IB HL Chemistry Medicinal Chemistry D1-4 Notes

Which form of administration is typically used for pills, liquids, capsules, and tablets?

Oral Administration

Which form of administration involves absorption through the small intestine?

Oral Administration

Which form of administration is usually used for digestive issues?

Rectal Administration

Which form of administration is typically used for gasses, volatile liquids, or solids?

Inhalation/smoking

What causes the affects of inhalation/smoking administration?

Extensive networks of blood vessels in lungs (pulmonary system)

Parenteral administration involves:

injections

Intravenous Injections Involve:

Near instantaneous effect; concentrations not affected by stomach content

Fat-soluble drugs are more easily absorbed because:

Blood vessels contain a fatty layer

TD50 (median toxic dose)

dose at which a specific toxic effect occurs in 50% of the individuals tested

LD50 (lethal dose)

the dose at which death occurs in 50% of subjects

The lower the LD50, the _____ toxic a substance is

more

Larger TI value indicates

Wider margin between effective and toxic doses

Phase I Clinical Trial

Clinical trials on volunteers AFTER drug prove safe for animals (50-100 volunteers)

Phase II Clinical Trial

Thorough investigation to remove investigator bias

Phase III Clinical Trial

Extended evaluation, 3000+ patients, half given drug and half a placebo

The activity of a drug is mostly determined by:

Its ability to bind to specific receptors in the body (in a virus, enzyme, cell membrane, etc.)

The binding of a drug to a receptor does what to body processes?

Typically prevents or inhibits normal biological activity -- interrupts disease development, pain, etc.

In order for binding of a drug to occur, there must be what?

A "chemical fit" (ionic attractions, hydrogen bonding, van der waals, hydrophobic interactions, covalent bonds, etc.)

Drugs that combine with a receptor through hydrogen bonding often form a:

supramolecular complex

How do analgesics work?

by blocking the production of prostaglandins (a pain receptor)

What are some substitutes to aspirin?

Acetaminophen (tylenol) -- no stomach irriation, not anti-inflammatory, can cause liver damage, brain damage if overdosed

Ibuprofen (motrin) -- similar to aspirin but fewer stomach problems

What is the function of a beta lactam ring?

Has a 4 member nitrogen-containing ring -- instability of ring "opens" and covalently bonds to transpeptidase (synthesizes bacteria cell wall), and weakens bacteria structure

Difference between penicillin G and V?

G = not acid resistance, must be injected to bypass stomach

V = acid resistance

What are disadvantages of penicillins?

10% allergic, harmful to benign bacteria (makes room for harmful bacteria as well), genetic resistance over time

How are antibiotics used on animals?

Prevent spread of infection throughout livestock (can encourage drug-resistant bacteria)

What are opiates?

opium (poppies) and its derivatives, such as morphine and heroin; they depress neural activity, temporarily lessening pain and anxiety -- are either opiates or narcotics

What is unique about morphine's structure?

It has two hydroxyl groups

What is unique about heroin's structure?

It has two ester groups

Where does protein breakdown occur and how?

In the stomach through the enzyme pepsin and also hydrochloric acid

What is the function of gastrin?

A hormone secreted by endocrine cells when pH is high to stimulate HCL production (negative feedback loop)

What is heartburn?

Result of excess acid which is forced into esophagus (acid reflex)

What are some causes of acid indigestion?

overeating, alcohol consumption, anxiety, smoking, certain drugs/foods, etc.

What are antacids?

WEAK bases that neutralize excess stomach acid (typically weak inorganic bases)

What are some examples of antacids?

Weak bases like CaCO3, NaHCO3, AL(OH)3, Mg(OH)2, MgO, Mg(OH)2

What is the effect of antacids?

They neutralize excess stomach acid, prevent inflammation, relieve pain and discomfort, and allow mucus layers to heal

What are antacids commonly combined with?

Alginates and anti-foaming agents

What do alginates do?

Form neutralizing layer over stomach contents preventing acid reflux

What do anti-foaming agents do?

Prevent gas formation and reduce flatulence

How do H2 Receptor Antagonists work?

Inhibit acid production by blocking histamine

What are proton pump inhibitors?

Reduce production of acid by blocking ATPase in stomach walls that produces acid using a proton pump

What are some common proton pump inhibitors?

Esomeprazole (Nexium)
Lansoprazole (Prevaid)
Omeprazole (Prilosec)
Rabeprazole (Aciphex)
(-prazole)

A beneficial effect is also known as the:

Therapeutic Effect

What are drawbacks of oral administration?

Affected by stomach content and drug concentration

Why is rectal administration typically used?

It's effective if a drug cannot be taken orally or ig a drug is pH sensitive

Skin patches involve:

Absorbing from skin --> blood stream

Subcutaneous Injections involve:

Absorbing from beneath the skin --> blood stream (slow absorption)

Intra-muscular Injections involve:

Using when immediate response is not required; Useful for large volumes of drug injection (ex. vaccines)

Bioavailability is:

the rate and extent of absorption of unchanged drug from its dosage form (fraction of drug that reaches blood in unchanged form and available for biological effect)

Oral bioavailability depends on:

amount absorbed and amount metabolized before reaching circulation/bloodstream (first pass metabolism)

What is the blood-brain barrier?

filtering/protective mechanism in brain involving denser capillaries to prevent diffusion of many substances into the brain

Dosage is:

the amount and frequency of a drug to be taken over time

What is the therapeutic window?

The target range where a drug yields desires results while maintaining no side effects

Therapeutic window is quantified by:

Therapeutic index (TI)

ED50 (effective dose)

The dose required to achieve desired/therapeutic response in 50% of the population

What is the formula for therapeutic index?

TD50/ED50

Animal studies compare ratio of ________

LD50/ED50

Human studies compare ratio of _______

TD50/ED50

Double Blind Study

An experiment in which neither the participant nor the researcher knows whether the participant has received the treatment or the placebo

Placebo Effect

Inert substance used to produce a significant (positive) reaction

What does most drug research focus on?

Identifying molecular targets and designing drugs to interact with them (rational drug design)

lead compounds are:

target molecules that show desired pharmaceutical activity (used to start drug design and development process)

How is the effectiveness of lead compounds tested?

Comparing to related substances known as analogues

What do prostaglandins do?

affect hypothalamus, regulate swelling, constrict blood vessels

How is "bayer's aspirin" made?

esterification rxn with salicylic acid, recrystallization

What are disadvantages of aspirin?

Can upset stomach (cause ulceration and bleeding), rare risk of allergy, infant poisoning

What are advantages of aspirin?

Pain relief, fever reduction (antipyretic), anti-inflammatory, anti-clotting

What is the difference between broad and narrow spectrum antibiotics?

Broad = effective against a wide variety of bacteria, but can wipe out harmless bacteria in digestive tract (tetracyclines)

Narrow = effective against certain bacteria (penicilins)

Who determined the structure of penicillin G. and how?

Dorothy Hodgkin (1945) using x-ray crystallography

What is the main structural component that causes penicillin's effectiveness?

A beta lactam ring

What is cloxacillin

an acid/penicillinase resistant compound (resistant to enzymes in bacteria that break down penicillin)

How do strong analgesics work?

Block opioid receptors in brain temporarily and prevent pain transmission to the brain (more addictive and narcotics can affect mood and behavior)

What determines the strength of an opiate

ability of the compound to pass through the blood-brain barrier (must be hydrophobic, since brain is mostly lipids)

Difference between opioid and opiate

Opiate = natural
Opioid = synthesized

What are the similarites between morphine, herion, and codeine?

They all have tertiary amines and a benzene (phenyl) group

What is unique about codeine's structure?

It has one hydroxyl group and an additional ether group

How do you go from morphine to heroin?

Esterification: morphine + ethanoic acid (--> w/ H2SO4 in warm/heated solution) heroin + 2H2O

How do you go from morphine to codeine?

Methylation (add a methyl group onto one of the OH's)

What is the role of dopamine?

It is a neurotransmitter which regulates pleasure and reward centers (also has to do with motion/movement)

Advantages of opiates:

(major effects on nervous system, eye, GI tract) strong analgesic, diarrhea treatment (causes constipation), cough supresssant

Disadvantages of opiates:

cross-tolerance, withdrawal due to addiction, mood change, sedation

What do stomach walls do?

They are lined with cells that secrete mucus, pepsinogen (converted to pepsin), and hydrochloric acid

What are the two exocrine glands in stomachs?

Parietal cells = secrete HCL
Chief cells.= secrete pepsinogen

What are some side effects of antacids?

Magnesium compounds = can cause diarrhea

Aluminum compounds = can cause constipation + interfere with absorption of phosphates in bone formation (more likely over extended periods)

Carbonates = can cause bloating and flatulence

What are some examples of H2 blockers?

Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid)
(-tidine)