Influence of

Potentiation of
Drug Action
Group 2 Section II-A
Barrozo, Basilan, Bautista,
Bordones, Bueno, Buton,
Caballero, Calugcug, Canlas
Potentiation
• arises when one drug with no intrinsic
therapeutic activity enhances or
strengthens the effect of another
therapeutically active drug
• 1+0=>1
• Thiopental and SKF 525A
 Thiopental Na (Pentothal)
• ultra short-acting barbiturate
• produces sedation (at lower doses) or hypnosis (at
higher doses)
• binds to molecular components of the GABA A
receptor (chloride ion channel) in neuronal
membranes in the central nervous system →
decrease neuronal activity
• enhance the inhibitory action of the GABA A
receptor (inc. duration of opening of chloride
channels)
• Has anesthetic, sedative, anxiolytic, anticonvulsant
and hypnotic properties; no analgesic effects
Thiopental Na (Pentothal)
• absorbed orally
• distributed widely
• metabolized in the liver
• excreted unchanged in the urine
• duration of action: 30 minutes
 SKF 525A (Proadifen)
• diethylaminoethyl-2,2diphenylvalerate.HCl
• inhibitor of cytochrome P450 enzymes
whose metabolites bind tightly to the heme-
iron of cytochrome P450 and quasi-
irreversibly inactivate the enzyme
(CYP2B6-, CYP2C9-, CYP2C19-, CYP2D6-
and CYP3A-)
• Other effects:
– also blocks glibenclamide-sensitive K+ channels
– inhibits neuronal nitric oxide
– stimulates endothelial cell prostacyclin
production
• Not marketed; only used in
studies/experiments
METHODOLOGY
RESULTS & DISCUSSION
Drug Latency Duration

SKF 525A 0 0

Thiopental 2 min 43 sec 60 min (max time

allotted)

SKF 525 A + 2 min 18 sec 60 min (max time

Thiopental allotted)

Theoretical Result:
SKF 525A + Thiopental → shorter latency, longer duration
Thiopental alone → longer latency, shorter duration
SKF 525A alone → no effect
RESULTS & DISCUSSION

Influence of Potentiation on Drug Action

4000
3500
3000
2500
Time (sec) 2000 3600 3600 Duration
1500 Latency
1000
500
0 163 138
0
SKF 525A Thiopental SKF 525A +
Thiopental
RESULTS & DISCUSSION
• Inhibition of the Thiopental’s
metabolism → reduced
clearance → increased plasma
concentrations →
accumulation of the drug →
minimum effective
concentration is reached faster
thereby producing an earlier
effect (latency) and extending
the duration of drug action
 CONCLUSION
• Potentiation is the augmentation of a drug’s
pharmacologic effect by another substance
which has no intrinsic pharmacologic effect.
• Enzyme inhibition caused a decrease in drug
elimination and accumulation of the drug, hence
an increased plasma concentration which is
above the minimum effective concentration
• Administration of SKF 525A with thiopental
produced shorter latency and prolonged
duration