Pharm Basics-Exam 1 Flashcards
Bioavailability = F =
% of the drug that makes it into circulation.
Calculate amount of drug in circulation for a given bioavailability
Drug in circulation = F x dose
Calculate a new dose for a new administration mode
new dose = (old dose x old F) / new F
MEC
Minimum effective concentration
ADME
Administration
Distribution
Metabolism
Excretion
henderson hasselbach
pH = pKa + log (non-protonated / protonated)
partition coefficient
lipid solubility of the non ionized form
[organic drug] / [aqueous drug]
First order kinetics
most drugs follow this clearance
constant fraction of the drug is cleared
rate of elimination directly proportionate to [ ]
zero order kinetics
Phenytoin, ETOH, Aspirin
Saturates- constant amount cleared
independent of [ ]
clearance
volume of blood cleared of drug/unit time
CL = rate of elimination / C
Volume of distribution (Vd)
Vd= dose / C
half life (t1/2)
t1/2 = (0.7 x Vd) / CL
steady state
plateau
takes about 4-5 t1/2’s to get to the plateau
loading dose
loading dose = (Vd x TC) / F
maintenance dose
maintenance dose = (dose rate x dose interval) / F
or
md = (CL x TC) x dose interval / F
or
md =((rate of elim / C) x TC) x dose interval / F
dosing rate
dosing rate = CL x TC
What are some great examples of very rapidly dividing cells that would be damaged with chemotherapy?
Lymphocytes, epithelium, hair follicles, RBCs
Primary resistance
Resistance to drugs after the first treatment due to inherent resistance
Aquired resistance
Resistance developed from multiple treatments
Selective toxicity
Ability of a drug to harm a target while sparing the good guys
- Unique target in pathogen (cell wall)
or - Target must be structurally different in pathogen (ribosomes)
or - Target must be more important to pathogen than to host
5 important aspects to consider when selecting antibiotics
- organisms identity and sensitivity to agent
- site of infection
- safety of the agent
- patient factors (ie pregnancy, gender, age, etc…)
- cost of therapy
Combination broad spectrum antibiotics
Clindamycin and gentamicin
Single broad spectrum antibiotics
Imipenem and cilastatin
3 targets of selective toxicity
Disrupt cell wall
disrupt protein synthesis (ribosomes)
inhibit enzyme unique to bacteria (dihydrofolate reductase)
Sulfonamides
Trimethoprim
suppress bacterial growth by inhibiting folic acid synthesis from PABA.
Works great with trimethoprim, which binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF)
Xenobiotics
Any foreign substance really
Bio transformation
The processing of xenobiotics for elimination
Two functions of biotransformation
Metabolism - phase 1, and elimination - phase 2
Sites of metabolism
LIVER, kidney, intestines, skin, lungs
Phase 1 reaction does what?
Who does the majority of the reactions?
Enzymes add a polar group to the molecule to make it somewhat more hydrophilic, allowing the drug to be conjugated. Drug is likely still active after phase 1.
Cytochrome p450 does the majority of the reactions (CYP)
Phase 2 reaction does what?
What is a possible negative effect of this reaction?
Phase 2 conjugates with endogenous stuff (OH, NH2, COOH, glucuronidation, acetylation, sulfation) making it quite polar and easily excreted. Drug probably inactive after phase 2.
ROS could result from conjugation!
Acetaminophen conjugation?
What about with overdose?
Normally, 95% of the drug is conjugated and excreted with no problems. 5% is converted via CYP450 to NAPQI which accumulates and forms protein adducts in the liver and kill you. GSH takes care of this problem under normal conditions, but with overdose, GSH gets saturated. He dead.