1. Binding of the ligand to the stimulatory receptor 2. GPCRs activate signals by inducing a conformation change. (exchange GTP for GDP) 3. alpha is active 4. G subunits dissociate with active alpha activating the the effector. 5. Lead to the second messager.

1. Binding of a ligand to the extracellular domain. 2. It cause dimerization of the receptor 3. stimulates a tyrosine kinase activity within the intracellular domain.

Lecture 1-4 Flashcards by Kim Phung Lo

Pharmacodynamics

How drug acts on its target cells and the body

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Pharmacokinetics

How your body does to the drug to get it to the target cells

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Pharmacokinetics steps

ADME (Absorption, distribution, metabolism, elimination)

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Bioavailability

amount of the drug that gets through the liver (varies between individuals)

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Selectivity

describe whether a drug has a more specific effect or more generalized effect. (selective drugs vs non-specific)

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Intracellular receptors

drugs able to cross the membrane into the cell and alter gene transcription/DNA and protein synthesis.

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Agonists vs Antagonists

Agonists activate receptors

Antagonists take place and inhibit activation of the agonists.

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V or F: Agonist and allosteric modulators are competitive.

False.

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Major features of receptors:

Quantitative relationship (affinity, concentration of drugs and number of receptor)
Specificity ( stereoselectivity)

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4 Major superfamilies

Ligand-gated ion channels (LGICs)
G protein-coupled receptors (GPCRs)
Receptor tyrosine kinase (RTKs)
Nuclear hormone receptors

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LGICs receptor responsible for

Nb of Subunits:

Fast synaptic transmission (release an electrical effect on the postsynaptic neuron)
4-5 subunits

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Nb of subunits on GPCRs

1 subunit composed of 7 transmembrane spanning domains.

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GPCRs function

Binding of the ligand to the stimulatory receptor
GPCRs activate signals by inducing a conformation change. (exchange GTP for GDP)
alpha is active
G subunits dissociate with active alpha activating the the effector.
Lead to the second messager.

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inhibitory receptor on GPCRs cause

GDP-GTP exchange on the alpha subunit. Which inhibits the 2nd messager.

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RTKs structure

extracellular ligand binding domains
one transmembrane spanning segment
intracellular tyrosine kinase domain.

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RTKs function

Binding of a ligand to the extracellular domain.
It cause dimerization of the receptor
stimulates a tyrosine kinase activity within the intracellular domain.

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Nuclear hormone receptors located

cytosol

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autocoid

biological factors which act like hormones with brief duration.

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Ion Channels 2 major types

Voltage-gated

2. Receptor-operated

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Autocrine

acting back on the same cell

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Endocrine

moving through the circulation

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Paracrine

acting on neighboring cells

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Juxtacrine

one cell contacts another

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T or F: Two G-protein coupled receptors cannot exist on the same cell and have opposite effects.

False. It can have opposite effects; activate and inhibit a particular enzyme

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Receptor turnover

cells continually making new receptors and recycling old ones.

T or F: Microtubules and other fibers that undergo mitosis are a site for drug action.

True. Anticancer drugs act on it, target rapidly dividing cells to prevent cells from dividing properly.

Magnitude of drug effect study with

- Dose response curve. (threshold and ceiling dose and ED50) - Receptor occupancy

dose at which 50% of the receptor are bound

T or F: ED50 is reach before reaching Kd.

True.

T or F: Partial agonists may occupy a huge number of receptors but only have a small response.

True.

T or F: Partial agonists can't block the access of a full agonist.

False. It can block the access of a full agonist (competitive)

Irreversible binding to a receptor

require synthesis of new receptors to overcome its effect.

indirect agonist or antagonist is bind to

an allosteric site

T or F: A higher concentration of an agonist is required to have the same response alone in the presence of a competitive antagonist.

True. But with SPARE RECEPTOR, even with the presence of antagonist, agonist will continue to activate receptors and will be possible to increase the dosage of the agonist to get the same response.

T or F: An increase of the amount of the natural ligand can overcome the presence of competitive agonist or antagonist.

True.

T or F: Noncompetitive antagonists will lower the dose-response curve, as they will always have an effect on the receptor.

True.

TD50

50% people will reach the drug's toxic effect

LD50

50% people will reach the drug's lethal dose (kill them)

Therapeutic index

Multiplication factor by which the ED50 will kill you (ex. TI of alcohol is 4)

Benefit outliers vs toxicity outliers

B: more or less sensitive to certain drugs T: get toxicity at very low doses

Non-ionized molecule

LIPID SOLUBLE

Ionized molecule

Water soluble

Weak acid

is a Non-ionized molecule. (Diffuse through the lipid membrane and be absorbed in the stomach more easily)

Weak base

is better absorbed in a more basic environment like the intestine.

First-pass effect

drugs move to liver via portal circulation before get to the venous circulation.

Bypass effect

by pass the liver and go directly in the circulation

T or F: Drugs with low bioavailbility will be metabolized in large part by the liver.

True.

Two compartment model

(Distribution) (can be more than 2 compartments) 1. blood 2. to the different Tissues (brain/heart-muscle-bone/fat)

AVD (apparent volume of distribultion)

volume it would take if the drug were evenly distributed throughout the body. AVD= Vd= amount of drug give (x) / Concentration in the plasma (Cp)

loading dose

amount of drug needed to give immediately to get an effective concentration in the blood.

T or F: AVD will be low with more protein binding.

True. and AVD will be high with more tissue binding.

prodrug

inactive drug convert to an active form.

Phase I:

reaction serve to inactive the drug or less active compound. By changing its chemical structure. (oxidation, reduction or hydrolyze)

Phase II:

Serve to make it more water-soluble for the excretion through the kidney. (conjugation)

Enzyme responsible in the phase I

Cytochrome P450 (CYP450)

drug disposition

drug metabolism

Enzyme induction

occurs when production of the enzyme is stimulated in the presence of the drug

T or F: Drug metabolism is not necesary affected by age.

True. Though liver volume tends to decrease with age, it is still above the level needed for necessary function.

T or F: Poor metabolizers of a given drug have a different quantity of enzyme.

False. Poor metabolizers of a given drug have a different GENE (Polymorphic distribution)

Phase II enzymes are

Transferases (transfer something onto the parent compound to make it more water-soluble.

Glucuronic acid and glutathione is

mose commun transferases enzymes.

T or F: As the free drug is filtered out of the blood by the kidney, more will be removed from albumin to maintain the equilibrium.

True. There is always an equilibrium between free and bound drug. This permit the drug to be filtered out entirely.

T or F: Drugs are only eliminated by the kidney and through exhalation.

False. Some drugs are excreted/secreted by salivary glands and sweat glands. ex. garlic, alcohol or onion.

Drug clearance

refer to quantity of a drug eliminated in a given amount of time.

Therapeutic window is:

the concentration range between which a reasonable number of people respond to the drug.

Low AVD:

mean that concentration of the drug in the blood is high (least in the tissues)

High AVD:

mean that the concentration of the drug in the blood is low, so mostly distributed in the tissues)

When there is more protein binding with the drug (ex.albumin or others plasma p+), its mean that the AVD will be:

Low. Bc not distributed highly in the tissues.

Some drugs cannot pass through the intestinal lumen so we cannot giving them orally because:

they are expelled by P glycoproteins

Lecture 1-4 Flashcards

(69 cards)