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SIB2007 1 & 2

Principles of Pharmacoloy

What is Pharmacology? Study of drugs on living systems (in relation to therapeutics and toxicology).
What is Pharmacodynamics? Molecular, biochemical, and physiological effects of drugs on cellular systems and their mechanisms of action.
What is Pharmacokinetics? Absorption, distribution, metabolism, excretion
What are drugs? Substances or chemicals.
What is medicine? Formulation of a drug that can be administered in a correct dose to produce a reproducible response in the body.
What are drugs used for? Alleviate symptoms, eg aspirin for pain Cure disease, eg antibiotics to clear infection Disease prevention, eg flu vaccine Aids to other procedures, general anaesthetics during surgery Lifestyle aids, eg oral contraceptives, HRT, vitamins.
What are the desired criteria for drugs? To use a drug that is easy and safe to administer That acts with high specificity—potency at low dose That acts with appropriate duration to give the max advantage and min damage/side effects to the body Low cost availability.
What are some of the types of formulations? Tablets Syrups Capsules Sprays Aerosols Patches Injections suppositories
Why formulation? To provide a product that can be administered To remain stable To allow for reliable dosing
What is the process of development? Up to 12 years: Isolation, purification of a chemical Pre-formulation: identify physico-chemical properties Formulation Pre-clinical research Clinical research Marketing & registration Post-marketing surveillance and development—drug withdrawal ca
What are clinical trials? Phase I: 50-100 healthy individual Phase II: 200-400 patients Phase III: 3000 and higher patients Licensing regulations and ethical committees are in force to prevent harm and protect patients.
How do drugs act? Access to receptor Binding to receptor Binding sites are drug targets
What are the types of drug action? Specific action on recognition sites (Most drugs) Non-specific action (Some drugs)
What are the targets for drug action? Specific macromolecules Protein in nature (except for DNA
What can protein targets for drug action be divided into? Receptors Ion channels carrier proteins enzymes DNA -- for cancer chemotherapeutics
Receptors were first proposed by...? Paul Ehrlich (1872)
"Receptors are switches which could be activated or blocked by specific molecules" John Langley (1905)
What is the "Receptor Theory"? applied laws of thermodynamics to drug-receptor interactions.
Who founded the "Receptor Theory" and when? Alfred Clark (1937)
What are some examples of drug acting on receptors? Histamine receptors: H1 receptors –blockade by antihistamines results in treating allergic and inflammatory response H2 receptors, blockade by antihistamines results in treating peptic ulcer
What is the specific action of drug on ion channels and where are they located? Pores in cell membrane can open/close to allow/prevent passage of ions down their conc gradient. Open/close of channels depends on structure of macromolecule protein forming the pore and the drugs that may bind to different sites of this macromolecule.
What are some examples of drug action on ion channels? Benzodiazepines Calcium channel blockers, such as verapamil Local anaesthetics such as lignocaine and amethocaine
What is Benzodiazepines used as? As an anti-anxiety hypnotic + anti-convulsant agent, increase conductance of Chloride ions by ^ing frequency of Chloride channel opening/extending opening time of channel making inside cell more neg(-) than outside + less likely for cells to get excited.
What are calcium channel blockers used as? Used in patients with angina and supraventricular arrhythmias, inhibit the entry of Ca2+ into cardiac and vascular cells leading to a reduction in contraction.
How do local anaesthetics exert their action? By blocking Na+ channels.
What is the specific action of drugs on carrier proteins and where are they located? Located in the cell membrane or intracellular organelles. Transfer materials against their concentration gradient (active transport process) by using energy from the cell.
What are examples of carrier proteins? Sodium pump Sodium chloride cotransporters
What is a sodium pump? pumps Na+ out and K+ into cells by using ATP (Na+/K+ ATPase, which splits ATP and releases energy). The action of pump can be inhibited by cardiac glycosides, eg digoxin in patients with heart failure.
How can sodium chloride cotransportersin the kidney be inhibited by Can be inhibited by: -thiazide diuretics, e.g. chlorothiazide -and loop diuretics, e.g. frusemide Both the above are used in patients with heart failure
What are specific actions of drugs on enzymes? Enzymes are macromolecular proteins that catalyze or speed up the rate of chemical reaction in the organism. Drugs can bind to the enzymes and inhibit or interfere with their action.
What are some examples of drug action on enzymes? Aspirin inhibits cyclo-oxygenase enzyme. Some diuretics inhibit carbonic anhydrase. Some antibiotics interfere with the synthesis of DNA of bacteria. Nitrates used in patients with angina activate the guanylate cyclase enzyme in blood vessels.
What does the inhibition of the cyclo-oxygenase enzyme lead to? Aspirin inhibits cyclo-oxygenase enzyme leading to inhibition of formation of prostaglandins (local mediators).
Which enzyme does aspirin inhibit? Cyclo-oxygenase enzyme
What does the inhibition of carbonic anhydrase lead to? An increase in urine output.
Which enzyme do some diuretics inhibit? Carbonic anhydrase.
What do some antibiotics interefere with? The synthesis of DNA of bacteria.
What does the activation of the guanylate cyclase enzyme result in? It results in an increase in formation of cyclic GMP leading to relaxation of the wall of blood vessels thus more blood can flow to supply the heart muscles.
Which enzyme do nitrates activate? Guanylate cyclase enzyme.
What are specific actions of drugs on DNA? Drugs may bind to DNA and modify their replication in cell division process.
What is an example of a drug that can bind to DNA and modify their replication in cell division process? Anti-cancer drug, cis-platin
What are the characteristics that non-specific action of drugs feature? 1. Exhibit poor structural relationship 2. Required in high concentration (mM)
What are some examples of non-specific drug actions 1. General anaesthetics 2. Some laxatives 3. Some diuretics
What are some of the effects of general anaesthetics? Work by diminishing the activity of the excitable tissues by dissolving in membrane. Their potency correlates well with degree of lipophilicity. Brain areas associated with consciousness are very sensitive.
What are some of the effects of laxatives and diuretics? Bulking effects, methylcellulose, bran Mannitol diuretics, faecal lubricants
What type of effects do drugs have? Beneficial or therapeutic Adverse
What are beneficial/therapeutic effects? Results from binding of a drug to sites with a high affinity,i.e. drugs show high affinity for a specific site, seen in most subjects
What are adverse effects? Results when drugs bind to sites that are not desired, may be seen in some individuals depending on genetic factors (variation in metabolism leads to idiosyncratic response, i.e. difficult to predict)
What is an example of a beneficial and adverse drug effect mediated by the same mechanism? Hypoglycaemia induced by insulin; anticoagulsny-induced bleeding.
What is an example of a beneficial and adverse drug effect mediated by the same mechanism but in different tissues? Cancer drugs kill both cancer and healthy tissues; corticosteroids reduce inflammation but induce adverse effects by modifying metabolism.
What is an example of a beneficial and adverse drug effect mediated by different mechanisms? anti-allergic action but also has anti-muscarinic effects; paracetamol as a pain killer but also damages liver; ibuprofen as a painkiller also damages the kidney.
What is the therapeutic index also known as? Therapeutic ratio.
What is the therapeutic index by comparison? A comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount thay causes toxic effects.
What is the therapeutic index quantitatively? Ratio given by the toxic dose divided by the therapeutic dose.
Which is preferable, a high or low therapeutic dose and why? High because it corresponds to a situation in which one would have to take a much higher amount of drug to do harm than the amount taken to do good.
What does a narrow margin mean on the therapeutic index? More likely it is that the drug will produce unwanted effects.
What does TDM stand for? Therapeutic drug monitoring.
What generally happens to a drug with a narrow therapeutic range? May have its dosage adjusted according to measurements of the actual blood levels acheived in the person taking it through TDM.
What is the specific action of drugs on receptors and where are they located? Most common site for the action of drugs Located on the cell membrane; receptors for steroids (lipophilic molecules) are located inside the cell.
Created by: Groberts00



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