Pharmacokinetics Flashcards
What is the ADME concept?
Absorption; Distribution; Metabolism; Excretion
Relates to Absorption..
- Oral and nonoral absorption
- First pass concept
- Bioavailability/ Bioequivalence w/ generic drugs
Relates to Distribution…
- definition and relation to body water
- application - loading dose
Relates to metabolism..
- Phase 1 vs Phase 2
- active metabolites
- Clearance vs. rate of elimination and maintenance dose
- Pharmacogenomics
Relates to Excretion…
-Renal clearance and factors effecting
Explain pharmacokinetics..
(What happens to the drug)
- dose administered
- (absorption)
- Drug concentration in systemic circulation
- (Distribution)
- Drug in tissues of distribution
- (Elimination)
- Drug metabolized or excreted
Main routes of drug administration:
- oral/rectal
- percutaneous
- Intravenous
- Intramuscular
- Intrathecal
- Inhalation
Main routes of elimination:
- urine
- feces
- milk, sweat
- expired air
Route of oral/rectal:
Gut –> portal system –> liver–> metabolites –> bile and back to the gut or kidneys and through urine
- drugs enter the system through the liver/gut/kidneysplasma
- excreted through the feces
- First pass metabolism of drugs goes through here
- Concentration of drugs will be different from ingestion to the site of action.
Route of percutaneous:
On the skin and absorbs into the plasma.
Route of Intravenous:
Straight into the plasma.
Route of Intramuscular:
Into the muscle and to the plasma.
Route of Intrathecal:
CSF Brain< –> Plasma
Route of Inhalation:
Lungs plasma
Other absorption areas to be aware of:
- Fetus Placenta plasma
- Breast/sweat glands plasma
Drug through the stomach..
Disintegration –> Drug in small particles –> Dissolution –> Drug in solution
Where is the site of maximum absorption?
Small intestines
Where must the drugs absorb to get to the liver? What is so significant about this site?
Portal vein into the liver. This is where First-pass metabolism occurs.
Gastric Emptying Rate Factors:
- volume of meal
- meal composition
- viscosity
- osmotic pressure
- position
- drugs
What’s important about volume of meal?
Putting a lot of food in initially empties the gut but is followed by decreases emptying. (Liquids empty faster)
What is important about meal composition?
High fat content retards emptying.
What is important about viscosity in gastric emptying?
Increased viscosity reduces the rate of emptying.
What is important about osmotic pressure in gastric emptying?
Increased osmotic pressure reduces the emptying rate.
What position creates the fastest gastric emptying?
On the right side.
What is important about drugs and gastric emptying?
Opioids, antcholinergics/antimuscarinics, ethanol, bile salts and acidification slow emptying.
What speeds gastric emptying?
Bicarbonate and metoclopramide.
What factors influence drug absorption?
MW, blood flow, solubility, concentration, disintegration/dissolution, partition coefficient, transporters, pH partition theory.
Sublingual administration:
- under the tongue
- rapid onset
- bypass portal vein
ex) nitroglycerine
Rectal administration:
- some drugs bypass portal vein
- erratic absorption patterns
ex) antiemetics, opioids, antipyretics
Pulmonary administration:
- rapid onset
- tremendous surface area
- also a route for excretion
ex) beta agonists, corticosteroids, antimuscarinics
Subcutaneous administration:
- popular/convenient
- tissue lies between epidermis and muscle
- popular sites: upper arm, abdomen, anterior of thigh, upper back, upper ventral or gluteal area
ex) insulin, opioids, heparin
PERFUSION-RATE LIMITED
Intramuscular administration:
- painful
- select spot away from large nerves/bones/blood vessels
- usually no more than 4 mL per one area
- sites include: vastus lateralis muscle, deltoid, gluteal
ex) insulin, opioids, antibiotics, antipsychotics
PERFUSION-RATE LIMITED
Intravenous administration:
- no absorption phase (F = 1)
- most rapid onset
- most dangerous (drug can’t be recalled and actions can’t be slowed)
What is the First Pass Effect? Where does it happen?
Where the concentration of a drug is greatly reduced before it reaches the systemic circulation. Metabolism of drugs begins in the gut lumen and continues through the gut wall, portal vein and liver. After leaving the liver, the new concentration is ready for site of action.
If the orally effective dose of a drug is much larger than the effective IV dose, what does this tell you?
Tells us that the drug is suspect to first pass clearance.
Drug absorption concepts:
- extent: total amount of drug entering systemic circulation
- rate: how quickly the drug enters the systemic circulation. changes w/ time.
What is Bioavailability?
The rate and extent an active/unchanged ingredient is absorbed from a drug product and is systemically available.
How is rate assessed?
- Tmax and Cpmax
- rate of absorption is a key determinant of peak concentration and peak effect for many drugs
How is extent assessed?
- AUC
- effected by absorption AND the fraction of drug which is removed by pre-systemic/first-pass clearance
- the extent of absorption (F) is used to convert IV doses and equivalent oral doses
What is Bioequivalence?
- When two drugs are similar in rate and extent to which the active ingredient is available at the site of drug action. (Assumption that the clearance is the same)
- drug vs drug
How else can F be written?
= (AUC PO) / (AUC IV)
How else can relative bioavailability be written?
= (AUC PO Test) / (AUC PO Standard)
What is Volume of distribution? What is the equation?
- it is the drug concentration to the amount of drug in the body.
- Amt drug in body = volume (L) x drug conc (mg/L)
Why is it “apparent” volume?
-bc of binding to tissues, binding to plasma proteins or absorption into bone.
When do you know drugs are being stored outside the blood?
- ~60L (stays within the blood)
- > 60L (released and stored outside the blood
- Vd»_space;> Tot body H2O
LD = ?
Why is it used?
(change in conc)xVd / F
units: L/kg
- used to rapidly establich a therapeutic conc of a drug, instead of waiting for it through maintenance doses
What is a Partition coefficient?
- described how substances distributes itself between immiscible solvents (typically water and octanol)
- useful in predicting absorption, distribution and elimination
- also helps predict onset of action/duration
Explain protein binding:
- drug protein binding can very from 0 >99%
- reversible in nature and nonspecific
What does it mean when it’s said that there is 15 mg/L @ 90% protein bound?
Means there is 1.5 mg/L of free drug. 13.5 mg/L are protein bound.
How well can free ionized drugs move across membranes?
- can only move paracellularly across the capillary endothelium.
How well can free un-ionized/lipophilic drugs move across membranes?
- can move transcellularly and paracellularly to the intracellular(only one that can) fluid/interstitial fluid/ and plasma
How well can bound drugs move through cell membranes?
-restricts movement tremendously
