Download Drug action via direct enzymatic activity or the activation of enzymes

Drug action via direct enzymatic activity or the activation of enzymes. Just as some drugs may act by inhibiting
enzymes, so others may activate enzymes or may themselves act as enzymes.
a) Enzyme replacement in genetic and acquired enzyme deficiencies. Genetic diseases whìch are due to enzyme
deficiencies should theoretically be susceptible to treatment by replacement therapy, although treatment of this kind
is limited by the difficulty of delivering enzymes to their sites of action. However, clotting factor deficiencies can be
treated in this way, the best examples being the parenteral use of factor VIII in patients with haemophilia and of
fresh frozen plasma in treating overdose with warfarin. Another example is the oral use of pancreatic enzymes in
treating malabsorption in patients with chronic pancreatic insufficiency.
b) Drugs acting on the clotting system. The clotting and fibrinolytic factors are enzymes, and certain drugs which act
on clotting and fibrinolysis do so by increasing their activity. Heparin acts as an anticoagulant by activating
antithrombin III. Streptokinase, urokinase, alteplase, and anistreplase are activators of plasminogen and thus cause
clot lysis. Snake venoms, such as ancrod (Malayan pit viper venom), have thrombin-like activity and thus activate
clotting.
c) Cancer chemotherapy. L-saparaginase is an enzyme which hydrolyses asparagines, the consequent depletion of
which in leukaemic cells may be of therapeutic benefit in some patients with acute lymphoblastic leukaemia. Other
enzymes which act on amino acids, folate, or RNA are also under study.
d) Other examples of drugs which activate or replace enzymes include pralidoxime,
which activates cholinesterase in poisoning with organophosphorus insecticides, and danazol and stanozolol,
which increase the activity of the C1 esterase inhibitor in patients with hereditary angiooedema. The enzyme
superoxide dismutase has been used in the treatment of paraquat poisoning, and it may also eventually
prove useful in treating inflammatory conditions.
1. Which is not an application of a drug that is an enzyme, or one that works by activating enzymes?
a. Enzyme replacement in genetic and acquired enzyme deficiencies
b. Enzyme inhibition in hyperparathyroidism
c. Drugs acting on the clotting system
d. Cancer chemotherapy
e. Treatment of poisoning or inflammatory conditions
2. What makes it difficult to replace enzymes in genetic diseases caused by enzyme deficiencies?
a. It's not easy to identify the proper enzyme.
b. It's not clear whether oral or intravenous administration is better.
c. It's hard to deliver enzymes to their sites of action.
3. Certain drugs that aid clotting and fibrinolysis
a. increase the activity of the enzymes involved
b. decrease the activity of the enzymcs involved
c. block the activity of the enzymes involved
4. A drug that works to promote clotting has a frightening source:__________________
5. Is it certain that L-saparaginase is useful in treating acute lymphoblastic leukaemia?
a. ves
b. no
6. What drug is used to treat insecticide poisoning?
a. cholinesterase
b. pralidoxime
c. organophosphorus
d. danazol
7. Superoxide dismutase, used to treat paraquat poisoning,
a. activates an enzyme.
b. replaces an enzyme.
c. is an enzyme.
Risposte: 1. B 2. C
3. A
4. ANCROD
5. B
6. B
7. C
New molecules have immense potential in the pharmaceutical and chemical industries, which have already invested
millions in databases to help them make faster and better quality research decisions. It's therefore no surprise to find
that the Unilever Center's director, Professor Bobby Glen, has been tempted back from the USA, where he made his
name co-inventing the anti-migraine drug, Zomig, and developing new treatments for glaucoma.
"New data in all the sciences are being captured increasingly on computers" says Glen, "so we can move information
around the scientific community more effectively than ever before. The problem is that over ninety per cent of
scientific findings remain unknown to the majority of scientists. The major advances of the future will depend on our
ability to handle masses of information. The beauty of informatics is that it enables us to access what we already
know, and to work more creatively - and at a much greater level of complexity - than we could have imagined even
five years ago."
According to Glen, the Center will provide on-line access to molecular data to scientists all over the world and allow
research that once took several years to be completed in an afternoon.
Glen has just fifteen staff in his shiny new building at present, but he expects that tally to double by the end of the
year. One key recruit he’ll be welcoming is Professor Chris Dobson, currently relocating from Oxford with his entire
"dark blue" team to a purpose-built lab in Cambridge. Dobson's research focuses on protein-folding, a specialization
with urgent medical implications. " Many debilitating conditions, including cystic fibrosis, Alzheimer's and new variant
CJD, are associated with the failure of proteins to achieve or maintain a biologically active fold after they're
synthesized in our cells," he explains.
"We're trying to discover why such "mis-folding" diseases occur so we can find ways of preventing or curing them."
1) Why is Dr. Glen famous?
a. he has invested millions in databases
b. he is the director of the Unilever Center
c. he helped invent drugs for treating migraines and glaucoma
d. he increasingly captures new data on computers
2. What does he identify as the problem for scientists?
a. most scientists don't know about 90% of scientific findings
b. the scientific community doesn't move effectively
c. scientists deal with masses of information
3. What isn't the beauty of informatics for Dr. Glen?
a. it helps us find information that is already known
b. it helps us communicate by internet
c. it lets us work faster and more creatively
4. What does Glen say Unilever will offer scientists worldwide?
a. a new building for staff
b. molecular data on-line
c. custom-built labs for protein-folding
5. How many people work for Dr. Glen now?
a. 5
b. 50
c. 15
d. several
6. How many people does he expect will work for him by December?
a. 5
b. 45
c. 30
d. several dozen
7. Who is Chris Dobson?
a. Dr. Glen's boss
b. Dr. Glen's new employee
Risposte: 1. C 2. A
3. B
4. B
5. C
6. C
c. a Cambridge University professor
7. B
Systemic availability (commonly known as bioavailability) is a term used to describe the proportion of the
administered drug that reaches the systemic circulation and is thus available for distribution to the site of action. The
term is usually applied in reference to formulations given by the oral route, although it can also refer to other routes
of administration, such as intramuscular or transdermal. When an intravenous dose of a drug is given it al enters the
systemic circulation. It thus has a systemic availability of 100 per cent. From the plot of plasma concentration of the
drug against time, with or without urinary or other tissue drug concentration analyses, the way the body handles the
drug (its pharmacokinetics) can be defined.
When a liquid solution of the drug is given orally, all the drug is theoretically available to the gastrointestinal mucosa
for absorption. The plot of plasma concentration versus time, and analysis of the concentrations of drug and its
metabolites in the urine compared with the corresponding intravenous data, will give an index of the degree of
absorption and the metabolic effect of the liver as it passes through for the first time (the so-called 'first-pass
effect').
When a tablet or capsule is given orally, by following the plot of plasma concentration versus time, and the
cumulative urinary excretion of the drug and its metabolites, and by comparing these data with those collected after
dosage with a liquid form, one can define those factors intrinsic to the formulation that affect its ultimate systemic
availability. These factors include the rate of disintegration of the tablet and the rate of dissolution of the drug
particles in the intestinal fluid. This may be termed 'pharmaceutical availability.'
1. Usually bioavailability refers to
a) drugs administered orally
c) drugs administered transdermally
b) drugs administered intramuscularly
d) drugs administered intravenously
2. What is another name for bioavailability? _______________________
3. What is a word for how the body absorbs the drug over time? _________________________
4. When a drug is given intravenously,
a) a sizeable part of it enters the systemic circulation
b) all of it enters the systemic circulation
c) a small proportion of it enters the systemic circulation
5. How the body handles a drug is measured by plotting the concentration of the drug in the blood at
varying __________________________
6. When a drug is administered in a solution orally, in order to understand the degree of absorption and
the metabolic effect of the liver as the drug passes through for the first time, what analyses are done? There are
two answers.
a. analysis of absorption by the gastrointestinal mucosa
b. the plot of plasma concentration versus time
c. analysis of the concentrations of drug and its metabolites in the urine compared with the corresponding
intravenous data
d. tissue drug concentration analyses
7. When a drug is given as a tablet or capsule, what factors in its formulation determine its pharmaceutical
availability? There are two answers.
a. the plot of plasma concentration of the drug against time
b. the rate of disintegration of the tablet
c. the 'first-pass effect'
d. the rate of dissolution of the drug particles in the intestinal fluid.
Risposte: 1. A 2. systemic availability 3. pharmacokinetics
4. B
5. times6. B,C
7. B,D