Basic Principles Flashcards
What is a drug?
Chemical substance used for the Dx, prevention or Tx of disease, and for the prevention of pregnancy
What is pharmacokinetics? What are the four major steps?
How a drug enters the body, circulates w/in the body, is changed by the body, and leaves the body. Absorption Distribution Metabolism Excretion
What is pharmacodynamics?
Biochemical and physiologic actions of drugs, and their mechanisms of drug action at the cell level and sub-cell level
What is a succinct difference between pharmacokinetics and pharmacodynamics?
Movement VS Action
What are the characteristics of drug molecules?
Lipid solubility, Degree of ionization, Molecular size, and Shape
How do drug molecules cross membranes?
Diffusion, Filtration, and Specialize transport
How does pKa affect the ionization of weak acid drugs and weak base drugs?
Weak Acid in acidic environment is lipid soluble.
Weak Acid in basic environment is water soluble (dissociates).
Weak base in acidic environment is water soluble (dissociates).
Weak base in basic environment is lipid soluble.
THEREFORE, a weak acid or a weak base in its native environment is lipid soluble, otherwise it is water soluble and dissociates
Are charged molecules lipid soluble?
No
Is aspirin an acid or a base?
Weak acid pKa = 4.4
What happens to aspirin in stomach?
It is dissociated 1000 uncharged:1 charged molecules. The uncharged aspirin is lipid soluble and can cross the wall of stomach into plasma. Once in plastma the pH is 7.4 and it’s ratio is reversed 1000 charged to 1 uncharged.
What are the routes by which drugs are administered in the body?
Everything other than oral and rectal is a parenteral route. The parenteral route is inhalation, insufflation, intravenous, intramuscular, topical subcutaneous, sublingual, and transdermal
What are the mechanisms by which drugs penetrate biological membranes?
Diffusion, filtration, and specialized transport
How do most drugs cross membranes?
By diffusion
What are the forms of specialized transport?
Facilitated diffusion and Active transport
What is the first pass effect?
Only an issue with oral route drugs. Drugs must go thru liver first before reaching systemic circulation. Intestinal epithelium and liver have P450 enzymes that metabolize (a certain percentage) the drug to inactive forms
What is bioavailability?
The fraction of the administered drug that becomes available in the plasma
What does bioavailability often depend on in generic drugs?
The “vehicle” that carries the drug into the system. Active drug molecule may be the same but vehicle may differ in generics
How do drugs get transported from the plasma to the tissue sites?
Drugs are either bound or unbound to plasma proteins. Only “free” unbound drug molecules can cross cell membranes to tissue sites.
What happens to the bound drug as unbound drug leaves the plasma into interstitial fluid?
The bound/unbound ratio of a drug stays the same, so bound drugs become unbound to maintain that ratio
What are the various body fluid compartments where drugs can pass? (3)
Plasma, interstitial fluids, and intracellular fluids
What are the potential barriers to drug distribution in the body?
Two main barriers are the BBB and placenta.
ALSO,
- Another drug may induce the metabolism of a drug, thereby reducing action of the first drug.
- First pass effect.
- Not being lipid soluble
- large size
- charged molecules cannot cross
- shape
What is a drug inducer? What is a drug inhibitor?
An inducer decreases the action of another drug, by increasing drug metabolism.
An inhibitor increases the action of another drug, by slowing down the metabolism of a drug; makes it stay around for longer.
What is drug redistribution?
Movement of the drug from the site of action to nonspecific sites of action
How does drug redistribution affect termination of drug activity?
When drug does from specific sites to nonspecific sites, the drug’s action will be terminated
What is drug biotransformation?
Body’s way of changing a drug so that it can be more easily excreted by the kidneys. Such as, conversion of lipid soluble drugs to water soluble metabolites
What are the phases of drug Biotransformation?
Two phases.
Phase 1 drug is modified by oxidation, reduction, or hydrolysis. Exposes site that can be further altered by Phase 2 reaction
Phase 2 drug is modified by conjugation to a larger endogenous molecule (eg, glucuronide, sulfate, glutathione)
Are Phase 2 metabolites pharmacologically active?
No, phase 2 metabolites are inactive. In contrast, phase 1 can still be active, but is usually rendered inactive also.
What are the characteristics of the microsomal oxidation enzyme system?
Cytochrome P450 enzymes metabolize the drugs. Microsomes are organelles in hepatocytes where most drug transformation takes place.
Where does drug metabolism also occur besides the liver?
Kidneys, lungs, nerves, plasma, and the intestines. But, all drugs are processed by liver eventually (?)
What is the principal organ of drug excretion?
The kidneys, they are the great “equalizers”.
All drugs in the blood are filtered by what organ?
Kidneys
What are the 6 ways for drug excretion from the body?
1) Kidney to urine
2) Bile to GI tract to feces
3) Sweat
4) Saliva
5) Lungs
6) Breast milk
What happens if a drug is still lipid soluble when it reaches the kidneys?
Drug will be reabsorbed by the kidneys a placed back into the bloodstream.
What is the biological “half-life” of a drug?
Amount of time needed for the plasma concentration of a drug to fall to one half its blood level
How many half-lives does it take for most drugs to be eliminated? How many half-lives to build up to a steady state level in the body?
4-5 half lives. Same amount of half-lives, 4-5
What is the difference between first order and zero order elimination?
First order elimination depends on a constant fraction that is eliminated per unit of time; most have a constant half-life; 50% eliminated per unit of time.
Zero order elimination is a given or set amount of drug eliminated per unit of time; as in alcohol is eliminated 1 g per hour regardless of initial amount of alcohol
What is distribution half-life? How is it related to first order drug elimination?
Rapid decline in plasma drug concentration as 50% of drug distributed throughout the body. It is a type of first order elimination
What is elimination half life? How is it related to first order drug elimination?
Time required to excrete 50% of drug from the system. It is a type of first order elimination.
