MT1 Flashcards
Define (medical) pharmacology and toxicology
Pramacolgoy: The study of stubstances that interact with living systems through chemical processes
Medical pharamcology: The study of substances used to prevent, diagnose, and treat disease
Toxicology: A branch of pharmacology that studies undesireable effects of chemicals on living systems and ecosystems.
When/where was pharmacology made, and how is it different from pharmacology today?
Found in 2500 BC records in China, Greece, Egypt, and India as there are lists of beneficical or toxic effects of remedies, but efficacy was unknown.
- They were reliant on theorization rather than observation and experimentation beginning in Roman times.
What is pharmacogenomics and its techniques?
The relation of an individual’s genetic makeup to his or her response to specific drugs; what are the side effects of a drug to an individual.
Individuals have different genetic makeup and could inherit diseases.
Genetic techniques: gene therapy, knockout mice
Role of academics and industries in pharmaceutical industry.
Academic institutions discover ‘new’ drug compound for a new drug target.
Industries develop new drugs as they are expensive to produce.
What is a drug and how can it operate?
A drug is any substance/ligand that brings a change in biological function through chemical actions
- Agonist: Activator of a biochemical pathway; mimic endogenous signaling which conformationally changes the receptor
- Inverse agonist: stabilize receptors in an inactive form; closes a receptor that is open/leaky
- Antagonist: inhibitor of a biological pathway (block endogenous signaling)
– Competitive: Binds to same site as natural ligand
– Noncompetitive: Binds to different site as natural ligand and causes a conformation change at the receptor site
– Irreversible: covalent modifaction of receptor
Considerations for drug making.
Drugs must have appropriate: size, electrical charge, shape, and atomic composition with its target receptor. Size varies from 100-1000 MW and exists in organic and inorganic compounds.
Drugs must be able to reach receptor (be able to pass blood brain barrier) and be inactivated/excreted.
Ways to administer drug
Fastest effect
Intravenous (blood vessel)
Intramuscular (muscle) <- painful but large volumes
subcutaneous (under skin) <- painful and small volumes
Inhalation <- often rapid onset
Oral <- Convenient but first-pass effect is significant
Parenteral Rectal <- Less first-pass effect than oral
Transdermal (through skin) <- Very slow absorption
Slowest effect
Types of drug-receptor bonds.
Drug molecuels interact with receptors via chemical bonds/forces
Covalent: very strong bond (usually nonreversible and uncommon)
Electrostatic: Common (charged ionic molecuels, hydrogen bonding, dipole)
Hydrophobic: Weak (highly lipid-soluble molecules)
How can drug action be terminated?
- Dissociation of drug from receptor
— Instant termination of effect as it is a primary channel
— Slow termination of effect as it sends secondary messenger - Destruction of receptor (drug is covalently bonded)
- Desensitization mechanisms
What factors do the receptor control?
Receptors determine the quantitative relations between dose/concentration of drug and effect (# of receptors = limitor of effect)
Receptors are responsible for selectivity of drug action
Receptors mediate the actions of agonists and antagonists
Which drug receptors are mainly targeted?
- G-protein coupled receptor as it mediates natural chemical signals and activates cellular responses
- Enzymes
- Transport proteins
- Strucutral proteins
What is the concentration-effect curve and its equation?
- Curve that describes the effect of a drug due to its concentration.
- Response increment diminishes as dose increases due to the limited amount of receptors
Equation
effect = (Emax*[drug])/([drug]+[drug = 50% of E)
Emax = maximum effect
What is the difference between potency and efficacy?
Potency: Concentration of drug required to achieve a pharmacological response (compared to other drugs). These comparisons are usually made with EC50 (concentration of drug for individual at 50% effectivness) or ED50 (Dose of drug for population at 50% effectivness).
Define alkylating agents
- Binding DNA by creating covalent bonds -> cross-link DNA -> prevent unwinding of DNA -> decrease protein synthesis
- Example: Cyclophosphamide
- oncology
Define epipodophyllotoxins
- inhibit topoisomerase II, enzyme responsible for DNA breaks, thereby inhibiting DNA synthesis
- Example: Etooposide
- Oncology
Define taxanes
- Promote assembly and stablization of microtubules, thus inhibiting cell replication
- may also inhibit angiogenesis
- Example: Docetaxel
- Oncology
Define antimetabolites
- Resemble naturally occurring nuclear structural components
- Incorporate into DNA or RNA -> interfere with function/synthesis
- May also inhibit enzymes involved in synthesis of DNA or proteins
- Example: Fluorourcail (5-FU)
- Oncolgy
Define antitumour antibiotics
- Insert between DNA base pairs -> uncoil DNA helix -> inhibit DNA + RNA synthesis
- May also inhibit polymerase (catalyzes formation of new DNA and RNA from existing strand of DNA or RNA)
- Example: Doxorubicin
- Oncology
Define a druge that is an Alkylating agent + antitumour antibiotic
- Drug: Streptozocin
- Undergoes spontaneous decomposition -> reactive methylcarbonium ions -> alkylate DNA -> interstrand cross links -> inhibits mitosis
- Nitrosurea specific for beta and exocrine cells of pancreas due to an attached suar moiety
- Naturally occurring methylnitrosurea produced from fermentation of Streptomyces archromogenes (Is a natural occuring)
- Oncology
