Drug Targets; pharmodynamics p1

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Questions and Answers

What is a primary role of enzymes in biochemistry?

Signaling processes only

Only drug metabolism

Gene activation and suppression (correct)

Only acting as catalysts

What typically causes voltage-gated sodium channels to open?

Membrane hyperpolarization

Normal membrane potential

Presence of specific cations

Membrane depolarization (correct)

Which mechanism is primarily responsible for the regulation of enzyme activity?

Environmental temperature changes

Natural variation in enzyme concentration

Changes in pH levels alone

Feedback processes and modulation (correct)

Which of the following ions are typically selective in ion channels?

Chloride ions (Cl-) Signup and view all the answers

What is the primary function of membrane transporters?

To move ions and small molecules across membranes Signup and view all the answers

What is the primary mechanism of action of atorvastatin?

Enzyme inhibition Signup and view all the answers

Which drug is associated with a receptor as its target?

Levothyroxine Signup and view all the answers

Which percentage represents the share of medical drugs targeting enzymes?

29% Signup and view all the answers

Which drug is primarily identified as a transporter target?

Omeprazole Signup and view all the answers

In the context of drug targets, what does GPCR-coupled refer to?

G-Protein Coupled Receptors Signup and view all the answers

Which of the following conditions is treated with a drug that targets an ion channel?

Hypertension Signup and view all the answers

What is the mode of action of aspirin in the treatment of thromboembolism?

Inhibiting enzymes Signup and view all the answers

What percentage of known drug targets are classified as receptors?

44% Signup and view all the answers

What is the primary function of ligand-gated ion channels?

Allow ion movement across the membrane Signup and view all the answers

Which receptor type is primarily involved in the long-lasting effects of gene regulation?

Nuclear receptors Signup and view all the answers

Which of the following receptor types is associated with fast neurotransmission?

Ligand-gated ion channels Signup and view all the answers

What is a characteristic of kinase-linked receptors?

They are usually activated by cytokines. Signup and view all the answers

Which receptor type has a pentameric structure?

Nicotinic acetylcholine receptors Signup and view all the answers

What distinguishes receptor subtypes from one another?

Different structural compositions Signup and view all the answers

Which of the following receptors is linked to protein phosphorylation?

Enzyme-linked receptors Signup and view all the answers

What do opioid receptors primarily regulate?

Nociception Signup and view all the answers

What is one potential result of the reduced expression of a drug target?

Decreased availability of receptors at the cell surface Signup and view all the answers

How can chronic use of CNS depressants affect physiological activity?

Increasing excitatory signaling Signup and view all the answers

What is a common pharmacokinetic change caused by chronic drug use?

Induction of liver enzymes that degrade the drug Signup and view all the answers

Which describes a mechanism of drug resistance?

Alteration of drug target affinity Signup and view all the answers

What physiological system is activated by systemic presence of corticosteroids?

Adrenal hypothalamic pituitary system Signup and view all the answers

What may be a result of removing corticosteroids after prolonged treatment?

Cortisol deficit Signup and view all the answers

Which of the following factors affects drug response?

Organ disease and receptor sensitivity Signup and view all the answers

Pharmacodynamics primarily studies the relationship between drugs and what?

Physiological activity changes in the body Signup and view all the answers

What is the primary function of G-protein coupled receptors (GPCRs)?

Detect and transmit signals through ligand binding. Signup and view all the answers

Which of the following is NOT a superfamily of receptors?

Chemokine receptors Signup and view all the answers

What is a common outcome of GPCR activation by Gs proteins?

Increase in cAMP levels. Signup and view all the answers

Which mechanism is associated with Gq proteins?

Increase of intracellular calcium. Signup and view all the answers

Which type of receptor is primarily involved in neurotransmission?

Ligand-gated ion channels Signup and view all the answers

The largest family of receptors in the human body is known as what?

G-protein coupled receptors Signup and view all the answers

Which of the following correctly describes a secondary messenger involved in GPCR signaling?

cAMP Signup and view all the answers

Which receptor type is involved in the regulation of inflammation?

Prostaglandin receptors Signup and view all the answers

What is the role of G-proteins in GPCR signaling pathways?

Relay signals from GPCRs to intracellular targets. Signup and view all the answers

Which of the following statements about GPCRs is incorrect?

They are all metabotropic receptors. Signup and view all the answers

Study Notes

Drug Targets

Drugs can act on a variety of targets including proteins, pathogens, fungi, parasites, dietary supplements, DNA, amino acids, and chemical messengers.
Approximately 1,591 medical drugs target known proteins, with receptors being the most frequent target (44%), followed by enzymes (29%) and transporters (15%).
Among the top 10 most prescribed primary care drugs (UK 2018), the majority target enzymes, transporters, or receptors.

Molecules to Cells: Pathways and Interactions

Cells possess complex biochemical pathways involving receptors, enzymes, and secondary messengers, influencing cellular function.
Drugs can interact with these pathways at various points, potentially resulting in unintended side effects.

Receptors

Receptors serve as key elements in cellular communication, mediating interactions within endocrine, paracrine, juxtacrine, and autocrine signaling systems.
There are four main receptor superfamilies: G-protein coupled receptors (GPCRs), ligand-gated ion channels, kinase-linked receptors, and nuclear receptors.
Receptors are often named after their ligands, either endogenous or pharmacological.

G-protein Coupled Receptors (GPCRs)

The largest receptor family, with approximately 900 known human GPCRs.
Ligand-activated receptors, characterized by a single polypeptide chain with seven transmembrane (TM) domains.
They interact with intracellular effectors known as G-proteins, triggering enzymatic signaling cascades.
These cascades involve metabotropic (slow) signaling, typically with induction times of over 100 milliseconds and effects lasting seconds to minutes.

Gs Proteins

Gs proteins stimulate adenylate cyclase (AC), leading to increased levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity.

Gi Proteins

Gi proteins inhibit adenylate cyclase (AC), leading to decreased levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity.

Gq Proteins

Gq proteins activate phospholipase C (PLC), resulting in increased intracellular calcium levels and activation of protein kinase C (PKC).

Examples of GPCRs

Muscarinic acetylcholine receptors are involved in the central nervous system (CNS), lungs, and gastrointestinal (GI) tract.
Adrenergic receptors affect the heart, vasculature, lungs, and CNS.
Histamine receptors influence the heart, vasculature, GI tract, and nociception.
Prostaglandin receptors play roles in inflammation, the GI tract, and the CNS.
Opioid receptors are involved in nociception, the GI tract, and the CNS.

Ligand-Gated Ion Channels

These channels are activated by ligand binding.
They open to allow ion movement across the membrane, resulting in ionotropic signaling.
This process is extremely fast, occurring within milliseconds, crucial for neurotransmission.

Examples of Ligand-Gated Ion Channels

Nicotinic acetylcholine receptors are found in the CNS, peripheral nerves, and the neuromuscular junction (NMJ).
NMDA glutamate receptors operate in the CNS.
GABAA receptors are located in the CNS.
P2X receptors are activated by purines, particularly adenosine triphosphate (ATP), and are present in the CNS, peripheral nerves, and blood cells.

Enzyme-Linked and Nuclear Receptors

Often activated by signaling molecules such as cytokines and hormones.
Primarily involved in regulating cellular processes and gene expression.
Typically, these receptors exhibit slow induction of effects with long-lasting consequences due to gene regulation.
Enzyme-linked receptors include receptor tyrosine kinases (RTKs) and receptor serine/threonine kinases (RSTKs).

Kinase-Linked Receptors

Activate protein phosphorylation.
This phosphorylation cascade influences gene transcription and subsequent protein synthesis.
The kinase-linked receptor family is vast and heterogeneous, often with enzymatic activity within their intracellular domain.
Growth factors commonly serve as ligands for these receptors.

Nuclear Receptors

These receptors are located either in the nucleus or cytoplasm and require ligand passage through the membrane.
They regulate gene transcription within the nucleus.
Nuclear receptors often serve as targets for hormones.
They can recognize foreign molecules and trigger metabolic processes.

Receptor Subtypes

Structurally similar receptor proteins may exhibit variations in their mechanisms of action and effects despite sharing the same endogenous ligand.
For example, muscarinic acetylcholine receptors (M1-M5) have distinct signaling pathways and G-protein coupling despite all being activated by acetylcholine.

Enzymes

Enzymes are critical regulators of physiological processes, playing essential roles in signaling, metabolism, and gene regulation.
Drug metabolism often occurs through hepatic enzymes.
Enzymes can be altered by factors like feedback processes, modulation, inhibition, activation, and phosphorylation.
Drugs can also influence enzymatic activity.

Ion Channels

Typically, channels are selective for either cations (K+, Na+, Ca2+) or anions (Cl-, HCO3-).
Cation channels can be specific for a particular ion or non-specific, allowing passage of all three.
Ligand-gated channels often serve as receptors.
Ion channels can be grouped into leak channels (with limited clinical relevance), voltage-gated channels (e.g., Na+, Ca2+), and other gated channels (e.g., Transient Receptor Potential (TRP) channels).

Voltage-Gated Sodium Channels

An example is the voltage-gated sodium channel (VGNaC).
These channels remain closed at normal membrane potential (-70 mV).
Membrane depolarization (-40 mV) induces the opening of Na+ channels.

Membrane Transporters ("Pumps")

Transporters are proteins that move ions and small molecules across the membrane, contributing to important functions like signaling, nutrient uptake, and waste removal.

Effects of Drug Actions on Transporters

Reduced expression of drug targets, e.g., decreased receptor number in the plasma membrane or reduced transcription of the drug target gene.
Increased activity in opposing physiological pathways.
Altered drug absorption, distribution, metabolism, and excretion (ADME).
Drug resistance through inactivation mechanisms.
Behavioral adaptations as the body learns to manage the drug effects.

Withdrawal

Withdrawal symptoms often arise from systemic up or downregulation of physiological systems to compensate for drug effects.
When treatment ends, the system may exhibit excessive opposing activity.
An example is corticosteroid withdrawal, where prolonged corticosteroid use suppresses endogenous cortisol production. Upon cessation, the body may experience cortisol deficiency, potentially leading to severe complications requiring hospitalization.

Summary: Drug Action and Pharmacodynamics

Drugs exert their effects by influencing molecular processes, thereby altering physiological activity.
Pharmacology is enhanced by understanding the systems that drugs target, including cellular biology and physiology.
Pharmacodynamics encompasses the study of drug actions on the body.
Key drug targets include receptors, enzymes, ion channels, and transporters, emphasizing specificity and selectivity.
Adverse drug reactions and tolerance and withdrawal phenomena also play significant roles in drug utilization.

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Description

Explore the various drug targets and their roles in cellular processes. This quiz covers key concepts of receptors, biochemical pathways, and the impact of drugs on cellular communication. Test your knowledge about how drugs interact with proteins, enzymes, and more.