Description

Phenylpropanolamine has been withdrawn in Canada and the United States. In November 2000, the Food and Drug
Administration (FDA) issued a public health advisory against the use of the drug.

Pharmacology
Indication

For the treatment of nasal congestion, control of urinary incontinence, priapism and obesity.

Pharmacodynamics Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat
nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in
cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products
containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used
phenylpropanolamine.
Mechanism of
action

Phenylpropanolamine acts directly on alpha- and, to a lesser degree, beta-adrenergic receptors in the mucosa of the
respiratory tract. Stimulation of alpha-adrenergic receptors produces vasoconstriction, reduces tissue hyperemia,
edema, and nasal congestion, and increases nasal airway patency. PPA indirectly stimulates beta-receptors,
producing tachycardia and a positive inotropic effect.

Absorption

Reduced bioavailability (about 38%) from gastrointestinal tract because of first pass metabolism by monoamine
oxidase in the stomach and liver.

NAME

CHLORPHENAMINE

Accession Number

DB01114 (APRD00001, DB09440)

Type

Small Molecule

Groups

Approved

Description

A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used
in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less
drowsiness and sedation than promethazine. [PubChem]

Pharmacology
Indication

For the treatment of rhinitis, urticaria, allergy, common cold, asthma and hay fever.

Pharmacodynamics In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils.
Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to
cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once
released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H 1-

receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction.
Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonis
(or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal
H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides
effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper
respiratory allergies.
Mechanism of
action

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which
subsequently leads to temporary relief of the negative symptoms brought on by histamine.

Absorption

Well absorbed in the gastrointestinal tract.

NAME

METHYLPREDNISOLONE

Accession Number

DB00959 (APRD00342)

Type

Small Molecule

Groups

Approved

Description

A prednisolone derivative with similar anti-inflammatory action

Pharmacology
Indication

Adjunctive therapy for short-term administration in rheumatoid arthritis.

Pharmacodynamics Methylprednisolone and its derivatives, methylprednisolone sodium succinate and methylprednisolone acetate, are
synthetic glucocorticoids used as antiinflammatory or immunosuppressive agents.
Mechanism of
action

Unbound glucocorticoids cross cell membranes and bind with high affinity to specific cytoplasmic receptors,
modifying transcription and protein synthesis. By this mechanism, glucocorticoids can inhibit leukocyte infiltration at
the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune
responses. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory
proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and
leukotrienes.

Absorption

Oral bioavailability 80-99%

Name

Acetaminophen

Accession Number

DB00316 (APRD00252)

Type

Small Molecule

Groups

Approved

Description

Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic
effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet,
and gastric ulcerative effects

Indication

For temporary relief of fever, minor aches, and pains.

Pharmacodynamics Acetaminophen (USAN) or Paracetamol (INN) is a widely used analgesic and antipyretic drug that
is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient
in numerous cold and flu medications and many prescription analgesics. It is extremely safe in
standard doses, but because of its wide availability, deliberate or accidental overdoses are not
uncommon. Acetaminophen, unlike other common analgesics such as aspirin and ibuprofen, has
no anti-inflammatory properties or effects on platelet function, and it is not a member of the class
of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. At therapeutic doses
acetaminophen does not irritate the lining of the stomach nor affect blood coagulation, kidney
function, or the fetal ductus arteriosus (as NSAIDs can). Like NSAIDs and unlike opioid analgesics,
acetaminophen does not cause euphoria or alter mood in any way. Acetaminophen and NSAIDs

have the benefit of being completely free of problems with addiction, dependence, tolerance and
withdrawal. Acetaminophen is used on its own or in combination with pseudoephedrine,
dextromethorphan, chlorpheniramine, diphenhydramine, doxylamine, codeine, hydrocodone, or
oxycodone.
Mechanism of
action

Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting
both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin
(PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral
tissues and, thus, has no peripheral anti-inflammatory affects. While aspirin acts as an irreversible
inhibitor of COX and directly blocks the enzyme's active site, studies have found that
acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of
peroxides. This might explain why acetaminophen is effective in the central nervous system and in
endothelial cells but not in platelets and immune cells which have high levels of peroxides. Studies
also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme
that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as
COX-3. Its exact mechanism of action is still poorly understood, but future research may provide
further insight into how it works. The antipyretic properties of acetaminophen are likely due to
direct effects on the heat-regulating centres of the hypothalamus resulting in peripheral
vasodilation, sweating and hence heat dissipation.

Absorption

Rapid and almost complete