(6) DSA | Intro to Pharmacodynamics (Konorev) Flashcards by Jaime Weber

Define:

Pharmacokinetics

Effect of the BODY on drugs

ADME

Absorption
Distribution
Metabolism
Elimination

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Define:

Pharmacodynamics

Effects of DRUGS on the body

Drug receptors
Dose-response curves
Mechanisms of drug actions

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Define:

A Receptor

A specific molecule in a biological system that plays a regulatory role

The receptor interacts with a drug and initiates the biochemical events leading to drug effects

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Define:

Inert binding site

A compontnet of the biologic system to which a drug binds without changing any function

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Define:

Ligand

A ligand is a molecule, such as a hormone or a drug, which binds to a receptor

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Describe the “lock and key” model of ligand receptor interaction

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Types of Drug-receptor interactions

Describe: Covalent bonds

Irreversible

Drug removal/receptor reactivation requires re-synthesis of the receptor or enzymatic removal of the drug

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Types of Drug-receptor interactions

Describe: Non-covalent bonds

Reversible

Most drugs bind to receptors via non-covalent bonds

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Rank the following types of bonds from WEAKEST to STRONGEST

Hydrophobic interactions

Ionic bonds

Hydrogen bonds

Weakest = Hydrophobic interactions

Middlest :) = Hydrogen bonds

Strongest = Ionic bonds

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What are the three parameters that describe the interaction of a drug with a receptor?

Affinity
Selectivity
Intrinsic activity

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What is affinity of a drug?

What does high vs low affinity mean?

The affinity of a drug for a receptor describes how readily and tightly that drug binds to its receptor

High affinity= good drug-receptor interaction; LESS drug needed to produce a response

Low affinity= poor drug-receptor interaction; MORE drug needed to produce a response

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What is the parameter that describes the affinity?

K_D

(equilibrium dissociation constant)

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Define KD

What are the units?

Drug concentration at which 50% of the drug receptor binding sites are occupied by the drug

Molar concentration

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What does a LOW K_D mean?

The lower the K_D…

The higher the affinity of a drug for a receptor

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What does a high K_D mean?

The higher the K_D …

The LOWER the affinity of a drug for a receptor

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What is the equation for calculating K_D?

[L] = ligand

[R]= receptor

[LR] = ligand-receptor complex

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What is drug selectivity?

A property of a drug determined by its affinities at various binding sites

*A MORE selective drug would affect fewer targets over a specific concentration range

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What is instrinsic activity?

The ability of a drug to change a receptor function and produce a physiological response upon its binding to a receptor

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What is an agonist?

Bind the receptor and stabilize it in a particular conformation (usually the active conformation) producing a physiological response

*HAS intrinsic activity

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What is an antagonist?

Bind to the receptor but do NOT CHANGE ITS FUNCTION

However, they prevent activation of the receptor in the presence of an agonist

**DO NOT have intrinsic activity

What are the three types of agonists?

Full agonists

Partial agonists

Inverse agonists

What do full agonists do?

FULLY activate receptors

Produce max. pharmacological effect when all receptors are occupied

Maximal intrinsic activity

What do partial agonists do?

PARTIALLY activate the receptor upon binding

Produce a sub-maximal pharmacological effect when all receptors are occupied

What do inverse agonists do?

Produce an effect OPPOSITE to a full or partial agonist

Decrease receptor signaling
Intrinsic activity is present and related to the inhibition of receptor function

Graphically, depict the response levels of Full agonist Partial agonist Antagonist Inverse agonist

What are the three types of antagonism?

Pharmacologic Chemical Physiologic

Describe: **Pharmacologic** antagonism

aka Receptor antagonism Action at the same receptor as endogenous ligands or agonist drugs

Describe: **Chemical** antagonism

When chemical antagonist makes the other drug unavailable

Describe: **Physiologic** antagonism

Occurs between endogenous pathways regulated by different receptors

Describe a: **Competitive** antagonist

COMPETES with endogenous chemicals or agonist drugs for binding of the receptor

Describe a: **Non-competitive** antagonist What subtypes does this include?

Receptor inactivation is not surmountable Irreversible antagonists= irreversibly bind to and occlude the agonist site on the receptor by forming covalent bonds Allosteric antagonists = bind to a site other than the agonist site to prevent or reduce agonist binding or activation of the receptor

Describe the **agonist effect (E)** vs **agonist concentration (EC)** relationships graphically for: Competitive antagonism Noncompetitive antagonism

What is a **dose-response** curve?

Graphic representation of the relationship between a **drug and its effects**

When you plot drug dose **arithmetically** on the x-axis vs drug effect on the y-axis, you get a \_\_\_\_\_\_\_\_\_\_\_

Hyperbolic curve

When you present the dose-response curve as graphing the **logarithm** of the drug dose vs the respone, you'll get a \_\_\_\_\_\_\_\_\_\_

Sigmoidal curve

What is the: E_max ED₅₀ Within a dose-response curve?

E_max= the maximal effect thta can be produced by the drug ED₅₀ = Effective dose, the dose that produces 50% of it's maximal effect

What questions does a **graded response** answer?

"How much?"

What questions does a **quantal response** answer?

[All or none; yes-no; "binary" responses] "Does the response occur or not?" "In how many?"

Describe what a **non-cumulative** quantal dose response curve looks like: What information does it include?

Number or % of individuals responding at a dose of a drug and **ONLY AT THAT DOSE**

Describe what a **cumulative quantal dose response curve** would look like: What information is contained here?

Number or % of individuals responding at a dose of a drug **AND at all doses loer than that dose**

# Define: ED₅₀ TD₅₀ LD₅₀

ED₅₀= median effective dose TD₅₀= median toxic dose LD₅₀ = median lethal dose

How do you claculate the **therpeutic index?** What does a HIGH TI mean?

Therapeutic Index (TI) : TD₅₀/ED₅₀ \*\*The higher the TI, the SAFER the drug

# Define: Therapeutic window

The range of doses of a drug or of its concentration in a bodily system that provides for the **safe and effective therapy**

# Define: ## Footnote **Potency**

The amout of drug required to produce specific pharmacological effect

# Define: **Efficacy**

The maximal pharmacological effect that a drug can produce

What are the major classes of drug targets?

Membrane receptors Nuclear receptors Ion channels Transport proteins Enzymes

What do **protein kinases** do?

Modify protein by covalently attaching a **phosphate group** to an amino acid residue

What are the effects of the following G protein subclasses? G_s G_i G_q G_12/13

G_s = activates all isoforms of adenylyl cyclase G_i= inhibits adenylyl cyclase G_q= activates phospholipase C G_12/13 = activates Rho GTPases

Note: didn't include the rest of the DSA info because it's all biochem review