Pharmacology Chapter 4 - Pharmacokinetics Flashcards
Pharmacokinetics
Study of drug movement throughout the body.
Pharmakon -
greek word for poison.
Four Basic Pharmacokinetic Processes are…
Absorption (movement from site of administration into blood), Distribution (movement from blood to intestinal space of tissue and then into cells), Metabolism (enzymatic alteration of drug structure), and Excretion (movement of drug and metabolites out of the body.)
Matter
anything that has mass.
Element
a substance that can not be broken down into simpler substances (O, C, etc). Each element has a set of properties that distinguish it from other elements.
Atom
smallest particle of an element that retains the characteristics of that element. Every atom has energy and ability to do work.
Compounds
substance made from elements are called compounds. (H20)
Molecules
smallest units of a compound that still have the properties of that compound. (In H20, the ratio of H and O is 2:1, so the formula is H20.)
Molecules are generally neutral.
Ions
Electrically charged molecules
Polar Molecules
molecules with uneven distribution of electrical charge. A polar molecule is any molecule with unbalanced charge distrubtion.
Polar Molecules and water…
Because water molecules are polar, they attract each other as well as other polar molecules and ions.
Solutes/Solvent
Solutes that dissolve in a SOLVENT are soluble.
Non polar substances Do/Do Not dissolve in water?
They DO NOT
Like dissolves?
Like.
Acid - what kind of donor is it?
proton donor. (a substance that releases hydrogen ions when mixed with water.)
Base - what kind of donor is it?
substance that separates in water…PROTON ACCEPTOR.
pH -
0-14. Acid is 0, most basic is 14.
Ionization -
the process of becoming charged (ion.)
Acids tend to become ___ in basic media and bases tend to ____ in acidic media.
Ionized
Diffusion - def
movement of a molecule/substance from a higher to a lower concentration.
Osmos - def
movement of water molecules through a semi-permeable membrane from a higher to a lower water concentration.
Ion Trapping or pH Partitioning
When there is a ph gradient on either side of a membrane, acidic drugs will accumulate on the alkaline side, and basic drugs will accumulate on the acidic side.
Membrane structure - basic
layers of cells - double layer of molecules - phospholipids - phospholipid bilayer.
Three ways to cross a cell membrane
Through channels or pores - very few do this.
With aid of a transport system - carrier protein, requires some energy.
Direct Penetration of membrane - most common.
Polar Molecules and ions Can/Cannot cross membrane.
CANNOT
Charged molecules Can/cannot cross membrane.
Cannot
Factors affecting absorption
Rate of dissolution, surface area, blood flow, lipid solubility pH partitioning
Routes of Administration - two types.
Enteral (via GI tract - Oral.) and Parenteral - outside the GI tract, like IV, IM, etc.
Intravenous Advantages and Disadvantages
Advantages - no barrier to absorption, rapid onset, use of large fluid volumes.
Disadvantages - high cost, inconvenience, difficult to administer, irreversible..etc.
Intramuscular - barrier?
Only barrier to absorption is capillary wall.
Intramuscular Advantages/Disadvantages
Adv - rate of absorption can be fast, etc. Disadvantages - painful, risk of local infection, and nerve damage.
Subcutaneous - similar to?
similar to IM.
Oral - per OS
by way of mouth. Must get through epithelial cell barrier of GI tract and capillary wall.
Factors that determine rate of absorption of PO
solubility and stability, gastric and intestinal ph, gastric emptying time, food in the gut, co-administration of other drugs, capsule.
Advantages of oral admin
easy, convenient, inexpensive. No risk of fluid overload, infection or embolism, etc. Can be reversed.
Disadvantages of Oral Admin -
variability of absorption (young vers old), etc.
Inactivation of proteases and acid, etc.
Why parenteral over oral?
When plasma drug levels have to be tightly regulated, emergenies, when drugs would not be absorbed through membranes, etc.
Preparations of oral meds (types) and what they are.
tablets (mixture of drug plus binders), enteric coatings (will dissolve in intestine), sustained release (capsules that release over time.)
Chemical equivalence
if drug contains the same amount of the identical chemical compound
Bioavailability -
amount of drug that can reach circulation.
if drug is absorbed at the same rate and to the same extent…two formulations of the same drug may be chemically equivalent but differ in bioavailability.
Other ways to deliver drug -
topical, transdermal, inhalation, rectal/vaginal suppositories, direct injection into specific tissue/organ.
Factors influencing distribution - think body functions.
blood flow to tissue, ability of drug to exit vascular system, and ability of drug to enter the cell.
Blood flow to tissue -
rate of delivery to tissues is determined by amount of blood flow to the tissue. Tumors? No blood flow.
Drugs have to leave blood and move into tissue.
Ability of drug to exit vascular system…BBB (what is it? def?)
Blood brain barrier - tight junctions that prevent movement of drug into CSF. Only lipid soluble drugs and drugs with transport systems with get across the BBB. NOT well developed at birth.
Exiting vascular system and the placenta.
No direct blood exchange between mother and fetus. Drug must cross membranes to get to fetus. Non-ionized compounds pass placenta, ionized compounds excluded.
Plasma Albumin and distribution -
drugs bind to albumin, then they travel from point A to point B.
Some bind strongly (warfarin) and some bind weakly (getamicin)
Biotransformation
Enzymatic alteration of drug structure.
LIver is the primary site of…
drug metabolism.
Cytochrome P450 (aka P450 system.)
System of enzymes. 12 enzymes. CYP1, CYP2, CYP3 metabolize drugs. The other 9 metabolize steroids, fatty acids, remove alcohols, toxins, etc.
Drug Metabolism- Implications (5). Therapeutic consequences (outcome of an event) of drug metabolism are…
- Accelerated renal drug excretion (less polar to more polar.)
- Drug inactivation. (active to inactive.)
- Increased therapeutic actions - (less to more active.) - codeine to morphine.
- Activation of pro-drugs - (inactive to active later on) - sleeping pills.
- Toxicity variations - (increased or decreased toxicity.)
Special considerations in drug metabolism …
age (infants do not have full liver function, etc.)
First Pass Effect
rapid hepatic inactivation of certain oral drugs. Example - give first dose parenterally - bypass liver and get therapeutic dose in system (like nitro under tongue.)
Nutritional status and metabolism
Hepatic metabolizing enzymes require co-factors (certain trace metals.)
Also watch for drug competition!
Drug Excretion - def
removal of drug from the body.
Drug Excretion … via (3) parts of kidney.
Glomerular filtration, passive tubular re absorption, and active tubular secretion.
Flow of urine…
Urine produced in the kidneys flows through the ureter. The ureters carry urine to the bladder, which empties through the urethra.
Outermost layer of the kidney?
Renal cortex.
Inside the cortex (layer?)
Renal medulla.
urine collects in a large cavity called the..
renal pelvis.
There are millions of units called…
nephrons.
Group of capillaries -
glomerulus.
What does the glomerulus sit inside?
Bowman’s capsule.
Tube structures…
Proximal tube, Henle’s loops, distal tube.
Nephron controls the composition of blood and urine…true or false?
True.
Two processes in this area (kidney) that have to do with fluid.
reabsorption and tubular secretion.
What the body needs (glucose, water, etc) are __ from the tubules
reabsorped.
Other foreign items are __ by the kidney.
Secreted.
Glomerular Filtration
capillary network & Bowman’s capsule. Proteins do not pass, but other substances diffuse across and may be actively transported across.
Passive tubular reabsorption
water and lipid soluble drugs may be reabsorbed back into blood.
Active tubular secretion
active transport of drugs from blood into urine in tubules.
Factors that modify renal drug excretion -
pH dependent ionization (converts lipid soluble compounds to ions so they cannot pass epithelial cells of tubule and stay in urine, like aspirin in children).
Competition for active tubular transport - competing for receptor, so it delays the process.
Age - newborn kidneys aren’t fully developed, and older kidneys don’t function as well.
Plasma drug levels - def
amount of drug in the blood.
To achieve the therapeutic objective, time course of drug response _____
must be regulated.
Plasma levels of drug …. can be measured and adjusted by…
adjusted up or down by changing dosage, time of administration, or both.
Minimum Effective Concentration - def
MEC - plasma drug level below which therapeutic effects will not occur.
Toxic Concentration - def
Occurs when plasma level of drug gets too high.
Therapeutic range - def
range of drug concentrations falling between MEC and toxic concentration.
Drug half-life - def
Time required for the amount of drug in the body to decrease by 50%. Can be short or long.
It takes __ half lives to reach the plateau.
4
Single Dose time course vs repeated.
Single - like taking and antibiotic. repeated is for continued use.
