Nature of Drugs (I, II, III)

Fundamental Requirements for Drugs, Drug Size, Reactivity & Drug-Receptor Bonds

Pharmacodynamics

• receptor, receptor sites

• inert binding sites

• mechanism of action of drugs

Pharmacokinetics

• movement of drugs in body

  • absorption

  • distribution

  • metabolism

  • excretion

elimination

metabolism & excretion

drug development and regulation

• safety and efficacy

• animal testing

• clinical trials

• patients and genetic drugs

drug

any substance that brings about a change in biologic function through its chemical action

agonist

activator of a specific molecule

antagonist

inhibitor of a specific molecule

chemical antagonist

interact directly with other drugs

osmotic agents

interact almost exclusively with water molecules

mannitol

example of osmotic agent

receptor

• drug interacts with the __

• “target molecule” for drug

hormones

a drug may be synthesized within the body

xenobiotic

• “stranger”

• chemicals not synthesized in the body

poison

refers to a drug that have almost exclusively harmful effects

paracelsus

the dose of the drug makes the poison

toxin

refers to poison of biologic origin and is usually synthesized by plants/animals

correct size
electrical charge
shape
atomic composition

drugs must have the __ to interact with their receptors

site of action

drugs must travel through the body to reach the ___

stability

drugs must have adequate __ to reach the target

inactivated / eliminated

be __ at a reasonable rate to maintain appropriate duration of action

aspirin

drugs may exist as solids (__)

ethanol, nicotine

drugs may exist as liquid (__)

nitrous oxide, xenon

drugs may exist as gases (___)

nitrous oxide

• N₂O

• laughing gas

carbohydrates
proteins
lipids
small organic molecules
inorganic elements
newer mRNA vaccines
oligonucleotide therapies

pharmacology includes a wide range of substances:

lithium ion

• very small (drug size)

• MW 7

alteplase

• large proteins (drug size)

• MW 59,000

erenumab

• monoclonal antibody

• MW >145,000

lower limit

• 100 MW

• needed for sufficient molecular complexity to bind selectively to a single receptor type

upper limit

• 1000 MW

• drugs must move through the body compartments

> 1000 MW

molecules ___ diffuse poorly

very large drugs

• proteins / enzymes

• often require direct administration into the intended compartment

IV alteplase

example of very large drug that is administered into the bloodstream

covalent bond
electrostatic bond
hydrophobic bond

3 major types of chemical bonds

covalent bonds

chemical bond: very strong and usually irreversible under biological conditions

aspirin’s acetyl group

covalently binds platelet cyclooxygenase

antiplatelet effects

last for days until new platelets are formed

anticancer drug

DNA-alkylating __ also form covalent bonds

electrostatic bonds

• most common type of drug-receptor interaction

• weaker than covalent bond

hydrophobic bonds

weak interactions important for lipid-soluble drugs and binding within __ pockets of receptors or membranes

weak bonds

drugs that bind through __ generally have higher selectivity, because precise fit is required

highly reactive

__, covalently binding drugs tend to be less selective

inert

even __ molecules (e.g., xenon gas) may show significant pharmacologic effects

anesthetic

inert molecules are __ at high pressure depending on the physical interaction