[GENERAL PRINCIPLES] Molecular Mechanism of Action - Protein Mediated

Proverbs 16:3

Pharmacodynamics

This refers to the effects of drugs through MOA - "What the drug does to the body?"

● Protein: Target Protein Mediated Action

● Non-protein: Non-Target Protein Mechanism

Categories of Mechanism of Action include:

● Structural protein

● Regulatory protein

Target Protein Mediated Action includes:

● Physical interaction

● Chemical interaction

● Counterfeit mechanism

Non-Target Protein Mechanism includes:

Structural protein

[PROTEIN MEDIATED]

These protein form cell framework of cytoskeleton.

● Tubulin

● Microtubules

[PROTEIN MEDIATED]

Examples of STRUCTURAL proteins include:

Tubulin

[STRUCTURAL PROTEIN]

This is a simple structural protein which is NOT yet functional.

Tubulin

[STRUCTURAL PROTEIN]

This is a simple structural protein that undergoes polymerization, forming microtubule which is now functional.

polymerization

[STRUCTURAL PROTEIN]

Tubulin is a simple structural protein that undergoes ________, forming microtubule which is now functional.

microtubule

[STRUCTURAL PROTEIN]

Tubulin is a simple structural protein that undergoes polymerization, forming ________ which is now functional.

Microtubule

[STRUCTURAL PROTEIN]

This structural protein is important for cell division, mitosis, and cell movement.

● Cell division

● Mitosis

● Cell movement

[STRUCTURAL PROTEIN]

Microtubule is important for ____________[3]

● Cancer (abnormal mitosis)

● Inflammation (abnormal cell movement)

[STRUCTURAL PROTEIN]

Abnormalities in microtubules include ___[2]

● Colchicine

● Vinca alkaloids (Vincristine)

● Taxanes (Paclitaxel)

● Griseofulvin

[STRUCTURAL PROTEIN]

Drugs for abnormalities in microtubules include ___[4]

Colchicine

[STRUCTURAL PROTEIN]

This is the first line anti-inflammatory agent for ACUTE gout (pain and inflammation).

Allopurinol

[STRUCTURAL PROTEIN]

This is the first line agent for CHRONIC gout.

● Vinca alkaloids (Vincristine)

● Taxanes (Paclitaxel)

[STRUCTURAL PROTEIN]

These are ANTI-CANCER and ANTI-MITOTIC drugs.

Griseofulvin

[STRUCTURAL PROTEIN]

This is an anti-fungal drug which specifically blocks FUNGAL MITOSIS.

Regulatory protein

[PROTEIN MEDIATED]

These proteins maintain and regulate cellular activity or function.

● Voltage Gated Ion Channel

● Carrier Molecules

● Enzymes

● Receptors

[PROTEIN MEDIATED]

Regulatory proteins include____[4]

Voltage Gated Ion Channel

[REGULATORY PROTEIN]

These channels conduct changes in ELECTRICAL signal.

● Excitatory

● Inhibitory

[REGULATORY PROTEIN]

Effects of Voltage Gated Ion Channel include [2]

Excitatory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

The inside of the cell becomes more positive (+) compared to the outside.

Excitatory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

● Na⁺ (Sodium) channels open → Na⁺ enters the cell

● Ca²⁺ (Calcium) channels open → Ca²⁺ enters the cell

Excitatory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

Depolarization

Excitatory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

Stimulation and Contraction

● Na⁺ (Sodium)

● Ca²⁺ (Calcium)

[VOLTAGE GATED ION CHANNELS]

Ions that produce EXCITATORY effect:

● Stimulation

● Contraction

[VOLTAGE GATED ION CHANNELS]

EXCITATORY responses include___[2]

Inhibitory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

The inside of the cell becomes more negative (−) compared to the outside.

Inhibitory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

● K⁺ (Potassium) channels open → K⁺ EXITS the cell.

● Cl⁻ (Chloride) channels open → Cl⁻ enters the cell

Inhibitory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

Hyperpolarization

Inhibitory

[VOLTAGE GATED ION CHANNELS]

Excitatory vs Inhibitory:

● Depression

● Relaxation

● Dilation

● K⁺ (Potassium) channels open

● Cl⁻ (Chloride) channels open

[VOLTAGE GATED ION CHANNELS]

Ions that produce INHIBITORY effect [2]

● Depression

● Relaxation

● Dilation

[VOLTAGE GATED ION CHANNELS]

INHIBITORY responses include_____[3]

● Sodium Channel Blockers

● Potassium channel stimulants

● Potassium channel blocker

[VOLTAGE GATED ION CHANNELS]

Drugs that act on VOLTAGE GATED ION CHANNELS include[3]

● Class I Anti-arrhythmic

● Local Anesthetics (Ester and Amide)

● Some anticonvulsants: Carbamazepine, Phenytoin

[VOLTAGE GATED ION CHANNELS]

Sodium Channel Blockers (inhibits depolarization = hyperpolarization = relaxant) include: [3]

Amide

[VOLTAGE GATED ION CHANNELS]

Xylocaine is an (ester, amide) anesthetic.

● Minoxidil

● Diaxozide

[VOLTAGE GATED ION CHANNELS]

Examples of K channel STIMULANTS (hyperpolarization = relaxation) [2]

Arteriolar vasodilator

[VOLTAGE GATED ION CHANNELS]

Minoxidil and diaxozide are K channel stimulants used as __________ in hypertension.

Insulin secretagogues

[VOLTAGE GATED ION CHANNELS]

Example of K channel BLOCKER (inhibits hyperpolarization = stimulation):

Carrier molecules

[REGULATORY PROTEIN]

These are cell membrane proteins with specific binding sites and undergo conformation changes.

● Na⁺- K⁺ ATPase Pump (NAP)

● K⁺- H⁺ Pump (Proton Pump)

[CARRIER MOLECULES]

Carrier molecules include:[2]

Na⁺- K⁺ ATPase Pump (NAP)

[CARRIER MOLECULES]

This pump is found in the HEART, causing Ca²⁺ ion extrusion (going out).

Calcium

[CARRIER MOLECULES]

This ion is important for HEART CONTRACTION.

Digoxin

[CARRIER MOLECULES]

This is a drug that inhibits the Na⁺- K⁺ ATPase Pump (NAP), leading to the inhibition of Na⁺/Ca²⁺ Exchanger (NCX).

This causes accumulation of Ca²⁺ inside the cardiac cells, resulting to increased myocardial contraction (positive inotropic effect).

Digoxin

[CARRIER MOLECULES]

This is a drug is used for HEART FAILURE.

Na⁺/Ca²⁺ Exchanger (NCX)

[CARRIER MOLECULES]

Digoxin is a drug that inhibits the Na⁺- K⁺ ATPase Pump (NAP), leading to the inhibition of ___________.

This causes accumulation of Ca²⁺ inside the cardiac cells, resulting to increased myocardial contraction (positive inotropic effect).

K⁺-H⁺ Pump (Proton Pump)

[CARRIER MOLECULES]

This pump is found in the parietal cells of the stomach, which functions for HCl acid production.

● Acetylcholine (ACh) → acts on M1 receptors

● Histamine → acts on H1 receptors

● Gastrin → stimulates ACh release

[CARRIER MOLECULES]

_____[3]

• These mediators stimulate the parietal cell but blocking these is not enough to fully stop acid secretion.

  • Therefore, Proton Pump Inhibitors (PPIs) are used because they directly inhibit the final step of acid secretion (the proton pump).

Proton Pump Inhibitors

[CARRIER MOLECULES]

These drugs are the MOST EFFECTIVE agent for hyperacidity.

Aripiprazole (ANTIPSYCHOTIC)

[CARRIER MOLECULES]

Proton Pump Inhibitors end in -PRAZOLE except _________.

Enzymes

[REGULATORY PROTEIN]

These are biological catalysts used to hasten biochemical reactions.

Monoamine oxidase

[ENZYMES]

Examples of enzymes include:

Monoamine oxidase

[ENZYMES]

This enzyme is responsible for the metabolism of MONOAMINES.

● MAO-A

● MAO-B

[ENZYMES]

Monoamine oxidase include ____[2]

● Norepinephrine

● Epinephrine

● Serotonin

[ENZYMES]

These monoamines are targeted by the MAO-A enzyme.

Dopamine

[ENZYMES]

This monoamine is targeted by the MAO-B enzyme.

● Major depression

● Parkinsonism

[ENZYMES]

Diseases related to monoamines include:[2]

● ⬇ Norepinephrine

● ⬇ 5-HT (5-hydroxytryptamine/SEROTONIN)

[ENZYMES]

Low levels of these monoamines cause MAJOR DEPRESSION.

⬇ Dopamine

[ENZYMES]

Low level of this monoamine causes PARKINSONISM.

● Moclobemide

● Phenelzine

● Isocarboxazid

● Tranylcypromine

● Selegiline

[ENZYMES]

Examples of MAO inhibitors include: [5]

Moclobemide

[ENZYMES]

This MAO inhibitor is MAO-A selective, used for MAJOR DEPRESSION only.

Selegiline

[ENZYMES]

This MAO inhibitor is MAO-B selective, used for PARKINSONISM only.

● Phenelzine

● Isocarboxazid

● Tranylcypromine

[ENZYMES]

These MAO inhibitors are NONSELECTIVE, which can be used BOTH for MAJOR DEPRESSION and PARKINSONISM.

● Moclobemide

● Phenelzine

● Isocarboxazid

● Tranylcypromine

[ENZYMES]

These MAO inhibitors are used for MAJOR DEPRESSION.

● Phenelzine

● Isocarboxazid

● Tranylcypromine

● Selegiline

[ENZYMES]

These MAO inhibitors are used for PARKINSONISM.

Receptors

[REGULATORY PROTEIN]

These are specific proteins where ligand interacts through lock and key fashion.

lock and key fashion

[REGULATORY PROTEIN]

Receptors are specific proteins where ligand interacts through ________ fashion.

● Depolarization/hyperpolarization

● Secondary messenger formation

● Phosphorylation

● Gene expression

[RECEPTORS]

Signal transduction effects of receptors include: [4]

● Type I (Ionotropic Receptor/ Ligand Gated Ion Channels)

● Type II (7-transmembrane/Serpentine/G-protein Coupled/Metabotropic Receptor)

● Type III (Kinase-Linked Receptor)

● Type IV (Gene Transcription Linked Receptor)

[RECEPTORS]

Types of receptors include: [4]