chapter 1

Question 1

penicillin SAFE DRUG

Answer 1

one of the safest and most effective drugs available on the market for treating bacterial infections- more strains have become resistant as time goes on
SIDE EFFECT: severe allergic rxns

Question 2

Morphine BAD DRUG

Answer 2

acts on mu opioid receptors in the brain- excellent analgesic ( painkiller)
SERIOUS SIDE EFFECTS
tolerance, respiratory depression (slow breathing and addiction!!!
can KILL taken in excess

Question 3

barbiturates
BAD- addictive
julia go over this

Answer 3

https://www.medicinenet.com/barbiturates-oral/article.htm#what_are_examples_of_barbiturates_available_in_the_us
https://www.drugs.com/drug-class/barbiturates.html
https://www.dea.gov/factsheets/barbiturates
https://sunrisehouse.com/barbiturates/
https://www.webmd.com/mental-health/addiction/qa/what-are-barbiturates
CENTRAL nervous system depressant
any class of sedative/ sleep inducing drug derived from barbituric acid
Example) belladonna- atropine (glaucoma- when someone goes for emergency eye surgery)
used for treating: headache, insomnia and seizures
CAUSES: muscle relaxation
enhances gaba- depressive nt
side effects: dizziness, lightheadedness, sedation, headache, n/v abdominal pain
PEARL HARBOR- people overdosed on this (1960s/70s) before going into surgery
more people died at the hands of anasththetists- people who give this

Question 4

diamorphine

Answer 4

used to treat patients that die of cancer- produces a euphoric effect counters depression faced by cancer patients- derivative of heroin

Question 5

heroin

Answer 5

best painkiller in 19th century medicine- banished pain forever and has addictive properties

Question 6

drug

Answer 6

compounds which interact with a biological system- bio response

Question 7

everyday drugs

Answer 7

coffee, nicotine(stimulants), alcohol(depressant)

Question 8

alcohol

Answer 8

if discovered today- would be restricted like cocaine is

Question 9

how does penicillin work

Answer 9

interacts with bacteria in order to produce a biological response

Question 10

theraputic index

Answer 10

indicates how safe a drug is- beneficial effect at a low dose- versus the harmful effects at a high dose

Question 11

high theraputic index means

Answer 11

there is a large safety margain between beneficial and toxic doses

Question 12

nabiximols

Answer 12

cannabis preparation- used to treat m.s. -doesn’t make cannabis safe
SIDE EFFECTS: paranoid delusions, panic attacks and hallucinations

Question 13

arsenic

Answer 13

well-known poison, compounds are used as anti-protozoal (inhibits growth) and anti cancer agents

Question 14

curare

Answer 14

deadly poison that is used by people in s.am to tip their arrows such that a minor wound would be fatal

Question 15

tubocurarine

Answer 15

active principle of curare- used in surgical operations in order to relax muscles

Question 16

ace inhibitors

Answer 16

cardiovascular drugs that were developed from snake venom

Question 17

broccoli, cabbage, cauliflower

Answer 17

high levels of a chemical that causes repro. abnormalities in rats

Question 18

peanuts, maize , radishes, brown mustard,

Answer 18

sometimes contain fungal toxins-responsible for biblic. plague

Question 19

“everything is a poison, nothing is a poison”

Answer 19

paracelsus- it is the dose that makes the poison- the father of toxicology

Question 20

just facts

Answer 20

anything taken in excess is bad- aspirin, whisky or 9kg of spinach- too much vitamin k - need heparin/warfarin

Question 21

selective toxicity

Answer 21

drugs can be viewed as actual/potential poisons

Question 22

many drugs are effective when they are toxic to problem cells

Answer 22

antibacterial, antifungal, antiprotozoal- selective toxicity to microbial cells
anti-cancer agents show a selective toxicity for cancer cells over normal cells

Question 23

pacilatel

Answer 23

taxol- microtubule agent

like vinca taxines! they prevent mitotic spindle formation

Question 24

sidenafil

Answer 24

viagra

Question 25

What type of molecule is the following structure?

Answer 25

A phospholipid
he ‘phospho’ of phospholipid indicates the presence of a phosphate group. The lipid part of the name refers to the two long hydrocarbon chains. The structure is also known as a phosphoglyceride. Proteins consist of amino acids linked by peptide bonds. Carbohydrates contain several hydroxyl groups. Nucleic acids consist of nucleic acid bases linked to a sugar phosphate backbone.
Page reference: 3-4

Question 26

Which of the following is an accurate description of the phospholipid bilayer in cell membranes?

Answer 26

d) It is made up of two layers of phospholipid molecules with the tails interacting with each other.
The cell membrane is made up of a bilayer of phospholipid molecules where the hydrophobic tails interact with each other in the centre of the membrane by van der Waals interactions. The polar head groups interact with water at the outer and inner surfaces of the membrane
Page reference: 3-4

Question 27

Which of the following statements is true regarding the phospholipid bilayer in cell membranes?

Answer 27

b) Water and ions are unable to cross the bilayer due the hydrophobic tails of the phospholipid molecules.

Feedback:

The tails of the phospholipid molecules are hydrophobic (water hating) and repel water and ions. The polar head groups do not have any role in preventing water or ions from crossing the cell membrane. The phospholipid molecules are certainly fluid, but no pores are formed as a result of that.
Page reference: 3-4

Question 28

Which of the following statements is true?

Answer 28

b) Drugs are generally smaller than drug targets.

Feedback:

There are situations where a drug may be a similar size to its target if the drug is a protein, but in the vast majority of cases, drugs are much smaller than their macromolecular targets.
Page reference: 4-5

Question 29

What is meant by a binding site?

Answer 29

a) The area of a macromolecular target that is occupied by a drug when it binds.

Feedback:

The binding site is part of the macromolecular target and not the drug. It is normally a hollow or cleft on the surface of the target. The functional groups and regions of the drug that are involved in binding to the binding site are known as the pharmacophore.
Page reference: 4-5

Question 30

Consider the molecule in blue bound to a binding site. Identify the binding interactions taking place at i and iv shown in red.

Answer 30

a) hydrogen bonds

Question 31

7Consider the molecule in blue bound to a binding site. Identify the binding interactions taking place at iii shown in red. julia go over this

Answer 31

c) van der Waals interactions

Feedback:

Van der Waals interactions take place between regions of molecules consisting solely of carbon and hydrogen atoms. Ionic bonds occur between charges of opposite sign. Hydrogen bonds occur between a molecule acting as a hydrogen bond donor (RXH; where X is normally oxygen or nitrogen), and a molecule acting as hydrogen bond acceptor where a heteroatom is present (normally oxygen or nitrogen).

Question 32

Consider the molecule in blue bound to a binding site. Identify the binding interactions taking place at ii shown in red. julia go over this

Answer 32

b) ionic bonds

Feedback:

Van der Waals interactions take place between regions of molecules consisting solely of carbon and hydrogen atoms. Ionic bonds occur between charges of opposite sign. Hydrogen bonds occur between a molecule acting as a hydrogen bond donor (RXH; where X is normally oxygen or nitrogen), and a molecule acting as hydrogen bond acceptor where a heteroatom is present (normally oxygen or nitrogen).
Page reference: 5-8

Question 33

Which of the following binding interactions is likely to be the most important initial interaction when a drug enters a binding site?
julia go over this

Answer 33

Your answer:

d) induced dipole-dipole interactions

Correct answer:

c) ionic

Feedback:

Ionic interactions fall off in strength more slowly with distance than the other interactions, and so they are likely to be the most important initial interaction. Van der Waals interactions are the least likely to be important as a molecule approaches its binding site.
Page reference: 5

Question 34

Which of the following underlined atoms is likely to be the strongest hydrogen bond acceptor?
i dont understand this question

Answer 34

Your answer:

d) carboxylate oxygen (RCO 2-)

Feedback:

Generally, the more electron rich the heteroatom, the better it will be as a hydrogen bond acceptor. Thus, a negatively charged oxygen will be the best hydrogen bond acceptor. The amide and aniline nitrogens will be poor hydrogen bond acceptors since the lone pair of electrons in each case interacts with a neighbouring group (carbonyl group and aromatic ring respectively). Therefore, it is not available to form hydrogen bonds.
Page reference: 6-8

Question 35

Which of the following underlined protons is likely to be the strongest hydrogen bond donor?

Answer 35

Your answer:

d) ammonium ion (RNH3+)

Feedback:

The best hydrogen bond donor will be the one where the hydrogen is the most electron deficient. In the ammonium ion, the nitrogen has a positive charge and this in turn will make the attached hydrogens electron deficient. The phenol is likely to be the next best hydrogen bond donor since the oxygen’s lone pair of electrons will interact with the aromatic ring giving it a slightly positive charge.
Page reference: 6-8

Question 36

Which of the following functional groups is most likely to participate in a dipole-dipole interaction? go over this

Answer 36

our answer:

c) Alcohol

Correct answer:

b) Ketone

Feedback:

The ketone will have the strongest dipole moment due to the electronegative oxygen polarising the carbonyl bond. The alcohol will also have a significant dipole moment, but less than that of the ketone. The alkene and aromatic rings may have small or negligible dipole moments depending on their substituents.
Page reference: 8-9

Question 37

Which of the following statements is untrue?

go over this

Answer 37

Your answer:

c) Interaction between the non-polar regions of a drug and the non-polar regions of a target require the removal of an ordered water coat and represents a gain in binding energy due to increased entropy.

Correct answer:

d) An increase in entropy results in a greater positive value of ΔG and a greater chance of binding.

Feedback:

An increase in entropy will result in a greater negative value of ΔG and a greater chance of binding. This derives from the equation ΔG = ΔH TΔS.
Page reference: 10

Question 38

salvarsan

Answer 38

Arsphenamine = generic name
Salvarsan = trade name
chemotheraputic agent
Arsphenamine was marketed as Salvarsan or Compound 606 in 1910.
The organoarsenic compound was the first modern chemotherapeutic agent.

Question 39

Syphilis

Answer 39

The earliest known depiction of an individual with syphilis is Albrecht Dürer’s Syphilitic Man (1496). Here, the disease is believed to have astrological causes.
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum.

Question 40

columbus hypothesis

Answer 40

hypothesis that states columbus’s crewmen had syphilis-

Question 41

syphilis signs and sx 1*

Answer 41

3-90 days after contact with a sick person- spread via lesions (sexually transmitted)
Lymph node enlargement frequently occurs around the area of infection.
The lesion may persist for three to six weeks without treatment.

Question 42

syphilis signs and sx 2*

Answer 42

Secondary syphilis occurs approximately four to ten weeks after the primary infection.
While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucous membranes, and lymph nodes.
There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles.
oy the pictures

Question 43

syphilis signs and sx 2*

Answer 43

The rash may become maculopapular or pustular. It may form flat, broad, whitish, wart-like lesions on mucous membranes. All of these lesions harbor bacteria and are infectious.
oy the pictures part 2 that looks painful
Other symptoms may include fever, sore throat, weight loss, hair loss, and headache.

Question 44

sx of 2* syphilis

Answer 44

The acute symptoms usually resolve after three to six weeks however, about 25% of people may present with a recurrence of secondary symptoms. Many people who present with secondary syphilis (40–85% of women, 20–65% of men) do not report previously having had the classic chancre of primary syphilis.

Question 45

Latent

Answer 45

Latent syphilis is defined as having serologic proof of infection without symptoms of disease.
It is further described as either early (less than 1 year after secondary syphilis) or late (more than 1 year after secondary syphilis) in the United States.
Early latent syphilis may have a relapse of symptoms. Late latent syphilis is asymptomatic, and not as contagious as early latent syphilis.

Question 46

tertiary syphilis

Answer 46

Tertiary
Tertiary syphilis may occur approximately 3 to 15 years after the initial infection, and may be divided into three different forms: 
gummatous syphilis (15%), 
late neurosyphilis (6.5%), and 
cardiovascular syphilis (10%).

Without treatment, a third of infected people develop tertiary disease.
People with tertiary syphilis are not infectious.
-the pictures

Question 47

Other manifestations of tertiary syphilis

Answer 47

Neurosyphilis refers to an infection involving the central nervous system. It may occur early, being either asymptomatic or in the form of syphilitic meningitis, or late as meningovascular syphilis, with apathy and seizure, and general paresis with dementia.
meningitis- inflammation- neuroscience
Cardiovascular syphilis usually occurs 10–30 years after the initial infection. The most common complication is syphilitic aortitis, which may result in aneurysm formation.
pictures

Question 48

Congenital Syphilis

Answer 48

Congenital syphilis is transmitted during pregnancy or during birth. If untreated, congenital syphilis may occur in 40% of patients- the face pictures

Question 49

Paul Ehrlich

Answer 49

a god
Father of modern Drug Discovery and Chemotherapy.

Discovered the first effective treatment of Syphilis in 1910 with the synthesis of Salvarsan.

Question 50

paul ehrlich part 2

Answer 50

“if a compound could be made that selectively targeted a disease-causing organism, then a toxin for that organism could be delivered along with the agent of selectivity”

Coined the term “magic bullet” for drugs that selectively target disease.
The concept of selective membrane receptors
Developed first treatment for syphilis
Nobel prize for medicine in 1908

Question 51

Biocidal Agents: Historical Perspective

theres a table

Answer 51

The use of antimicrobial biocides is centuries old, with early applications including their use in food preservation (salting and spices).
Silver products have been used for thousands of years for their beneficial effects.
Syphilis was originally treated with mercury. - fun fact
Iodine, chlorine and phenol were introduced much later in clinical applications

Question 52

Development of Salvarsan

Answer 52

The ancient Greek had known about “therapeutic” power of arsenic trisulfide, As2O3.
Atoxyl: amino derivative of phenylarsonic acid

Question 53

Development of Salvarsan

pt 2

Answer 53

Ehlich discovered that Atoxyl had a different structure, because it reacted with nitrous acid to form diazonium salts (this reaction only occur if atoxyl had a free amino group).
Atoxyl was originally thought to be the sodium salt of the meta-anilide of phenylarsonic acid.

Question 54

what happened to salvarsan in the 1920s

Answer 54

it was replaced by penicillin
By 1920 Salvarsan had been shown to be effective against other parasitic disease and 2 million doses a year were produced in the US alone.

Question 55

more cool stuff

Answer 55

The structure of Arsphenamine has been proposed to be akin to the azobenzene (A),…
but mass spectral studies published in 2005 suggest that it is actually a mixture of the trimer B and the pentamer C
these cyclic species slowly release an oxidized species, RAs(OH)2, that is likely responsible for Salvarsan’s antisyphilis properties

Question 56

Why the current interest?

salvarsan

Answer 56

Given its widespread use as a cure for syphilis, surprisingly little is known about the mode of action.

Discovering the site of action for a compound of uncertain composition is not easy.

Since Salvarsan is effective against a range of obligate pathogens, it must presumably affect a target present in the pathogen but absent (or reduced) in the human host.

In 1997 the complete genome of the syphilis organism was sequenced so that, in theory, every protein the pathogen synthesizes can be identified. These advances in molecular biology and in our understanding of the structure of the active components of Salvarsan create new opportunities to detect the target and understand the mode of action.
ooh

Question 57

How common is Syphilis?

Answer 57

44,828 cases from all stages of syphilis were reported in 2009. Of these, nearly 14,000 were in the primary and secondary (P&S) stages where transmission to a partner most often occurs.

After declining for years, rates of P&S syphilis leveled off in the 1990s and increased every year between 2001 and 2009. Between 2005 and 2009 alone, rates of P&S syphilis in the U.S. surged by 59%.

Question 58

all the problems with syphilis

Answer 58

Untreated, Syphilis has a mortality up to 58%, with a greater death rate in males.
Syphilis is difficult to diagnose. Confirmation is either via blood tests or direct visual inspection using microscopy. Diagnostic tests are, however, unable to distinguish between the stages of the disease.
No vaccine for syphilis is available as of 2019. Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis.
Syphilis is believed to have infected 12 million additional people in 1999, with greater than 90% of cases in the developing world. It affects between 700,000 and 1.6million pregnancies a year, resulting in spontaneous abortions, stillbirths, and congenital syphilis. In 2010 syphilis caused about 113,000 deaths.

Question 59

Tuskegee Syphilis Experiment

Answer 59

The Tuskegee study of untreated syphilis was an infamous and unethical clinical study conducted between 1932 and 1972 by the U.S. Public Health Service.
The purpose of this study was to observe the natural history of untreated syphilis.
The African-American men in the study were only told they were receiving free health care from the United States government.
The Public Health Service started the study in 1932 in collaboration with Tuskegee University, a historically black college in Alabama.

Investigators enrolled 600 impoverished, African-American sharecroppers from Macon County, Al. Of these men, 399 had previously contracted syphilis before the study began, and 201 did not have the disease. The men were given free medical care, meals, and free burial insurance for participating in the study. The men were told that the study was only going to last six months, but it actually lasted 40 years.

Question 60

Tuskegee Syphilis Experiment

Answer 60

The 40-year study was unethical for reasons related to ethical standards.
Researchers knowingly failed to treat patients appropriately after the 1940s when penicillin was found as an effective cure for the disease that they were studying.
The revelation in 1972 of study failures by a whistleblower led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies require informed consent, communication of diagnosis, and accurate reporting of test results.-

Question 61

terrible results from the study

Answer 61

By 1947, penicillin had become the standard treatment for syphilis. Choices available to the doctors involved in the study might have included treating all syphilitic subjects and closing the study, or splitting off a control group for testing with penicillin.
Instead, the Tuskegee scientists continued the study without treating any participants; they withheld penicillin and information about it from the patients. In addition, scientists prevented participants from accessing syphilis treatment programs available to other residents in the area.
The study continued, under numerous US Public Health Service supervisors, until 1972, when a leak to the press resulted in its termination on November 16 of that year.
By the end of the study in 1972, only 74 of the test subjects were alive. Of the original 399 men, 28 had died of syphilis, 100 were dead of related complications, 40 of their wives had been infected, and 19 of their children were born withcongenital syphilis.

Question 62

Syphilis Experiment

the apology

Answer 62

The Tuskegee Syphilis Study led to the 1979 Belmont Report and to the establishment of the Office for Human Research Protections (OHRP).
It also led to federal laws and regulations requiring Institutional Review Boards for the protection of human subjects in studies involving them.
The OHRP manages this responsibility within the US Department of Health and Human Services (HHS).

On May 16, 1997, President Bill Clinton formally apologized on behalf of the United States to victims of the experiment. He said:
“What was done cannot be undone. But we can end the silence. We can stop turning our heads away. We can look at you in the eye and finally say on behalf of the American people, what the United States government did was shameful, and I am sorry … To our African American citizens, I am sorry that your federal government orchestrated a study so clearly racist.”

The presidential apology led to the establishment of the National Center for Bioethics in Research and Health Care at Tuskegee, which officially opened in 1999 to explore issues that underlie research and medical care of African Americans and other under-served people.
In 2009 the Legacy Museum opened in the Bioethics Center, to honor the hundreds of participants of the Tuskegee Study of Untreated Syphilis in the Negro Male.

Question 63

google an article about this

Answer 63

go over functional groups