Module 1 Objectives

oral drug advantages

oral drug advantages

ease of administration, slow absorption rate

oral drug disadvantages

Drugs must pass through liver before entering systemic circulation, reducing bioavailability

IV drug advantages

rapid onset, bypasses first-order metabolism leading to increased bioavailability

IV drug disadvantages

Risk of infection, invasive

IM drug advantages

moderate onset of action (faster than oral), sustained drug release over time

Im drugs disadvantages

small volume of drug can be administered

SubQ drugs advantages

controlled, slower absorption b/c of sustained release

SubQ drugs disadvantage

Slower onset, limited to small volumes administered to prevent irritation

how ROA affects absorption

Drugs that must pass through GI tract has slower and less complete absorption

how drug solubility affects absorption

lipophilic more easily absorbed compared to hydrophilic

how pH affects absorption

Weak acids better absorbed in stomach, weak bases better absorbed in the intestines

how first-pass metabolism affects absorption

Drugs absorbed from GI tract pass through liver before reaching systemic circulation, reducing bioavailability

how blood flow affects distribution

Organs with higher blood flow receive more drug from systemic circulation

how plasma binding protein affects distribution

High binding to albumin can inactivate the drug and reduce the amount of free drug available for distribution to the tissues

how lipid solubility affects distribution

Lipophilic more widely distributed in tissue, hydrophilic stays more in blood and extracellular fluid

how Vd affects distribution

Drugs with high Vd distribute widely, but low Vd will stay in the blood

how metabolism affects 1/2 life

Drugs rapidly metabolized by the liver will have shorter half life, while those that are slowly metabolized have longer half lives

how elimination affects 1/2 life

Drugs eliminated by kidneys quickly have shorter half life

how plasma binding protein affects 1/2 life

Highly protein bound drugs have longer half lives because not filtered by kidneys or metabolized

how Vd affects 1/2 life

Higher Vd has longer half life b/c stored in tissues and released slowly back into the bloodstream

how renal function affects elimination

Impaired renal function reduced drug clearance, prolonging drug presence in the body

how liver metabolism affects elimination

Drugs are usually metabolized into water soluble compounds that are excreted, hepatic impairment can slow drug metabolism

how drug ionization affects elimination

drugs ionized in kidneys more likely to be excreted in urine, while non-ionized drugs may be reabsorbed into the blood stream

passive diffusion

movement down a concentration gradient, no energy input. EX: lipophilic and small hydrophilic

facilitated diffusion

carrier-mediated transport down a concentration gradient

active transport

carrier-mediated transport against concentration gradient, energy required

endocytosis

engulfment of large molecules into cells

paracellular transport

passage between gaps between cells

GPCR ligand

hormones, neurotransmitters

GPCR MOA

activates G protein, produces second messengers

Ion channel ligand

neurotransmitters, ions

Ion channel MOA

opens/closes ion channels, alters membrane potential

RTK ligand

growth factor, insulin

RTK MOA

autophosphorylation, kinase activated

intracellular receptors ligand

steroid and thyroid hormones

intracellular receptors MOA

regulates gene expression

What is saturation in pharmacology?

At larger concentrations of a drug, more receptors are occupied, leading to a greater biological response.

What happens when all receptors are occupied by a drug?

When all receptors are occupied, further increases in drug concentration do not lead to a greater biological response.

drug selectivity

ability of a drug to preferentially bind to a specific type of receptor, producing a targeted biological response

potency

Amount of drug needed to produce a given effect

efficacy

Ability of a drug to produce a maximal response

partial agonist

Drugs that, even with full receptor occupancy, produce a submaximal response compared to full agonist.

full agonist

Drugs that produce a maximal response

antagonist

Binds to receptor, but inhibits the response, it blocks the agonist from binding

What does the one compartment model assume?

Instant and uniform distribution of a drug throughout the body after administration

How does the one compartment model describe drug elimination?

First-order elimination, with the rate depending on the drug concentration

What does the two compartment model assume about the body?

It consists of a central and peripheral compartment.

How does drug distribution occur in the two compartment model?

First into the central compartment, then slowly to the peripheral compartment.

Where does elimination occur in the two compartment model?

From the central compartment.

relationship between Vd and plasma protein binding on drug distribution

Drugs with high affinity for plasma binding proteins will have a lower Vd due to having a reduced unbound drug to distribute to the tissues

first-order

Drug elimination where the rate of elimination is directly proportional to the drug concentration in the body.

zero-order

Rate of drug elimination is constant and independent of the drug concentration. A fixed amount of drug is eliminated per unit of time

dose-dependent

Occurs when drug elimination changes from first order at low doses to zero order at high doses due to the saturation of metabolic pathways

How does the rate of drug administration affect the time to reach steady state?

Higher dosing rates will achieve steady state faster if elimination rates remain constant.

What is the benefit of frequent dosing in drug administration?

Frequent dosing helps maintain drug levels within the therapeutic range.

How does clearance rate affect steady state concentrations?

Higher clearance rate results in lower steady state concentrations.

What is the relationship between half-life and reaching steady state?

Drugs with a shorter half-life reach steady state quicker than those with a longer half-life.

renal blood flow affect renal clearance

Higher renal blood flow increases the amount of blood reaching the kidneys, which enhances filtration and elimination of drugs

glomerular filtration rate affect renal clearance

A higher GFR increases the rate at which drugs are filtered.

reabsorption affect renal clearance

Lipid soluble drugs are more likely to be reabsorbed, decreasing their clearance rate

How does protein binding affect renal clearance?

Drugs bound to plasma proteins are not filtered at the glomerulus.

What type of drug is available for filtration and excretion in the kidneys?

Only free unbound drug.

How does protein binding affect hepatic clearance?

Drugs bound to plasma proteins are not filtered at the liver.

What form of drugs is available for filtration and excretion in the liver?

Only free unbound drug.

hepatic blood flow affect hepatic clearance

increased hepatic blood flow enhances the delivery of drugs to the liver, facilitating metabolism.

What is intrinsic clearance?

The liver's ability to metabolize drugs, independent of blood flow.

How does intrinsic clearance affect hepatic clearance?

Intrinsic clearance is influenced by enzyme activity and the drug's ability to bind to hepatic enzymes.

enzyme activity affect hepatic clearance

Activity of hepatic enzymes (cytochrome P450) is crucial for drug metabolism