‫معهد واكادميية النهال‬ DR.

Marwan Imad
Analgesics
OPIOIDS
MORPHINE

Morphine contains 5 chiral centers and has 16 optical isomers. The naturally occurring,
active form of morphine is the levorotatory enantiomorph The first mention of the opium
poppy was found in Iraq on clay tablets inscribed in cuneiform script in about 3000 BC.
Morphine is extensively metabolized via phase II conjugation to morphine-3-glucuronide
(60%), morphine-6- glucuronide (9%), and, to a lesser extent, the N-demethylated
metabolite (3%). Morphine, or another potent opioid drug, is introduced in the WHO
stepladder when pain is severe and no relief is obtained from NSAIDs or a combination of
NSAIDs and a less potent opioid.

CODEINE

Most commercial codeine is prepared from morphine by methylating the phenolic OH

group. It occurs as levorotatory, colorless, efflorescent crystals, or as a white crystalline
powder. It is light sensitive.
The general pharmacological action of codeine is similar to that of morphine, but it
does not possess the same analgesic potency.

HEROIN
Heroin is the 3,6 diacetylated form of morphine heroin can pass through the blood-brain
barrier quicker than morphine and lead to the euphoric “rush” that becomes so addictive to
addicts, especially after IV injection. Once heroin is in the brain, it is quickly metabolized to
3-acetylmorphine.

DEXTROMETHORPHAN
It is available in more than 140 over-the-counter (OTC) cough and cold formulations.

DIPHENOXYLATE
Is a weak opioid agonist and is available combined with atropine (Lomotil) for use
as an antidiarrheal agent.
 ‫معهد واكادميية النهال‬ DR.Marwan Imad
LOPERAMIDE
It acts as an antidiarrheal by directly binding to the opiate receptors in the gut wall. Loperamide
inhibits acetylcholine and prostaglandin release, decreasing peristalsis and fluid secretion.

Opioid Antagonists
NALOXONE
Naloxone is a pure antagonist at all opioid receptor subtypes.

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

All classes of NSAIDs strongly inhibit prostaglandin synthesis in various tissues, especially at the
site of the tissue damage or inflammation by inhibiting cyclooxygenase 1 and 2.

Structure–Activity Relationships of NSAIDs

It is well established that the therapeutic potency of the conventional NSAIDs are highly
correlated with their ability to induce upper GI toxicity. But, are all NSAIDs other than
coxibs really equally effective in the treatment of pain and inflammation? Some insight
might be found by exploring how these chemically diverse classes of drugs bind to their
molecular targets (i.e., their selectivity for COX-2 relative to COX-1). Thus, the benefit/risk
profile of individual NSAIDs, as reflected by their COX selectivity, may be more clinically
relevant for predicting the risk of GI complications.
Most of them posses carboxylic moiety which attached directly or indirectly to aromatic ring.
To enhance their lipophilicity an alkyl chain added.
 ‫معهد واكادميية النهال‬ DR.Marwan Imad

Benzodiazepines

Aromatic or heteroaromatic ring A is required for the activity. An electronegative substituent at

position 7 is required for activity, and the more electronegative it is, the higher the activity. Positions
6, 8, and 9 should not be substituted. A phenyl ring C at position 5 promotes activity. If this phenyl
group is ortho (2) or diortho (2,6) substituted with electron-withdrawing groups, activity is increased.
On the other hand, para substitution decreases activity greatly. In diazepine ring B, saturation of the
4,5-double bond or a shift of it to the 3,4-position decreases activity. Alkyl substitution at the 3-
position decreases activity; substitution with a 3-hydroxyl does not. The presence or absence of the
3-hydroxyl group is important pharmacokinetically.
 ‫معهد واكادميية النهال‬ DR.Marwan Imad
Compounds without the 3-hydroxyl group are nonpolar, 3-hydroxylated in liver slowly to active
3-hydroxyl metabolites, and have long overall half-lives. In contrast, 3-hydroxyl compounds are
much more polar, rapidly converted to inactive 3-glucuronides, which are excreted in urine and
thus are short-lived. The 2-carbonyl function is important for activity, as is the nitrogen atom at
position 1. The N1-alkyl side chains are tolerated. A proton-accepting group at C2 is required.
Other triazole or imidazole rings capable of H-bonding can be fused on positions 1 and 2
and increase the activity.

Diazepam

Barbiturates

The replacement of both hydrogens at position 5 with alkyl or aryl groups confers the
activity. Both hydrogen atoms at the 5-position of barbituric acid must be replaced.
Consequently, the compound is largely in the anionic form at physiological pH, with little
nonionic lipid-soluble compound available to cross the blood-brain barrier. Beginning with
lower alkyls, there is an increase in onset and a decrease in duration of action with
increasing hydrocarbon content up to about seven to nine total carbon atoms substituted on
the 5-position. It is because that lipophilicity and an ability to penetrate the brain in the first
case and an ability to penetrate liver microsomes in the second may be involved. In addition
for more lipophilic compounds, partitioning out of the brain to other sites can be involved in
the second instance. There is an inverse correlation between the total number of carbon
atoms substituted on the 5-position and the duration of action.
 ‫معهد واكادميية النهال‬ DR.Marwan Imad
Absorption from the GI tract is good. Binding to blood proteins is substantial. Compounds with low
lipophilicity may be excreted intact in the urine, whereas highly lipophilic compounds are excreted
after metabolism to polar metabolites. Increasing the lipophilicity generally increases the rate of
metabolism, except for compounds with an extremely high lipophilicity (e.g., thiopental). N-
methylation decreases duration of action. 2-Thiobarbiturates have a very short duration of action
because its lipophilicity is extremely high, promoting depotization. Barbiturates find use as sedatives,
as hypnotics, for induction of anesthesia, and as anticonvulsants.
‫معهد واكادميية النهال‬ ‫‪DR.Marwan Imad‬‬