Week 2 Weak Acids & Bases & pKa (Everything) Flashcards
LA are:
weak bases
Acid + Acid =
Base + Base =
non ionized
Acid + base =
ionized
Onset of LA
pH where 50% ionized and 50% non-ionized
pKa
Lipid solubility:
potency of LA
the more lipid soluble:
the more potent.
More lipid soluble impact on blood flow…
less likely for blood flow to carry it away
Protein binding=
duration of LA
Na+ channel are voltage gated and exist in
3 phases
The 3 phases of Na+ channel voltage gates:
- Resting or closed (M-gate closed)
- Activated or open (M-gate and H-gate are open)
- Inactivated (inactivated b/c H-gate is closed)
the LA interacts with the ______ to cause the effect
the H-gate
is a positive or negative charge of the LA required for the interaction with the H-gate to happen?
positive charge
what is the position of the M-gates and the H-gate when the na-channel is RESTING:
M-gates: closed
H-gate: open
what is the position of the M-gates and the H-gate when the na-channel is ACTIVATED:
M-gates: open
H-gate: open
what is the position of the M-gates and the H-gate when the na-channel is INACTIVATED:
M-gates: open
H-gate: closed
M-gates: open
H-gate: closed
the na-channel is:
inactivated
M-gates: open
H-gate: open
The na-channel is:
Activated
M-gates: closed
H-gate: open
The na-channel is:
Resting
Recover from the inactivated, refractory state requires closure of the _____ and opening of the _____.
closure of the m-gates
and opening of the h-gate.
LA bind to the (R) where?
within the channel
How do LA access the Receptor?
via the membrane phase OR from the cytoplasm
What form of the LA is needed to cross the phospholipid layer?
non-ionized
What for of the LA is needed to get inside the membrane in order to bind w/the H-gate?
ionized
Lipid soluble (non/ionized?)
non Ionized
Uncharged form ((non/ionized?)
non Ionized
Acid form (non/ionized?)
non Ionized
Generally hydrophobic (non/ionized?)
non Ionized
Readily penetrates BBB and Placenta (non/ionized?)
non Ionized
Water soluble (non/ionized?)
ionized
Charged Form (non/ionized?)
ionized
Conjugate base form (non/ionized?)
ionized
What delays onset?
- drug with pKa farther from physiological pH (7.4). In this state more of the drug exists in the ionized form
- environmental pH is acidic (<7.4);
examples of environments where pH is more acidic (<7.4):
- wound infections
- ischemic areas
examples of environments where pH is more acidic (<7.4):
- wound infections
- ischemic areas
Highly protein bound = what 2 things?
- harder to dissociate from Na channel
2. Longer DOA
DOA is associated with
Protein binding!
-higher protein binding = longer DOA
The closer pKa is to physiologic pH the faster the
onset (relatively)
to speed up onset:
pKa closer to physiologic pH
pKa of Chloroprocaine:
9.1
protein binding of Chloroprocaine:
none (Zero)
pKa of Procaine:
9.1
protein binding of Procaine:
None
Drug that’s the Exception to the rule of faster onset
Chloroprocaine
pKa of Lidocaine
7.6-7.9
what can be used/added to the LA to either prolong the duration?
EPINEPHRINE
What can be used/added to LA to gain quicker onset:
Bicarbonate
What LA can precipitate when adding bicarbonate?
Bupivacaine
**What is the dose of bicarbonate when mixed with Bupivacaine?
0.1 mEq per 20mL of Bupivacaine
**What is the dose of bicarbonate when mixed with Lidocaine?
1 mEq of Bicarb per 10mL of Lidocaine
***Epi will not increase DOA for
Why?
Bupivacaine
Etiocaine
Ropivacaine
-b/c they have a long duration naturally
Which LA are short acting?
“Pro-C”
Procaine
Chloroprocaine
Which LA are intermediate acting?
“LMP”
Lidocaine
Mepivacaine
Prilocaine
Which LA are long acting?
“BET on a LONG shot”
Bupivacaine
Etidocaine
Tetracaine
Prilocaine Short/Intermediate/Long acting LA?
short
Lidocaine Short/Intermediate/Long acting LA?
Intermediate
Bupivacaine Short/Intermediate/Long acting LA?
Long
Tetracaine Short/Intermediate/Long acting LA?
Long
Chloroprocaine Short/Intermediate/Long acting LA?
short
Etidocaine Short/Intermediate/Long acting LA?
long
Mepivacaine Short/Intermediate/Long acting LA?
intermediate
Drug X (a weak acid) has a pKa of 8.4 and is administered to a patient with a pH 7.4. Which of the following is true regarding the drug? A) more than 50% ionized
B) more than 50% unionized
C) 50% unionized and 50% ionized
D) cannot be determined with information provided
B: more than 50% unionized
Drug X (a weak acid) has a pKa of 3.5 and is administered to a patient with a pH 7.4. Which of the following is true regarding the drug? A) more than 50% ionized
B) more than 50% unionized
C) 50% unionized and 50% ionized
D) cannot be determined with information provided
A: more than 50% ionized
Drug X (a weak acid) has a pKa of 3.5. Which of the following is true regarding the drug? A) more than 50% ionized
B) more than 50% unionized
C) 50% unionized and 50% ionized
D) cannot be determined with information provided
D): cannot be determined with information provided
Drug X (a weak base) has a pKa of 3.5 and is administered to a patient with a pH 7.4. Which of the following is true regarding the drug? A) more than 50% ionized
B) more than 50% unionized
C) 50% unionized and 50% ionized
D) cannot be determined with information provided
B) more than 50% unionized
Drug X (a weak base) has a pKa of 9.5 and is administered to a patient with a pH 7.4. Which of the following is true regarding the drug? A) more than 50% ionized
B) more than 50% unionized
C) 50% unionized and 50% ionized
D) cannot be determined with information provided
A) more than 50% ionized
Lidocaine has a pKa of 7.7 and is administered to a patient with a pH 7.7. Which of the following is true regarding the drug?
A) more than 50% ionized
B) more than 50% unionized
C) 50% unionized and 50% ionized
D) cannot be determined with information provided
C) 50% unionized and 50% ionized
Weak bases become more ________ as pH increases
Non-ionized
Should a weak acid be stored in a low or high pH solution? Why?
High pH solution (base)
Base + Acid = Ionized form
Should not precipitate
Mixing a weak acid with low pH solution would cause precipitation
When a local anesthetic is injected into a physiologic pH environment, it will be:
A) less than 50% ionized
B) less than 50% unionized
C) 50% unionized and 50% ionized
D) Cannot be determined with information provided
B: less than 50% unionized (LA are weak bases)
pKa range for LA
7.6-9.1
how would an area of infection alter a LA block
Speed of onset is slower when LA is injected into an area of infection b/c it increases the extent of ionization which slows diffusion through the lipid bilayer
what creates a faster onset for LAs
more unionized form = faster the onset
bc unionized is what crosses the membrane then it is activated to ionized form
which LA are short acting
“Pro-C”
procaine & chloroprocaine
which LA are intermediate acting
“L,M,Pri”
Lidocaine, Mepivicaine, Prilocaine
which LA are long acting
“BET on a long shot”
bupivicaine, etidocaine & tetracaine
(not appropriate for outpatient surgery centers where we need to move the patients quickly. tetracaine last around 4 hours)
LA with high a pKa are ____ at physiologic pH?
and require what fore effect?
Are highly ionized at physiologic pH
Has to have an open (activated) Na+ channels for effect
which nerves have more frequent depolarization and what LA pKa are they susceptible to?
sensory & autonomic nerves
susceptible to high pKa LA
which nerves have less frequent depolarization and what LA pKa are they susceptible to?
motor nerves
susceptible to lower pKa LA
where is a sympathetic block compared to a sensory block
Sympathetic block is 2-6 dermatomes higher than sensory block
where is a motor block compared to a sensory block
Motor block is 2 dermatomes lower than sensory block
How does the LA progress in a blockade?
- Autonomic, Temperature, Pain (ATP)
- Touch, Pressure (TP)
- Motor, Vibratory, Proprioception (MVP)
what form of a drug can diffuse across the lipid bilayer into the axon in a conduction block?
Non-ionized
what is the role of the ionized form of a LA in a conduction block
Ionized is needed to attach to the inside of the sodium channel and lock it in the inactivate state
conduction blocks are _____ dependent?
frequency dependent
frequency of the Action Potential
special consideration about myelinated axons. what must happen to achieve a block
2-3 nodes of Ranvier must be blocked to stop nerve conduction myelinated axons
WEAK ACIDS COMBINE WITH POSITIVE CHARGED IONS SUCH AS:
Na+
Mg++
Ca++
WEAK BASES COMBINE WITH NEGATIVELY CHARGED IONS SUCH AS:
CHLORIDE
SULFATE
Example: are the following “drugs” weak acids or weak bases?
LIDOCAINE HYDROCHLORIDE:
SODIUM CETO:
MAGNESIUM TIBUCAINE:
LIDOCAINE HYDROCHLORIDE: weak base
SODIUM CETO: weak acid
MAGNESIUM TIBUCAINE: weak acid
example question:
Drug X (a weak acid) has a pKa of 8.5 and is administered to a patient with a pH 7.4. Which of the following is true regarding the drug?
A) more than 50% ionized
B) more than 50% unionized
C) 50% unionized and 50% ionized
D) cannot be determined with information provided
B: more than 50% unionized
