Introductory Pharmacology

  • Created by: LBCW0502
  • Created on: 02-04-18 14:54
What is pharmacology?
The branch of medicine concerned with the uses, effects and modes of action of drugs (concerned with the science of drugs - design, synthesis, measurement, mechanisms, ADME)
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What is pharmacy?
The science or practice of the preparation and dispensing of medicinal drugs (concerned with handling drugs - preparing, preserving, compounding, dispensing)
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What are therapeutics?
The branch of medicine concerned with the treatment of a disease and the action of remedial agents (concerned with medicinal use of drugs - remedies for diseases, used to ameliorate symptoms of disease)
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What is toxicology?
The branch of medicine concerned with the nature, effects and detection of poisons (concerned with unwanted drug effects - toxic effects of drugs, actions of poisons, hazardous unwanted effects of therapeutic drugs)
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What is a drug?
A chemically defined agent that can be used to provoke a measurable response in a biological system (can be therapeutic or abused)
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Give examples of therapeutic drugs
Aspirin, penicillin, propanolol, furosemide
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Give examples of abused drugs
Cocaine, alcohol, LSD, MDMA, amphetamine
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Give examples of drugs which are both therapeutic and abused
Cannabinoids, morphine and tamazepam
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Conventional drugs have at least how many names?
Three
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Describe features of the nomenclature of drugs
Proprietary name (brand name), common name and chemical name (drugs are usually grouped into therapeutic use e.g. analgesic or mechanism of action e.g. COX inhibitor)
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What is a drug and how do they work?
Drugs are exogenous molecules, mimic/block action of endogenous molecules/systems. Although derived from exogenous source, a given drug might be: chemically identical to an endogenous molecule or chemically distinct from any known endogenous molecule
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Describe features of drugs and their receptors
The concept of the receptor is central to pharmacology. Receptors have specific binding sites for a drug. Lock and key model
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What are physiological receptors?
Endogenous proteins that are receptors for endogenous chemical signalling compounds such as hormones or neurotransmitters. Many drugs bind to such receptors
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What are other proteins (pharmacological receptors?)
Enzymes and ion channels. Drugs may bind to specific sites on proteins and prevent them from doing their job, or less commonly, they may stimulate them e.g. ion channel membrane may be blocked or opened
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What are nucleic acids (pharmacological receptors)?
Drugs may bind to regulatory sites in nucleic acids to influence gene expression or protein synthesis
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What is an agonist?
A drug with occupies receptors and active them
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What is an antagonist?
A drug that occupies receptors but does not activate them
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Which factors determine the primary effects of a drug?
The type of binding site and the nature of the interaction of the drug with its binding site on the receptor
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Give an example of a reversible drug interaction
Interactions between drug and receptor binding site mediated by ionic attractions or hydrophobic interactions
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Give an example of an irreversible drug interaction
Interactions between drug and receptor binding site mediated by covalent bonds
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What is pharmacodynamics?
What a drug does to an organism - the sum of all actions of a drug
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What is pharmacokinetics?
What the organism does to the drug - ADME - determines how quickly a drug acts in a patient
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Describe features of absorption
Considers how much drug enters the system and how quickly the drug enters the system
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Which factors influence the amount of drug absorbed and speed of absorption?
Molecule size, lipid solubility, ionisation, chemical and metabolic vulnerability
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Give examples of routes of administration?
Inhalational, intra-arterial, intradermal, intramuscular, intrathecal, intracerebroventricular, intravaginal, intravenous, nasal, oral, rectal, subcutaneous, sublingual, topical, transcutaneous
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Which properties of the subject/patient affects the amount of drug absorbed and speed of absorption?
Fat/thin, light/heavy, fed/empty stomach, healthy/infirm
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Describe features of distribution
Considers where the drug goes after it has been absorbed (local or systemic)
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In order to achieve its effects, what is the drug required to do?
Diffuse through tissue or be carried in the blood
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Which factors are considered for the distribution of a drug?
Is the drug soluble in blood? Does the drug stick or proteins/cells in the blood? Will the drug concentrate in fats or in aqueous environment? Does the patient have an adequate circulation?
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Describe features of drug metabolism and drug excretion?
Considers how long the effects of the drug last
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Which factors are considered for drug metabolism and excretion?
How long does the effect last, is the duration of action reduced when metabolised (liver), if drug is excreted rapidly, it many have a short duration of action
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What other questions are considered for metabolism and excretion?
Where is the drug metabolised (does the patient have a healthy liver)? How is the drug excreted (does the patient have good kidneys)? Are metabolites active? Are metabolites toxic?
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Describe features of drug properties and structure
Small changes in chemical structure alter both PK and PD properties of a drug (e.g. salicylic acid to acetyl salicylic acid, methyl salicylate to diflusinal)
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Describe the history of drugs as medicines (1)
4000BC (euphoria from extract of opioid Poppy plant). 2375BC (Ephedra, stimulant/respiratory disease). 1550BC (herbal drugs). 460BC (practice medicine). 240AD (pharmacology). 1809 (nux vomica, spinal cord). 1842 (curare, ACh receptors, antagonist)
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Describe the history of drugs as medicines (2)
1878 (modern pharmacology). 1905/6 (receptors). 1930s (pharmacology, biological responses)
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Describe features of experimental pharmacology
Human Genome Project. Identify all genes in human DNA. Develop genetic linkage map of human genome. Know function of genes. Develop tools fo data analysis. Transfer related technologies to private sector
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What are the consequence of the human genome being deciphered?
Pharmaceutical industries aimed to develop custom based drug treatments
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Pharma companies fall into which two overlapping categories?
Sell drugs that are not protected by patients (sell cheap versions of common drugs/no extensive research/don't develop new drugs). Those with extensive research facilities (global corporations)
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What are the three points for the drug discovery model?
Basic research hypothesis (at the bench), idea and hypothesis
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What are assay systems?
Measurement systems - devised to identify chemical tools to test the hypothesis
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Give examples of test chemicals
Natural products (e.g. from plants/animals). From chemical libraries of compounds held/bought by the company. From techniques in combinational chemistry (generates large numbers of chemical in laboratory)
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Outline the process of pre-clinical drug development
Idea, basic research, hypothesis, assay systems, test hypothesis in animal model, change chemical structure of active compound (test for PK properties/toxic effects)
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How long does it take for an original idea to become a drug candidate?
5-10 years or longer
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Describe features of clinical drug development
Divided into four phases (or 5 if phase 0 is counted). At all stages, patients are monitored for side effects and information on drug safety is gathered as a priority
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Describe features of phase 0
Transitional phase between pre-clinical testing stage and full clinical trials. Sub-therapeutic doses monitored for unexpected effect. Phase more commonly used in development for chemotherapeutic agents for cancer treatment
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Describe features of phase I
Small scale, 20-80 healthy volunteers, find dose/tolerability, larger doses given until effect registered, estimate amount of drug needed without side effects, several rounds, different groups
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Describe features of phase II
Medium size, 100-300 patient volunteers, drug tested for effectiveness against specific disease (for indication), several studies
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Describe features of phase III
Large scale, 1000-3000 patients, test for effectiveness, compare with other available treatments, if drug survives, drug can be registered/sold as therapeutic agent, several trials (need confidence in phase III due to cost)
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Describe features of Ecuadorian frog
Secretes epibatidine (a putative alkaloid), discovered as analgesic, causes numbness and eventually paralysis (deadly at very low doses), nicotinic and muscarinic ACh receptor agonist
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Describe features of leeches
Hirudin is a naturally occurring peptide in salivary glands of medicinal leeches. Blood anti-coagulant activity, thrombin inhibitor
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Describe features of monks hood
Most common poisonous garden plants. Interacts with voltage dependent Na ion channels. Uses in very small doses as an analgesic. Causes channel to stay open longer (results in nausea, vomiting, and heart arrhythmias)
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Describe features of penicillin
Found on salted food products, source of several antibiotics, mould spores discovered in bacterial specimens (petri dish). When analysed under microscope, bacteria under mould spores appear to be dying (prevents bacteria from reproducing)
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Describe features of willow bark
Salicylic acid (used to removed outer layer of skin), used to treat warts, psoriasis, acne, ringworm, aspirin is the starting material
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Describe features of opium poppy
Species of flowering plant. Used to produce opium in pharmaceutical industry. Produces alkaloids (process codeine and oxycodone). Morphine activates bodies endogenous opioid receptors to cause analgesia
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