Pharmacodynamics Principles

Pharmacodynamics

study of the biochemical and physiologic effects of drugs in biological systems and the mechanisms by which these effects are produced.

Receptors

Most drugs exert their effects interacting with _____

Natural compounds

Drugs are not the only ones interacting with receptors, there are also?

Endogenous compounds

Natural compounds are also?

• Hormones

• Neurotransmitters

• Autacoids

Examples of Endogenous compounds

• Norepinephrine

• Acetylcholine

• Glutamate

• Gamma-aminobutyric acid

• Glycine

Examples of Neurotransmitters

• Bradykinin

• Eicosanoids

• Serotonin

• Histamine

Examples of Autacoids

Local Hormone

• The site of release

• Same w/ the SoA

• Produced by many cell

Enterochromaffin like cell

Histamine is produced by

They release histamine which stimulates production of HCl

How will the stomach acid rise in the context of Enterochromaffin like cells

Mast cells

Histamine is also produced by?

• Skin

• Lungs

Mast cells are found in?

Hormone

• Systematic effect

• Produced by specific cells

B cells found in the pancreas released in the islet of langerhans

Insulin is produced by?

Histamine - Local effect

Insulin - Systematic effect

Which are systematic and local effect:

• Histamine

• Insulin

Exogenous compounds

• Drugs/Xenobiotics

• Foreign substances

• Capable of interacting with receptors (CHONS, NA)

• Target Protein-Mediated

• Non-Target protein-mediated

MoA of Drugs can be

• Structural proteins

• Regulatory proteins

Target protein-mediated are two types of proteins

Target Protein-mediated

Drugs must bind to receptor for an effect

• Voltage-gated ion channels

• Carrier molecules

• Enzymes

• Receptors

Subcategory of regulatory proteins

• Ligand-gated ion channel

• G protein-coupled receptors

• Kinase-linked receptors

• Gene transcription-linked receptors/nuclear receptors

Types of receptors

Structural protein

The cell framework and cytoskeleton

• Tubulin

• Microtubule

Examples of structural protein

• Cell movement

• Mitosis

• Axonal movement of neurotransmitters

Structural proteins are important for?

Drugs that target structural protein

These drugs:

• Colchicine

• Vinca alkaloids

• Taxol (Paclitaxel)

• Griseofulvin

are?

Anti Gout

Indication of Colchicine?

Depolymerization of Tubulin

MoA of Colchicine

• Vincristine

• Vinblastine

Examples of Vinca Alkaloids:

• Anti cancer agents

• Anti neoplastic

• Chemotherapy drugs

• Vincristine

• Vinblastine

• Taxol

what indication?

Anti-microtubule

• Vincristine

• Vinblastine

• Taxol

what MoA?

Paclitaxel

Taxol is the brand name of?

Antifungal

Griseofulvin indication?

Inhibit fungal mitosis

Griseofulvin MoA

Regulatory proteins

The regulators

• Na+ channel

• K+ channel

• Ca+ channels

Examples of Voltage-Gated ion channels

Voltage-Gated Ion channels

Transport system of our cell membrane that facilitates the passage of ion

Potassium in

Sodium out

PiSo

• Stimulated

• Depolarized

Ions are moved along the gradient if channel is

Magnesium in

Calcium out

MiCo

Sulfate in

Bicarbonate out

SuliBio

Phosphate in

Chloride out

PhiClo

Local anesthetics

Drugs: Na+ Channel blocker are the

• Ester type

• Amide type

Na+ channel blockers specifically the local anesthetics have 2 types:

Caine

Local anesthetics usually end with?? but not applicable to all

Bemocaine

Ester type drug

Lidocaine

Amide type drug

• Dihydropyridine

• Non-dihydropyridine

CCB drugs have two types

Amlodipine

Example drugs of Dihydropyridine

dipine

Dihydropyridine usually ends with?

• Verapamil

• Diltiazem

Examples of non-dihydropyridine drugs

Cardiovascular drugs

CCBs are good for?

• Anti-arrhythmic

• Sulfonylureas

K+ channel blockers are drugs that are

Insulin secretagogues

Sulfonylureas are also known as

Class III Amlodipine

Examples of Anti arrhythmic drugs

Anti diabetic

Indication of sulfonylureas

Gli, Gly

Sulfonylureas usually start with

• Glimepiride

• Glipizide

• Glyburide

Sulfonylureas drug examples

Carrier molecules

• Found in cell membrane with specific binding sites

• Undergoes conformational changes

Proton pump/ k+ H+ pump/ H+ K+ pump

Example of carrier molecules is?

PPI or drugs that end with prazole except aripripazole

Drugs that mediate with proton pumps are

• Acetylcholine

• Gastrin

• Histamine

PPIs mediate the release of ______ which are vital in HCl secretion

Enzymes

• they end with the suffix -ase

• Biological catalyst (Facilitates chemical rxns)

• Steroids

• NSAIDs

• Zileuton

Drugs that target enzyme examples

Phospholipase II

Steroids targets what enzyme?

Cyclooxygenase

NSAIDs target what enzyme?

Lipoxygenase

Zileuton targets what enzyme

Prostaglandin

When arachidonic acid is metabolized by Cox it yields?

Leukotriene

When arachidonic acid is metabolized by Lox it yields?

Bronchoconstriction

Leukotriene stimulates ?

LT1 receptor (receptor for leukotrienes

Montelukast binds to?

Receptors

• Functional proteins

• Embedded in cell membrane

• w/ stereochemical configuration

• Where the ligands interact to illicit effect

Lock and key theory

Receptor and ligands interact in what manner?

Non-target protein mediated

Interact with the boy without binding

• Colligative Mechanism

• Direct Chemical Interaction

• Counterfeit Mechanism

Non-target protein-mediated MoA

Mannitol

Drug example in Colligative mechanism

• Draws out water molecules from blood compartment to Urine compartment

• Osmotic diuretic

MoA of Mannitol

Direct chemical interaction

Causes direct chemical reaction

• Neutralization

• Chelation

Example of direct chemical interaction are drugs that undergo?

Hyperacidity

Antacids are use for the treatment of

Metabolic acidosis

NaHCO3 is use to treat

Protamine Sulfate

Antidote for heparin poisoning

Chelation (Complexation

Forms complex

Deferoxamine

Antidote for iron poisoning

Ferri-oxamine (Excretable form of iron)

Deferoxamine + Fe =

• deferoxamine

• EDTA

Drug examples of chelation

Anti metabolites

• Purine analogues

  • 6-mercapopurine

• Pyrimidine analogues

  • 5-fluorouracil

Drug examples of Counterfeit mechanism

DNA synthesis

Analogues are drugs that inhibit