hsci 323 quiz 1

Pharmacology

The science that deals with the fate of drugs in the body and their actions on the body.

Pharmacy

The art, practice, or profession of preparing, preserving, compounding, and dispensing medical drugs.

Therapeutics

Broadly defined as the treatment of disease or injury.

drug

any substance, other than a normal constituent of the body or one that is required for normal bodily function (i.e. food, water, oxygen), that, when applied to or introduced into a living organism, has the effect of altering biological function(s).

“Required for normal bodily function”

• this usually refers to substances as they are acquired through a normal diet, respiration, etc.

• Vitamin C in large doses is a drug, in orange juice it is not

• Hormones produced in the body are not drugs unless they are administered (i.e. hormone replacement therapy)

Toxicology

The study of the adverse effects of chemical, physical, or biological agents on living organisms and the ecosystem.

Poison

A substance that in relatively small doses produces serious illness or death.

Toxin

A poisonous substance secreted or created by plants or animals (such as certain snakes, insects, and spiders).

Venom

A poisonous substance secreted by animals such as certain snakes, insects, and spiders.

Toxicant

Any substance that produces toxicity following exposure; generally used as distinct from toxin and often associated with human-made substances.

Xenobiotic

Any substance that is foreign to the body (e.g., not a biochemical), including drugs, toxicants, toxins, and poisons.

focal efforts in toxicology

• Ecological-studies how chemicals impact nonhuman organisms. We make a distinction between this and veterinary.

• Veterinary-concerned with the effects of toxic substances on farm animals and pets

• Medical-focuses on chemicals that are used in the treatment of disease (pharmaceutical agents)

• Occupational-focuses on toxic substances of concern in the workplace

selective toxicity

drugs ability to kill target without harming host

can be done thru specificity in:

• Differences in translocation factors – how drugs get into cells and their site of action

• Differences in biotransformation – drugs will get removed from body or inactivated differently depending on amount and type of drug metabolizing enzymes.

• Differences in the presence or absence or nature of receptors – drugs bind receptors to elicit their effects.

types of exposures

• acute <24 hrs

• subacute <1 month

• subchronic 1-3 months

• chronic >3 months

Persistent Organic Pollutants (POPs), Polychlorinated Biphenyls (PCBs) and Dioxins

• Also termed “ubiquitous” environmental contaminants

• Route of exposure - ingestion/oral • Considered “endocrine disruptors” - thyroid, androgen and estrogen physiology

• Extremely lipid soluble

• Adverse effects include - cancer, development defects of the uro-genital tract in offspring, fertility problems, chloracne

Lead

• Major sources - car batteries, lead-based paint

• Route of exposure - oral (ingestion)

• Blood, kidney and neurological disorders* are common

• Children are far more susceptible than adults

  • development of blood-brain barrier

• Treatment - chelation (DMSA, EDTA)

  • DMSA - Dimercaptosuccinic acid

  • EDTA - ethylenediaminetetraacetic acid

Galenicals (Natural Preparations)

Crude extracts or preparations of plant or animal material.

Pure Compounds

Active ingredients isolated or purified from natural compounds.

Semi-synthetic Compounds

chemical modification of pure compounds, usually to increase bioavailability or receptor affinity

• fluorination of hydrocortisone

• hydroxylation of morphine

Purely Synthetic Compounds

created based on predicted chemical properties or industrial processes that have therapeutic properties.

Biological Drugs

Complex molecules synthesized in living cells and organisms, such as monoclonal antibodies, clotting factors, and hormones.

Ebers Papyrus (~1500 B.C.)

Ancient record containing information on poisons including hemlock, aconite, opium, and metals like lead, copper, and antimony.

Dioscorides

Greek physician (A.D. 50-100) who classified more than 600 plant, animal, and mineral substances as toxic or therapeutic.

Paracelsus

German Renaissance physician (1493-1541) who established that dose determines toxicity ("the right dose differentiates a poison from a remedy").

Mathieu Orfila

French academic (1787-1853) who wrote the first formal treatise on toxicology in 1815.

Bioavailability

The proportion of an administered drug dose that reaches the systemic circulation.

Pharmacokinetics

The study of drug disposition in the body, encompassing Absorption, Distribution, Metabolism, and Elimination (ADME).

Pharmacodynamics

The study of the mechanisms of drug action and how drugs interact with biological targets (receptors, enzymes, carrier molecules, ion channels).

Pharmacometrics

The study of the quantitative relationship between drug dose or concentration and the magnitude of effect.

Structure-Activity Relationships (SAR)

The molecular properties and chemical structure of a drug that dictate its affinity and binding to its receptor.

Specificity

A characteristic of a drug to selectively target specific receptor binding sites.

Affinity

The tendency or strength with which a drug binds to its target receptor.

Efficacy (Intrinsic Activity)

The tendency or ability of a bound drug to activate the receptor and produce a biological response.

Agonist

A drug or ligand that binds to a receptor and initiates a biochemical or biophysical change (mimicking endogenous substances).

Full Agonist

An agonist capable of producing the maximal biological response (Emax) of a given system.

Partial Agonist

An agonist that cannot induce a full maximal response even when occupying 100% of available receptors (reduced efficacy).

Antagonist

A drug or ligand that binds to a receptor without activating it (efficacy = 0) and blocks or prevents agonist/endogenous binding.

Inverse Agonist

A compound that binds to a receptor and reduces its constitutive (basal) activation level, producing the opposite effect of an agonist.

Competitive Antagonist

A reversible antagonist that binds to the same active site as the agonist; its blockade can be overcome by increasing agonist concentration.

Irreversible Competitive Antagonist

An antagonist that binds covalently or with a very low dissociation rate to the agonist binding site; cannot be overcome by increasing agonist concentration.

Constitutive Activation

The state where a receptor adopts an active conformation and elicits a biological response in the complete absence of an agonist.

Biased Agonism

The phenomenon where different agonists binding to the same receptor selectively activate one downstream signaling pathway over another.

Law of Mass Action

The physical law stating that the rate of drug-receptor binding and dissociation is proportional to the concentrations of free drug and free receptors.

Dissociation Constant (Kd)

The ratio of off-rate to on-rate (koff / kon); the ligand concentration at which 50% of total receptors are bound at equilibrium (lower Kd indicates higher affinity).

Bmax

The maximum binding capacity, representing the total concentration or density of functional receptors in a tissue or cell sample when fully saturated.

Emax

The maximal biological effect or response that a drug can produce in a given system.

EC50 (ED50)

The effective concentration (or dose) of a drug required to produce a 50% maximal biological response.

Spare Receptors

The excess receptors present in a tissue allowing full maximal response (Emax) to be achieved even when less than 100% of total receptors are occupied by an agonist.

Radioligand Binding Assay

An experimental method measuring specific and non-specific drug-receptor binding using radioactively labeled drug molecules.

Specific Binding

Saturable drug binding specifically to target receptors (calculated as total binding minus non-specific binding).

Non-Specific Binding

Non-saturable uptake or binding of a drug to cellular structures other than the target receptor.

Allosteric Modulation

Binding of a drug at a distinct site on a receptor that alters the affinity or efficacy of a ligand binding at the primary (orthosteric) site.

Ligand-Gated Ion Channels (Ionotropic Receptors)

Cell-surface ion channels (Type 1) that open or close directly upon ligand binding to allow rapid ion flux across membranes (e.g., nicotinic acetylcholine receptor).

G-Protein-Coupled Receptors (GPCRs / Metabotropic Receptors)

Seven-transmembrane cell-surface receptors (Type 2) that activate intracellular heterotrimeric G-proteins to regulate second messengers.

Gas Subtype

G-protein alpha subunit that stimulates adenylyl cyclase, increasing intracellular cAMP levels (activated by Cholera toxin).

Gai Subtype

G-protein alpha subunit that inhibits adenylyl cyclase, decreasing intracellular cAMP levels (inhibited by Pertussis toxin).

Gaq Subtype

G-protein alpha subunit that activates phospholipase C (PLC), increasing production of IP3 and DAG.

Cyclic AMP (cAMP)

A second messenger generated from ATP by adenylyl cyclase that activates Protein Kinase A (PKA).

Inositol Trisphosphate (IP3)

A second messenger cleaved from PIP2 by phospholipase C that triggers the release of Ca2+ from intracellular stores.

Diacylglycerol (DAG)

A second messenger cleaved from PIP2 by phospholipase C that remains in the cell membrane and activates Protein Kinase C (PKC).

four broad categories of receptors

1. ligand gated ion channels

2. G protein couples receptors

3. kinase linked receptors

4. nuclear receptors

Phospholipase C (PLC)

A target enzyme activated by Gaq that cleaves phosphatidylinositol bisphosphate (PIP2) into second messengers IP3 and DAG.