

Inhibits adenylate cyclase activity and decreases cAMP production Signup and view all the answers

Which of the following accurately describes the role of cAMP in signal transduction?

It promotes calcium influx, which triggers exocytosis of neurotransmitters. Signup and view all the answers

Which mechanism can lead to a decrease in norepinephrine exocytosis?

Direct block of norepinephrine release Signup and view all the answers

What is a common effect of B2 adrenergic receptor activation?

Bronchodilation Signup and view all the answers

How do specific adrenergic antagonists differ from nonspecific antagonists?

They block either a or B receptors for targeted effects. Signup and view all the answers

Which of the following statements about adrenergic receptors is correct?

a1 receptors are involved in vasoconstriction. Signup and view all the answers

Which option describes a method of affecting norepinephrine release?

Decreasing available intracellular NE stores Signup and view all the answers

What physiological response can result from specific adrenergic agonist activation?

Increased heart rate and vasoconstriction Signup and view all the answers

Study Notes

Reaction Rates

The reaction rate can be determined by measuring the disappearance of the reactant A or the appearance of the product M.
The order of a reaction depends on the relationship between the rate and the concentration of reactant A.
A zero-order reaction has a constant rate that does not depend on the concentration of A.
A first-order reaction has a rate that is directly proportional to the concentration of A.
The half-life of a zero-order reaction changes over time, while the half-life of a first-order reaction remains constant.

Drug Administration and Pharmacokinetics

Enteric-coated capsules protect drugs from stomach acid and release them in the intestines, leading to delayed but effective absorption.
Time-release capsules provide a sustained drug level over time, reducing the need for frequent dosing.
Distribution of drugs can be affected by diseases like liver or kidney issues, which can affect blood flow, protein binding, drug levels, and toxicity risk.
Elimination of drugs can be affected by liver or kidney diseases, which can lead to slower drug clearance, accumulation, and prolonged effects.
Children have immature metabolism and renal function, requiring dose adjustments.
Elderly individuals have reduced liver and kidney function and altered body composition, leading to slower drug metabolism, elimination, and longer half-lives.
Food can enhance, delay, or reduce drug absorption depending on the drug. For example, fatty meals can enhance the absorption of lipophilic drugs, while calcium can reduce the absorption of certain antibiotics.

Ion Channels

Ion channels are characterized by selectivity for a particular ion, gating properties, and molecular structure.
Ion channels can be cation or anion selective.
Ligand-gated ion channels open when one or more agonists bind.
Voltage-gated ion channels are gated by changes in the transmembrane potential.

Ligand-Gated Ion Channels

Receptors of this type control the fastest synaptic events of the nervous system.
Examples include acetylcholine receptors.
They are associated with excitation and permeability changes.
They work in a fraction of a millisecond, indicating a minimal number of biochemical steps involved in transduction.

G-Protein-Coupled Receptors (GPCRs)

GPCRs make up a large and abundant family of receptors that are common targets for drugs.
Many neurotransmitters can interact with both GPCRs and ligand-gated ion channels.
The same molecule can produce fast (ligand-gated) and relatively slow (GPCRs) effects.

GPCR Components

Receptor: Located in the cell membrane, it possesses seven transmembrane alpha helices.
Ligand binding domain: Small molecules (noradrenaline, acetylcholine) bind in a cleft formed by alpha helical segments, while larger molecules (peptide ligands) bind in an extracellular loop.
Intracellular G-protein binding domain: Allows for selective binding to G Proteins.

G-Protein

Function: Recognizes activated GPCRs and transmits the "message" to effector systems that generate a cellular response.
It is located on the cytoplasmic side of the cell membrane.
G-Protein activation results in amplification, as the dissociation of the G-protein from the activated agonist-receptor complex allows for the activation of another G-protein.

Adverse Drug Reactions (ADRs)

Changes in ADME can often cause adverse drug reactions.
Type A ADR: Dose-related, predictable, and often reversible.
Type B ADR: Bizarre, unexpected responses unrelated to pharmacological effects, unpredictable, idiosyncratic, and independent of dose.
Type C ADR: Chronic reactions.
Type D ADR: Delayed reactions.
Type E ADR: Effects from withdrawal of the drug.
Pharmaceutical interactions can occur prior to administration (e.g., mixing acidic drug with basic drug), potentially causing inactivation.
Post-marketing surveillance is necessary to identify ADRs not detected during clinical trials, particularly rare or long-term effects in diverse and larger populations.

Limitations of Post-Marketing Surveillance

Underreporting.
Difficulty detecting delayed effects.
Challenges in linking ADRs to specific drugs due to concurrent drug use.

General Mechanisms of Toxic Damage to Cells

Oxidative destruction: Lipid peroxidation can damage cell membranes.
Protein modification: Can disrupt enzyme function or structural proteins.
DNA damage: Covalent binding to DNA can lead to mutations and cancer.
Impaired metabolism: Interference with cellular respiration or energy production.

Mutagenesis

Process of inducing genetic mutations, typically involving changes in DNA sequence.

Carcinogenesis

Multi-step process that results in the formation of cancer.

Muscarinic Agonists Effects

SLUDDE: Salivation, Lacrimation, Urination, Diarrhea, Defecation, Emesis.
These are muscarinic effects.

Muscarinic Antagonists

Anti-SLUDDE: Block muscarinic effects.

Nicotinic Agonists

Two possible sites of action:
- Autonomic ganglia.
- Neuromuscular junction.
Can lead to muscle twitches.

Indirect Agonists

Don't directly activate the receptor but influence the activity of substances like acetylcholine in different ways:
- Preventing acetylcholine breakdown (metabolism).
- Promoting acetylcholine release.

Anti-Cholinesterases

Indirectly enhance acetylcholine's action by inhibiting the enzyme that breaks it down (acetylcholinesterase).
This leads to more acetylcholine in the synapse.

Types of Cholinesterases

Acetylcholinesterase (AChE)
Butyrylcholinesterase (BuChE) also known as pseudocholinesterase.

Inhibition of Acetylcholine Synthesis

Prevents the production of acetylcholine.

Inhibition of Acetylcholine Release

Blocks the release of acetylcholine into the synapse, preventing it from transmitting signals from neurons or neurons to muscles.

Adrenergic Neurotransmitters

Norepinephrine (NE)
Epinephrine
Dopamine

Norepinephrine Release

Stored in vesicles until needed.
Release involves exocytosis triggered by calcium influx during depolarization.
Regulated by:
- Autonhibitory feedback via presynaptic α2 receptors.
- Calcium influx promoted by cAMP produced by adenylate cyclase.
- α2 receptors inhibit adenylate cyclase, reducing cAMP, calcium influx, and NE exocytosis.

cAMP as a Secondary Messenger

Produced by adenylate cyclase.
Helps relay signals from neurotransmitter receptors (α2 adrenergic receptors) on the presynaptic neuron to intracellular processes.
Regulates calcium influx, promoting calcium movement through ion channels, which triggers the release (exocytosis) of NE.

Feedback Mechanism for NE Release

When α2 receptors are activated, they inhibit adenylate cyclase activity, reducing cAMP production.
This reduction in cAMP decreases calcium influx, leading to decreased norepinephrine exocytosis.

Adrenergic Receptor Types

All adrenergic receptors are GPCRs.
α2 receptors: Inhibit NE release into the synapse.
β1 receptors: Increase cardiac rate and force.
β2 receptors: Bronchodilation, relaxation of visceral smooth muscle.

Ways to Affect NE Release

Directly block NE release.
Interfere with nerve action potential.
Presynaptic receptor agonism that inhibits release or stimulates extra-normal release.
Promote or reduce available intracellular NE stores.

Adrenergic Antagonists

Specific adrenergic antagonists selectively block either α or β adrenergic receptors.
This allows for more targeted effects with reduced risk of unwanted side effects.

Nonspecific Adrenergic Antagonists

Block both α and β adrenergic receptors.
Can lead to a range of physiological effects due to various receptor types.
May cause side effects related to both α and β inhibition.

Specific Adrenergic Agonists

Activate both α and β adrenergic receptors.
Produce a wide range of physiological responses due to the activation of multiple receptor types.
Can lead to both increased heart rate and vasoconstriction.

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Description

Explore the fundamentals of reaction rates and drug administration. This quiz covers key concepts such as reaction orders, half-lives, and the effects of drug delivery methods on absorption. Test your understanding of how these principles apply to pharmacokinetics.