Medicinal Chemistry IB SL Chemistry

Drug

Something that causes a physiological change in the body

Medicine

Something used to treat or prevent diseases

Medicine and Drugs must do one of the following…

• alter incoming sensory sensations

• alter a person’s mood or emotions

• alter the physiological state of the body, including consciousness and coordination

Therapeutic effect

beneficial effect of a medicine

What are the 3 parenteral methods of administration?

• intramuscular - into muscle

• subcutaneous - directly under the skin

• intravenous - bloodstream(most rapid effect)

bioavailability

fraction of administered dosage of a drug that enters the bloodstream and have an active effect

What factors affect bioavailability?

• method of drug administration

• polarity of drug

• type of function groups in drug

True or False? Intravenous administration has a bioavailability of 100%

True

True or False? Oral doses need to be 3 times stronger than an intravenous dose

False. They must be 4 times stronger

What are the best type of molecules to be administered, in terms of solubility

One that is largely hydrophobic but still has some solubility

Which functional groups are able to form hydrogen bonds easily?

• carboxyl

• hydroxyl

• amine

Which functional groups enhance lipid solubility(non-polar)?

Ones that lack the ability to ionize or form hydrogen bonds

• phenyl group(benzene ring)

• hydrocarbon chain

How is the solubility of aspirin increased?

It reacts with NaOH

True or False? Ionic salts increase solubility

True

Therapeutic window

Measure of safety of a drug. A wide window means a wide margin between toxic and safe doses

Therapeutic Index(TI) for humans

TI = TD(50)/ED(50)

• TD(50) - median toxic dose

• ED(50) - median effective dose

What are the main stages of drug development?

• drug is synthesized

• Drug is tested on animals to find lethal dose

• Drug is tested on humans in a double blind experiment

• Unwanted side effects and tolerance must be determined

How can you test the purity of aspirin?

Can be determined by melting points and IR spectrum

True or False? More impurities means higher a melting point

False. More impurities means a lower melting point

Analgesic

painkiller

• aspirin

• ibuprofen

• paracetamol

• morphine

• codeine

• dimorphine

How does aspirin block the sensation of pain?

It blocks the action of enzymes that produce prostaglandins, which are involved in the transmission of pain impulses to the brain

Anticogulant

prevents blood from clotting

What are 5 common methods of drug administration?

• oral

  • polar, water-soluble

• intravenous

  • unstable or poorly soluble

• transdermal(skin patch or ointment)

  • non-polar, lipid-soluble

• rectal

  • unstable in gastric acid

• inhalation

  • volatile

Antibiotics

Drugs that kill or inhibit the growth of bacteria

* penicillin

What is a beta-lactam ring?

A box shaped structure found in penicillin consists of three carbons and a nitrogen to make the base. One of the carbons in double bonded to an oxygen

What doe beta-lactam antibiotics do?

They interfere with cell wall formation in bacteria by inhibiting the enzymes responsible for creating cross-links in the cell wall

Antibiotic resistance

Bacteria that resists the effects of an antibiotic

What are the causes of antibiotic resistance?

• overprescription of antibiotics for basic illnesses

• patients don’t complete their course of antibiotics

How are antibiotics released into the environment?

• antibiotics are given to healthy farm animals

• Improper disposal by hospitals or companies

• excreted by human urine

• pharmaceutical waste

Opiates

Natural analgesics derived from opium. Bind to opioid receptors in the brain and block transmissions of pain impulses.

• morphine

• codine

• dimorphine

What are the advantages and disadvantages of strong analgesics/opiates?

Advantages:

• provide relief for pain

• wide therapeutic window

• improve quality of life

• reduce anxiety

  Disadvantages:

• euphoria and lack of self-control

• regular usage can lead to addiction, dependence, and withdraw

Blood-brain barrier

Tightly packed cell restricting passage of substances from bloodstream to brain that is largely composed of lipids

How is dimorphine created from morphine?

morphine + ethanoic acid →dimorphine + water

algmates

type of antacids that prevents acid from rising in the esophagus

Proton pump inhibitor

inhibits the secretion of H+ ions into gastric juice. Stomach acid inhibitor that can last up to three days.

* omeprazole

H2 Receptor antagonists(H2 blockers)

stomach acid inhibitor that blocks histamine receptors in acid-producing cells in the stomach

* ranitidine

Virus

submicroscopic organism that replicates inside living cells of other organisms. Consist of a protein coat and nucleic acid

Bacteria

small single cell microorganisms that are self reproducing, living, and contain various cell organelles. They are larger than viruses

Why are viruses harder to target with drugs than bacteria?

• they lack a cell structure

• they lack subunits that can be targeted by antivirals

• they mutate quicker

• they must be targeted at a genetic level

True or False? Antibiotics are effective against bacteria but ineffective against viruses

True

How do antiviral drugs work?

• alter a cell’s genetic material

• block enzyme activity

• bind to cellular receptors targeted by viruses

• prevent release of viruses

What are some examples of antiviral drugs for the common flu?

• oseltamivir(oral)

• zanamivir(inhalation)

Why is HIV hard to treat?

• mutates rapidly

• has host cells to replicate

• drugs that treat HIV may harm the host cell

• high price of anti-viral drugs

What are Socio-Cultural factors that affect AIDS?

• condom use

• ignorance and misinformation

• stigmas

• prostitution

What are the three levels that nuclear waste is classified into?

• Low-Level waste(LLW)

  • produces weak radiation for a short time

• Intermediate-Level Waste(ILW)

  • produces strong radiation for a short time

• High-Level Waste(HLW)

  • produces strong radiation for a long time

What levels of radiation are typically found in medical settings?

* Low-Level and Intermediate-Level

What are examples of low-level waste?

• gowns

• protective clothing

• shoe covers

• tissues

• needles

• mops

How do you dispose Low-level waste?

Store in shielded containers until the isotopes have decayed, then dispose of as non-radioactive waste

What are some examples of Intermediate-level waste?

• sources for radiotherapy

• Co-60

• Cs-137

How do you dispose of Intermediate-level waste?

* long term storage in shielding containers or concrete chambers, then buried underground

In green chemistry, what are the preferred solvents in synthesizing drugs?

• water

• methanol

• ethanol

In green chemistry, what are the undesired solvents in synthesizing drugs?

• pentane

• dichloromethane

• dichloroethane

True or False? Many undesirable solvents are VOC(volatile organic compounds)

True

Why are VOCs used as solvents?

They have high volatility

Chlorinated vs non-chlorinated solvent types

Chlorinated:

• ozone-depleting

• accumulates in ground water

• forms toxins if burned

• toxic, irritant, and forms greenhouse gases

Non-chlorinated:

• flammable

• toxic, irritant, and forms greenhouse gases

What are some of the Green Chemistry principles?

• prevent waste

• design less hazardous chemical synthesis

• design safer chemicals and products

• use safer solvents

How are some bacteria inactivating penicillin?

They produce penicillinase/enzyme that deactivates penicillin

How has the structure of penicillin been modified to overcome this resistance?

the side chain has been changed to preserve the beta-lactam ring

How do antacids neutralize stomach acid

weak base + stomach acid(HCl) →XCl + water

• CaCO3 + 2HCl →CaCl2 + H2O + CO2

• MgO + 2HCl → MgCl2 + H2O

What are the advantages of taking ranitidine instead of antacid?

• ranitidine can treat stomach ulcers

• ranitidine prevents long term damage

• ranitidine lasts longer

• ranitidine doesn’t cause bloating