Pharmocokinetics and Pharmocodynamics 10/7

What do all body cells do

exchange materials with immediate environment, reproduce, obtain energy from nutrients, synthesize hormones/NT, communicate with each other via biological chemicals

Drugs effects

Local vs Systemic

local: at sight of application

systemic: circulates in blood stream to get to site of action

Pharmocokinetics

what body does to drug

What is absorption

Bioavailability

Different routes bioavailability

time drug enters body, bloodstream/tissue (onset), how quickly therapeutic effects

portion of drug that reaches systemic circulation unchanged (influenced by drug rate)

IV: 100% bioavailability

IM/SQ: higher than oral drugs, more blood supply in muscles

PO: longer to get to blood circulation, liquid absorbs faster than tablets

What is Distribution

PAD

transport of drug in bloodstream to body tissue

drugs carried by blood to: action/metabolism/excretion sites

depends on adequacy of blood circulation

peripheral artery disease: arteries are narrow, restricted bloodflow, decrease perfusion of blood flow

First Pass Effect

Distribution rocess affected by

Mouth, portal, vein, liver (detox), circulate to body

protein binding, BBB (restricts hydrophilic), lipid/water soluble, pregnancy

Lipophilic (fat soluble), how its excreted

Hydrophilic (water-soluble), how its eliminated

easily diffuse across cell membranes, cross BBB, not all lipophilic bound by plasma membranes
excreted by bile duct (feces), kidneys (if bio-transformed)

distributed to muscle, cross membranes via ion channels/carriers, eliminated in kidney

What are different ways drug can cross

via lipid soluble, gated channels (hydrophilic), carrier proteins (very specific, hydrophilic drugs)

What is metabolism

how drugs are inactivated or biotransformed by the body

drugs changed to inactive/active metabolites, prodrugs

drug-metabolizing enzymes located: liver, kidney, RBS/plasma, lung

Cytochrome P450

metabolize lipophilic drugs, found mainly in liver. up or down regulated

Enzyme induction

increase enzyme levels/activity, faster breakdown, reduce drug activity

ex. St. John Wart induces 3A4, breakdown faster, causes blood clot

Enzyme inhibition

decreases enzyme activities, slow breakdown

ex. ketoconozole inhibits 3A4, slows breakdown, increases toxicity, increase muscle pain/aches

Liver Function Tests (LFTs)

Alkaline phosphatase (ALP): 40-129 uL

Alanine aminotransferase (ALT): 7-56 u/L

Aspartate aminotransferase (AST): 8-48 u/L

last two increase if damaged

Excretion

dependant on

lipophilic drugs

hydrophilic drugs

elimination of medication from body

circulatory system, kidney, lungs

excreted in bile, feces, kidneys

do not bind to plasma proteins, so less help for metabolism, leaves body unchanged

Renal Function Test

Blood urea Nitrogen (BUN): 5-20. waste from protein breakdown

Serum Creatinine (Cr): 0.6-1.2 mg/Dl. waste from muscle activity

Glomerular Filtration Rate (GFR): more than 90 nl, less than 15 failure

Receptor sites

What drugs don’t act on receptor sites

drugs exert their effects by chemically binding with receptor cells

antacids, osmotic diuretics, anticancer drugs

Theraputic Index

What are the steps

What is a high therapuetic window/example

Serum Drug Levels

1. drug action starts (1st pt it reaches minimum effective concentration)

2. Peak serum drug level (below toxic concentration)

3. drug action stops (back to MEC)
   
   1 and 3: duration of drug action
   want to keep drug within therapuetic concentration

high window: more wiggle room, can take more/less time

ex. vancomyocin: very narrow therapuetic window, need to get serum level to make sure it doesn’t go to toxic

Serum Half Life

time it takes for serum concentration of drug to decrease by 50% in the body

after 4 half lives, more than 90% of drug is eliminated

drugs with short half-life need more frequent dosing

helps us understand excretion rate and how to mantain steady concentrations

Drug-Diet interactions

tyramine (fermented, effect on depression)

grapefruit (enzyme inhibitor)

Vitamin K (antagonize warfarin)

minerals

Drug-Drug Interactions

adative effects (benzo+alcohol=more sedation)

synergism (tylenol+opoids=more pain med)

interference (enzyme inhibition+induction)

displacement (stronger drug bumps other out of receptor site)

Pt. related variables

pre-existing pathological conditions

liver problems, Gi problems effect absorption, kidney problems delay excretion

Drug tolerance

Cross tolerance

body breaks down more, less of it reaches bloodstream

tolerance of 1 drug reduces effect of another drug

Pregnancy Labeling

3 sections

pregnancy

lactation

females +males of reproductive potential

Children consideration

reduced first pass metabolism, higher total body water, thin BBB so drugs can cross faster

Older adult consideration

polypharmacy

absorption

decreased hepatic/enzymatic functions, meds take longer to break down in body

higher risk of drug interactions

PO takes longer, decrease P-glycoprotein (guard of BBB)

adverse effects

common ones

any undesired response to medication administration, more likely with high dosing, likely with polypharmacy

CNS: stimulation/depression

GI: nausea, vomiting, diarrhea

hematoligic: anemia, blood clots