D.1 Pharmaceutical products and drug action

Yeet

The human body’s defense system

• Metabolism
• The thousands of chemical reactions that keep our body running
• Can break down easily
• Injury, bad genes, environmental effects
• All increase with age
• Affected by microorganisms
• Affectionately called “invaders”, but inorganic materials can be called “alien material”
• The body’s line of defense (white blood cells, increased blood flow, pain receptors, etc) manifest themselves as symptoms (fever, etc)
• Medicines supplement the body’s natural defenses

Medicines and drugs

Definitions

• Drug
• Any chemical that changes how the body works
• Can be beneficial or harmful
• Often associated with Narcos or Breaking Bad or private school kids’ house parties but has a much broader meaning
• Medicine
• A substance that improves health.
• It contains beneficial drugs that can be either natural or synthetic, or a combination of both
• Synthetic medicines often contain drugs that help in delivery
• Beneficial effect, aka Therapeutic effect

Nature of Science: The placebo effect

• Sometimes referred to as “the power of suggestion”
• Where the patient gains a therapeutic effect through just believing that they have received a beneficial drug (when they really haven’t)
• No real empiricism, but around ⅓ of a group taking a placebo show some improvements
• Used as a constant in double blind tests, because apparently double blind tests need to be made more confusing smh
• There has been no identified mechanism linking a placebo and the therapeutic effect
• No reliable quantifiable data, subjective studies without clear conclusions (Look it’s just like our IA’s)
• Because of this, it’s rather controversial

Administering drugs

• Administered in different ways, based on;
• Chemical nature of drug
• Condition of patient
• Most effective way of getting the drug to the target organ(s)
• How susceptible the drugs are to breakdown by metabolism
• E.g. proteins such as insulin are injected

​

(more about injecting drugs)

Bioavailability

​

• Defined as the fraction of the drug that reaches the blood supply
• Not all of the drug reaches the blood, breakdown by metabolism, etc etc.
• By definition, intravenous injections have a 100% bioavailability
• Important for calculating dosage
• This is affected by the types of administration of the drug, the drug’s solubility, and the drug’s functional groups

​

How administration affects bioavailability

• Orally taken drugs have a bioavailability as low as 20%. This is due to the “first pass effect”, where metabolic processes and other digestive enzymes break down
• Due to this, orally taken drugs are about 4 times as more concentrated as intravenous drugs
• E.g. Morphine only has a 30% bioavailability when swallowed so is injected intravenously

How solubility affects bioavailability

• Blood has water
• Drugs need to be water soluble to dissolve in blood for circulation
• The less soluble, the lower the bioavailability

​

How functional groups affect bioavailability

• Acid/base groups affect it greatly
• The pKa/pKb values of these groups on different parts of the molecule determine the charges on the molecule (now an ion) at different pH’s, affecting solubility and reactivity at different parts of the body

​

Psychological effects of drugs

• Complex (very hard to pinpoint)
• Cannot always predict the products of metabolism, so more than one effect will occur
• Side effects
• Different individuals respond to drugs differently
• Based on physical characteristics, genes, etc etc
• Healthcare providers keep these factors in mind when prescribing drugs (guess and check lol)

Side effects

• Total effects can be split
• Intended effect
• Therapeutic effect
• Side effects
• Unintended physiological effects
• Side effects vary largely
• Some are beneficial
• Aspirin
• Some are benign
• Headaches, nausea
• Some are :angrysad:
• Damage to organs, etc

• These impacts must be evaluated before administration
• Patients must be aware of their own conditions
• Patients lifestyles must be adjusted to fit - ask question
• The worst case afaik was the thalidomide drug - ask question

Tolerance and addiction

• People can develop tolerances after multiple doses of drugs
• Reduced response to the same dose of drug
• The result is higher doses, and more risk of side effects
• Mechanism is not well known
• Metabolism?
• Receptors go kaput?
• Some symptoms decrease while others maintain? Idk
• Note: Different to Dependence and Addiction
• These occur when the patient requires the drug to feel normal
• Withdrawal symptoms
• Symptoms can be mild (headaches) to very much worse (permanent psychological damage)

Dosage

• Refers to the amount taken at one time, and the frequency of administration
• Must take into account tolerance, side effects, bioavailability and addictions into account
• Dependent on more variables
• Sex
• Age
• Weight
• Environment
• Diet
• Other drugs
• Ideal dosage is constant, but only possible via IV drip
• All other methods lead to fluctuation
• Must keep drug conc. within therapeutic window

Dosage - Therapeutic window

Dosage cont’d

• Range of therapeutic window is varied for different drugs
• If small, dosage must be measured
• If big, less risk
• Therapeutic window can be quantified as the Therapeutic index
• Ratio of the dose that produces toxicity to the dose that produces therapeutic effects
• Relevant terms;
• ED₅₀ is the dosage that produces therapeutic effects in 50% of the population
• LD₅₀ is the dosage that produces lethal effects in 50% of the population
• Only used on animals (and on animal abusers and pedophiles, in my world)
• TD₅₀ is the dosage that produces toxic effects in 50% of the population
• Used on humans (this is why overpopulation is a thing, just use LD smh)

Dosage cont’d [2]

• High TI shows large margin (not too much risk)
• Smol TI shows smol margin (much risk)
• Is penicillin, b) is warfarin

Drug action and interaction with receptors

• Activity depends on how it binds to certain receptors
• Receptors are usually proteins, chemical structures, enzymes, etc. on cells
• This binding prevents normal biological activity, preventing the development of the disease
• Requires a “chemical fit”, the better the fit, the better the effect.
• Kind of like insanely hard 4D chess, but your body does it every time you take some panadol or whatever
• Binding depends on non-covalent bonds
• Ionic, hydrogen, van der waals, hydrophobic
• Drug-receptor interactions made important contributions to advances in drug design

Development of new drugs

• Long and expensive
• More investment in first-world issues
• Less investment in third-world issues
• That’s capitalism for you (capitalist pigs)
• Large demand for seasonal flu vaccines, etc
• Very strict laws on which drugs are allowed into the market
• Many drugs fail to meet criteria
• Around 10-12 years for a drug to go from development to market
• Knowledge of drug-receptor interactions has changed how we synthesize them
• Molecular target is set, and drug is engineered to interact with it
• Known as Rational drug design, one of the few rational things this world does
• Better than trial and error

Development of drugs cont’d

• Once this target molecule is identified, a lead (pronounced ‘leed’, not Pb) compound is found
• This compound shows the desired pharmaceutical activity to target the target molecule
• Good start for the drug development process
• Often derived from plants
• Anti-cancer agent from yew trees to get taxol (and also Lord Voldemort’s wand, when combined with a phoenix feather)
• Digitalis from foxglove for heart medications (however this is digitoxin, and in large doses is lethal)
• Insulin from genetically modified E-Coli (not a plant, i know)
• The effectiveness of the compounds synthesized are optimised by testing chemically relatable compounds called analogues
• Process is called Combinatorial chemistry
• Enables production and testing of many compounds and potential medicines in a short amount of time

Development of drugs cont’d [2]

• Following this, tests are done on animals, then humans, both under strict legislative control (with an ethics committee hounding the scientists’ asses the whole time)
• Due to ethics, testing is kept to a minimum
• Determining the safety and effectiveness of the drug gives an early insight into the therapeutic index at an early stage
• From this, the therapeutic index for humans is and the dosage for human trials is determined