Pharmacokinetics/dynamic Flashcards
Simple definitions of pharmacokinetics and dynamic?
Kinetics—>what the body does to the drug
Dynamic—>what the drug does to the body
What are the 4 factors that determine a drug’s permeation?
Solubility/concentration/surface area/vascularity
What is pKa and which form of the drug can cross the membrane and which form is better excreted?
pKa--->pH when the drug is 50% ionized and 50% nonionized Nonionized form (uncharged) can cross membrane Ionized form (charged) is better excreted
Ionized and nonionized forms are water or lipid soluble?
Ionized—>water
Nonionized—>lipid
What are some examples of weak acid and base drugs?
Acid—>aspirin/loop and thiazide diuretics
Base—>local anesthetics/amphetamines/PCP
What pH environment would produced the most nonionized form of weak acid and base drugs?
Weak acid—>acidic
Weak base—>basic
Bound or unbound/ionized or unionized drugs are filtered through the kidney?
Unbound
Both ionized and nonionized are filtered (nonionized form undergo secretion and reabsorption)
What could you use to acidify the urine to increase renal excretion of weak base drugs?
NH4Cl
Weak acid and base drugs are better absorbed in the stomach or the small intestine?
Weak acid—>stomach
Weak base—>small intestine
What do we use lactulose to treat hepatic encephalopathy?
Hepatic encephalopathy—>increase ammonia/enlarged abdomen—>lactulose is converted to acidic acid—>acidify the guts—>convert NH3 (ammonia) to NH4+ (ammonium)—>increase ammonium excretion
If you keep increasing the drug dose and more is absorbed, and you keep doing that and no more is absorbed, what kind of transport is it for this drug?
Facilitated diffusion or active transport (saturable)—>the presence of ATP distinguish these two
Is IV a process of drug absorption?
No. Absorption is the entry of a drug from one compartment into the blood
Why should we be caution when taking warfarin and sulfonamide/UCB and sulfonamide at the same time?
They are both highly protein bound—>displace warfarin—>increase serum warfarin level
Kernicterus and bilirubin encephalopathy
What kind of drug can cross the blood brain barrier?
Lipid soluble or very small
What is the equation for Vd?
Vd=dose/plasma drug con.
Low plasma con. (drug leave plasma and goes into tissue)—>high Vd
A drug that is highly protein bound has a high or low Vd?
Low Vd (it stays in the plasma)
What is redistribution of a drug?
Drug goes to the target organ–>comes back out—>usually end up in fat (storage site)
What is an example of metabolizing an active drug into active metabolite?
Benzo
What are phase I and II drug metabolism?
Phase I—>reduction/oxidation/hydrolysis–>CYP450
Phase II—>Methylation/glucuronidation/acetylation/sulfation (More GAS) (transferases)
What are some common CY450 inducers?
Smoking and drinking in Barb’s Car Rifs her Phen
Smoking/drinking/Barbiturate/carbamazepine/rifampin/phenytoin
What are some common CY450 inhibitors?
COKE + grapefruit juice with your PI
Cimetidine/Omeprazole/ketoconazole/erythromycin/grapefruit juice/protease inhibitor
What is the most common drug that interacts with grapefruit juice?
Increase statins level
What drugs causes drug induces lupus and how?
Hydralazine/procainamide/isoniazid
with slow metabolizers (acetylators)
How to distinguish between drug induced and regular lupus?
Drug induced has antihistone antibodies
What does it mean when clearance of the drug is greater or smaller than GFR?
Cl greater than GFR—>secretion
Cl smaller than GFR—>reabsorption
What is the definition of therapeutic window?
Dose between min effective and min toxic con.
Does the time to steady state depends on the dose? if you increase dose, what will you see?
Nah brah
You will see a higher steady state drug con.
Why do we use loading dose?
To achieve steady state faster (about 2x maintenance dose)
What is the equation for half life/loading dose/maintenance dose?
Half life—>(0.7 x Vd)/Cl
Loading dose—>Cp x Vd
Maintenance dose—>Cp x Cl
When will an antagonist has no affect on a receptor?
When there is no agonist existed for this receptor
Under what situation can you compare the affinity of the 2 drugs? Left or right ward shift increase affinity?
When they are parallel to each other on the dose-response curve (meaning they work on the same receptor)
Left ward shift
Define full and partial agonist in terms of efficacy
Full—>reach max efficacy
Partial—>well they don’t
What happens if a partial agonist is in the presence of a full agonist? and what are some examples?
Partial agonist would compete with full agonist—>decrease the affect of full agonist—>thus partial agonist becomes an antagonist
Pindolo and tamoxifen—>when put in the body with natural full agonist (epi/norepi/estrogen)—>act as antagonists
What if you keep adding partial agonist into full agonist?
Eventually you would only see the affect of partial agonists
What does potentiation mean to a drug?
Increase potency
What is physiologic antagonism?
2 opposing agonist against each other (like a vasodilator and a vasconstrictor)
What is chemical antagonism?
One drug bind to another one to inhibit it
What does therapeutic index mean?
E.g. TI=5
It means if you take 5x the normal dose of the drug—>you will get toxicity
What are some common drugs with low TI?
Theophylline/digoxin/warfarin/Li+
Beta receptors/alpha 2/M2/D2 are Gs or Gi coupled?
Beta—>all Gs
Alpha2/M2/D2—>Gi (MAD2)
Gq coupled protein activates ___? and release ___ and ___?
Phospholipase C/IP3 (increase Ca) and DAG (activate PKC)
What receptors are coupled with Gq protein?
M1/M3/alpha1
Gs increase cAMP and then activate __?
PKA
cGMP is 2nd messenger in what tissue?
Vascular smooth muscle
What kind of receptors are for cytokines like EPO/interferon? and what does it activate?
JAKs?STATs
What are the 4 phases of drug development?
Phase I---->find out the safe dosage Phase II--->test for effectiveness Phase III---->test for side effects Approved by FDA Phase IV--->look for long term side effect
Which phase of the drug development does it usually fail?
Phase II
What are the FDA classification of drugs for pregos?
A—>very safe
B—>safe
C—>may be safe (unknown drugs)
D/X—>harmful
What cells in the stomach secretes gastrin?
Chief cell
When is the best time to dose PPI and why?
Half an hour before breakfast/parietal cell needs to be turned on
PPI is activated in basic or acidic environment?
Acidic
How is the protective layer of the stomach formed?
Epithelial cell produces bicarb + mucus neck cell produces mucus
What are some risk factors for peptic ulcers? and what can impair mucosal defense?
Smoking/stress/genetics
NSAIDs/H. pylori
Bismuth salts need what kind of environment to work?
Acidic
How is misoprostol used?
Prevent chronic NSAIDs induced peptic ulcer (inhibit prostaglandin production)
How is H. pylori affect stomach lining?
It eats the lining—>decrease acid resistance—>predispose the pt with ulcers
