Lecture 4 Flashcards by Amro Amora X

The study of the biochemical and physiological effects of drugs, in certain period is called ?

Pharmacodynamics

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Give me another definition of Pharmacodynamics :

What the drug does to the body.

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Pharmacodynamics have 4 stages , mention them :

Drug receptors
Effects of drug
Responses to drugs
Toxicity and adverse effects of drugs

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Describe the pharmacodynamics in 2 points :

1- The actions of a drug on the body .
2- The influence of drug concentrations on the magnitude of the response .

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Most drugs exert their effects, both beneficial and harmful, by ?

Interacting with receptors

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The specialized target macromolecules that present on the cell surface or within the cell is ?

Receptors

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The drug–receptor complex initiates alterations in biochemical and/or molecular activity of a cell by a process called ?

Signal transduction

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Unoccupied receptor does influence intracellular processes . (T/F) ?

F—>( does not)

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Receptor is actived . This sentence can be true if :

If the receptor is linked with the agonist

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Drugs can act through three methods , mention them :

Physical action
Simple chemical reaction
Receptors

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Binding to different receptors and causing a biological response. This statement describe any method ?

Receptors

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Drug can produce a therapeutic response because of it’s physical properties. Give me example to describe this statement :

Mannitol as diuretic because it increase osmalerity.

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Drug may act through a chemical reaction . Give me examples to explain this statement :

1- Gastric antacids work by neutralizing the stomach acidity with a base
2- Chelating agents that bind heavy metals in body.

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Drugs act as ……….., and their receptors act as ………… .

1- signals
2- signal detectors

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How the receptor transduce their recognition of a bound “agonist” ?

By initiating a series of reactions that ultimately result in a specific intracellular response.

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• “agonist” refers to ?

Naturally occurring small molecule or a drug that binds to a site on a receptor protein and activates it .

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The part of the cascade of events that (( translates )) agonist binding into a cellular response named as ?

((Second messenger)) or effector molecules .

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Cells have many different types of receptors, each of which is specific for a particular agonist and produces a same response .
(T/F) ?

F—> (produces a unique response) . 🌚

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Cells have many different types of receptors, each of which is specific for a particular agonist and produces a unique response. Explain this statement with an example :

• Cardiac cell membranes, for example, contain β receptors that bind and respond to epinephrine or norepinephrine, as well as muscarinic receptors specific for acetylcholine.

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What is the importance of having a different receptor populations ?

To control the organ vital functions.

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The magnitude of the response is proportional to the number of drug–receptor complexes. (T/F) ?

True

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These interactions have many common features , mention the most important one :

Specificity of the receptor for a given agonist.

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How most receptors are named ?

For the type of agonist that interacts best with it (the receptor for histamine is called a histamine receptor).

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Receptors exist in at least two states , mention them :

1- inactive (R)
2- active (R*)

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The state that usually favouring is ?

Inactive state.

Binding of agonists causes ?

The equilibrium to shift from R to R* to produce a biologic effect.

…………… occupy the receptor but do not increase the fraction of R* and may stabilize the receptor in the inactive state.

Antagonists

Some drugs cause similar shifts in equilibrium from R to R* , but the fraction of R* is less than that caused by an agonist (but still more than that caused by an antagonist) named as ?

Partial agonists

The magnitude of biological effect is directly related to the fraction of R . (T/F) ?

F —>(R*) 😊

Agonists, antagonists, and partial agonists are examples of ?

Ligands, or molecules that bind to the activation site on the receptor

enzymes, nucleic acids, and structural proteins can act as receptors for drugs or endogenous agonists. (T/F) ?

True

The richest sources of therapeutically relevant pharmacologic receptors are ?

Proteins

The function of protein receptors is ?

Transduce extracellular signals into intracellular responses.

These receptors may be divided into four families , mention them:

1) ligand-gated ion channels, 2) G protein–coupled receptors, 3) enzyme-linked receptors, and 4) Intracellular receptors .

All drugs exert their effects, both beneficial and harmful, by interacting with receptors . (T/F) ?

F—> (most not all)

The type of receptor a ligand interacts with depends on ?

The chemical nature of the ligand.

Hydrophobic ligands interact with receptors that are found on the cell surface . In contrast, hydrophilic ligands enter cells through the lipid bilayers of the cell membrane to interact with receptors found inside cells . (T/F)

F —> (“Hydrophilic” ligands interact with receptors that are found on the cell surface . In contrast, “hydrophobic” ligands enter cells through the lipid bilayers of the cell membrane to interact with receptors found inside cells) 🌚

The extracellular portion of ligand-gated ion channels usually contains ?

Ligand binding site.

The function of ligand binding site is ?

Regulates the shape of the pore through which ions can flow across cell membranes

The channel is usually closed until the receptor is activated by an ………. , which opens the channel briefly for a few………. .

1- agonist 2- milliseconds

the receptor of ligand-gated ion channels have diverse functions , including ………..…………. .

neurotransmission, and cardiac or muscle contraction.

Voltage-gated ion channels can’t possess ligand-binding sites . (T/F)

F —> (Voltage-gated ion channels may also possess ligand-binding sites that can regulate channel function)

Now, give me three examples about transmembrane ligand-gated ion channels :

1. stimulation of the nicotinic receptor by acetylcholine results in sodium influx and potassium outflux, generating an action potential in a neuron or contraction in skeletal muscle. 2. agonist stimulation of the γ-aminobutyric acid (GABA) receptor increases chloride influx and hyperpolarization of neurons. 3. local anesthetics bind to the voltage-gated sodium channel, inhibiting sodium influx and decreasing neuronal conduction.

The extracellular domain of this receptor contains the ligand-binding area, and the intracellular domain interacts (when activated) with a G protein or effector molecule. This sentence describe any method ?

Transmembrane G protein–coupled receptors

Intracellular domain interacts with a G protein or effector molecule in any condition . (T/F)

F—>(the intracellular domain interacts (when activated) with a G protein or effector molecule) .

There are many kinds of G proteins , give me three examples of these kinds :

Gs, Gi, and Gq

G proteins ‏composed of three protein subunits , mention them ?

- The α subunit binds guanosine triphosphate (GTP) . - β and γ subunits anchor the G protein in the cell membrane .

Transmembrane G protein–coupled receptors take about ?

several seconds to minutes.

Sometimes, the activated effectors produce …….. ……….. that further activate other effectors in the cell, causing a signal cascade effect.

second messengers

Mention the reason that causing dissociation of the α-GTP complex from the βγ complex.

Binding of an agonist to the receptor increases GTP binding to the α subunit .

“These two complexes” !! In this sentence, the doctor means in two complex ? 😊

GTP & α subunit

These two complexes can then interact with other cellular effectors, usually an ………………., that are responsible for further actions within the cell

enzyme, a protein, or an ion channel

The function of adenylyl cyclase is ?

produces the second messenger cyclic adenosine monophosphate (cAMP)

A common effector, activated by…… and inhibited by……. , is adenylyl cyclase

1. Gs 2. Gi

Gq activates ?

phospholipase C

What happens when Gq activates phospholipase C ?

Generating two other second messengers: inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).

The function of DAG and cAMP is ?

activate different protein kinases within the cell, leading to a myriad of physiological effects.

The function of IP3 is ?

regulates intracellular free calcium concentrations, as well as some protein kinases.

This family of receptors consists of a protein that may form dimers or multisubunit complexes is called ?

Enzyme-linked receptors

What happens when Enzyme-linked receptors activated ?

These receptors undergo conformational changes resulting in increased cytosolic enzyme activity, depending on their structure and function .

Enzyme-linked receptors take about ?

minutes to hours.

Mention the most common enzyme linked receptors :

A. epidermal growth factor, B. platelet-derived growth factor, C. atrial natriuretic peptide, D. insulin, and E. others

The most common enzyme linked receptors (epidermal growth factor, platelet-derived growth factor, atrial natriuretic peptide, insulin, and others) possess tyrosine kinase activity as part of their structure.(T/F)?

True

The activated receptor phosphorylates tyrosine residues on other specific proteins and then itself . (T/F) ?

F —> (The activated receptor phosphorylates tyrosine residues on itself and then other specific proteins) .

Phosphorylation can substantially modify the structure of the target protein, thereby acting as a molecular switch. Give me example to explain this statement :

When the peptide hormone insulin binds to two of its receptor subunits, their intrinsic tyrosine kinase activity causes autophosphorylation of the receptor itself.

The phosphorylated receptor phosphorylates other peptides or proteins that subsequently activate other important cellular signals , result to :

cascade of activations results in a multiplication of the initial signal, much like that with G protein–coupled receptors.

The receptor is entirely intracellular, and, therefore, the ligand must diffuse into the cell to interact with the receptor. This method called ?

Intracellular receptors

What the ligand need in order to move across the target cell membrane ?

The ligand must have sufficient lipid solubility.

The primary targets of these ligand–receptor complexes are ?

Transcription factors in the cell nucleus.

Binding of the ligand with its receptor generally activates the receptor via ?

Dissociation from a variety of binding proteins.

The activated ligand–receptor complex then translocates to the …………

Nucleus

The activated ligand–receptor complex dimerizes before binding to transcription factors that regulate gene expression . This process happens when?

The activated ligand–receptor complex translocates to the nucleus

The activation or inactivation of these factors causes ?

Transcription of DNA into RNA and translation of RNA into an array of proteins .

The time course of activation and response of these receptors is on the order of ?

Hours to days .

Give me example of Intracellular receptors method :

Steroid hormones exert their action on target cells via intracellular receptors.

Mention Other targets of intracellular ligands :

1- structural proteins 2- enzymes 3- RNA 4- ribosomes

Give me example to describe the other targets of intracellular ligands :

1. Tubulin is the target of antineoplastic agents such as paclitaxel . 2. The enzyme dihydrofolate reductase is the target of antimicrobials such as trimethoprim . 3. The 50S subunit of the bacterial ribosome is the target of macrolide antibiotics such as erythromycin.

Mention two characteristics of signal transduction :

1) the ability to amplify small signals 2) mechanisms to protect the cell from excessive stimulation

Give me example about signal amplification ?

A single agonist–receptor complex can interact with many G proteins, thereby multiplying the original signal many folds.

Activated G proteins persist for a longer duration than does the original agonist–receptor complex . (T/F) ?

True

Give me other example related to signal amplification :

Binding of albuterol, for example, may only exist for a few milliseconds, but the subsequent activated G proteins may last for hundreds of milliseconds.

Further prolongation and amplification of the initial signal are mediated by ?

The interaction between G proteins and their respective intracellular targets ?

only a fraction of the total receptors for a specific ligand may need to be occupied to elicit a maximal response . Explain this statement :

Because of this amplification

Systems that exhibit this behaviour are said to have ………

spare receptors.

Spare receptors are exhibited by………… receptors, where it is estimated that 99% of receptors are spare.

Insulin

in the human heart, only about 5% to 10% of the total ………. are spare.

β-adrenoceptors

little functional reserve exists in the failing heart . Why !!

Because most receptors must be occupied to obtain maximum contractility .

When a receptor is exposed to repeated administration of an agonist, the receptor becomes ………….. resulting in a diminished effect.

Desensitized

due to either phosphorylation or a similar chemical event that renders receptors on the cell surface unresponsive to the ligand. This phenomenon called ?

tachyphylaxis

The receptors are internalized and sequestered within the cell, unavailable for further agonist interaction. This method called?

Down-regulation

These receptors my be ?

1- recycled to the cell surface, restoring sensitivity 2- further processed and degraded, decreasing the total number of receptors available.

particularly ion channels, require a finite time following stimulation before they can be activated again. This finite time called ?

Refractory period

During this recovery phase, unresponsive receptors are said to be……….. .

“refractory.”

repeated exposure of a receptor to an antagonist may result in ?

up-regulation of receptors

How the up-regulation of receptors happens

in which receptor reserves are inserted into the membrane, increasing the total number of receptors available.

Up-regulation of receptors can make the cells more sensitive to agonists and/or less resistant to the effect of the antagonist. (T/F) ?

F —>( Up-regulation of receptors can make the cells more sensitive to agonists and/or more resistant to the effect of the antagonist ) .

The fastest receptors family is ?

ligand-gated ion channels

The lowest receptors family is ?

Intracellular receptors

The picture in slide ( 11,15,18,19) is

U know the answer bro , go to study them

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