Inflammation - Pharmacology - Basic Principles; Disposition & Metabolism; Pharmacokinetics Flashcards
Pharmacodynamics is the study of what ________ do(es) to ________.
Pharmacokinetics is the study of what ________ do(es) to ________.
Pharmacodynamics is the study of what drugs do to the body.
Pharmacokinetics is the study of what the body does to drugs.
_______________ is the study of what the body does to drugs.
_______________ is the study of what drugs do to the body.
Pharmacokinetics;
pharmacodynamics
Most drugs are in what molecular weight range?
rarely selective < 100 — 1000 > not well absorbed / distributed
While some drugs don’t have a specific ‘site of action’ (e.g. a binding site), most drugs are ____________ that bind a specific site.
Ligands
While both can bind drugs/substances, what is the difference between a receptor (e.g. the TSH receptor) and a binding site (e.g. albumin)?
Receptors transduce a signal to produce a biological effect;
binding sites don’t
Which of the following is the most common type of drug ligand binding?
Covalent bonds
Electrostatic interactions
H+ , Van der Waals, & hydrophobic interactions
Electrostatic interactions
Which of the following is the most common type of ligand binding seen in lipophilic drugs?
Covalent bonds
Electrostatic interactions
H+ , Van der Waals, & hydrophobic interactions
H+ , Van der Waals, & hydrophobic interactions
Which of the following is the least common type of drug ligand binding?
Covalent bonds
Electrostatic interactions
H+ , Van der Waals, & hydrophobic interactions
Covalent bonds
True/False.
Stererospecificity matters to proper drug ligand function.
True.
What is the difference between ligand affinity and efficacy in pharmacodynamics?
Affinity — binding attractiveness
Efficacy — strength of effect
How are ligand antagonists different from agonists in terms of affinity and efficacy?
Antagonists possess affinity only
(no efficacy)
A high KA indicates ________ affinity.
A high KD indicates ________ affinity.
High;
low
What are K1 and K-1 in terms of ligand-receptor binding?
The __ is the amount of drug required to saturate 50% of receptors.
KD
(ratio of K-1 to K1)
The Law of Mass Action: the number of receptors [R] occupied by a drug depends on:
________ concentration
L-R association [__] rate constant
L-R dissociation [__] rate constant
Ligand;
K1;
K-1
The KD is the amount of drug required to saturate ________________.
50% of receptors
Where can KD and binding max (Bmax) be identified on a graph of [drug] on the X-axis and percent of receptors bound on the Y-axis?
True/False.
Drugs with high affinity are usually better structural fits with the receptors they bind.
True.
What is a dose-response curve?
A curve comparing drug dosages (X axis) and physiological responses (Y axis)
What is this type of graph called?
A dose-response curve
On a dose-response curve, what is EMax?
What is EC50?
The maximal effect (Y axis)
the drug concentration (X axis) at 50% of Emax
Why are drug dosages on dose-response curves given on log scales?
Easier visualization and math on the sigmoidal curve
What is indicated if the dose-response and the ligand-binding curves don’t line up so that EffectMax is obtained at less than 100% of Bmax?
Spare receptors are present
(maximal effect is obtained at less than 100% binding)
For a certain drug, EC50 = Kd.
Are spare receptors present?
No.
(Only if EC50 < Kd; as shown below)
If spare receptors ____ (are / are not) present, then the duration of the biological effect will be longer than the duration of drug-receptor interactions.
If spare receptors are present, then the duration of the biological effect will be longer than the duration of drug-receptor interactions.
True/False.
We are typically more sensitive to agonists with fewer receptors than agonists with spare receptors.
False.
We are typically more sensitive to agonists with spare receptors.
The drug with the _______ (lowest / highest) EC50 is the most potent.
The drug with the lowest EC50 is the most potent.
(Less drug for more effect)
A. Drug X
(Lower EC50)
Would any of the drugs in this image qualify as partial agonists?
Or antagonists?
B and C;
D
Describe how increasing drug efficacies changes a dose-response curve.
Drug X
(higher Emax)
What is inverse pharmacological agonism?
Decreasing a consititutively active receptor
(i.e. decreasing basal tone / intrinsic activity)
True/False.
Inverse agonism is just another term for antagonism.
False.
(Inverse a. refers to a drug that decreases the activity of receptor’s constitutively active basal tone)
________ drugs increase receptor activity to levels above basal tone.
________ ________ drugs decrease receptor activity to levels below below basal tone.
Agonist drugs increase receptor activity to levels above basal tone.
Inverse agonist drugs decrease receptor activity to levels below below basal tone.
Drugs are often compared against what to determine their levels of agonism?
The endogenous agonist
True/False.
By definition, partial agonists have both agonistic and antagonistic activity.
True.
By definition, partial agonists have both agonistic and antagonistic activity.
__________ic antagonists bind the same receptor as the agonist drug in question.
__________ic antagonists bind a different receptor as the agonist drug in question.
Pharmacologic antagonists bind the same receptor as the agonist drug in question.
Physiologic antagonists bind a different receptor as the agonist drug in question.
__________ antagonists bind or alter the agonist drug in question, not a receptor.
Chemical antagonists bind or alter the agonist drug in question, not a receptor.
D. Pharmacologic antagonist
C.
The _____ is the drug concentration at which 50% of the population manifests the desired effect.
The ED50 is the drug concentration at which 50% of the population manifests the desired effect.
(Effective Dose)
The _____ is the drug concentration at which 50% of the population is killed by the drug.
The LD50 is the drug concentration at which 50% of the population is killed by the drug.
(Lethal Dose)
The _____ is the drug concentration at which 50% of the population manifests a given toxic effect.
The TD50 is the drug concentration at which 50% of the population manifests a given toxic effect.
(Toxic Dose)
The ED50 is the drug concentration at which 50% of the population manifests a given ______ effect.
The TD50 is the drug concentration at which 50% of the population manifests a given ______ effect.
The LD50 is the drug concentration at which 50% of the population is ______ by the effects of the drug.
The ED50 (effective dose) is the drug concentration at which 50% of the population manifests a given desired effect.
The TD50 (toxic dose) is the drug concentration at which 50% of the population manifests a given toxic effect.
The LD50 (lethal dose) is the drug concentration at which 50% of the population is killed by the effects of the drug.
How is the therapeutic index of a drug calculated?
*LD50 / ED50
*(or TD50)
The median effective dose (ED50) for a certain medication is 3 mg, and the median lethal dose (LD50) is 150 mg.
What is the therapeutic index?
150/3 = 50
Which is preferable, a high therapeutic index or a low therapeutic index?
High!
(LD50 / ED50)
Drug B
Agonists typically ______-regulate receptors on target tissues.
Antagonists typically ______-regulate receptors on target tissues.
Agonists typically down-regulate receptors on target tissues.
Antagonists typically up-regulate receptors on target tissues.
B.
E. Partial agonist
Gα<strong>s</strong> is a(n) _______ subunit.
Gαi is a(n) _______ subunit.
Gαq increases intracellular _______.
Gs is a stimulatory subunit.
Gi is an inhibitory subunit.
Gq increases intracellular calcium.
D. Activation of adenylate cyclase
C. RTKs
What are two methods via which agonists might cause receptor down-regulation?
- Increased synthesis of receptor-blocking proteins
- Increased degradation of receptors
True/False.
Differing drugs will have various and complex methods of transport and metabolism in the body.
True.
Describe some of the different forms of drug intake and distribution in the body.
True/False.
All drugs undergo this basic mechanism:
Administration –> Absorption –> Distribution –> Metabolism –> Excretion
False.
True/False.
The GI tract is highly permeable to many medications (given they are lipophilic).
True.
The GI tract is highly permeable to many medications (given they are lipophilic).
P-__________ is an outward transporter found in several areas of the body and acts to __crease drug absorption.
P-glycoprotein is an outward transporter found in several areas of the body and acts to decrease drug absorption.
Lipo_____ drugs are more easily absorbed.
Lipophilic drugs are more easily absorbed.
What type of drug is readily absorbed in the stomach?
Weak acids
True/False.
Weak bases are well-absorbed in the stomach.
False.
Weak acids are well-absorbed in the stomach.
(Weak bases are almost not absorbed at all)
Both weak acids and weak bases are decently well absorbed in the ______________.
Both weak acids and weak bases are decently well absorbed in the small intestine (~70% for WAs and ~50% for WBs).
Will decreasing the ionization of a drug increase or decrease its reabsorption?
Increase
What is pharmacologic ion trapping?
Drugs are ionized after being taken up
(and thus trapped)
What do the pharmacologic abbreviations qd, bid, tid & qid mean?
qd : every day
bid : twice a day
tid : three times a day
qid: four times a day
With most drugs, why is only a small amount of the absorbed drug is in contact with body receptors at any particular point in time?
The majority of the drug is often localized in areas removed from the site of action (e.g. bound to plasma proteins).
Drugs in the plasma are often ____ly bound to ______.
Drugs in the plasma are often weakly bound to albumin.
Which three organs receive the majority of cardiac output and, thus, the majority of drugs in the plasma passing through (especially for fat-soluble medications)?
Liver, kidney, brain