Analgesics
also called painkillers, are medications that relieve different types of pain
Opoids
Opioids are a broad group of painrelieving drugs that work by
interacting with opioid receptors in
your cells. Opioids can be made
from the poppy plant — for
example, morphine (Kadian, Ms
Contin, others) — or synthesized in
a laboratory — for example,
fentanyl (Actiq, Duragesic, others).
Ex. Morphine
SAR
free phenolic group leads to first pass
glucuronidation which results in poor bioavailability
3ry amine is important for activity
N-Methyl substitution shows good agonist activity
Increasing the number of carbon in substitution on
nitrogen or having a double bond or small carboxylic
ring gives antagonist activity
Metabolism
The metabolism of morphine occurs not only in
the liver, but may also take place in the brain and
the kidneys. The glucuronides are mainly
eliminated via bile and urine. Glucuronides as a
rule are considered as highly polar metabolites
unable to cross the blood-brain barrier
NSAIDs
Nonsteroidal anti-inflammatory
drugs (NSAIDs) are medications that
relieve or reduce pain. The most
popular examples of drugs in this
group are aspirin and ibuprofen
Adjuvant Drugs
An adjuvant analgesic, or coanalgesic, is a
medication that is not primarily designed to
control pain but can be used for this
purpose. Some examples of adjuvant drugs
are antidepressants (which are typically used
for mental health conditions) and
anticonvulsants (used in the treatment of
seizure disorders)
Ex: Aspirin
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Substitution on carboxyl groups may affect the
potency and toxicity.
Reducing the acidity of the -COOH, retains the
analgesic action of salicylic acid , but it is devoid of
the anti- inflammatory properties.
Placing the phenolic hydroxyl group, meta or para
to the carboxyl group abolishes the activity.
Substitution of halogen atoms on the aromatic ring
enhances potency and toxicity.
Substitution of aromatic rings at the 5 position of
salicylic acid increases anti-inflammatory activity.
Metabolism
aspirin has a very short half-life. Salicylate, in turn,
is mainly metabolized by the liver. This
metabolism occurs primarily by hepatic
conjugation with glycin or glucuronic acid, each
involving different metabolic pathways. The
predominant pathway is the conjugation with
glycin, which is saturable
Done by:
Saba Alkathiri 441200466
Ex: Dexamethasone
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Hydroxy substitution required for
glucocorticoid activity
Substitution on 16 position tends to decrease
mineralocorticoid activity
21-OH required for mineralocorticoid activity
but not an absolute requirement for
glucocorticoid activity
Metabolism
Dexamethasone (DEX) is extensively metabolized
to 6-hydroxyDEX (6OH-DEX) and side-chain
cleaved metabolites in human liver both in vitro
and in vivo with CYP3A4 responsible for the
formation of 6-hydroxylated products.