Pharmacokinetics Flashcards
What are some drugs/properties that are inducers?
Anticonvulsants:
Phenobarbitone, Phenytoin, CBZ
Anti-TB: Rifampin
Omeprazole
Griseofulvin
St. John’s work
Cigarette Smoking
What are some drugs/properties that are inhibitors?
Erythromycin,
* Cimetidine
* Grapefruit juice
* Disulfiram
* Ethanol
* Antifungals: Itraconazole,
Ketoconazole
* Antivirals: Ritonavir, Saquinavir
What is consider phase I metabolism?
Oxidation, reduction, hydrolysis
What are phase II metabolism?
Glucuronide conjugation
Sulfate conjugation
Glutathione conjugation
Acetylation
Methylation
Glycine conjugation
What does drug clearance means?
CL= Metabolism + Excretion
What condition is caused by a decrease in expression of UGT1A1 glucuronidation?
Gilbert syndrome, neonatal hyperbilirubinemia (milder than Crigler Najjar)
In acetaminophen poisoning, what is the metabolizing mechanism?
Metabolized by glucuronidation, Sulfation, oxidation & conjugation with glutathione
What drugs undergoes acetylation?
SUlfonamides, hydralazine, Isoniazid
PAS
What is Crigler Najjar syndrome
Crigler Najjar syndrome is a rare autosomal recessive inherited disorder characterized by the absence or decreased activity of UDP-glucuronosyltransferase, an enzyme required for glucuronidation of unconjugated bilirubin in the liver.
Why are NSAIDs contraindicated in elderly for long term use?
NSAIDs inhibit the production of prostaglandins and therefore reduces renal perfusion and GFR.
**Drugs that are mainly excreted by kidneys
Antibiotics such as:
Penicillin, Cephalosporin
Aminoglycosides (gentamycin)
Sulfonamide
Imipinem
Non Steroidal Anti Inflammatory Drugs (NSAIDs) : Aspirin, Paracetamol
Coxibs
Lithium
Digoxin
Immunosuppressant drugs such as Cyclosporine
Anticancer drugs such as Cisplatin
When would the alkalinization of urine be applicable?
When there is salicylates or barbiturate poisoning. (ion trapping to remove weak acids with alkalinization
What effect does probenecid have on penicillins?
It blocks the tubular secretion of penicillin, decrease excretion of penicillin and prolongs penicillin action.
What increases T1/2 in drugs?
Impaired renal clearance
Loading dose is affected by which factors?
Target Cp and volume
What factors is maintenance dose affected by?
Clearance rate ,concentration ,half life , and dosing time
Formula of Half life?
Half life= V d / Clearance
How many half lives is needed for nearly elimination of a drug?
4 to 5 half lives
What is constant in first order kinetics?
The clearance is constant
What is constant in zero order kinetics?
The rate of elimination is constant
Zero-order kinetics of drug elimination occurs when:
A) The rate of elimination is proportional to the drug concentration
B) The rate of elimination remains constant over time
C) The rate of elimination decreases as drug concentration decreases
D) The rate of elimination increases as drug concentration increases
B) The rate of elimination remains constant over time
First-order kinetics of drug elimination occurs when:
A) The rate of elimination is proportional to the drug concentration
B) The rate of elimination remains constant over time
C) The rate of elimination decreases as drug concentration decreases
D) The rate of elimination increases as drug concentration increases
A) The rate of elimination is proportional to the drug concentration
Which variables below contribute directly to the maintenance dose? ( May choose more than 1)
A. Bioavailability
B. Clearance
C. Drug plasma concentration
D dosing interval
E. Volume of distribution
A. Bioavailability
B. Clearance
C. Drug plasma concentration
D dosing interval
Which variables below contribute directly to the loading dose? ( May choose more than 1)
A. Bioavailability
B. Clearance
C. Drug plasma concentration
D dosing interval
E. Volume of distribution
A. Bioavailability
C. Drug plasma concentration
E. Volume of distribution
Which of the following drugd do not follow zero order kinetics?
- Phenytoin
- Ethanol
- salicyclates
- Paracetamol
- Paracetamol
Role of P glycoprotein
Primary Transport drug out of cell- associated with MDR 1 gene.
Role in ADME:
Limit intestinal absorption
Distribution of drugs into brain, testes and fetal tissue, promote biliary and renal elimination
Role of SLC transporter
Secondary active transport- uses the energy stored in the ion concentration gradient from primary active trasnport (potential energy) to drive the secondary active transport.
It mediates both uptake and efflux of drugs and metabolites.
What are the 2 secondary active transport
Symport ( Cotransport): both the
solutes move in the same direction
e.g. sodium glucose symporter
Antiport (Counter transport): move in
opposite direction e.g. sodium calcium
exchanger
Examples of SLC:
OATP-organic anion transporting
polypeptide
* OCTOCT-organic cation transporter
* DAT, NET, SERT : Na+/Cl Cl-dependent
neurotransmitter transporters
* SGLTSGLT1, SGLT SGLT2: glucose transporters in
intestine & renal tubules
Drug that undergo substantial first pass elimination
Aspirin, GTN, ISDN, Levodopa, Lidocaine, Verapamil, Salbutamol, Morphine, Metoprolol, Propanolol.
** Extraction ratio-discuss FPM and BA based on high and low ER
Low ER, low FPM, High BA
High ER, High FPM, Low BA
What does a large Vd mean
Low PP binding, and widely distributed in body fluids
Formula of Vd
Vd= Dose administered IV/Plasma concentration
How does the body metabolize acetaminophen?
Metabolized by glucuronidation, sulfation, oxidation & conjugation with glutathione.
What happens to first order kinetics at higher dose?
Elimination process get saturated, kinetics changes from first order to zero order kinetics
Drugs with narrow therapeutic window
DIgoxin, aminoglycosides,
anti-arrthmics, lidocaine, warfarin, phenytoins, carbamazepine, valproic acid, theophylline, cyclosporine, tacrolimus, lithium, vancomycin, colistin
What is loading dose influenced by?
a. clearance
b. volume
c. T 1/2
d. dosing time
b. volume
Loading dose =
target Cp x V.
Factors affecting excretion
Age, renal clearance, pH of urine, Disease
Formula of renal clearance
CLr= Excretion rate (CuVu) / Plasma concentration (Cp)
Cu- drug concentration in urine,
Vu= volume of urine in 24hrs
Which part of the nephrons is used for excretion mainly?
Tubular secretion (main mechanism of excretion)
