Monthly Archives: August 2021

Acidic and Basic drugs

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DO YOU KNOW❓

3 drugs with delayed recovery are weak bases: Diazepam, Midazolam & Etomidate (pKa ranging from 3-6)

5 drugs which are potent analgesics are strong bases: Morphine, Fentanyl, Ketamine, Bupivacaine, Lignocaine (7.5-8.5)

4 most commonly used drugs are weak acids: Paracetamol, Propofol, Atropine, Thiopentone (7.5-11)

LASI (lasix) and SALI (salicylic acid) are strong acids (3-4)

At pH < pKa, acidic drugs become less ionised:

HA ⇌ H+ + A–

At pH < pKa, basic drugs become more ionised as they accept protons:

B + H+ ⇌ BH+

Drugs cross membranes in the un-ionised state and so their pKa and the pH of the surrounding environment affect their rate of absorption. Hence, acidic drugs will be more readily absorbed in the highly acidic stomach, whereas basic drugs are better absorbed in the intestine where pH is higher.

Note: You can not find from pKa whether a drug is acidic or basic

CONTEXT SENSITIVE HALF TIME (CSHT)

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CSHT
  • Context sensitive half-time is defined as the time for the plasma concentration to fall to half of the value at the time of stopping an infusion.
  • The half time will usually alter in the setting of varying durations  of drug infusion
  • The higher the ratio of distribution clearance to clearance due to elimination, the greater the range for context-sensitive half-time
  • The longest possible context-sensitive half-time is seen when the infusion has reached steady state, when there is no transfer between compartments and input rate is the same as elimination rate
  •  Draw and label the axes; draw the curve for the drug with the shortest CSHT first before plotting the others
  • REMIFENTANIL: Here the elimination always dominates distribution and so there is very little variation in CSHT with time and so it is context insensitive. Draw a straight line starting from the origin and becoming near horizontal after the CSHT reaches 5 min. This demonstrates that the half time is not dependent on the length of infusion as clearance by plasma esterases is so rapid. For remifentanil the longest possible CSHT is only 8 minutes
  • PROPOFOL: For propofol the clearance due to elimination is similar to that for distribution into the second compartment, so plasma concentration falls rapidly after a propofol infusion mainly due to rapid elimination with a smaller contribution from distribution. Propofol is not context insensitive as its CSHT continues to rise; however it remains short even after prolonged infusions. Starting at the origin, draw a smooth curve rising steadily towards a CSHT of around 40 min after 8 h of infusion. (NB: CSHT of propofol is 20 minutes after 2 hours of infusion, 30 minutes after 6 hours of infusion and 50 minutes after 9 hours of infusion).
  • ALFENTANIL: The curve rises from the origin until reaching a CSHT of 50 minutes around 2 h of infusion. Thereafter the curve becomes horizontal. This shows that alfentanil is also context insensitive for infusion durations of 2 h or longer
  • THIOPENTONE SODIUM: The curve begins at the origin but rises more steeply than the others so that the CSHT is 50 min after only about 30 minutes of infusion duration. The curve should be drawn like a slightly slurred build-up exponential reaching a CSHT of 150 min after 8 h of infusion. As the CSHT continues to rise, thiopental does not become context insensitive
  • FENTANYL: This is the most complex curve and it begins at the origin and is sigmoid in shape. It should cross the alfentanil line at 2 h duration and rise to a CSHT of 250 min after 6 h of infusion. Again, as the CSHT continues to rise, fentanyl does not become context insensitive.
  • It is important to realize that the CSHT does not predict the time to patient awakening but simply the time until the plasma concentration of a drug has fallen by half. For example the patient may need the plasma concentration to fall by 75% in order to awaken
  • Decrement time: The time taken for the plasma concentration of a drug to fall to the specified percentage of its former value after the cessation of an infusion designed to maintain a steady plasma concentration (time). The CSHT is, therefore, a form of decrement time when the ‘specified percentage’ is 50%.
  • When using propofol infusions, the decrement time is commonly quoted as the time taken to reach a plasma level of 1.2 μ g.ml−1 , as this is the level at which wake up is thought likely to occur in the absence of any other sedative agents.
  • It must be remembered that after one CSHT, the next period of time required for plasma concentration to halve again is likely to be much longer. This reflects the increasing importance of the slower redistribution and metabolism phases that predominate after re-distribution has taken place. This explains the emphasis on half-time rather than halflife: half-lives are constant whereas half-times are not!