CLINICAL APPLICATION OF UNDERSTANDING MECHANISMS OF ACTION (EXAMPLE)

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Presentation transcript:

CLINICAL APPLICATION OF UNDERSTANDING MECHANISMS OF ACTION (EXAMPLE) ELIMINTION OF HYPNOTIC DRUG PHENOBARBITAL (AND OTHER ACID SUBSTANCES) FROM ORGANISM (E.G. OVERDOSING)

DISSOCIATION CONSTANT Diffusion of a drug across biological membrane – the substance must be non-ionised. Level of ionisation affect: dissociation constant of the drug pH of environment DISSOCIATION CONSTANT Constant for each drug It is not changed owing to factors of environment Indicated with symbol pK

Barbiturate hypnotic drug phenobarbital has pK value = 7,5 Hypnotic drug phenobarbital has pK = 7,5 this means that at pH = 7,5 we find 50 % of the substance in the form of ions – ionised (I) and 50 % in the form of molecules – non-ionised (NI).

The effect of different pH in organism on phenobarbital dissociation. Phenobarbital is a very weak acid. The effect of different pH in organism on phenobarbital dissociation. BLOOD (pH = 7,4) 48,7 51,3

The effect of different pH in organism on phenobarbital dissociation. Eliminated to acidic URINE (pH = 5,0) 0,7 99,3 Acidic substances are in acid solution mainly in non-ionised form.

The effect of different pH in organism on phenobarbital dissociation. When eliminated to alcaline URINE – shift of urine pH by alcalising substances (pH = 8,5) Acidic substances are in alkaline solution mainly in ionised form. Ionised part of the drug does not cross biological membranes by diffusion, because it is not soluble in lipids.

Phenobarbital is eliminated via urine pH 7,4 (blood plasma) pH 5,0 (acidic urine) Phenobarbital is eliminated via urine Usual pH of urine = 5,0 Phenobarbital is immediately converted to almost non-ionised form in urine (99,3 % non-ionised)

Therapy: acidic substances arte in alkaline environment Normally phenobarbital crosses biological membranes of kidneys back to the blood stream and to the brain - its sedative effects continues. Therapy: acidic substances arte in alkaline environment present mainly in ionised form – they cross the membranes only to very limited extent.

Use of alkalising substances suppresses reverse resorption in kidneys Non-ionised part in urine = 9,1 %, ionised part = more than 90 % - significantly decreased reverse diffusion of phenobarbital. pH 7,4 (blood plasma) pH 5,0 (acidic urine) pH 8,5 (alkalised urine) E.g. NaHCO3