Module 1 Flashcards
What is pharmacology
The study of drugs
What are some of the various aspects that can be included in the study of drugs?
1) How a drug is delivered (it’s route of administration).
2) How a drug works (it’s mechanism of action).
3) The therapeutic effect of drugs on patients.
4) The adverse effects of drugs on patients.
What are the classifications of therapeutics?
1) Drugs – Traditional drugs (i.e., chemical agents).
2) Biologics – antibodies, hormones.
3) Natural Health Products – herbals, vitamins, minerals.
What are the three directorates used to oversee therapeutics in Canada?
- Therapeutic products directorate
- Biologics and Generic Therapies directorate
- Natural Health Products directorate
Summarize Canadian Drug Legislation (photo)
Food and Drugs Act and Regulations –> Health Canada –> Health Canada Products and Food Branch –> Various Directorates
How must we think of drugs?
As chemicals
Within every pill, tablet, or capsule is what?
The many molecules of a chemical; it is the chemical that actually produces the pharmacological effect.
What are the three types of names used for naming drugs?
- Chemical Name
- Generic Name
- Trade Name
Describe chemical name
Describes the chemical structure of the molecule. Is used by chemists but not by many others. Not commonly used in pharmacology.
Describe generic name
A unique name that identifies a drug. The generic name is the name most often used in Pharmacology.
Which type of name is used by health care professionals?
Generic (not always the case but should be)
Describe trade name
The name assigned by a drug company. It is usually easy to remember and marketable. The major problem with trade names is many companies may make the same drug, therefore it may have many different trade names.
How can drug routes of administration be broadly classified?
Enteral, Parenteral, Other (such as topical)
Describe the preclinical testing phase (of approval of marketed drugs in Canada)
-In cultured cells, living tissues, or experimental animals
-evaluate biological effects, pharmacokinetics, and toxicity
-lasts approx 6.5 yrs
Describe the clinical trial application (approval of marketed drugs in Canada)
must be submitted to Health Canada prior to any human studies
Describe the phase I clinical trial phase (of approval of marketed drugs in Canada)
-20-100 healthy volunteers
-evaluation of pharmacokinetics and pharmacodynamics
Describe the phase II clinical trial phase (of approval of marketed drugs in Canada)
-300-500 patients with the targeted disorder
-therapeutic effectiveness, side effects, and dosing information is gathered
Describe the phase III clinical trial phase (of approval of marketed drugs in Canada)
-500-5000 patients with the target disorder
-therapeutic effectiveness verified, long term side effects assessed
Describe the phase IV clinical trial phase (of approval of marketed drugs in Canada)
-Post marketing surveillance. Health Canada monitors the efficacy and safety of the drug after it has been marketed (after new drug submission (NDS) submitted to Health Canada
Describe new drug submission (NDS) submitted to Health Canada
After phase III clinical trial.
A report that details therapeutic effectiveness and safety. Includes results from pre-clinical and clinical studies. If approved, Health Canada issues a Notice of Compliance (NOC) and a Drug Information Number (DIN). Both are required to market the drug.
List the 7 steps for approval of marketed drugs in Canada
- Preclinical testing
- Clinical trial application
- Phase I clinical trial
- Phase II clinical trial
- Phase III clinical trial
- New drug submission (NDS) submitted to health Canada
- Phase IV clinical trial
What do enteral routes of administration involve?
Oral or Rectal
What do parenteral routes of administration involve?
Intravenous, Intramuscular, Subcutaneous
What do topical routes of administration involve?
Creams or Patches
Which routes of administration involve the gastrointestinal tract?
Enteral (oral and rectal)
What is the primary site of drug metabolism in the body?
Liver
Define Pharmacokinetics
The branch of pharmacology concerned with the movement of drugs within the body. Is what the body does to the drug.
What does ADME stand for
Absorption, Distribution, Metabolism, and Excretion
What are all the major components of the cell?
Nucleus – Contains genetic material (i.e., DNA).
Smooth Endoplasmic Reticulum – Metabolizes drugs, carbohydrates and steroids.
Rough Endoplasmic Reticulum – Synthesizes proteins.
Golgi Apparatus – Processes and packages proteins and lipids.
Mitochondria – Produces ATP (cell’s source of energy).
Cell membrane – Separates the intracellular and extracellular environments.
Our body has many well-developed barriers to help protect us. List various physiological barriers to drug transport
- Intestinal villi - form a barrier against ingested drugs, toxins, and nutrients
- Some cells have tight junctions which prevent molecules from passing between cells.
- In order to exert its effect, a drug must have the right chemical properties to pass through these barriers.
Define lipid bilayer
A lipid bilayer is a biological membrane consisting of two layers of lipid molecules. Each lipid molecule, or phospholipid, contains a hydrophilic head and a hydrophobic tail. The tail regions, being repelled by water and slightly attracted to each other, congregate together. This exposes the head regions to the outside, creating a barrier between two bodies of water.
What is a very important barrier to drug movement in the body?
The cell membrane
Describe the cell membrane
- Composed of phospholipids which have a polar (water soluble) phosphate containing head and two fatty acid (lipid soluble) tails.
- The cell membrane is often called a lipid bilayer because of the arrangement of the phospholipids.
- The cell membrane is “fluid” because the phospholipids are flexible allowing them to undulate back and forth.
- The cell membrane also contains proteins embedded in the phospholipids.
How do drugs cross the cell membrane?
1) Direct penetration of the cell membrane.
2) Through ion channels and pores.
3) Specific transport proteins (drug transporter’s).
To directly penetrate cell membranes, drugs must be what?
lipid soluble (lipophilic)
- Remember that cell membranes are composed of primarily lipid, therefore drugs must be able to dissolve into the lipids of the cell membrane in order to pass through it.
- Molecules that are not lipophilic cannot pass through cell membranes.
Would a hydrophilic (water soluble) drug be able to pass through the cell membrane by direct penetration?
No
Describe the important characteristics of polar molecules
- Are water soluble.
- Have an uneven distribution of electrical charge yet have no net charge.
What are some examples of polar molecules?
water, glucose, and the antibiotic drug kanamycin
What are the different types of drug molecules that we encounter?
1) Polar Molecules
2) Ions
3) Quaternary Ammonium Compounds
4) Ionizable Molecules
5) Lipophilic Molecules
Describe drug transporters
Are carrier proteins that move drugs from one side of the cell membrane to the other
Which type of drug transporter moves drugs from outside the cell to inside?
Uptake transporters
Describe uptake transporters
- move drugs from outside the cell to inside.
- uptake transporters are important in mediating intestinal absorption, renal excretion and reaching target sites of action inside cells.
Which type of drug transporter moves drugs from inside the cell to outside?
Efflux transporters
They are important for protecting cells and are present in the intestine, placenta, kidney and at the blood brain barrier.
Describe ion channels and pores
- The channels and pores in cell membranes are very small.
- Only very small compounds (molecular weight < 200) can pass through channels and pores.
- Channels are selective meaning only certain small compounds can fit through them.
- Examples of compounds that cross membranes through channels include sodium, potassium and lithium, a drug used in the treatment of bipolar disorder (lithium will be discussed more in Module 14).
Define ions
Ions are atoms or molecules where the total number of electrons is not equal to the total number of protons.
* Ions have a net charge (negative or positive).
* Due to their charge, ions cannot directly pass through the cell membrane. Very small ions pass through ion channels or pores.
What are some examples of ions?
Sodium (Na+), Potassium (K+), Chloride (Cl-) and Lithium (Li+)
Describe quaternary ammonium compounds
- Have at least one nitrogen atom and have a positive charge at all times.
- Due to the positive charge, these molecules are unable to cross cell membranes.
Describe ionizable molecules
- Ionizable molecules can exist in charged or uncharged form.
- These molecules are weak acids or weak bases.
- Determination of whether a weak acid or a weak base carries a charge depends on the pH of the surrounding medium.
Describe lipophilic molecules
- These molecules are quite lipid soluble, unlike polar molecules, ions, quaternary ammonium structures and charged ionizable molecules
How do very small ions pass through the cell membrane?
ion channels or pores
An example of an acidic medium/environment is what?
the stomach
An example of an alkaline medium/environment is what?
the small intestine
Which type of ionizable molecule is non-ionized in an acidic medium?
weak acid
Which type of ionizable molecule is ionized in an acidic medium?
weak base
Which type of ionizable molecule is non-ionized in an alkaline medium?
weak base
Which type of ionizable molecule is ionized in an alkaline medium?
weak acid
Only which type of drugs can directly penetrate the cell membrane?
non-ionized drugs
Most drugs are _____ _____ and therefore cross membranes more easily in an _____ medium.
weak bases; alkaline
Another name for a weak base (drug) is what?
basic drug
An acidic drug in an acidic environment is _____ and there fore _____ cross the cell membrane.
unionized; can
A basic drug in a basic environment is _____ and there fore _____ cross the cell membrane.
unionized; can
A basic drug in an acidic environment is _____ and there fore _____ cross the cell membrane.
ionized; can’t
An acidic drug in a basic environment is _____ and there fore _____ cross the cell membrane.
ionized; can’t
Describe ion trapping
- Ion trapping occurs when there is a difference in pH on different sides of a membrane.
- Drugs accumulate on the side of the membrane where they are ionized.
When can ion trapping be put into clinical use?
In some cases of drug overdose
Give an example of ion trapping
- In the example on the right an acidic drug is placed into an acidic environment. Since acidic drugs are unionized in acidic environments, the drug is able to cross the membrane.
- The other side of the membrane is basic, therefore when the drug crosses the membrane is becomes ionized. Since ionized drugs are unable to cross cell membranes, the drug is now “trapped” on the basic side of the membrane.
What are the smallest blood vessels in the body?
capillaries
Capillaries have fenestrations. Define fenestrations
Fenestrations are small holes within the endothelial cells that allows for molecules to pass through
Capillary beds supply tissue with _____ _____ and allow the drugs and other molecules to move from the _____ to the _____.
oxygenated blood; blood; tissue
What type of drugs must pass between fenestrations to leave the blood?
Hydrophilic
What type of drugs can either pass between fenestrations or directly through the plasma membrane of capillary endothelial cells?
Lipophilic
Capillaries at the blood brain barrier have _____ _____. They do not have fenestrations. In order to penetrate the brain drugs must either be _____ or have a specific _____ _____ that carries them into the brain.
tight junctions; lipophilic; transport protein
Define blood brain barrier (BBB)
a filtering mechanism of the capillaries that carry blood to the brain and spinal cord tissue, blocking the passage of certain substances.
What are the cells that line the capillary endothelial cells at the BBB?
Astrocytes
What type of drugs are not able to penetrate into the brain?
Hydrophilic
If we were developing a new drug for a neurological disorder, we would not be able to use a _____ drug from this purpose.
Hydrophilic
The Natural Health Products Directorate reviews and approves what?
vitamins, minerals and herbal preparation
Capillaries in the brain form what?
the blood brain barrier
The endothelial cells in the brain do not have what?
fenestrations
Following oral absorption, drugs pass directly into what?
the portal vein
Define portal vein
The portal vein is the blood supply that carries nutrients and drugs from the intestine to the liver
A blood vessel that carries blood to the liver from the intestines, spleen, pancreas, and gallbladder.
