week 2 - pharmacology key concepts

what is the difference between pharmacokinetics vs pharmacodynamics

pharmacokinetics - what the body does to the drug

pharmacodynamics - what the drug does to the body

movement of a drug through the body

• absorption - mouth, stomach, intestines

• distribution - bloodstream

• metabolism - hepatic/liver

• excretion - renal/kidneys

absorption

movement of a drug from the site of administration, across membranes, to circulation

some things that affect absorption:

• drug route

• physical form of drug

• size of drug

• ionization

• lipid-water solubility

  • lipophilic drugs absorb better

• vascularity

• digestive motility (presence of certain foods or drugs may alter rate of absorption)

• co-morbidities

some membranes that enteral drugs must pass before reaching target cells:

1. stomach (HCI and other digestive enzymes may break down drug molecules)

2. portal vein

3. liver (FIRST PASS EFFECT)

4. systemic circulation (immune response may be triggered if drug is seen as foreign)

5. target tissue

6. target cell

7. cell nucleus (if applicable, depends on mechanism of drug)

first-pass effect

enteral drugs will pass the liver before it reaches circulation

• enzymes in liver may chemically change the drug molecule to deactivate it/make it less active

• decreases bioavailability of drug

fastest to slowest drug forms to absorb:

1. liquids

2. suspension solutions

3. powders

4. capsules

5. tablets

6. coated tablets

7. enteric coated tablets

bioavailability

the amount (%) of a drug that is absorbed in systemic circulation and is available to reach target cells and produce its effect

• from 0% to 100%

what is the bioavailability of IV drugs and why

100%; drugs injected directly into the blood stream and do not go through the first pass effect

topical drugs

absorb through the surface

in what pH do drugs absorb best

depends on the chemical nature of drug and surrounding fluids

• acids absorbed in acids (stomach)

• bases absorbed in bases (small intestine)

which type of drug is more easily absorbed: lipid soluble or water soluble?

lipid soluble drugs (lipophilic)

• not limited by the lipid membranes (barriers for water soluble drugs)

• therefore crosses more easily and is able to reach circulation quicker

what is the relationship between rate of absorption, blood flow, surface area, and temperature?

increased blood flow = increased rate of absorption

increased surface area = increased rate of absorption

warmer temperature = increased blood flow = increased rate of absorption

how should you change a dose when changing the route from PO to IV?

IV to PO?

PO to IV: decrease dose because it will no longer go through the first pass effect and bioavailability will be 100%

• not decreasing dose will lead to toxic drug concentrations

IV to PO: increase dose due to first pass effect

• not increasing dose will risk not having enough bioavailability to reach therapeutic drug concentrations

distribution

transportation of drugs throughout the body (through circulation) to target tissue after being administered

factors affecting distribution:

• blood flow

  • increased blood flow = more drug reaching target tissue

• drug solubility

  • hydrophilic drugs transported in solution

  • portion of lipophilic drugs in solution (free drug - able to diffuse to target tissue) and portion is bound to albumin (become inactive; reversible binding)

    • equilibrium

    • some drugs bind better (more affinity = greater attraction)

• drug-protein complexes

• ability to pass through membranes

  • properties of drug

  • diffusion - simple or facilitated

  • active transport

• special barriers

  • BBB

  • FPB

Blood-brain barrier (BBB)

• protects the brain from pathogens and toxic substances

• capillaries in the endothelial cells sealed by tight junctions - no pores

• only lipophilic drugs can diffuse

  • most antitumor and antibiotics can’t cross, explaining why brain cancers/infections are difficult to treat with chemotherapy

• becomes more permeable when inflammed

• not fully developed in neonates, allowing many drugs to enter

fecal-placental barrier (FPB)

• protects potentially harmful substances from passing from the mother’s bloodstream to the fetus

• alcohol, cocaine, caffeine, and certain medications can easily cross this barrier

metabolism

aka biotransformation

• process by which structure and function of drug is altered

• usually makes drug more hydrophilic and excretable

factors affecting metabolism

• age

  • infants - immature liver, not enough enzymes to metabolize

  • older adults - reduced liver function due to age and/or disease, may impact the enzymes

• decreased metabolism with liver disease

• genetic variations in CYP

• P450 (CP450) - hepatic microsomal enzymes that carry out most metabolic activities

  • cytochrome P450 (CYP) - enzyme that metabolizes many drugs

excretion/elimination

removal of drug from body

• most free drugs filtered into kidney nephron

• pH of urine and drug can influence reabsorption of drug from nephron

factors affecting drug exretion

• renal damage - reduces excretion

• enterohepatic recirculation - lipophilic drugs reabsorbed with bile and stay in the bloodstream for longer until all eventually excreted

  • longer half life

minimum effective concentration

smallest amount needed for a therapeutic effect

toxic concentration

amount that is dangerous to the ody and can produce adverse effects

therapeutic range

plasma concentration of drug needed to produce a therapeutic response

drug half life

provides estimate of duration of action; time it takes for plasma concentration of drug to be reduced by 50%

• shorter half life = given more frequently (with exceptions)

• longer half life = given less frequently

loading doses

for when drug needs to reach therapeutic range quickly

• larger dose leads to more rapid absorption and shorter onset of action

maintenance doses

for maintaining a drug within the therapeutic range

• repeated dosing required to maintain steady plasma concentrations of drug

more than 90% of a drug is excreted after how many half lives

4

receptor

cellular molecule to which a drug binds in order to produce effects

intrinsic activity

ability of a drug to bind to receptor and produce an effect

affinity

degree of attraction

• some drugs are more attracted to the receptor than albumin and will bind to receptor instead

true or false: most drugs enhance or inhibit existing physiological or biochemical processes

true

agonist drug

mimics or enhances action of receptor

• responses may be greater than that of endogenous substances

• e.g, morphine

• higher effect than partial agonist drug

partial agonist drug

has both agonistic and antagonistic effects

• weaker responses than endogenous substances

antagonists

prevents action; inhibitor/blocker

• eg. naloxone

• competes with endogenous substances and drug agonists for receptor binding sites

  • competitive - competes for same receptor site

  • noncompetitive - binds to a different receptor site but still inactivates agonist receptor

synergistic

drugs administered together; combined effects exceed that of each individual drug’s effects

• can create toxic effects

additive

drugs used together but in smaller doses so that adequate drug action is maintained

• avoids toxic effects