General principles of pharmacology Flashcards
Pharmacodynamics
Mechanism of action, what drug does to your body
Pharmacokinetics
Time course, how your body metabolizes drug
Drug action
Change at the molecular level, biochemical event
Drug effect
**Clinical practitioner more concerned with this
Change in physiological function
MEC
Minimum effective concentration: concentration needed to start seeing drug effect
Maximum tolerated concentration
Concentration above which toxicity occurs
Effect of drugs is dose dependent
Some level before which no effect occurs
Some level above which no extra effect occurs
Ideal range of drug concentration between when drugs begin being effective and cutoff for toxicity
Therapeutic window
Between MEC and max tolerated concentration
Depends on absorption, distribution, elimination, and drug action + effect
Percutaneous administration
Slow and sustained absorption
Lipid soluble > water soluble
Enteral
Via GI
Sublingual administration
Rich blood flow
More rapid than oral
Oral administration
Most common but slower 2 barriers to absorption Intestine > stomach Absorption highly variable among patients (gastric emptying, pH, food, other drugs) Drug recall is possible Lipid > water soluble Some drugs (PROTEINS) inactivated in GI First pass metabolism GI irritation
Rectal administration
For vomiting patient
Parenteral
Non-oral
IV
No barrier to absorption - easier to control concentration Rapid but NO recall Needs to be aqueous solution No big "chunks" due to possible embolism Possible infection at injection site
Intra-arterial
More diagnostic
Subcutaneous injection
Barriers to absorption: Slower absorption and sustained action
Can be poorly water soluble
Allows for depot preparations
Protein drugs
Most need to be delivered IV or SQ
Intramuscular injection
Only barrier is capillary, high blood flow in muscle
Time is dictated by water solubility (water > lipid)
Can inject oily and particulate matter
Lipid/oily drugs
Oral, SQ, IM, percutaneous
Water soluble drugs
Better with IV, faster with IM
Particulate drugs
IM
Depot preparations
Can release effective amounts of drug for weeks or months
SQ or IM
Inhalation
Keep localized to minimize systemic effects
Large SA
Particle size important
Intranasal
Lots of it swallowed
Absorption
Movement of drug into the blood
Rate - how soon effects start
Amount - intensity of effects
Rate of dissolution
Dissolved = free in solution, not bound, free to move into cells
Smaller size and liquid are better
Concentration gradient
Drug always moves down gradient
Blood flow readily changes gradient
Lipid absorption
Faster
Can more easily cross the membrane (hydrophobic)
Charged molecules
CANNOT diffuse
pH
Determine amount of drug that is ionized
Tissue condition
Damaged tissue less likely to absorb
Distribution
To all areas perfused with blood
Can move into interstitial fluid or within cells
Volume of distribution
Hypothetical volume of fluid into which the drug is distributed
May calculate to be larger than 42L if drugs build up in tissues
Water compartments
Plasma: 4L
Extracellular: 14L
Total: 42L
Drug redistribution
Drugs are constantly moving along gradient into different compartments
Blood brain barrier
Lipid soluble, nonpolar, noncharged cross more easily
Drug elimination
In urine, breath, stool, or sweat
Unchanged or biotransformed (active, inactive, larger or smaller)
Major site of biotransformation
Liver
Major biotransformation pathway
Conjugation: larger and more water soluble
Metabolites that are too large
Secreted into bile
Major form of elimination
Urine
Involves glomerular filtration of plasma
Drugs may be reabsorbed
Free drug
Unbound drug in solution
Most common type of drug movement into cell
Diffusion
Function of lipid solubility, conc. gradient, size, and charge
Concentration of drug at site of action (cell) is function of
absorption, biotransformation, distribution, and elimination
Active transport
Special tissues: renal, choroid, hepatocytes
Rate of diffusion
Directly related to concentration gradient
Nonionized only
Maintain steep conc. gradient
High blood flow
Ionized and polar molecules
More water soluble
Harder to cross membrane
Nonionized and nonpolar molecules
More lipid soluble
Easier to cross membrane
Concentration of ionized and nonionized form
Influenced by pH
High lipid water partition coefficient (above 1)
Very lipid soluble
Low lipid water partition coefficient (below 1)
Very water soluble
Weak acid in more acidic environment (pH<pKa)
NONIONIZED
Weak base in more acidic environment (pH<pKa)
IONIZED
Strong acids and bases
Not effected by pH
Always ionized
Drugs are mostly weak electrolytes
Excretion of weak acids increases with
Basic urine
Less reabsorbed
Excretion of weak bases increases with
Acidic urine
Less reabsorbed
Plasma concentration at equilibrium of weak acid
Higher than intracellular
Plasma concentration at equilibrium of weak base
Lower than intracellular
Ionized with large hydrophobic structure
May diffuse easily if hydrophobic enough
Why is IV drug so concentrated near stomach?
Lots of H+ available to ionize drug and trap in there
Acidosis
Weak acid more nonionized and moves into tissues
Alkalosis
Weak base ionized, builds up in plasma, and is then readily excreted
Quaternary salts
Permanently charged
Does not cross BBB
Quickly excreted if given IV
Anion transport
Penicillins and related antibiotics
Cation transport
Quaternary ganglionic blocking drugs
Albumin
Primary binding protein in plasma
Favors weak acids and lipid soluble drugs
Drug bound to protein
Cannot be used, cannot be filtered in kidney, and cannot cross membrane
Protein binding affects
Loading dose, all binding proteins must be saturated before therapeutic concentrations can be achieved
Elimination may be prolonger
Drug interactions and protein binding
More than one drug may compete for same binding protein
Most problematic when drug binds in excess, has low Vd, is eliminated slowly, and has low therapeutic index
Drugs may displace endogenous substances
Thyroxine, steroids, billirubin
Drugs can be pre-bound to protein
Slower release
Drug redistribution concerning brain
High lipid solubility allows to enter quickly and lots of blood flow changes gradient causing drug to leave quickly as well
Ex. thiopental
