Pharma lecture 2

What is the difference between Pharmacodynamics and Pharmacokinetics?

• Pharmacodynamics: The biological effect of the drug on the body (what the drug does to the body).

• Pharmacokinetics: The way the body affects the drug with time (what the body does to the drug).

What are the 5 main molecular targets for drug action?

1. Enzymes

2. Carrier molecules

3. Ion channels

4. Nucleic acids

5. Receptors

What is the difference between an Agonist and an Antagonist?

• Agonist: Activates a receptor (mimics the effect of an endogenous messenger).

• Antagonist: Blocks a receptor (prevents the endogenous messenger from its usual effect).

What two properties govern how drugs interact with receptors?

• Affinity: Ability to bind to receptors.

• Efficacy: Ability to activate receptors after binding to produce a biological response.

Which type of drug has Affinity but Zero Efficacy?

Antagonists. (Agonists have both affinity and efficacy).

What is a Partial Agonist?

A drug that binds to and activates a receptor but produces a response that is less than the maximum (less than a full agonist).

What does EC50 represent?

The dose or concentration of a drug that produces a response which is 50% of the maximum. It is a measure of potency.

What effect does a Reversible Competitive Antagonist have on an agonist's concentration-response curve?

It shifts the curve to the RIGHT. There is no change in the slope or the maximum response.

List the 3 main routes of drug administration.

1. Topical: Applied directly on epithelial surfaces (skin, eyes, nasal).

2. Enteral: Involves any part of the GI tract (oral, sublingual, rectal).

3. Parenteral: Avoids the GI tract (injections: IV, IM, Subcut, Intrathecal).

What is "First Pass Metabolism"?

The metabolic degradation of a drug by GI tract and liver enzymes before it reaches the systemic circulation. This reduces the bioavailability of the drug.

Why is the Sublingual route (under the tongue) useful?

• Good blood flow allows rapid entry into systemic circulation.

• Useful for rapid response (e.g., angina).

• Avoids "First Pass" liver metabolism.

Which route of administration is the fastest and most certain?

Intravenous (IV) injection.

Why are lipid-soluble drugs absorbed better orally than ionized (charged) drugs?

Lipid-soluble (non-ionized) drugs can diffuse directly through the lipid bilayer of cell membranes. Ionized (charged) drugs are NOT lipid soluble and cannot cross easily.

What does the acronym ADME stand for?

• Absorption

• Distribution

• Metabolism

• Excretion

What is Bioavailability?

The amount of active drug that passes into the circulation and is available to have an effect.

Why is only "Free Drug" pharmacologically active?

Many drugs bind to plasma proteins (like albumin). The bound drug forms a "Drug-Protein complex" which is inactive. Only the unbound (free) drug can act on tissues.

What is the Blood-Brain Barrier (BBB) and how do some drugs bypass it?

A barrier that prevents many drugs (especially charged/large molecules) from entering the brain. Some drugs bypass it using carrier-mediated transport (e.g., L-Dopa is carried into the brain to treat Parkinson's).

Which organ is the main site of drug metabolism, and which enzyme family is primarily responsible?

• Organ: Liver.

• Enzyme family: Cytochrome P450 (CYP450).

What is a "Pro-drug"?

An inactive parent drug that requires metabolism to become an active drug. (e.g., L-Dopa converted to Dopamine).

What is the primary goal of Phase 1 and Phase 2 metabolism?

To make the drug less lipophilic (more water-soluble) so it can be excreted by the kidneys.

Phase 1: Oxidation, reduction, hydrolysis.

Phase 2: Conjugation (adding groups like glucuronide or sulfate).

What is the most important route of drug excretion?

Via the kidney in the urine.

What are the 3 major renal processes involved in drug excretion?

1. Glomerular filtration (small molecules pass through).

2. Active filtration (carrier-mediated transfer).

3. Passive reabsorption (lipid-soluble drugs diffuse back into blood).

Why are lipid-soluble drugs poorly excreted by the kidneys?

Because they undergo Passive Reabsorption. They cross the tubular membrane and diffuse back into the bloodstream instead of staying in the filtrate to be excreted.

Why is grapefruit advised against when taking certain medications (e.g., statins)?

Grapefruit interferes with drug metabolism (specifically inhibits CYP450 enzymes in the liver), leading to higher-than-normal drug levels in the blood and risk of toxicity.