Pharmacokinetics 1 & 2 Flashcards
What is the most rapid method of drug delivery?
Parenteral- routes of drug delivery that completely bypass the hepatic circulation. It included Intravenous and subcutaneous.
What are the advantages of IV administration of drugs?
Very high bioavailability
No First Pass metabolism
Flexible rate of administration
Veins are insensitive to irritation by drugs
What are some of the disadvantages of IV administration?
It is expensive Requires sterility Trained Personell Risk of infection Once you administer the drug there is no recall.
What is subcutaneous drug administration?
What are the major pros and cons?
Injection of the drug dose just under the skin.
you bypass first pass metabolism, can be given by the patient, absorption can be varied.
Disadvantages: not good for large volume of drug.
What type of compounds would be suitable for inhalation?
Gaseous and volatile compounds, provides rapid absorption and is efficent due to the large alveolar surface area. Some concern of allergic reaction and can be a route of administration for drug abuse.
What are the advantages of topical administration of a drug?
The mucous membranes provide for rapid absorption of drugs but can lead to systematic toxicity.
What factors affect the rate of drug distribution? (3)
- Cardiac output
- Tissue Volume
- Capillary Permeability
What factors affect the extent of distribution?
Physiochemical factors affeting transport across membranes
Plasma protein binding
Intracellular binding
Permeability and or transport characteristics of specific tissue membranes
What affects drug distribution to an organ?
Blood perfusion. the greater the blood perfusion rate the more drug is distributed to an organ.
What organs have the maximum blood perfusion?
The brain, kidneys, liver, and muscle
What can cause drugs to stay in the central blood compartment and limit distribution of free drug to its sites of action .
Binding to plasma proteins
What is the most common blood plasma protein?
Albumin which commonly binds to acidic drugs.
What blood protein binds to basic drugs?
Globulins which binds many endogenous substances, steroids, vitamins, and metal ions
Describe the specifity of drugs binding to plasma proteins?
The binding is generally nonspecific reversible process that maintains a dynamic equilibrium between bound and unbound drug.
What determines the fraction of drug bound to plasma proteins?
- Drug concentration
- Its affinity for binding sites
- The number of binding sites
What is the major determinant of the fraction of drug bound at low drug conc.
The affinity for the binding sites.
At high drug conc describe the effect of the binding sites?
At high concentrations the number of binding sites becomes the limiting variable.
Does the bound or unboud drug in the plasma which equilibrates with the site of pharmacological or toxic response?
The unbound or free drug determines the pharm or toxic response.
A slight change in the concentration of bound drug can result in significant changes in clinical response or toxic responses.
Can drugs accumulate or bind to tissue?
Yes, many drugs accumulate in tissues at higher concentrations than those found in extracellular fluids and blood.
What causes drug accumulation in tissues?
Active transport
What drives tissue binding to drugs?
Tissue binding usually results from the interaction with proteins and or phospholipids
Describe the binding of drugs to cellular constituents.
Binding to reversable and saturable. this is dependent on the concentration, affinity, and binding capacity of the tissue as well as the physiochemical properties of the drug.
What represents a reservoir of a drug?
The charged and ion trapped drugs represent a reservoir of drug that can sere to prolong the duration of response.
What are the four most common drug reservoirs?
- Stomach
- Albumin
- Tissue (Liver, thyroid, and bone)
- Fat
What type of drugs accumulate in the stomach?
Basic drugs due to ionization
What type of drugs accumulate in albumin?
Albumin limits the availability of free drug and thus alters kinetics (Warfarin is 99% bound)
What types of durgs accumulate in tissues (Liver, Bone, and Thyroid)
The liver concentrates drugs sich as quinacrine via active transport.
The thyroid concentrates iodine
Bone- accumulates tetracycline and other divalent chelating compounds. Heavy metals may also accumulate in bone.
What type of drugs accumulate in FAT?
Lipid soluble compounds can readily partition into fat tissue which then acts as a sortage depot for compound prolonging its action. This represents an important source of interpatient variability.
What causes termination of a drug?
Metabolism and excretion
**May aso arise from redistribution from the site of action to the other tissues or to bound proteins.
Describe the redistribution of Thiopental
Look this up
What are the four variations of drug distribution
- Vascular System
- Body Water distribution
- Concentration to one or more specific tissues
- Non-uniform distribution in the body.
Describe the drug distribution in the vascular system?
Plasma substitutes such as dextran are an example of this type, but drugs which are strongly bound to plasma protein may also approach this pattern.
Describe the drug distribution throughout the body water.
Low molecular weight compounds such as ethanol will be distributed in the body water.
Describe the drug distribution specifically in one or more tissues that may not be the site of action.
Iodine is concentrated by the thyroid gland Tetracycline is almost irrecersibly bound to bone and developing teeth. Another type of specific concentration may occur with highly lipid soluble compounds which distribute into fat tissue.
Describe the nonuniform distribution in the body.
Most drugs are unevenly distributed throughout the body based on their ability to pass through the plasma membrane and their relative solubility in water and lipids.
What is the formula for the volume of distribution (Vd)
Vd = ( Amount of drug administered / plasma concentration of drug )
What is volume of distribution (Vd) ?
Vd is a clinically relevant parameter that indicates the apparent body colume that a given drug is located within and is generally indicative of the compartment to which it distributes. It is a very useful diagnostic value.
What is to total body water in Liters?
40 L
What is the plasma volume?
4 L
What determines the desired therapeutic affects as well as unwanted side effects of a drug?
The drug’s presence at an appropriate concentration at an appropriate time.
What is the therapeutic window?
The range between the minimum toxic concentration ( Or maximum tolerable conc) and the Minimum effective concentration.
What does pharmacokinetics deal with?
Pharmacokinetics deals with the disposition of the drug within the body
How does it get in?
Where does it go?
What changes are made to it?
How does it get out?
What determines the pharmacokinetics of a drug?
Absortption, distribution, metabolism and excretions. These factors dictate the onset, intensity, and duration of drug action.
What type of compounds can pass through the cell membrane?
Lipophilic and non polar and nonionized compounds.
True or false? The the lipid phase of the plasma membrane contains aqueous channels or pores.
True, they are located in the lipid phase of the cell membrane.
What type of drugs can pass through these pores?
Low Molecular Weight Drugs can pass through these pores.
Can proteins and peptides pass through the plasma membrane?
No the plasma membrane is relatively impermeable to proteins and peptiees.
What do membrane proteins embedded in the bilayer serve as?
Membrane proteins embedded in the bilayer serce as receptors, ion channels, pr transporters to elicit a electrical and chemical signaling pathways and are often targets of drugs.
How do most drugs pass through the plasma membrane?
Via passive diffusion. This occurs when the concentration of drug outside the membrane is higher than the concentration of the drug inside the plasma membrane.
What governs the diffusion rate?
Fick’s Law
Diff Rate = -DAK (Cout - Cin) / DeltaX
D= diffusion coefficient K= partition coefficient A= surface area Delta X= membrane thickness Conc Gradient=
How do large polar drugs cross the biological membrane?
Via carrier proteins.
What is an example of a drug that crosses the membrane via facilitated diffusion?
Riboflavin, Vit B12
What is an example of a drug that crosses the membrane via active transport?
5-Flurouracil
What are two mechanisms that carrier transport can be linked to?
Cotransport and Countertransport.
How can a drug be taken in when a cell membrane invaginated?
Endocytosis forming a pinocytic vessicle
What substances does p-glycoprotein transport?
Chemotherapeutic agents.
What must happen for a drug to cross a membrane ?
It must be soluble in the lipid material of the membrane and has to be soluble in the aqueous phase to get out of the membrane.
Do drugs get absorbed when they are ionized or nonionized?
A drug must be non-ionized to be effectively absorbed. This gives them a higher solubility.
What is the driving force that drives drugs to cross a biological membrane?
The concentration gradient that exists for the nonionized form of the drug.
Most drugs are weak ________ meaning they can exist in charged and uncharged forms in solution.
Weak Electrolytes
What is HH equation for weak acids?
pH = pKa + log ( [A-] / [HA] )
HA —–> A- + H+
What is the HH equation for weak bases?
pH = pKa + log ( [B] / [BH+] )
BH+ ——> B + H+
Is a protinated acid ionized?
When an acid is protinated it is nonionized
HA A- + H+
HA is the protinated from and you can see it is not ionized
Is a protinated base ionized?
yes a protinated base is ionized
BH+ B + H+
You can see the protinated form of the base is in fact ionized.
At steady state where will acidic drugs accumulate?
Acidic drugs will accumulate on the more basic side of the membrane.
**ION TRAPPING
At steady state where will basic drugs accumulate?
At steady state the basic drugs will accumulate on the more acidic side of the membrane.
**ION TRAPPING
What is drug absorption?
The rate at which a drug leaves its site of administration and the extent to which that occurs.
What is bioavailability?
A clinically relevant parameter which refers to the fractional extent to which a given dose of a drug reaches either its site of action.
What is first pass metabolism?
The portion of a drug that is inactivated in the liver when it passes from portal circulation to systemic circulation.
What is the rate limiting step for drugs that are administered in the solid form?
They must be dissolved before absorption can take place.
What will an enteric coating do to a drug?
It will delay the rate at which the drug is dissolved.
What are the pros and cons of oral drug administration?
Pros: Safe cheap
Cons: Bioavailability, patient compliance.
Does buccal absorption bypass portal circulation?
Yes.
What is the drug transit time for drugs absorbed in the stomach?
30-40 minutes.
What happens to a basic drug in the stomach?
Basic drugs will be ionized in the acidic environment of the stomach thus they will not be absorbed until they reach the basic environment of the intestines.
Will acidin drugs be ionized or nonionized in the stomach? How will this affect absorption?
Most acidic drugs will be nonionized in the acidic environment of the stomach. Thus they will readily be absorbed.
What effect will gastric emptying time have on drug absorption?
Increased gastric emptying time will cause increased drug absorption.
Will sublingual drug administration bypass portal circulation?
Yup
What are the advantages of rectal drug administration?
It bypasses portal circulation and can be very useful when the patient is unconsious or can not stop vomiting.
Does the ionized or nonionized form of a drug get absorbed?
Drugs are only absorbed when they are nonionized.
Will acidic drugs be ionized or nonionized in the stomach?
Acidic drugs will be nonionized. This is because the low pH of the stomach, Or high H+ concentration causes the drug to be protinated. Acidic drugs that are protinated are nonionized and can thus be absorbed.
