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PHPY 304 (Pharmacology I) - Midterm Prep

Terms in this set (45)

What are the components of pharmacokinetics?
[5]
1)Absorption
2)Distribution
3)Metabolism
4)Excretion
What are the components of pharmacodynamics?
[5]
1)Drug-receptor interaction
2)Signal Transduction
3)Bodily Responses
Explain what is an enteral administration route, and describe the different types.
-It involves the esophagus, stomach, and small and large intestines
1)Oral
2)Sublingual (placed under the tongue)
3)Rectal
Explain what is an parenteral administration route, and describe the different types.
-A route other than through digestive tract
1)Intravenous
2)Intramuscular
3)Subcutaneous
3)Intra-arterial
4)Intrathecal (in subarachnoid space)
5)Intraperitoneal
What is drug absorption?
Refers to the passage of the drug from where it was administered into the general circulation.
(IVs are 100% absorbed)
What would negatively affect/impede drug absorption?
If the drug is:
-ionized;
-contains large molecules
-is lipid insoluble
What would aid with drug absorption?
[6]
If the drug is:
-Not ionized;
-contains small molecules;
-is lipid soluble
What two organs allow for drug absorption despite molecules being polar, large and lipophobic to pass through easily?
-Kidney - glomerulus
-Liver
Drugs must be __________ in order to cross the blood-brain barrier as well as nearly all body compartments?
Lipid-soluble
What is allowed to pass through uninterrupted cell layer (has no gaps) vs a capillary barrier (which has gaps between endothelial cells)?
Uninterrupted - ONLY lipid soluble molecules can pass.
Capillary barrier - ALL molecules with the exception of large proteins can pass.
What are some factors that affect oral absorption?
[6]
-they are destroyed by the stomach
-polarity of molecules prohibiting them from crossing membranes
-undergo extensive metabolizing
Where do most drugs sit on the pH scale and how does this affect drug absorption?
[6,7]
-Most drugs are a weak acid/base.
-acids - proton donor; protonated form is unchared which is better absorbed.
-bases = proton acceptor; protonated form is charged and is not well absorbed.
Explain "ion trapping".
[7]
This is the phenomenon where acidic drugs accumulate on the more basic side of the membrane and basic drugs collect on the acidic side.
Provide an example of clinically significant ion trapping in fetuses/babies.
[7]
ex:
- In babies, drugs taken by the more can accumulate in the fetal circulation/breast milk and can have harmful effect on the fetus/baby.
Describe the "first pass metabolism" phenomenon.
-First entry into the blood
-the concentration of a drug is greatly reduced before it reaches the systemic circulation (enzymes break it down)
-Big molecules are not easily absorbed.
Exaplain the Cheese-Wine Reaction
[8]
-Tyramine (which is found in cheese and wine), is usually metabolized by monoamine oxidases in the GI tract and liver.
-However, when patient is taking MAO inhibitor, tyramine is absorbed into circulation and nerve terminals where it releases norepinephrine (NE).
-NE stimulates adrenergic receptors which causes tachycardia and high BP.
Adrenergic Receptors
-Are a class of G protein-coupled receptors.
-Cause vasoconstriction & high BP
Bioavalability
[5]
The fraction of an orally given drug that reaches the circulation.
Acidic/Basic drugs bind to plasma proteins. What are plasma proteins and which proteins to the drugs bind to?
Plasma protein: are charhed molecules on the surface which attract other molecules.
Acidic --> Albumin
Basic --> aplha 1 - acid glycoprotein
Binding of drugs to plasma proteins.
[9]
-Reversible binding
-Slows the transfer of drugs out of the vascular component.
-may act as a drug reservoir.
-maintains the free-drug concentration and avoids toxicity
What does it mean if most of the drug is extravascular?
[9]
-most of it is not within the vessels;
-very little drug is bound and most is free;
-if a few molecules which are bound are released, the concentration of the free drug is not increased much.
What does it mean if most of the drug is intravascular?
[9]
-most of the drug is within the vessel;
-most of the drug bound;
-is the bound drug is displaced, then the concentration of free drug will largely increase and cause toxicity.
Distribution
The reversible movement of a drug between body compartments.
(some compartments will receive more drug than others)
What factors affect distribution of drugs?
[6]
1)Ionization
2)Capillary permeability - determined by the fraction of the membrane which has gaps (exposure) between endothelial cells.
3)Blood Flow - this determines how much drug reaches a specific organ (depends on organ's need for blood)
4)Plasma protein binding - how much drug is bound vs free
Give examples of two organs with differences in capillary permeability.
[10]
-In the liver and spleen; Capillaries are very leaky: drugs leave the capillaries regardless of lipid solubility, charge or polarity.
-Brain; won't allow polar molecules to enter.
Blood-Brain Barrier + clinical implications
[11]
-only lipophilic drugs may diffuse across brain capillaries (because they have tight junctions)
-most drugs must be metabolized before they enter
-the B-B barrier doesn't work when there's an area of injury/infection
-Clinical implication: Radioactive iodine albumin to treat tumours - penetrates tumour easily but not BB barrier.
How does blood flow affect absorption?
When drugs are treated via circulation:
-tissues that receive more blood will receive more drug.

ex: Brain, liver kidneys > skeletal muscle > fat, skin
Volume of distribution (Vd)
[12]
-The theoretical volume in which the total amount of administered drug should be uniformly distributed to account for its plasma or blood concentration.
-Gives us an idea how much of drug is present in the body - and which compartment it has accumulated.

Vd = dose administered / plasma concentration

NOTE:
-A high Vd means that most of the drug is extracellular.
-A low Vd means that most of the drug is within the vascular compartment (bound to plasma proteins).
Biotransformation (Drug Metabolism)
[13]
Chemical modification of drugs by enzymes to make them more polar (less lipid soluble), to be readily excretable by the kidneys.
Where are metabolizing enzymes located?
[13]
-LIVER***
-gastrointestinal wall**
-lungs*
-kidneys
-skin
-blood
-brain
What factors affect drug metabolism?
[6]
1)Lipid solubility of drug
2)Rate of metabolism (zero/first)
3)Blood flow (to the liver)
4)Mutation of metabolizing enzymes
5)Disease (in liver/kidneys)
What is a zero/first order drug metabolization?
Zero Order - enzymes and
rate of metabolism are saturated and
the body can only handle a certain
amount of drug over a certain amount
of time
First Order - lots of enzyme are available
and enzymes are not saturated.
Prodrugs
[15]
-These are inactive precursors with favourable pharmacokinetic, which metabolize into the active drug in the body
(certain drugs do not reach their target site because of obstacles, prodrugs can be used to substitute)

ex:
-proton-pump inhibitors: omeprazole/lansoprazole
-Levo-dopa turned into dopamine
Explain the two phases of biotransformation
[13]
-Phase I: functionalization rxn - oxidatiohn, reduction, hydrolytic rxn.
-Phase II: conjugation rxn - conjugation to polar groups, glucuronidation, sulfation, acetylation.
Describe Phase I enzymes and their properties.
[14]
-Mainly oxidize drugs
-Located in the endoplasmic reticulum of the cell
-Require O2
-Metabolize lots of drugs
-Usually inactivate a drug.
Describe Phase II enzymes and their properties.
[14]
-Conjugation reactions
-rapidly excreted
-enzymes are located in the cytosol
Clinical significance - they slowly metabolize drugs
What are Cytochrome P450 enzymes?
Main Phase 1 enzymes
-Monooxygenase family
-accounts for 90% of drug oxydation
(CPY 1A2, 2C9, 2C19, 2D6, 2E1, 3A4*)
Factors affecting drug biotransfomation
[14]
-Enzyme induction (which can lead to significant decrease in plasma concentrations of drugs metabolized) / Inhibition
-Some drugs can stimulate or inhibit the expression of some metabolizing enzymes
What groups of people more frequently use drugs?
-Women
-Elderly
-Hospitalized patients
-nursing home residents
What three types of drug interaction are there?
[21]
1)Drug-Drug (DDI)
2)Drug-Food
3)Drug-Herb
For Drug-Drug interactions, what are the pharmacodynamic and pharmacokinetic interactions?
[22]
Pharmacodynamic - two drugs affecting the same system
Pharmacokinetic - One drug affects absorption, distribution, metabolism, excretion of another drug.
For Drug-Drug interactions, what are some examples which affect: absorption, distribution, excretion, metabolism [22]
-Absorption - antacids reduce absorption of tetracycline (antibiotics)
-Distribution - competition for plasma protein binding by non-steroidal anti-inflammatory drugs and warfarin
-Excretion - Probenecid reduces excretion of penicillin by competition for the kidney tubule transport system.
-Metabolism - one drug affecting the metabolism of another drug.
Summary: Caution using DDIs in with....
-The elderly
-receiving two+ drugs
-receiving warfarin, NSAIDs, antiplatelets, satins, thyroxin.
What is P-glycoprotein and what is its purpose?
-Efflux plump that is dependent on ATP which removes compounds in and out of the cell.
-can be increased (rifampin)/inhibited(quinidine, antibiotics) by some drugs
-
Located at:
-colon/small intestines, kidney tubules, brain, liver, placenta, cancer tissue.
-blood-brain barrier: protects the CNS
What is the clinical significance of P-glycoprotein
Plays a role in drug resistance to cancer chemotherapeutic agents.
It is over expressed in tumor cells after exposure to anti-cancer agents and pumps out anti-cancer drugs.
-->Calcium channel blockers inhibit P-glycoprotein and help reverse resistance.
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