Pharmacology Unit 1

What is pharmacology?

The study of drugs and their effects on living organisms.

What is pharmacodynamics (PD)?

What the drug does to the body—how drugs interact with targets to produce effects.

What is pharmacokinetics (PK)?

What the body does to the drug—how the drug moves through the body.

What does ADME stand for?

Absorption, Distribution, Metabolism, Excretion.

What is the difference between a therapeutic drug and a toxic drug?

The effect depends largely on the dose; too much of a drug can produce toxic effects.

What are the two broad ways drugs can act?

Through specific targets or through nonspecific actions.

Give an example of a nonspecific drug action.

Mannitol increases osmotic pressure and draws water into the urine.

What are major specific drug targets?

DNA, microbial organelles, receptors, enzymes, and other target macromolecules.

How do alkylating agents affect DNA?

They add alkyl groups to DNA, which can interfere with DNA replication and function.

What is a receptor?

A molecule that recognizes and binds a specific ligand/drug and produces or influences a cellular response.

What is a ligand?

A molecule that binds to a receptor.

What is an agonist?

A drug that binds to a receptor and activates it to produce a response.

What is an antagonist?

A drug that binds to a receptor but blocks activation and prevents/reduces a response.

What are the four major receptor types?

Ionotropic receptors, GPCRs, enzyme-linked receptors, and nuclear receptors.

What is an ionotropic receptor?

A ligand-gated ion channel that opens or closes when a ligand binds.

What happens when an ionotropic receptor opens?

Ions move across the membrane, rapidly changing the cell's electrical state.

What is an example of an ionotropic receptor?

The nicotinic acetylcholine (ACh) receptor.

What does GPCR stand for?

G-protein-coupled receptor.

How do GPCRs work in general?

A ligand binds the receptor → activates a G protein → the G protein affects an effector → intracellular signaling molecules produce a response.

What is the main idea behind Gs signaling?

Gs stimulates adenylyl cyclase → increases cAMP → activates PKA.

What is the main idea behind Gi signaling?

Gi inhibits adenylyl cyclase → decreases cAMP.

What is the main idea behind Gq signaling?

Gq activates PLC → produces IP₃ and DAG → increases intracellular Ca²⁺ and activates PKC.

What is cAMP?

A second messenger that helps transmit and amplify signals inside the cell.

Why can GPCR signaling produce large cellular effects?

Signal amplification occurs because one receptor activation can activate multiple downstream molecules.

What are enzyme-linked receptors?

Receptors linked to or containing enzymatic activity that can trigger intracellular signaling pathways.

What are nuclear receptors?

Intracellular receptors that bind ligands and regulate gene transcription.

Why are nuclear receptor effects generally slower?

They involve changes in gene expression and protein production.

How can drugs affect enzymes?

They can inhibit or alter enzyme activity, changing the production or breakdown of substances.

What enzyme is inhibited by aspirin and many NSAIDs?

Cyclooxygenase (COX).

What is the general effect of COX inhibition?

It decreases production of prostaglandins, contributing to analgesic and anti-inflammatory effects.

What is specificity?

The tendency of a drug to interact with a particular target rather than many different targets.

What is affinity?

How strongly a drug binds to its receptor/target.

What is efficacy?

The ability of a drug, once bound, to produce a biological response.

What is potency?

The amount of drug needed to produce a given effect.

What does EC50 represent?

The concentration of drug that produces 50% of the maximal effect in a graded dose-response curve.

If Drug A has a lower EC50 than Drug B, which is more potent?

Drug A is more potent because it produces the effect at a lower concentration.

What is a full agonist?

An agonist capable of producing the maximum response of the system.

What is a partial agonist?

An agonist that activates the receptor but produces a lower maximum response than a full agonist.

Can a partial agonist act as an antagonist?

Yes. In the presence of a full agonist, a partial agonist can compete for receptors and reduce the overall response.

What is tolerance?

A decreased response to a drug after repeated exposure, often requiring a higher dose to produce the same effect.

What is sensitization?

An increased response to a drug after repeated exposure.

What is competitive antagonism?

The antagonist competes with the agonist for the same receptor site. Increasing agonist concentration can overcome the antagonism.

What is noncompetitive antagonism?

The antagonist prevents the agonist from producing its full effect, and increasing agonist concentration cannot fully overcome the antagonism.

What is the difference between a graded and quantal dose-response curve?

Graded: measures the magnitude of response in an individual/system.
Quantal: measures whether a defined response occurs across a population.

What are ED50, TD50, LD50, and therapeutic index (TI)?

ED50: dose producing the desired effect in 50% of the population
TD50: dose producing toxicity in 50%
LD50: dose causing death in 50%
TI: TD50 / ED50 A larger TI generally indicates a wider safety margin.

What is pharmacokinetics (PK)?

What the body does to a drug → ADME.

What is absorption?

Drug movement from administration site → bloodstream.

What is distribution?

Drug movement from blood → tissues.

What is metabolism?

Chemical modification of drugs, mainly in the liver.

What is excretion?

Removal of drugs, mainly by the kidneys.

Which route has the fastest onset and 100% bioavailability?

IV.

Rank these routes from fastest → slowest.

IV → IM → SC → oral.

What is bioavailability (F)?

Fraction of a dose reaching systemic circulation unchanged.

What is first-pass metabolism?

Oral drug is metabolized in the gut/liver before reaching circulation, reducing bioavailability.

What type of drug crosses membranes most easily?

Non-ionized + lipid-soluble.

What is passive diffusion?

Drug moves high → low concentration without energy.

What is pKa?

pH where 50% of the drug is ionized and 50% is non-ionized.

What is ion trapping?

Drug becomes ionized on one side of a membrane and gets trapped there.

What is active vs. facilitated diffusion?

Facilitated: transporter, no ATP, down gradient.
Active: transporter + energy, can move against gradient.

Which form of a drug is pharmacologically active?

Unbound/free drug.

What determines how quickly a drug reaches a tissue?

Blood flow.

What does the blood-brain barrier do?

Restricts many drugs from entering the CNS.

What is redistribution?

Drug moves from one tissue → another tissue after initial distribution.

Give an example of redistribution.

Thiopental: brain initially → then redistributes to other tissues.

Where does most drug metabolism occur?

Liver

What enzyme system is important in drug metabolism?

Cytochrome P450 (CYP450).

What happens during Phase I metabolism?

Oxidation, reduction, hydrolysis.

What happens during Phase II metabolism?

Conjugation, usually making drugs more water-soluble.

What factors affect drug metabolism?

Genetics, age, disease, diet, and other drugs.

What is pharmacogenomics?

How genetic differences affect drug response/metabolism.

What is the major organ for drug excretion?

Kidneys

What are the 3 renal processes involved in drug elimination?

Filtration → reabsorption → secretion.

What happens during glomerular filtration?

Unbound drug moves from blood → renal filtrate.

Which drug form is more likely to be reabsorbed?

Non-ionized + lipid-soluble.

What is tubular secretion?

Active transport of drug from blood → renal tubule.

How does urine pH affect drug excretion?

Changes drug ionization, affecting reabsorption and excretion.

What is enterohepatic recirculation?

Drug → bile → intestine → reabsorbed → bloodstream.

What is volume of distribution (Vd)?

Relates the amount of drug in the body to plasma concentration.

What is the Vd formula?

Vd = Amount of drug in body ÷ Plasma concentration.

What does a large Vd indicate?

Drug has moved extensively into tissues.

First-order vs. zero-order elimination?

First-order: constant percentage eliminated.
Zero-order: constant amount eliminated.

What is half-life?

Time required for drug concentration to decrease by 50%.

How long does it take to reach steady state?

About 5 half-lives.

What happens when half-life increases?

Longer time to reach steady state and longer elimination.

What is a loading dose?

Larger initial dose used to rapidly reach desired drug concentration.

Loading-dose relationship?

Dose = Vd × desired plasma concentration.

What are the two divisions of the ANS?

Sympathetic + Parasympathetic.

What neurotransmitter do ALL autonomic preganglionic neurons release?

ACh.

What do most sympathetic postganglionic neurons release?

Norepinephrine (NE).

What do parasympathetic postganglionic neurons release?

ACh.

What are the major adrenergic receptors?

α1, α2, β1, β2, β3.

What does α1 activation do?

Vasoconstriction + pupil dilation.

What does β1 activation do?

↑ Heart rate + ↑ contractility + ↑ conduction.

What does β2 activation do?

Bronchodilation

What are the key receptor associations to memorize?

α1 = vessels/eyes
β1 = heart
β2 = lungs
β3 = adipose/metabolism

What is the rate-limiting enzyme in catecholamine synthesis?

Tyrosine hydroxylase.

What enzymes break down catecholamines?

MAO + COMT.

What is the major urinary catecholamine metabolite?

VMA.

What are dopamine's dose-dependent effects?

Low → dopamine receptors
Moderate → β1/cardiac
High → α1/vasoconstriction

What is an adrenergic agonist?

A drug that activates adrenergic receptors.