Topic 12; Medicinal Chemistry Flashcards
Drug
a chemical that affects how the body works (both positive and adverse)
- affects physiological, sensory and emotions of a human
Medicine
a substance that improves health (beneficial drug); brings around a therapeutic effect
therapeutic effect
beneficial effect of a medicinal treatment
- intended physiological effect
placebo effect
when patients gain therapeutic effect from their belief that they have been given a useful drug even when they have not
placebo
drugs containing no active ingredient which ‘fool’ the body into healing
drug administration
the manner in which drugs are delivered to a patients body
subcutaneous
directly under skin surface into fat
intraveneous
directly into blood stream
intramuscular
directly into muscle
side effect
unintended physiological effect that ranges from drug to drug and person to person
dosing regime
the amount of a drug used for each dose and frequency of administration relative to patients state
therapeutic window
range of doses between minimum amount of drug that produces desired effect that the medically unacceptable adverse effect
tolerance
reduced response to the drug due to repeated dosage; therefore larger quantities of drug needed for effect
lead compounds
compounds with biological activity that are made and tested
analogues
chemically related compounds that are made and tested
effective dose
required dose to bring about an effect in 50% of the patients
lethal dose
dose required to kill 50% of patients
LD/ED= therapeutic index
TD; toxic dose used for humans
bioavailability
fraction of administred drug that reaches the target molecule in the body
analgesic
pain killer; can be strong or weak
target at source or pain receptors in brain
antibiotic
chemically produced by a microrganism to have action against another microorganism (bacteria)
antacid
a weak base that regulates stomach acidity
virus
- live in a host cell
- rapidly mutate and reproduce
- don’t have metabolism like a bacteria does
- antibiotics dont effect it
HIV
- retrovirus; turns RNA into DNA
- releases RNA into a cell to create viral DNA to then produce viral particles
- destroys helper T cells
- mutates rapidly
- lies dormant in host cell
body immune response
- produces antibodies to attack virus
- build immunity
types of treatments against a virus
- prophylatic
- antiviral
prophylatic
- (preventative measure) stimulate body to prepare specific antibodies to gain immunity (VACCINE)
- limit of this is that viruses can mutate
antiviral
interferce with viral life cycle and prevent release of new viral particles from the host cell
e. g. - alter cells DNA to prevent virus’s multiplication
- block enzyme activity within host cells to stop virus’s mutliplication
example of a preventative anti-viral
Amantadine; changes cell membrane to prevent virus’s entry into host cell
Flu virus proteins
- hemmaglutinin
- neuraminidase
hemaglutinin (H)
glycoprotein that enables a virus to attach with hose cell before entering
neuraminidase (N)
enzyme that catalyzes a cleavage reaction that allows a vrisus to release viral particles from the host cell to spread infection
- snips sialic acids form glycoproteins on host cell sufrace membrane
Tamiflu
(oseltamivir) - taken orally - inhibits neuraminidase action - taken within first 48 hours of symptoms - some resistance reported nausea and vomitting as side effects
Relenza
(zanamivir) - taken by inhalation - inhibits neuraminidase action - taken within first 48 hours of symptoms - no resistance reported possibly asthma as side effect
aids
acquirred immune defiency syndrome
- pandemic
- when the white blood cell count becomes too low
- HIV becomes aids
how is aids/hiv transmitted?
- sexually from person to person
- sharing of needles
- blood transfusions
- mother to child
why is HIV hard to combat?
- virus is dormant in cells
- virus destroys helper t cells (attacks own immune system)
- virus tends to mutate rapidly so a lot of variation exists
how do we combat HIV?
- using antiretroviral drugs (ARV’s)
- don’t cure it, but supress/treat its effects
- target the binding and fusion of the virus and its reverse transcription from rna to dna
- also target integreation of viral DNA into host chromosome and release of new particles from host cell surface
aspirin
a mild analgeisc; prevents stimulation of nerve endings at site of pain and inhibit the release of new prostagladins at site of injury
- antipyretic
- relieves infmallatory reponse
- anticoagulant (reduces ability of blood to clot)
aspirin reaction
esterification reaction
saliclylic acid + ethanoic anhydride to produce aspirin and ethanoic acid
problems with aspirin use
- syngergy
- increases effects of stomach ulcers
synthesis of aspirin
- esterification reaction of salicylic acid and ethanoic anhydride
- concentrated sulfuric or phosphoric acid added to reactants
- mixture is warmed gently
- aspirin product is isolated and purified from mixture
how is aspiring purified?
- prooduct is cooled to allow chrystals to form, then suction filtered and washed with chilld water
- recrystalization occurs; disolving of impure chrystals with hot ethanol
- mixture is let cool; aspirin crystallizes out of solution and then separated by filtration
- purity of product determined by melting point determinition
modification of aspirin
- aspirin isn’t very soluble (large non polar molecule)
bioavailability is increased by increasing solubility - aspirin is reacted with an alkali (such as NaOH and NaHCO3) so it forms an ionic salt
penicillin
antibiotic; targets bacterial cell wall building enzyme
- alexander fleming + chain-florey
who was penicllin discovered and produced
- alex fleming noticed had cultures had grown mold in his bacterial cultures that killed the bacteria
- ernst chain and howard florey extracted and purified i and conducted animal and human trials on it
penicillin action
- has a beta lactam ring with reduced bong angles (to 90 degrees) which makes it unstable
- it inhibits bacterial enzyme TRANSPEPTIDASE that contructs the cell wall (ring binds and inhibits it)
- this makes the cell wall of the bacteria unstable
= osmosis causes it to burst and die
disadvantage of peniciilin G
broken down by stomach acid; has to be intravenously injected
- R groups are played with to change this
antibiotic resistance
- beta lactamase/penicillinase inhibit the beta lactam ring action by opening up the ring and make it inactive
- this is due to mutation and overuse of antibiotics
response to antibiotic resistance
- modified side chains (r groups) to prevent penicillinase enzyme binding
- control and restriction of antibiotic use by legilisation (make them prescription only drugs)
- doctors encouraged to not over prescribe and educate patients on use
- educate patients to finish term
- reduce use in animal produce
antacid
- a weak base that neutralizes stomach acid
e. g. Calcium Carbonate, Aluminium hydroide, magnesium hydroxide
excess acid production?
- causes heart burn and damage to the stomach lining
- creates good envrionment for helicobateria pylori to cause peptic ulcers
proton pump inhibitors
inhibit proton pumps from release acid into stomach lumen
e.g. osomeprazole (nexium)
How does the proton pump work?
- in the last step of gastric acid secretion, the parietal cells in the gastric glands pump hydrogen ions accros their membranes and into the lumen of the stomach
- for each hydrogen ion pumped into the lumen, a potassium ion is pumped in opposition direction so there is no charge build up
- the movement of ions requires ATP and happens in the use of the gastric proton pump
H2 Receptor antagonists
block histamine-h2 interaction by competitive inhibition
histamine
in stomach; stimulates the secretion of stomach acid by interacting at receptors known as H2 in the parietal cells in the gastric gland
- target for antacid action
example of a H2 receptor antagonist
- rantitidine (zantac)
acidic buffer solution
pH= pKa + log10[salt]/[acid]
opiate
strong analgesic that kills pain by preventing pain impulse transmission in brain rather than at source
- known as narcostics (cause changes in behaviour and mood)
what are strong analgesics derived from?
opium found in poppy seeds
where do our analgesic properties arise from?
because we possess opiod receptors in the brain to which they bind to;
- the binding blocks the transmission of impulses between brain cells that would signal pain
- they interfere with the perception of pain without depressing the CNS
strong analgesic action
- bind to opion receptors in the brain
- must pass through blood-brain barrier (hydrophobic, lipid, nonpolar environment) that protects the brain from chemicals
- has to be both blood and lipid soluble (polar and non polar)
codeine
- derived through methylation reaction of morphine
- 0.5% derived from opium
- sometimes used in prep with nonnarcostic drug like aspiri in second stage of pain managemanent ladder
- used in cought medications + short term diarrhoea treatment
- semi-synthetic drug
morphine
- derived from raw opium 10%
- used in severe pain management
- can form addiction; must be regulated my medical professional
diamorphine (heroine)
- found in opium, usually obtained by esterification reaction of morphine
- used medically only in few countries
- rapid acting and strong narcostic
- produces euphoic effects
- high addiction and tolerance potential
- dependence leads to withdrawal symptoms
- broken down into morphine in brain (pro-drug)
pain management ladder
- use mild analgesics
- use weak opioid
- use strong opioid
side effects of strong analgesics
- constipation
- suppression of cough reflex
- constriction of pupil in eye
- narcotic effects (suppression of brain function like sleep and addiction; dulls pain)
- illegal + criminal actions and other social problems
- HIV due to dirty, shared needles
solvent waste
emission of drug industry
involve incineration during disposal which releases toxins to environment
- solvents are the biggest contributor to the emissions of the pharmaceutical industry
-solvent recycling can cut emissiosn to air, water and soil
how is the suitability of solvents determined
- toxicity to workers
- saftey of process
- harm to environment
preferred solvents
water, ethanol, ethyl ethanoate, propanone
undesirable solvents
methanal
benzne
dichloromethane
principles of green chemistry
- use of safer solvents
- avoid use of auxillaries where possible
- prevent waste and recyle
nucelar waste
- use of nuclear chemistry in diagnosis and treatment of disease
- assosiated with radioactive waste (can be hazardous to living things and environment)
high level waste
gives off large amounts of ionizing radiation for a long time; the isotopes have long half lives
low level waste
gives off small amounts of ionizing radiation for a short time
- the isotopes have short half lives
examples of low level waste
clothing
protective show covers
paper towels
(implements that have been contaminated with radioactive matieral)
how is low level waste disposed of?
- involves first interim storage in sealed containers that are safe and secure and enrivonmentally sound
- radioactivity decays in hours or days
- waste can be disposed of by concentional means (compaction, landfill, sewers)
high level waste examples
- spent isotopes from medical diagnosis techniques (e.g. MRI’s)
- toxic and radioactive
how is high level waste disposed of
- stored underwater in cooling ponds for a couple o fyears
- transferred to dry stroage and buried deep in the earth
how can we reduce nuclear waste?
- extracting enriched uranium from incerinerate ash using supercritical carbon dioxide
- reduce use of radioactive isoptopes in dianogsis by placing them in fluorscent dye
superbug
super resistant and strong bacteria that arise from mutations
e. g. methicillin-resistant staplyoccocus aureus (MRSA)
- hospitals often face problems with them
how does antibiotic resitante arise
- overuse and extensive use of antbiotics
- use in humans, animals, sanitation, research and pest control
- inproper disposal (leaks into water systems and ground supplies)
tamiflu
antiviral obtained from shikimik acid (from the chinese star anise)
- low yield
how has green chemistry enhanced tamiflu
- as it has a low yield from star anise; other sources have bee developmnd
- production of shikimate from fermentation reactions of genetically engineered bacteria
- harvesting of shikimate from pine needles
- extraction o fshikimate from indian sweetgum tree culture suspensions
examples of green chemistry success stories
- viagra drug production (modified reaction route to reduce solvent and toxic reagant use)
- ipuprofen production (6 step to 3 step route)
- Lyrica analgesic; use water reagant to reduce non-renewable organic compound solvent use
what determines the administration of a drug?
- its solubility
- the functional groups of the drug
- the situation of the patient
