Chemistry and Pharmacy of

Organic Medicinals
Prepared by: Guada Marie O. Ruiz, RPh, DHA-RPh
Topics up ahead...
Definition, Classification, Structure-activity relationship,
preparations and uses of:

• Sulfonamides
• Antimalarials
Pharmacologic classification:
• Based on mechanism of action
• Describe drug’s properties
Structure activity relationship:
• The structure of a compound determines the
biological effects it has
• Determination of structure-function
relationships helps medical
chemists/pharmacists to synthesize new drugs
and pharmaceutical agents
Pharmaceutical preparation
• Formulation into dosage forms

Two types of Pharmaceutical formulation

Manufactured - large scale pharmaceutical industry
Compounded - individually compounding pharmacies
(Extemporaneous preparation)
Click to add text
 Sulfonamide
Have bacteriostatic action against gram positive & gram negative bacteria
Quick review:
History
• Experiments with Prontosil began in 1932 in the
laboratories of Bayer AG.
• Gerard Domagk studied bright red dye,
Prontosil.
MOA:
How resistance is developed?
• Sulfonamides are competitive inhibitors for the
enzyme, the bacteria can increase the production of
PABA to compete with sulfonamide at the active site
and become resistant to sulfa drugs.
• In such case, the dose of sulfonamide agents should
be increased to overcome this resistant mechanism.
But this high dose is accompanied with an increase in
side effects especially the crystalluria.
General structure of sulfonamide
Para-amino
group

N1
substitution

Aromatic ring
Sulfonamide
group
1. Para-amino group
• Essential for the activity and must be unsubstituted
(except: mefenide)
• It should always be situated on para position of
aromatic ring otherwise antibacterial activity is lost.
• Can be substituted with amides.
Just a quick review...
2. Aromatic ring
• Minimal requirement
• Important for activity
• Should always be para substituted
• Other substitution deemed sulfonamide inactive
loss of activity.
3. Sulfonamide group
• essential for antibacterial activity
• sulfur atom should be directly linked to aromatic ring
• Substitution of free sulphonic acid (-SO3-H) destroys activity
• Replacement of sulphinic acid (-SO2H) and acetylation at N4
position retains activity
4. N1 Substitution
• Sulfonamide nitrogen should be primary or secondary.
• R could be substituted with hydrogen, aromatic ring, or
heterocyclic ring
• Heterocycling ring substitution leads to highly potent
compound
• Those that contain single benzene ring at N1 position are
toxic.
Classification of sulfonamides
according to duration of action
1. Short-acting
a.Sulfadiazine
b.Sulfadimidine
c. Sulfacetamide
d.Sulfafurazole
e.Sulfisomidine
(aka sulfaisodimidine)
2. Intermediate-acting 3. Long-acting
a. Sulfamethoxypyrazine
• Sulfamethoxazole
b. Sulfadoxine
• Sulfamoxole c. Sulfadimethoxine
• Sulfanitran d. Sulfamethoxypyridazine
e. Sulfametoxydiazine
Ends with “ine”
Ends with “ole” (short acting)
Sulfafurazole (short acting) Sulfadiazine
Sulfadimidine
Sulfisomidine
METABOLISM
• Sulfonamides are metabolized by N-acetylation
• N-acetylation increases hydrophobic character
• Reduces aqueous solubility
• May lead to toxic side effects
Cystalluria
SJS (Stevens Johnson syndrome
Classes of Sulfonamide
 Sulfanilamide (SNM)
• Very less soluble in water
• Should be taken with NaHCO3
• More effective against skin
infection

Indication/Dose: • Adult: As vaginal cream: 1

applicatorful (about 6 g of 15%
cream) once or bid for 30 days.
• As vaginal suppository: 1
suppository (1.05 g) bid for 7 days
 Sulfadimidine
• Very similar with sulfanilamide
• very soluble in water

• Oral
Indication/Dose • Initially, 2 g then 0.5-1 g every
6-8 hr.
 Sulfadimidine
• Very similar with sulfanilamide
• very soluble in water

• Oral
Indication/Dose • Initially, 2 g then 0.5-1 g every
6-8 hr.
 Sulfadiazine (SDZ)
• 10 times more potent
• More soluble in water than SNM
but can crystallize in kidney due
to high acidic level so should be
given with NAHCO3.

Indication/Dose
• Oral
• Adult: Initially, 2-4 g, followed by 2-
4 g daily in in 3-6 divided doses.
Max treatment duration: 7 days.
• Child: Initially, 0.075 g/kg, followed
by 0.150 g/kg daily in 4-6 divided
doses. Max: 6 g daily.
 Indication/Dose
• Topical
• Adult: Apply a 1% cream onto
affected area once or twice
daily.

Silver sulfadiazine
• Very similar with sulfanilamide
• very soluble in water
 Sulfathiazole
• Slow moderate solubility in
water
• Relatively low toxicity
• Much more effective than SNM

Indication/Dose
• Vaginal
• Adult: Cream (Sulphathiazole 34.2 mg/g, sulphacetamide
28.6 mg/g, sulphabenzamide 37 mg/g and urea 6.4 mg/g):
5g is applied intra-vaginally bid for 4 to 6 days. Thereafter
the dosage may be reduced to one-half or one-quarter.
 Sulfixosazole
• Effective against gram negative
• very soluble in water
• Plasma half-life of 6 hours
• Pka = 5.0
 Sulfamethizole
• Oral absorption is adequate
• more potent than SNM
• Plasma half-life of 2.5 hours

Indication/Dose
• Oral
• Urinary tract infections
• Adult: 1.5-4 g/day in 3-4 divided doses.
• Child: 30-45 mg/kg/day in 4 divided doses
 Indication/Dose
• Oral
• Urinary tract infections, Otitis media, Chlamydial infections,
Prophylaxis of meningococcal meningitis
• Adult: Initially, 2 g followed by 1 g bid. Severe infections: 1 g tid.
• Child: Initially, 50-60 mg/kg, followed by 25-30 mg/kg bid. Max daily
dose: 75mg/kg.

Sulfamethoxazole (SMX)
• lesser oral absorption than
sulfisoxazole
• Efficacy is similar with
Sulfisoxazole
• t 1/2 = 11 hours
 Sulfacetamide
• Very soluble in water
• used for opthalmic & skin
infection
• t 1/2 = 7 hrs
• pKa = 5.4

• Opthalmic Indication/Dose
• Adult: As 10%, 15% or 30% sulfacetamide
• Na soln: Instill 1-2 drops into the conjunctival sac of the
affected eyes(s) 2-3 hourly. As 10% sulfacetamide Na ointment:
Apply approx half inch onto affected eye(s) 3-4 hourly and at
bedtime. Taper dose by increasing dosage time interval as
condition responds. Usual duration of treatment: 7-10 days.
 Sulfapyridine
• Very slightly soluble
• t 1/2 = 9 hrs.
• pKa = 8.4
• First chemical cure for
pneumonia
 Sulfamerazine
•5 times more active than SNM.
•50% less active than SDZ due to
addition of –CH3 group in
pyrimidine
ring.
•Water solubility is more than
SULFADIAZINE (SDZ).

Indication/Dose
• Oral
• Adult: As sulfadiazine 167 mg, sulfadimidine 167 mg, sulfamerazine 167
mg combination per tablet: Initially 4-8 tablets, then 2 tablets every 6
hr.
 Indication/Dose
•Oral
•Adult: 6-12 g/day in 2
divided doses
•Child: 100mg/kg/day

Sulfaguanidine
•Not well absorbed orally.
•Used for GIT infections.
 TMP-SMX
• Treatment of gram
positive and gram
negative organism.
• Tx. of MRSA
infection
• t-1/2 = 10-12 hrs.
Dosage:
MOA
Know more about TMP...
(Trimethoprim)
• Originally introduced in combination with SMX
• Used for the treatment of uncomplicated UTI (as a single agent).
• Treatment of bladder infections.
• Other uses include for middle ear infections and travellers'
diarrhea
COTRIMOXAZOLE

• Optimal ratio of two drugs

is 5:1
• (sulfamethoxazole:
trimethoprim)
Advantages of Cotrimoxazole
• Expanded number of microorganisms inhibited
• Bactericidal
• Decreased resistance
• Decreased toxicity
PHARMACOKINETICS - SULFONAMIDE
• A- from the stomach to the small intestine
• D – widely to tissues and body fluids (CSF),
placenta, and fetus.
Plasma protein bound 20-95%
• M – liver by acetylation
• E – urine, as unchanged drug and as metabolite
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