Exam 1: Pharmacodynamics Flashcards
T/F Drugs being a solid/liquid/gas does NOT affect the route of administration
False; all 3 affect the route of administration
How is drug size expressed in units?
Daltons
What size are most drugs?
100-1000 MW
Can a drug diffuse if it is >1000 MW?
No; the drug is too big and will not diffuse as readily
What mechanism can describe how receptors and drugs bind together?
Lock and key mechanism; Drugs have a specific structure and fit/bind into a specific receptor
What 4 things affect receptor interactions?
- Appropriate size
- Electrical charge
- Shape
- Atomic composition
What are the 3 main types of chemical bonds seen with receptors?
- Covalent
- Electrostatic (charged molecules, hydrogen bonds, Van der Waals forces)
- Hydrophobic (lipid-soluble drugs)
Which bond type is the strongest? Which is the weakest?
Covalent = Strongest
Hydrophobic = Weakest
How do bond strength and specificity relate to one another?
They are inversely related to one another; As bond strength increases, specificity decreases and as bond strength decreases, specificity increases
What is specificity?
How specifically a drug has to fit into a receptor site to elicit an effect
Are agonists endogenous, exogenous, or both?
Both
What happens when an agonist binds to a receptor?
It elicits a downstream response
What are isomers?
Compounds with the same chemical equation but different shapes
Why are isomers important in pharmacology?
Drugs are optical isomers; each isomer has different effects on the body and in pharmacology, we take an average of the two isomers and give the racemic mixture to the patient
What drug is an example of a racemic mixture?
Esketamine = purified form of Ketamine
What 3 things affect the duration of drug action?
- How long the drug binds and releases from the receptor
- How long the downstream effect is and what type of bonds are present (if it is a covalent bond the receptor will need to be degraded)
- Desensitization (cells being shut down via signalling processes)
What are the 2 properties of “good” receptors?
- Selective - binds to one receptor/type of receptor
- Alteration - the ligand binds to the receptor and has some sort of conformational change to cause a downstream effect
What are “bad” receptors?
Non-regulatory molecules that bind drugs with no detectable change
What are 2 properties of “bad” receptors?
- “Inert binding sites” - a binding site where the drug binds but nothing changes at all
- Drug carriers - they can carry drugs but they won’t have an effect on the body
What is the most important drug carrier?
Albumin
When a plasma protein is bound to a drug, can it cross barriers? Why or why not?
No; albumin is too large to cross barriers
T/F When plasma protein is unbound, it can cross barriers.
True
What is another name for the “unbound form” of something?
The free form
Is albumin a bad or good receptor?
Bad
How does a decrease in the amount of albumin affect how much of a drug you need to give a patient?
Patients with a lower level of plasma will have a higher level of the free form of the drug. This will cause a bigger effect and potentially toxic effects than with a patient who has normal levels of plasma
Albumin binds mostly to ___ drugs
Acidic
Alpha1-acid glycoproteins bind mostly to ____ drugs
Basic
Lipoproteins bind mostly to ___ drugs
Neutral
Describe an agonist mimic/indirect agonist
Indirect agonists are those that increase the level of direct agonists often by reducing the rate of metabolism of the direct agonist “downstream”
What is a competitive antagonist?
Bind to receptor and inhibit agonist response. Surmountable.
Describe a partial agonist
Produces a lower response at full receptor occupancy. Acts as an antagonist in the presence of a full agonist.
Describe physiologic antagonist/antagonism
Drugs that act at different receptors to squelch the effect of other drugs.
Example: acetylcholine, bound to another receptor, inhibits the effect of epinephrine.
Describe receptor theory
theorizes that a receptor oscillates (on its own) between an active (Ra) and inactive state (Ri).
What is an inverse agonist?
binds to a receptor and forces it toward its inactive state. In practice it is a really strong agonist.
Beta-1 Receptor “Direct agonist” (Example)
Epinephrine, Norepinephrine
Beta-1 Receptor “Indirect agonist” (Example)
Amphetamine, cocaine
Beta-1 Receptor “Partial agonist” (Example)
Pindolol, Acebutolol
Beta-1 Receptor “Antagonist” (Example)
Propranolol, Atenolol
Beta-1 Receptor “Inverse agonist” (Example)
Carvedilol, Nadolol
Name two GOOD receptor properties
Selective: specific to a certain drug(s)
Alteration: receptor changes conformation to illicit a change inside the cell
What is a BAD receptor property?
Bind drugs with no detectable change in function. i.e drug carriers (albumin) binds drugs so they can’t reach destination.
What type of drugs does albumin mostly bind to? (neutral, acidic, or basic)
Acidic
Define Potency
concentration (EC 50) or dose (ED 50) of a drug to produce 50% of that drugs maximal effect
Define [maximal] Efficacy
the greatest possible response a drug can deliver.
What is the ED50?
The median effective dose is the dose that produces a therapeutic response in 50% of people
What is the LD50?
Lethal dose. The dose that is lethal in 50% of people
What is the TD50?
Toxic dose. The dose that results in toxic effects in 50% of people.
Describe therapeutic index
TI establishes a margin of safety. A wide TI means that it takes more of that drug, to produce toxic effects, than a drug with a low TI. TI = TD50/ED50
What are 2 reasons drug responsiveness varies among people?
drug-drug interactions
genetic factors (hypo-reactive, hyper-reactive)
In order to cross barriers, drugs need to be charged? (T/F)
False - need to be uncharged
Weak acids: if pH < PKA
protinated/unprotinated?
Charged/uncharged?
Protinated
Uncharged
Weak acids: if pH > PKA
protinated/unprotinated?
Charged/uncharged?
Unprotinated
Charged
Weak Bases: if pH > PKA
protinated/unprotinated?
Charged/uncharged?
Unprotinated
Uncharged
Weak Bases: if pH < PKA
protinated/unprotinated?
Charged/uncharged?
Protinated
Charged
Weak acids are excreted faster in alkaline urine (T/F)
True
Weak bases are excreted faster in acidic urine (T/F)
True
What are biologic drugs? (i.e monoclonal antibodies)
Drugs created by living organisms.
Extracted from living systems
