Pharmacology: Drug-Receptor Interactions

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Questions and Answers

What is meant by 'full occupancy' in pharmacology?

Receptors can function even when not fully occupied by the drug.

Maximum response occurs only when some receptors are free.

The occupancy of receptors has no impact on drug efficacy.

It requires that all receptors be occupied by the drug to achieve maximal response. (correct)

What does the law of mass action state about the interaction between a drug and its receptor?

The response is proportional to the drug concentration and the number of available receptors. (correct)

The drug interacts with receptors regardless of their availability.

The response is independent of the drug concentration.

Maximum response occurs without receptor occupancy.

What is the significance of spare receptors in pharmacology?

They do not interact with drugs and are irrelevant to drug action.

They allow a maximal response with lower drug concentrations when not all receptors need to be occupied. (correct)

They offer additional binding sites for drugs, enhancing their effects.

Their presence indicates that higher drug doses are required for full efficacy.

Which type of receptor requires drugs to cross the cell membrane for binding?

Intracellular receptors. Signup and view all the answers

How do ligand-gated ion channels function upon drug binding?

They trigger the opening or closing of the channel to let ions pass. Signup and view all the answers

What characterizes intracellular receptors compared to other receptor types?

They are involved in longer-term cellular responses. Signup and view all the answers

Which receptor is an example of a ligand-gated ion channel that allows chloride ions to pass through?

GABA_A receptor. Signup and view all the answers

What is a key feature of the drug-receptor interaction in terms of concentration as indicated by the law of mass action?

Lower drug concentrations can still achieve maximal effects if spare receptors are present. Signup and view all the answers

What structural characteristic defines G-protein coupled receptors (GPCRs)?

They consist of seven transmembrane regions. Signup and view all the answers

Which of the following statements best describes the selectivity of a drug?

It reflects a drug's ability to affect a specific receptor. Signup and view all the answers

Which enzyme-linked receptor is specifically activated by insulin?

Insulin receptor. Signup and view all the answers

In the context of GPCRs, what effect does the beta-adrenergic receptor mediate?

It stimulates adrenaline effects. Signup and view all the answers

What does affinity indicate regarding drug-receptor interactions?

The strength of binding between a drug and its receptor. Signup and view all the answers

Which of the following is a common feature of approximately 50% of therapeutic drugs?

They target G-protein coupled receptors. Signup and view all the answers

Which downstream effect occurs when a ligand binds to a G-protein coupled receptor?

Activation of phospholipase C leading to the generation of IP3. Signup and view all the answers

What is an example of a therapeutic drug target that exhibits high selectivity?

Drugs that bind to specific receptors without impacting others. Signup and view all the answers

What does a high Therapeutic Index (TI) indicate about a drug?

The drug is relatively safe. Signup and view all the answers

Which statement correctly defines the Therapeutic Index (TI)?

TI is the ratio of lethal dose to effective dose. Signup and view all the answers

Why is warfarin considered to have a narrow therapeutic index?

It requires careful dosing due to risks of side effects. Signup and view all the answers

What is the structure of G-Protein Coupled Receptors (GPCRs)?

GPCRs are single subunit proteins with 7 transmembrane domains. Signup and view all the answers

What is the role of the α subunit in G-proteins?

It separates from the βγ subunits and facilitates signaling. Signup and view all the answers

In terms of therapeutic index, which of the following pairs represents a safe drug and a risky drug?

Lithium - Warfarin Signup and view all the answers

Which statement best describes the extracellular domain of GPCRs?

It interacts with ligands such as hormones or neurotransmitters. Signup and view all the answers

What is one characteristic of a drug that has a low therapeutic index?

It has a narrow range between therapeutic and lethal doses. Signup and view all the answers

What is the role of first-pass metabolism in orally administered drugs?

It reduces the effective concentration of the drug before it reaches systemic circulation. Signup and view all the answers

Which tissue type is likely to experience slower drug distribution due to lower blood flow?

Fat Signup and view all the answers

What is the primary role of cAMP in cellular signaling?

It activates protein kinases like PKA to mediate cellular responses. Signup and view all the answers

How does capillary permeability affect drug distribution in the body?

Tight capillaries (like in the brain) limit drug access to the central nervous system. Signup and view all the answers

Which of the following describes the main function of phosphorylated CREB?

Binding to specific DNA sequences to promote gene transcription. Signup and view all the answers

What is the significance of plasma protein binding in pharmacology?

It renders drugs inactive until they are released from their binding. Signup and view all the answers

What is the immediate effect of the activation of Gαt in the rhodopsin signaling pathway?

Hydrolysis of cGMP to GMP. Signup and view all the answers

Which example illustrates a medication that undergoes extensive first-pass metabolism?

Propranolol Signup and view all the answers

What is the significance of signal amplification in GPCR signaling?

It allows one ligand-bound receptor to activate multiple G-proteins and downstream effectors. Signup and view all the answers

What physiological feature primarily limits drug distribution to the central nervous system?

Presence of the blood-brain barrier. Signup and view all the answers

Which of the following best describes long-term cellular responses facilitated by activated kinases?

They influence gene expression and protein production over time. Signup and view all the answers

What occurs in the photoreceptor cell when cGMP levels decrease?

cGMP-gated ion channels close, reducing Na+ and Ca2+ influx. Signup and view all the answers

What impact does perfusion have on the distribution of drugs throughout the body?

Higher blood flow leads to faster distribution of drugs. Signup and view all the answers

How does the activation of PKA affect cellular proteins?

It phosphorylates specific target proteins, altering their activity. Signup and view all the answers

Which statement is true regarding free drugs in the bloodstream?

Only free drugs are capable of undergoing metabolism. Signup and view all the answers

What role does transducin play in the rhodopsin signaling pathway?

It activates phosphodiesterase to regulate ion channel activity. Signup and view all the answers

Study Notes

Law of Mass Action

Drug-receptor interactions are governed by the law of mass action; response correlates with drug and receptor concentrations.
Full occupancy of receptors results in maximal response; nonetheless, some tissues can reach maximum response with unoccupied receptors, known as spare receptors.
Spare receptors mean that effective responses can occur at lower drug concentrations.

Types of Receptors

Intracellular Receptors: Reside within the cell and require drugs to penetrate the cell membrane. Examples include steroid hormone receptors like cortisol and estrogen.
Ligand-Gated Ion Channels: Binding of drugs leads to opening or closing of channels, allowing ion movement. These receptors enable rapid processes, e.g., GABA_A receptor allows chloride ions through when activated.
G-Protein Coupled Receptors (GPCRs): Characterized by seven transmembrane domains, activated by ligands to initiate signaling via G-proteins. GPCRs are targets for approximately half of therapeutic drugs; an example includes beta-adrenergic receptors.
Enzyme-Linked Receptors: Ligand binding activates associated enzymes, triggering cellular responses. A notable example is the insulin receptor, which regulates glucose uptake.

Selectivity, Affinity, and Intrinsic Activity

Selectivity: Describes a drug's ability to selectively affect specific receptors, minimizing side effects.
Affinity: Measures the strength of interaction between a drug and its receptor.

Therapeutic Index (TI)

TI is calculated as the ratio of lethal dose (LD50) to effective dose (ED50).
LD50: Dose that results in death for 50% of a population.
ED50: Dose that produces the desired therapeutic effect in 50% of a population.
A high TI indicates a safer drug with a larger margin between effective and lethal doses, while a low TI suggests closer lethal and therapeutic doses, indicating a higher risk.

GPCR and G-Protein Signaling

GPCRs are single proteins with seven transmembrane domains interacting with ligands.
Activation leads to rapid responses through second messengers such as PKA and PKC, typically reversible within seconds to minutes.
Long-term signaling affects gene expression and can modulate cell function over extended periods.

Rhodopsin and Gαt Signaling Pathway

Rhodopsin functions as a GPCR in rod cells of the retina, activated by light.
Light induces a conformational change in rhodopsin, activating transducin (Gαt) by promoting GTP binding.
Gαt activation leads to stimulation of phosphodiesterase (PDE), reducing cGMP levels, which in turn causes closure of cGMP-gated ion channels and hyperpolarizes photoreceptor cells.

Signal Amplification in GPCR Signaling

GPCR signaling amplifies signals; one ligand-bound receptor can activate multiple G-proteins.
Each activated G-protein can trigger various downstream effectors, leading to extensive second messenger production.

First-Pass Metabolism

Orally administered drugs undergo first-pass metabolism in the liver via the hepatic portal vein before systemic circulation.
This process may significantly reduce the active drug concentration reaching the target site, exemplified by drugs like propranolol.

Blood Flow and Drug Distribution

Tissues with high blood flow (e.g., brain, liver, kidneys) facilitate rapid drug delivery; conversely, poorly perfused tissues (like fat) slow distribution.
Capillary permeability varies; loose capillaries (e.g., liver) allow easier drug passage, while tight capillaries (e.g., blood-brain barrier) limit access to certain tissues.

Plasma Protein Binding

Drugs can attach to plasma proteins (e.g., albumin), temporarily inactivating them.
Only unbound drugs are pharmacologically active and subject to metabolism, affecting their overall efficacy and potency.

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Description

Explore the fundamental concepts of drug-receptor interactions and the law of mass action in this pharmacology quiz. Understand the different types of receptors, including intracellular receptors, ligand-gated ion channels, and G-protein coupled receptors. Test your knowledge on how these mechanisms influence drug efficacy and response.