Lecture 4 Flashcards
What is the fraction of administered drug that reaches systemic circulation following administration by any route?
Bioavailability
What are three things that influence bioavailability?
1st pass hepatic metabolism
Solubility
Stability
Where is drug concentration measured?
In the plasma
What three things affect drug distribution into the tissue?
o Blood Flow
o Capillary permeability (ex- BBB)
o Drug structure (hydrophobic, hydrophillic)
What is volume of distribution?
Dose/ concentration of drug in plasma
What does a high volume of distribution mean?
Drugs distribute really well into the tissues
When a drug is bound to a protein is it active?
No, it is inactive
What is an example of a major protein that acidic drugs can bind to?
Albumin
What route of administration avoids the blood brain barrier?
Intrathecal route
What type substances diffuse easily across the blood brain barrier?
Lipid-soluble
What is the fastest equilibrium b/w mother and fetus?
40 minutes
What material move easily across the placenta?
Lipid-soluble
Where does most drug elimination take place?
Kidney
What is the disappearance of a drug when it is changed chemically into another compound?
Metabolism
What type of drugs can kidneys not eliminate?
lipophilic drugs
What ability have neonates not fully developed?
Conjugation
What is responsible for conjugating biliruben?
UDP-glucuronyl transferase
What competitively inhibits p450 enzyme?
Ketaconazole (binds to this instead of medication it should metabolize)
What drug permanently inactivates p450?
secobarbitol alkylates
These drugs do what to P450? Cimetidine, ciprofloxacin, erythromycin, ketoconazole, OCPs, quinidine, ETOH
Inhibit
These drugs do what to P450? Barbituates, phenytoin, steroids, isoniazid, rifampin, ETOH
Induce (increase metabolization)
What type drugs move easily across membranes?
Hydrophobic
What protein do acidic drugs bind to?
Albumin
What protein do basic drugs bind to?
Alpha 1-acid glycoprotein
When you don’t want a drug to act on the brain should you use a water-soluble drug or a lipid-soluble drug?
Water-soluble as it can’t pass the BBB (ionized molecules also can’t pass this barrier)
What is the name of a drug that is administered in an inactive form and is then activated by metabolism?
Prodrugs
Phase I of drug metabolism involved the ______ system.
Cytochrome P450 system
Whatare are P450 isozymes located?
In most cells but mainly liver and intestinal tract
What are the primary families in the P450 system?
CYP1, CYP2, and CYP3 families
What is involved in phase II of drug metabolism?
Conjugation with 2nd endogenous substrate
Monoamine oxidase (MAO) involved the oxidation of catecholamines and tyramine. Does it use the P450 pathway?
No, it utilizes a different pathway
Small doses of what drug help treat jaundice as they upregulate the expression of UDPGT.
Phenobarbital
Proximal tubular secretion involved in renal elimination of a drug is a _____ process
active
Where are all of these eliminated? PCN, cephalosporins, salicylates, thiazides, “loop” diuretics, sulfonamides, lactic acid, uric acid
Proximal tubular secretions
What type of drugs can’t be reabsorbed?
Ionized drugs
What should you do to enhance the elimination of weak bases?
Acidify the urine with ammonium chloride
What should you do the enhance the elimination of weak acids?
Alkalinize the urine with sodium bicarbonate
What are 5 routes of elimination
Renal Biliary secretion and enterohepatic cycling Exhalation Sweat Secretion into breast milk
What is is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%
half life
What makes up total body clearance?
Cl renal + Cl hepatic + CL other
What is non-linear kinetics where a constant amount of drug is metabolized per unit time
zero-order kinetics
What is drugs catalyzed by enzymes and follows Michaelis-Menten kinetics
1st order kinetics
In first order kinetics, the rate of metabolism is directly proportional to the ______
concentration of free drug
What is when drug levels in blood when input= output?
Steady-state drug levels
Steady state is about how may 1/2 lives?
4-5
A loading dose is administered to achieve what?
Rapid plasma level
Foods containing pyridoxine (vit B6) increases the metabolism of what drug?
levodopa in patient’s with Parkinson’s
_______ can alter the urinary pH making the urine more alkaline thus increasing the proportion of non-ionized drug thus increasing reabsorption of the drug systemically.
Fruit juices
A premature infant is considered less than how many weeks?
Less than 36 week gestational age
A neonate is less than ____ days
30
Gastric pH is _____ for the first two years of life.
Alkaline (improves absorption of weakly basic drugs and decreases absorption of weakly acidic drugs)
Neonates in the first 24 hours of life have what?
Decrease gastric emptying
increased gastroesophageal reflux
irregular peristalsis
increased absorption size of duodenum
Rectal absorption avoids what effect?
1st pass effect (drug absorbed by the hemorrhoidal veins which aren’t part of the portal circulation)
Peds have lower ________ _________ __________ creating larger volume of distribution and increased free drug concentrations.
Plasma protein binding
What drug could lead to gray baby syndrome?
Chloramphenicol
When does GFR approach adult rates?
2 years
When do tubular secretion and absorption reach adult rates?
5-7 months
Injections are limited to how mLs in peds?
2 mL
Elderly patients have decreased what affect?
First pass effect
elderly have higher ___________ of these drugs- digoxin, warfarin, theophylline)
bioavailability
Elderly will have an increased rate of absorption of ______ medications due to loss of subQ fat.
topical
Are serum albumin levels altered in the majority of elderly?
No, unless they are severely malnourished or have advanced chronic disease
What is the preferred drug pathway for geriatric patients?
Phase II (conjugation)
After age 40, GFR decreases ____ to _____ % for every decade of life.
6-10%
Why may geriatric patients have an artificially lowered BUN?
Inadequate protein intake
Why may geriatric patients have an artificially lowered creatinine and not altered renal clearance?
Diminished muscle mass
What type of antibiotics have poor absorption from the GI tract so they must be administered via a parenteral route?
Aminoglycosidae antibiotics
What weight should be used for dosing of aminoglycoside antibiotics?
IBW or adjusted body weight
almost all of the clearance of aminoglycoside antibiotics occurs where?
Renal
What drugs inactive aminoglycosides invitro (clinically significant in patients w/ renal failure)
Extended-spectrum penicillin
What is the normal 1/2 life for aminoglycoside antibiotics? what about for a dialysis patient?
2-3 hours
dialysis- 30-60 hours
What is an aminoglycoside antibiotic that is given orally?
Neomycin (Gi infections)
When do you want to take a peak sample?
1 hour after the end of the infusion
When do you want to take a trough sample?
1/2 before next dose
What drug is poorly absorbed orally but is useful in the treatment of C. difficile w/ the PO route.
Vancomycin
When is the only time vancomycin will get into the meningeal system?
With inflamed meninges
Clearance of vancomycin approximates what clearance?
Creatinine
Vancomycin may increase levels/ effects of what drugs?
Aminoglycosides
This drug is a P450 inducer, highly protein bound, has slow absorption from the oral route and goes into zero order kinetics?
Phenytoin
In an acute setting how often should levels of phenytoin be monitored?
2-3 days after therapy initiation and another 3-5 days after
Stable patients should have their phenytoin levels monitored how often?
At 3-12 month intervals
What are some signs of phenytoin toxicity?
Drowsiness fatigue lateral nystagmus ataxia, slurred speech sever confusion seizures, death
What is a more soluble ester of phenytoin and can be administered IM?
Fosphenytoin (doesn’t use propylene glycol)
What is the diluent in phenytoin IV that has cardiac depressant properties?
Propylene glycol (anti- freeze)
