Pharmacokinetics Flashcards
What is a Drug?
Any Substance that , when administered to a living organism brings about functional changes as a consequence of interactions at the molecular level
What is Pharmacokinetics?
The Absorption , Distribution , Metabolism , Elimination of Drugs
What is the Pharmacological effect , action and Mechanism of Action of NorEpi on Cardiac tissue?
Pharmacological Effect
The observed event which has been produced by the drug ( Tachycardia)
Pharmacological Action
The functional modification that leads to that effect( Increased frequency of spontaneous depolarization of the SA node)
The Mechanism of Action
The molecular modification that causes that action ( Cardiac beta receptors)
What are the Two Permeation processes for the movement of Drugs?
Diffusional Transport ( Cell Membrane)
Bulk Flow Transport ( Intercellular Pores)
What is the most frequent process for the movement of drugs across the cell membrane?
Lipid Diffusion
Proportional to the Concentration Gradeint and the Area of Diffusion
Inversely Proportional to the Thickness of the Membrane
How is Lipid Diffusion mainly determined?
Oil/Water Partition Coefficient
Passive Process
Nonselective Process
Most Drugs around 100 to 1500D
What are the Characteristics of Aqueous Diffusion of a drug across the Cell Membrane?
Occurs through protein channels ( 7 Angstrom wide)
Maximum MW of 100
Proportional to protein channels and concentration gradient
Passive Process
Nonselective Process
What is the Oil/Water partition coefficient?
Index of the Relative Solubility of the drug in lipid and water
What do Ionized and Nonionized Molecules readily associate with in the cell?
Ionized: Water (Hydrophillic)
Nonionized: Lipid Soluble ( Lipophilic)
What quantitative difference is required between pH and pK to ensure the molecule is Ionized?
Above 3 = 99.99% Ionized
Weak Acid
pKa - pH
pK higher then pH ensures non ionized ( Lots of Protons)
Weak Base
pH-pK
pK lower then pH ensures non ionized
What is the Ion Trapping Mechanism?
Aspirin (pKa of 3.5)
In the Gastric Lumen: 1.5 pH = NI
In the Cell: 7 pH = Ionized and Trapped
What does the Ion Trapping Mechanism Ensure?
A concentration gradient of the nonionized form will remain high
What is the clinical importance of the Ion trapping mechanism?
Can accelerate the elimination of drugs from the kidneys
Acidic Drugs can be trapped in the tubular lumen by making urine alkaline (Basic= Ionized)
Basic Drugs can be trapped in the tubular lumen by making the urine acidic ( Acidic=Ionized)
What are characteristics of Facilated Diffusion?
Protein Carrier
Passive
Selective
Saturable
Subject to Inhibition
What are the Characteristics of Active Transport of a Drug across a cell membrane?
Protein Carrier
Active
Selective
Saturable
Subject to Inhibition
Against Concentration Gradient
What are the four mechanism carrier mediated drug transport?
GI Tract
Biliary Tract
Renal Tubule
Blood Brain Barrier
What size molecules of drugs will enter with endocytosis and exocytosis?
100,000 Daltons
Active Transport
NonSpecific: Physicochemical Character
Specific: Receptor Mediated
What drug molecules transport through Bulk Flow through Intercellular Pores?
Pressure Gradient
Passive Process
Nonselective Process
Drugs with Molecular Size of 15000-16000 Daltons
Through Capillary Pores
Any higher then that
What is first order kinetics and how does it relate to the processing of drugs?
A process is called first order when a constant fraction ( or percentage) of what must be processed , is processed per unit time
What compartment model is the human body assumed to be?
One Compartment Model
Drug is Instantly and Uniformly Distributed
What is Drug Absorption?
the process by which the unchanged drugs proceeds from the site of administration to the site of measurement within the body
What is Bioavailability and how is it influenced?
The fraction of a drug dose reaching unchanged the systemic circulation when administered by any route
The Route of Administration
What is Cmax , Tmax and AUC?
Peak Concentration(Cmax): the maximum drug concentration reached in plasma after administration of a given dose ( related to ADME)
Time to Peak Concentration (Tmax): the time to maximum drug concetration in plasma. Inversely proportional to the rate of drug absorption
Area Under the Curve(AUC): the total amount of drug that reaches the systemic circulation and relfects absorption , distribution and elimination factors of a drug
What are the Advantages and Disadvantages of Oral Drug Administration?
Advantage
Hastened and Delayed
Safest , Cheapest and Easiest
Disadvantages
GI upset
Digestive secretion
First Pass Effect
What are the Factors that affect Oral Drug Administration?
How can Gastric Emptying be hastened and delayed?
What is Presystemic Elimination?
The fraction of the drug that is eliminated during the first pass through the liver
What are the Advantages and Disadvantages of Sublingual/Buccal Drug Administration?
What is the Advantages and Disadvantages of Rectal Drug Administration?
Advantages
Avoid the First Pass Effect
Do not need to be awake
Seizures
Disadvantages
Lower oral absorption then most cases
Influenced by degree of rectum content
Can Irritate the Mucosa
What are the Advantages of Cutaneous Drug Administration(Topical)?
Advantages
Drug Concentration is locally high
Systemic adverse effects are minimal
Disadvantages
Systemic adverse effects can occur if the skin is damages
What is the Advantage and Disadvantages of Transdermal Administration?
Advantages
First Pass effect is avoided
Dont need to be Awake
Repeated administration are minimized
Disadvantages
Few drugs can be absorbed this way
