Basic Pharm 4 Flashcards
What is distribution?
The process of translocating drugs reversibly from the blood stream into the tissues/interstitium
What is the volume of distribution (Vd) equation?
Vd = Dose (L) / Plasma Conc (mg)
What property of a drug increases its volume of distribution?
The drug is more ionized inside cells than it is in the plasma
A drug typically distributes into what 3 compartments?
Plasma = 4 L ECF = Plasma (4L) + Interstitial fluid (10 L) = 14 L TBW = Plasma (4L) + IF (10 L) + ICF (28L) = 42 L
When does the drug distribute?
Once the drug reaches the max plasma concentration
What happens after distribution?
It starts eliminating –> clearance
How do you calculate plasma concentration?
Mg of drug / liters of plasma
How do you calculate concentration in general?
Mass / volume
What is a loading dose?
A priming dose that’s given to rapidly establish a therapeutic plasma drug concentration
If Vd is high, then loading dose is also, which makes loading dose what to Vd?
High, so loading dose is directly proportional to Vd
Loading Dose (LD) equation?
Plasma concentration (Cp) x Vd
What are the 2 areas of safeguard in our body? And what what kind of drugs can easily cross?
BBB and Placenta
High lipid soluble drugs can easily pass
What CYP enzyme metabolizes 60% of drugs?
CYP3A4
What are drugs that induce CYP450?
Carbamezepine, phenobarbitone, phenytoin (anti-convuls)
Rifampin, chronic alcohol, glucocorticoids
Makes CYP450 active, and these drugs get meatbolized more, decreasing effectivness
Drugs that INHIBIT CYP450?
Cimetidine, Erythromycin, Ketoconazole
What juice inhibits metabolism of alprozolam, atorvastatin, and midazolam?
Grapefruit juice
PPBinding: High affinity drugs will do what to low affinity drugs?
Displace them.
E.g. Sulphonylureas displace Warfarin (99% protein bind, 1% free)
Sulfonamides displace bilirubin in neonates (leading to kernicterus
What is redistribution?
Drugs that first go to organs with high blood flow (i.e. brai, heart, liver, and kidney) - E.g. Thiopental (anesthetic)
Then redistribute to other tissues (e.g. muscle and fat)
When drug administration is stopped, redistribution causes brain levels to drop and patient comes out of anesthesia
Hangover effect due to drug slowly leaking out of tissue droplets
Metabolism (Biotransformation)
Process to increase water solubility, inactivate drug, and convert to excretabe form
What are prodrugs?
Inactive compounds that require biotransformation to become active
E.g. enalapril –> enalaphilat (Active form)
Morphine is active to active
What is first pass metabolism in the liver?
Mostly oral route,
some loss of drug before reaching circulation
What is Phase II Biotransformation?
Drugs undergo conjugation rxns to become water soluble for excretion
Phase II Biotransformation: glucuronide Conjugation
UDP - glucuronyl transferase
e.g. Chloramphenicol - drug glucurinodes exrected in bile can be hydrolysed by bacteria in the gut –> the liberated drug is absorbed
E.g. OCP
Phase II Biotransformation: Acetylation
E.g. Isoniazid: slow acetylators, risk for peripheral neuritis
Procainamid, hydralazine –> SLE
Phase II Biotransformation: Glutathione Conjugation
Acetaminophen poisoning (glutathione supply falls short)
