D1: Pharmaceutical products and drug action Flashcards
Distinguish between drugs and medicine
DRUGS: any substance that brings about a change in the biological function of a living organism through chemical action
- Can be both positive biological changes (medicine that produce therapeutic effects) or negative biological changes (drugs that produce toxic effects)
MEDICINE: drugs that have therapeutic actions and effects by preventing/alleviating/treating the symptoms of diseases and conditions
Describe the stages of drug synthesis in drug development
DRUG SYNTHESIS:
1) Identification of lead compounds
- Lead compounds: compounds with desirable biological activity that are therapeutically relevant
- Identification of lead compounds: biological testing of compounds obtained by isolation from natural resources/chemical synthesis/existing ‘banks’ of pre-synthesised compounds
2) Lead optimisation
- Numerous analogues are synthesised and tested to find more active and less toxic lead compounds for further development
3) Preliminary testing on animals
- Selected compound is tested on animals to test for toxicity
Describe the phases of clinical trials during drug development
CLINICAL TRIALS:
1) Phase I: on small number of healthy volunteers
- Find dose range needed for therapeutic effect
- Identify possible side effects
2) Phase II: on small number of volunteer patients with targeted disease
- Test effectiveness
- Identify side effects
3) Phase III: on larger numbers of volunteer patients
- Confirm effectiveness
- Compare activity with existing drugs and placebos (double-blind placebo test is performed)
Define therapeutic effect
THERAPEUTIC EFFECT:
desirable/beneficial effect that alleviates symptoms or treats particular diseases
Define side effects
SIDE EFFECTS:
undesirable and unintended secondary effects of drugs on the human body
Describe how drug doses (therapeutic index) are determined
LD₅₀: drug dosage needed to kill 50% of the tested animal population
TD₅₀: drug dosage needed to produce toxic effects in 50% of the tested population
ED₅₀: drug dosage needed to produce therapeutic effect in 50% of the tested population
TI= LD₅₀/ED₅₀ (animals)
TI= TD₅₀/ED₅₀ (humans)
- High TI: safer drug –> large difference between TD and ED –> larger dose needed to produce toxic effects
- Low TI: small difference between TD and ED –> more likely to cause toxic effects
Describe what is meant by the therapeutic window
THERAPEUTIC WINDOW:
range of dosage between the minimum dose required to produce a therapeutic effect and the dose which produces toxic effects
(range of drug concentration in the blood plasma that gives both safe and effective treatment)
Describe what is meant by tolerance and addiction/dependence
TOLERANCE:
when body becomes less responsive to the drug and requires larger doses to produce the same therapeutic effect, hence increasing risk of toxic effects
- Increased drug metabolism rate: body excretes drug more quickly and leaves lower levels in the body to produce therapeutic effect
- Adaptation of body to drug: effect of the drug is offset by the body (Eg. by desensitising its target receptors)
ADDICTION/DEPENDENCE:
- Psychological dependence: user craves the drug when deprived for a short time, and needs to take drug to feel good
- Physical dependence: body cannot function without the drug and user needs to take the drug to avoid averse withdrawal effects
State 5 ways that drugs can be administered and describe the advantages and disadvantages of each
1) ORAL (via tablets/capsules/syrups/suspensions)
- Convenient to self-administer
- Slow absorption and onset of drug action: drug needs to pass through the digestive system, be absorbed into the bloodstream and travel to the target area
- Not suitable for drugs that are easily hydrolysed (destroyed by acidity and enzymes in the digestive system)
2) RECTAL (via suppositories)
- Suitable for patients with certain conditions unsuitable for oral administration (Eg. unconscious/vomiting)
- Can bring about local effect (haemorrhoid treatment) or effects in other parts of the body (drug is absorbed into the bloodstream via thin skin in the rectum)
3) PULMONARY (via gases/volatile liquids/aerosol powders)
- Rapid absorption and onset of drug action: large surface area of lungs
- Drug can be delivered directly to site of action when used to treat lung diseases
4) TOPICAL (via creams/ointments/lotions)
- Can produce both local effects and penetrate skin to be absorbed into the bloodstream
5) INJECTION
- Intravascular: drug is injected directly into bloodstream and can bring about fastest onset of therapeutic response
- Intramuscular: drug is injected into the skeletal muscle (needle is injected into muscle dense regions — eg. arm/thigh/buttock), and can be rapidly absorbed or suspended in oil for slow release from the muscle to the bloodstream for sustained release over a long period of time
- Subcutaneous: drug is injected directly under the skin, resulting in slow absorption and sustained release
Define bioavailability and explain the factors that affect it
BIOAVAILABILITY: fraction of the administered drug dosage that reaches the target part of the human body, and is affected by:
- Method of administration
- Water-solubility: affects whether drug can pass through intestinal wall and can be transported to the blood plasma
- Fat-solubility: affects whether drug can pass through cell membrane (made of lipids)
Explain how drugs interact with receptors
Drugs act by binding with receptors (proteins found on cell membranes or cytoplasms that serve as receptors for molecular signals)
- AGONISTIC: drug binds to the substrate molecule and mimics the effect of the normal molecule by causing similar biological responses upon binding with it
- ANTAGONISTIC: blocks the substate-binding site by binding with it, such that the normal molecule cannot bind with it and activate the receptor
- ALLOSTERIC: binds to the surface of the receptor and alters the 3D-shape of the protein such that the receptor response to the substrate changes
