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Pharmacology RCOA > pKa, buffering, ionisation > Flashcards

pKa, buffering, ionisation Flashcards

1
Q

What are the pKa values of the main analgesic agents?

A

Para: 9.4
Ibu: 4.9
Tram: 9.4
Fent: 8.4

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2
Q

What does -log[H+] mean?

A

pH

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3
Q

What is a non-protein intracellular buffering system?

A

Phsophate buffer system
HPO4 + H+ <> H2PO4

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4
Q

Which weak base is essential in buffering urine when excess H+ needs removing?

A

Ammonia

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5
Q

At pH 7.4 the ratio of ionised to unionised morphine is what?

A

3:1

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6
Q

At physiological pH which is more ionised morphine or Fentanyl?

A

Fentanyl

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7
Q

What 2 properties of a drug determine how rapidly it reaches the brain?

A
  • pKa (unionised form passes BBB more rapidly)
  • Lipid solubility
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8
Q

What form of a drug is most water-soluble?

A

Ionised form

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9
Q

What form of a drug is most lipid-soluble?

A

Non-ionised form

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10
Q

How is a pKa worked out (loosely) for a drug?

A
  • Weak acid = ionised above pKa
  • Weak base = ionised below pKa
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11
Q

What anaesthetic drug shows geometric isomerization?

A

Mivacurium

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12
Q

What are a pair of optical isomers called?

A

Enantiomers

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13
Q

What effects do enantiomers have on anaesthetic agents?

A
  • Potencies
  • Intrinsic activity (e.g antagonist)
  • Pharmacological response
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14
Q

What are the forms of aminosteroids & isoquinolones?

A

A: Vec & Roc, contain many chiral centres, synthesised as single isomers
I: Atra, Miva, 4 chiral centres, 16 stereoisomers

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15
Q

How does the structure of Midazolam change in acid & plasma?

A
  • In acid is ionised & water soluble
  • In plasma forms benzo ring which is lipid soluble and crosses BBB
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16
Q

How are COX inhibitors classified?

A
  • Structure
  • Inhibition: Non- selective (Aspirin, Ibuprofen, Diclofenac) or Selective (Parecoxib)
17
Q

What is MAC?

A
  • Measure of potency
  • Minimum alveolar concentration at steady state that prevents reaction to standard surgical stimulus in 50% of subjects.
18
Q

What factors increase MAC?

A
  • Infancy
  • Hyperthermia
  • Hyperthryroid
  • Catecholamines & sympathomimetics
  • Chronic ETOH/opioid use
  • Hypernatraemia
  • Amphetamine use
19
Q

What factors decrease MAC?

A
  • Neonates
  • Inc age
  • Pregnancy
  • HypoT
  • Hypothermia
  • Hypothyroidism
  • a2-agonists
    Sedatives
  • Lithium
20
Q

What are the ideal biochemical properties of a volatile agent?

A
  • High oil:gas partition coefficient (low MAC)
  • Low blood:gas partition coefficient
  • Not metabolised
  • Non-toxic
  • Only affects CNS
  • Not epileptogenic
  • Some analgesic properties
21
Q

What does a low blood:gas partition mean?

A

Reaches equilibrium more rapidly
(exert higher partial pressure so more rapid onset/offset)

22
Q

How is Nitrous oxide made?

A

Heating ammonium nitrate to 250 degrees

23
Q

What is the concentration effect?

A
  • 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
24
Q

What is the second gas effect?

A
  • 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
25
Q

What is diffusion hypoxia?

A
  • 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
26
Q

How does N2O toxicity occur?

A
  • 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
27
Q
A

Pharmacology RCOA (10 decks)

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