Term
| What was an early example of preventive medicine for nutritional needs due to a new environment? |
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Definition
| Captain James Cook forced men to eat fresh food to prevent scurvy |
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Term
| "All things are poison and nothing is without poison, only the _______ permits something not to be poisonous." |
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Definition
| "All things are poison and nothing is without poison, only the DOSE permits something not to be poisonous." |
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Term
| Is N,N-dimethyltryptamine effective when taken orally? Why? |
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Definition
| Psychotria viridis (N,N-dimethyltryptamine) contains the physiologic bioactive amine, DMT. It’s rapidly degraded by monoamine oxidases and if an extract of plant were consumed orally, it would have minimal effect. (Combine with another plant that inhibits DMT degradation to induce trances) |
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Term
| *The _________ of a therapeutic can be dramatically influenced by a second drug or other non-therapeutic agent |
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Definition
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Term
Who documented the systematic uses of herbs and other plants in the practice of medicine in the 19th and early 20th centuries?
What superseded them? |
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Definition
Eclectics
Eclectics were superseded by the arrival of synthetic organic chemistry and “modern” pharmacology |
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Term
| What is the study of composition and classification of natural products |
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Definition
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Term
| What is the study of the modes of action of bioactive substances and the development of modified lead compounds to optimize biological effects |
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Definition
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Term
| Who founded Institute of Pharmacology in Germany |
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Definition
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Term
| Who was the father of Pharmacology showed that the plant alkaloid muscarine had a similar effect on the heart as electrical stimulation of the vagus nerve |
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Definition
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Term
| Who came of up with the concept of chemotherapy and the “magic bullet” (had a Hollywood movie made of his work) |
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Definition
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Term
| What steps in Federal legislation set the scene for expansion of a Pharmaceutical Industry, based on the synthesis and manufacture of specific compounds? |
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Definition
1906 Food and Drugs Act
1930 Establishment of the FDA
1938 Food, Drug, and Cosmetic Act |
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Term
| Are the compounds from the pharmaceutical industry more or less like their plant predecessors? |
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Definition
| The compounds, unlike their plant predecessors, are not generally present in the living world (bioactive botanicals) |
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Term
| ethinyl estradiol, cimetidine, oral penicillins are all examples of what kind of drugs? |
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Definition
| Because oral administration was ineffective, derivatives of the lead compounds were made |
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Term
Drug discovery was initially built from discoveries made in the developing world of __________.
What is NOT an example of one of the early isolated active substance?
Insulin
Steroids
Pituitary Hormones
Thyroid Hormones |
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Definition
Physiology
Thyroid hormone is NOT early isolated active substance |
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Term
Who actually discovered penicillin?
Who RE-discovered penicillin?
Who isolated penicillin? |
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Definition
Duchesne
Fleming
Florey and Chain |
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Term
Why could Chain not make penicillin in the lab to produce it on a large enough scale?
What was discovered accidentally to become the source of synthetic penicillins? |
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Definition
No one knows how to make the 4 membered ring
Ampicillin (6APA) discovered accidentally in fermentation broth |
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Term
Why did penicillin have to be given in the muscle?
What helped with this? |
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Definition
Penicillin is acid/alkali-labile and is excreted rapidly in urine
Probenecid slowed urinary excretion |
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Term
| What was chocolate known as to the Aztecs (bitter drink or warm liquid)? |
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Definition
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Term
| What did Hollenberg rediscover about chocolate by studying the Kuna Indians? |
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Definition
| It prevented salt-induced hypertension |
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Term
| What allowed us to characterize targets (receptors, enzymes)? |
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Definition
| compounds that interacted with them were identified and therefore allowed their characterization |
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Term
| What are the targets of pharmacology? |
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Definition
-Enzymes (inhibitors and activators)
-Receptors (membrane [insulin receptor] and intracellular [estrogen receptor])
-Ion channels (Na/K ATPase, voltage-gated ion channels)
-Transporters (Glucose/AA [in], multi-drug resistance [out]) |
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Term
| What are compounds that have physiological action and many interact with a protein target, change its shape and alter who binds to it |
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Definition
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Term
| Targets (receptors) have endogenous ______ that control the activity of the receptor |
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Definition
| ligands (we make drugs to look like ligand) |
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Term
| Ligands alter the ratio of what 2 states of the receptor? |
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Definition
| constitutive (Ri) and active (Ra) |
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Term
When drugs bind to the receptor and increase its “activity” (Ra state) they are known as?
When they bind to the receptor and prevent its transfer to the active state, they are known as? |
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Definition
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Term
| What is the agonist called when there is a competitive inhibitor that delays the agonist activity until there is a large increase of agonist to where you get the same activity |
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Definition
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Term
| What causes no activity no matter how much of the agonist you add? |
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Definition
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Term
| What causes an agonist to work better? |
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Definition
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Term
| What is the drug called if addition of the drug produces an enhanced effect that is equivalent to the natural ligand |
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Definition
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Term
| What is the drug called if it does not induce full activity? |
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Definition
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Term
| What is the drug called if it inhibits any increase in activity? |
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Definition
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Term
| What is the drug called when it traps receptor in Ri (low constitutive activity/reduction of basal activity) state? |
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Definition
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Term
| What are the forces determining drug-receptor binding? |
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Definition
-covalent (aspirin binds to cyclooxygenase chemically)
-non-covalent
-electrostatic charge
-Hydrogen bonding
-aromatic ring stacking
-hydrophobic interaction (Van der Waals)
-2D or 3D pattern |
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Term
| What is the problem with chirality in pharmacology? |
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Definition
| Chemically synthesized drug compounds are mostly racemic; The unnatural form may be an antagonist of the natural form |
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Term
Glucose has a __-configuration
Amino acids have a __-configuration |
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Definition
Glucose has a D-configuration, whereas amino acids have an L-configuration
(These isomers bend the plane of polarized light) |
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Term
| Future research may make use of ___________ into which groups of genes are inserted that manufacture specific compounds and ensure the correct chirality |
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Definition
| Future research may make use of BACTERIAL SYSTEMS into which groups of genes are inserted that manufacture specific compounds and ensure the correct chirality |
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Term
| What is the challenge in applying pharmacology in the clinical setting? |
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Definition
| selecting the right drug, and at the right dose for the particular patient in front of you |
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Term
| As the dose of a drug is increase, what are the ranges? |
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Definition
| As the dose of a drug is increased, it has a range where it is ineffective, another where it is effective, and finally a range where it is toxic |
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Term
| Drugs should have a wide ______ (ex: Tylenol, combination of over-the-counter "safe drugs" exhibiting life threatening toxicities) |
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Definition
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Term
| What can drug combinations do? |
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Definition
Combinations of over-the-counter “safe drugs” may exhibit marked, life-threatening toxicities
Drug combinations to prevent side effects
Drug combinations to prevent side effects |
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Term
| In 1990-2008, the pace in the search for successful therapeutics was quickened by the introduction of ______________ |
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Definition
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Term
| Has drug discovery progressed in relation to investments? |
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Definition
| No, it is going in the opposite direction (most of the money spent is on evidence. We don’t know whether metabolism is an issue or whether the drug is safe to give) |
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Term
| What is possibly cheaper/faster way for testing drugs rather than having robots testing hundreds of thousands of compounds a day? |
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Definition
| Testing the toxicity first (Paradigm change-use of micro-engineered organoids for high throughput toxicity screening) |
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Term
| What are the routes of administration? |
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Definition
| Inhalation, intravenous (iv), intraperitoneal (ip), intramuscular (im), intrathecal (it), skin lotion, oral and rectal |
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Term
| What are the issues for oral drugs? |
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Definition
ADME
Absorption-affected by pH
Distribution
Metabolism
Excretion-through liver, renal, lungs |
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Term
| How do drugs avoid from being affected from acid? |
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Definition
| encapsulation (Penicillin was administered intramuscularly before the newer acid-resistant modifications were introduced) |
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Term
| Why was penicillin administered intramuscularly at first? |
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Definition
Was not metabolized before excretion into urine.
It was then recovered and recycled. |
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Term
| In order for most oral drugs to be effect, it must pass through _________ |
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Definition
| Most drugs have to pass through the gut wall into the bloodstream to be effective (But the gut wall is there to prevent the uptake of “foreign” compounds) |
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Term
| What is the Lipinski rule of five (based on the properties of oral medications) |
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Definition
An effective medication should not violate more than one of these rules (refers to multiples of 5 in each rule):
-Not more than 5 hydrogen bond donors (nitrogen or oxygen atoms with one or more hydrogen atoms)
-Not more than 10 hydrogen bond acceptors (nitrogen or oxygen atoms)
-A molecular weight under 500 daltons
-An octanol-water partition coefficient log P of less than 5 (a higher ratio of being absorbed have a higher ratio in octanol, but still needs to be water soluble) |
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Term
| What type of transport can occur in both directions – shape-dependent (ex: Na+-dependent glucose transporter, Amino acid transporters, P-glycoprotein – multi-drug resistance protein) |
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Definition
| Facilitated/Active Transport |
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Term
| What type of transport is in both directions (concentration-dependent), uptake rates a balance of hydrophobicity and hydrophilicity, Membrane behaves as if it were n-octanol |
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Definition
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Term
| What type of transport is between cells, size limited (also extent of hydration may affect “size) |
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Definition
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Term
| What disease is a failure to reabsorb water secreted into the intestines due to cAMP-dependent Na+ transport compromised (Very rapid dehydration - untreated, death can occur within 15 h of symptoms onset) |
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Definition
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Term
| How do you treat cholera? |
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Definition
Treatment with i.v. electrolytes
Oral electrolytes given with glucose
(sodium-dependent glucose uptake to generate energy and uptake of material into cells drags water into the cells with them) |
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Term
| Some drugs are mixed with _____ so that they are dispersed in the acid parts of the upper intestine (in fine particles and not big chunks=increases rate of absorption) |
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Definition
| NaHCO3 (sodium bicarbonate)-- can change pH in urine to alter rate of drug excreted |
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Term
| What contains the drug, prevents premature absorption and smooth transit through the esophageal passage, prevents acidic destruction in the stomach, and made of gelatin that is dissolved by proteases in the upper small intestine |
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Definition
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Term
___________ is decreased by charge on a drug
A drug containing an ______ group will have a net positive charge at low pH [NH3-R]+ |
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Definition
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Term
Is a positive charged drug more or less hydrophobic?
Is it more or less likely to be absorbed? |
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Definition
This makes it less hydrophobic, and therefore less likely to be absorbed
(So, don’t take it on an empty stomach since the pH will be very low) |
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Term
| pka = pH when the drug is _______ |
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Definition
| half-ionized (knowing pKa will help in determining how it will be absorbed |
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Term
| What are the treatments for gastric and duodenal ulcer disease complicated by excess acid production (stress and other factors or gastrin-producing tumor) or sensitization (inflammation caused by H. pylori)? |
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Definition
| Treatment involves adjusting the excess acid (with weak alkalis), or reducing acid secretion with targeted therapy (H2 receptor antagonist), or inactivating the proton pump |
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Term
| What may happen when you treat ulcer diseases by altering the acidity of the stomach? |
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Definition
These pharmacological interventions will change the luminal environment and alter the bioavailability of pH-sensitive drugs
-Proton pump inactivation will last several days
-May also alter the microbial flora in the upper intestine |
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Term
Hydrophobic drugs will partition into the _____ phase and have (reduced or increased) intestinal uptake.
This is an issue in what types of patients? |
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Definition
Hydrophobic drugs will partition into the oily phase and have reduced intestinal uptake
This is an issue in patients with Cystic Fibrosis and pancreatic insufficiency and liver failure
This is an issue in patients with Cystic Fibrosis and pancreatic insufficiency and liver failure and Paraffins given to assist in stool passage in postoperative patients will slow uptake of fat-soluble vitamins |
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Term
| What is essential for fat-soluble vitamins (A, D, E, & K) to be absorbed? |
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Definition
| Bile acids (cholesterol metabolite) from the liver that form water-soluble aggregates (micelles) |
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Term
| If someone has liver disease, the amount of drug given to them might need to be (increased or reduced) |
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Definition
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Term
Ideally, drugs would only go to __________?
However, drugs that enter the blood stream will be ______? |
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Definition
Ideally, drugs would only go to the target of interest
However, drugs that enter the blood stream will be distributed throughout the body |
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Term
The endothelial cell layer represents a barrier, just like the intestine.
-If the receptor is on the cell membrane, access is _________.
-If the receptor is inside the cell, then the issues of _________ are important |
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Definition
-If the receptor is on the cell membrane, access is straightforward
-If the receptor is inside the cell, then the issues of transport (influx and efflux) are important |
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Term
| Why is difficult for many drugs and microorganisms (very difficult to treat) to pass through the blood-brain barrier? |
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Definition
Due to very tight junctions between the endothelial cells
Another barrier in the choroid plexus separates the blood from the cerebrospinal fluid that bathes the brain
There are specific transporters for amino acids and glucose to enter the brain
There are specific transporters for amino acids and glucose to enter the brain |
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Term
| What drug is used for controlling diarrhea but it passes into the brain and causes dependence? |
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Definition
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Term
| What is the alternative to codeine that does NOT cross the blood-brain barrier? |
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Definition
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Term
| Drugs must be metabolized to more easily excretable metabolites, however, one drug didn't. What was it? |
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Definition
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Term
| To eliminate drugs, they are changed by the cytochrome P450 system (_________ metabolism-removes an alkyl group or adds an oxygen) that activates or deactivates a drug |
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Definition
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Term
| In _______ metabolism, a drug is conjugated (tagged) with another chemical group to become more easily excitable since they are passively recovered with difficulty |
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Definition
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Term
In phase II metabolism, what increases the rates of excretion and lower hydrophobicity?
What increases hydrophobicity only? |
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Definition
Hydrophilic conjugates (b-glucuronides, sulfonates, amino acids) increase the rates of excretion and lower hydrophobicity
Methylation (with S-adenosylmethionine) increases hydrophobicity |
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Term
| What are the routes of excretion? |
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Definition
-Many metabolites are extracted from the blood by the liver and are excreted into the bile and pass into the feces (or may be reabsorbed)
-The kidney filters blood through its glomeruli (may be reabsorbed selectively in proximal tubule) |
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Term
| What reflects the concentration of a drug needed to cause its effect (It’s the inverse of the EC50) |
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Definition
| Potency (more potent=works at lower concentration) |
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Term
| What is a measure of the maximum effect |
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Definition
| Efficacy (more efficacy=bigger effect) |
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Term
| What is the study of how well a drug is absorbed in its active form |
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Definition
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Term
| What is how long a drug remains in the blood or other target sites |
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Definition
| half-life (The time for the concentration of the drug in the blood or other fluid to fall by one half) |
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Term
| What is the ratio of highest non-toxic dose to lowest effective dose |
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Definition
| therapeutic index (target range) |
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Term
Which histamine antagonists enter the brain and other tissues?
Which histamine antagonists have their activity in the GI tract? |
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Definition
H1 histamine antagonists enter the brain and other tissues
H2 histamine antagonists have their activity in the GI tract |
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Term
-Many drugs are chemically similar to _______________
-Providing estrogens orally requires that 17b-estradiol, the “drug”, is modified to prevent ______________
-Designing an antihistamine requires that the drug is orally active, gets to the ____________ which may or may not be in the brain |
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Definition
Many drugs are chemically similar to endogenous substances
Providing estrogens orally requires that 17b-estradiol, the “drug”, is modified to prevent rapid metabolism in the intestinal wall
Designing an antihistamine requires that the drug is orally active, gets to the histamine receptor which may or may not be in the brain |
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Term
| What were medicinal chemists concerned about? |
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Definition
| Concern about slow pace and chirality issues |
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Term
| What does high throughput screening by robotic synthesis not take into account? |
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Definition
| metabolism or toxicity to other organs |
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