pKa, buffering, ionisation Flashcards
What are the pKa values of the main analgesic agents?
Para: 9.4
Ibu: 4.9
Tram: 9.4
Fent: 8.4
What does -log[H+] mean?
pH
What is a non-protein intracellular buffering system?
Phsophate buffer system
HPO4 + H+ <> H2PO4
Which weak base is essential in buffering urine when excess H+ needs removing?
Ammonia
At pH 7.4 the ratio of ionised to unionised morphine is what?
3:1
At physiological pH which is more ionised morphine or Fentanyl?
Fentanyl
What 2 properties of a drug determine how rapidly it reaches the brain?
- pKa (unionised form passes BBB more rapidly)
- Lipid solubility
What form of a drug is most water-soluble?
Ionised form
What form of a drug is most lipid-soluble?
Non-ionised form
How is a pKa worked out (loosely) for a drug?
- Weak acid = ionised above pKa
- Weak base = ionised below pKa
What anaesthetic drug shows geometric isomerization?
Mivacurium
What are a pair of optical isomers called?
Enantiomers
What effects do enantiomers have on anaesthetic agents?
- Potencies
- Intrinsic activity (e.g antagonist)
- Pharmacological response
What are the forms of aminosteroids & isoquinolones?
A: Vec & Roc, contain many chiral centres, synthesised as single isomers
I: Atra, Miva, 4 chiral centres, 16 stereoisomers
How does the structure of Midazolam change in acid & plasma?
- In acid is ionised & water soluble
- In plasma forms benzo ring which is lipid soluble and crosses BBB
How are COX inhibitors classified?
- Structure
- Inhibition: Non- selective (Aspirin, Ibuprofen, Diclofenac) or Selective (Parecoxib)
What is MAC?
- Measure of potency
- Minimum alveolar concentration at steady state that prevents reaction to standard surgical stimulus in 50% of subjects.
What factors increase MAC?
- Infancy
- Hyperthermia
- Hyperthryroid
- Catecholamines & sympathomimetics
- Chronic ETOH/opioid use
- Hypernatraemia
- Amphetamine use
What factors decrease MAC?
- Neonates
- Inc age
- Pregnancy
- HypoT
- Hypothermia
- Hypothyroidism
- a2-agonists
Sedatives - Lithium
What are the ideal biochemical properties of a volatile agent?
- High oil:gas partition coefficient (low MAC)
- Low blood:gas partition coefficient
- Not metabolised
- Non-toxic
- Only affects CNS
- Not epileptogenic
- Some analgesic properties
What does a low blood:gas partition mean?
Reaches equilibrium more rapidly
(exert higher partial pressure so more rapid onset/offset)
How is Nitrous oxide made?
Heating ammonium nitrate to 250 degrees
What is the concentration effect?
- Disproportionate rate of rise of the alveolar fraction compared with inspired fraction when high Conc N2O are inspired
- Driving force is the large gradient
-Large amounts of N2O are absorbed into the pulmonary capillaries - To keep alveolar vol constant gas in conducting airways is drawn down into alveoli
What is the second gas effect?
- Result of concentration effect
- O2 +/- volatile alongside high conc N2O is concentrated by rapid uptake of N2O
- Augments alveolar ventilation
- Leads to inc conc of O2/volatile
What is diffusion hypoxia?
- At end when N2O/O2 replaced by air, reverse of 2nd gas effect seen
- Vol of N2O entering alveolus will be greater than the vol of N2 entering pulmonary capillaries
- Results in dilution of all alveolar gases
How does N2O toxicity occur?
- Cobalt ion present in B12 oxidised by N2O
- Unable to act as co-factor for methionine synthetase
- Results in reduced synthesis of Methionine, Thymidine, Tetrahydrofolate & DNA
- After few hours = megaloblastic BM changes
- Chronic exposure = neurological syndrome similar to subacute combined degeneration of the cord
