pharmacology 5 Flashcards
define partial pressure
Partial pressure is the pressure exerted by a
gas in a mixture of gases if it occupied the
container alone (Dalton’s law of partial pressures)
Tell me about wash-in curves
wash in curves demonstrate FA/FI ratio.
FA/FI of 1 = equilibrium
This is a negative exponential because the rate at which equilibrium is reached decreases with time..
blood:gas partition effects wash-in curves/ onset & offset time. A high blood:gas coefficient means the vapour is highly soluble in blood therefore has a slow onset and offset time e.g halothane
low blood:gas doesnt dissolve so readily so partial pressure in the blood will rise more quickly facilitating rapid diffusion into the brain, leading to faster onset and offset e.g nitrous oxide
‘No Don’t Sing It Excites Horses’
How does patient physiology effect onset?
-higher Vm: equilibrium reached more quickly
-CO: lower CO =faster the FA/FI will be reached. in low cardiac states, a higher proportion of effective blood circulation (with anaesthetic agent) travels to the brain. FA will increase more rapidly also, as slower transfer of agent into the blood occurs.
-FRC: higher FRC results in greater dilution of the agent. Therefore PA is increased with a smaller FRFC
-CBF: the higher the CBF, the more agent is delivered over time. hypercapnia increases CBF (& hyperventilation), volaties increase CBF, hence increased ICP. A conc of 1 MAC is usually safe, N2O is best avoided.
Tell me about volatile agent potency
potency reflects how much of a drug is required to produce an effect. In volatiles, potency is reflected by MAC and dependent on oil:gas partition coefficient (lipid solubility).
the higher the oil:gas partition coefficient, the lower the MAC, and the higher the potency of the volatile, is this correct?
Key Points of the Meyer-Overton Hypothesis:
Core Idea:
The potency of an anaesthetic agent is directly proportional to its lipid solubility.
The more lipid-soluble an anaesthetic is, the lower the concentration required to induce anaesthesia.
Relationship:
Potency is measured by the Minimum Alveolar Concentration (MAC).
Lipid solubility is measured by the oil:gas partition coefficient.
Inverse relationship:
Higher oil:gas partition coefficient → Lower MAC → Higher potency.
log MAC graph log oil:gas partition coefficient ‘No Dont sing Everyone is High’
Which volatile anaesthetics are ethers?
all are ethers except halothane.
Ethers are less lipid soluble, hence halothane hast the highest oil:gas partition coefficient. Halothane O:G 224, MAC 0.75. (high O:G means more potent therefore lower MAC- less needed)
Halothane has CL, Br, and F in addition to hydrocarbons.
Ethers are also less water-soluble hence are more resistant to metabolism (Des being most resistant)
what is the boiling point of nitrous oxide?
-89 degrees celcius
Desflurane
B:G
O:G
MAC
B:G= 0.42 (lowest of all, fastest onset of all anaesthetic gases)
O:G= 19 (2nd lowest, after N2O at 1.4, before Sevo at 53)
MAC= 6
Sevo
B:G
O:G
MAC
Sevo
B:G= 0.69
O:G=53 (47-53 on different resources)
MAC= 2
Isoflurane
B:G
O:G
MAC
ISO
B:G =1.4
O:G =91
MAC= 1.2
Enflurane
B:G
O:G
MAC
Enflurane
B:G =1.9
O:G =98
MAC = 1.68
halothane
B:G
O:G
MAC
Halothane
B:G = 2.4
O:G =224
MAC= 0.75
what is the O:G of Des
19
what is the B:G of Des
0.42
what is the concentration effect
tendency for alveolar conc to rise towards equilibirum of FA/FI more rapidly with higher concs of inhaled drug.
This only applies to N2O as it is the only agent to be used in sufficiently high concs to produce this effect.
N2O is 20x more soluble in blood than nitrogen. this means n2o leaves alveoli faster than n2 entering alveoli from the blood, meaning FGF is required from upper airways to replace what is lost and prevent collapse (augmented ventilation). This explains the second gas effect of how using N2O can result in faster FA/FI ration, thus a faster induction
What is diffusion hypoxia
reverse of second gas effect. N2O leaves the blood more rapidly than N2, resulting in dilution of gas in alveoli , reducing PAO2.
This is why supplemental O2 should always be given during emergence from anaesthesia with N2O.
Low B:G PC also means n2O will leave blood and enter air filled cavitites, e.g pneumothorax and therefore should b avoided in theses scenarios
What is the metabolism of the anaesthetic gases?
Horses Sound Excited If Drunk
H -20%
S-2-5
E-2
I- 0.2
D-0.02%
Sevo is the most metabolised of the ethers in liver by CYP2E1.but is the only one that is not metabolised to trifluoracetic acid (implicated in halothane hepatitis). This is induced in chronic alcoholism which increases the MAC of agents
what happens if warfarin is taken with fluconazole
fluconazole is an enzyme inhibitor (SICK FACES.COM) and increase warfarin effect 3-fold.
which drugs are metabolised by CYP2C9.
which populations are these missing from?
phenytoin
warfarin
NSAIDS
pro-drug losartan.
This can lead to reduced drug clearance and higher risk of drug toxicity
CYP2C9 is missing in most afro-caribbeans & 1% caucasians
This does not affect universally or to an extent that dose changes are warranted
which drugs are metabolised by CYP2D6
which populations are these missing from?
codeine, tramadol, atenolol, metoprolol, TCA, SSRIs, flecanide, ondansetron.
CYP2D6 alone is responsible for the metabolism of >25% of drugs.
CYP2D6 is absent in 7-10% of caucasians and 1-3% of non-caucasians.
upto 30% pf east africans have mutiple copies of the enzyme and are extensive metabolisers.
Genetic polymorphism at CYP2D6:
1. poor metabolisers: caucasians 7-10%- codeine and tramadol may be ineffective as these drugs are not metabolised into their active form.
3..ultrarapid metabolisers: Ethiopians 30%. antidepressants and neuroleptics are ineffective. Pro drugs such as tramadol and codeine are converted more rapidly increasing side effects
Tell me about elimination based on one-compartment model
once drug enters circulation it can metabolismed and excreted or excreted unchanged.
Rate of elimination is proportional to plasma concentration, following a first order relationship (see graph- negative exponential)
y=e^-x or C=Co.e^-kt
where -kt is -rate constant for elimination (no units)
Co= conc at time o mg/ml
C=plasma conc
plasma conc can be effected by input type (infusion or boluses), Vd and output (rate of elimination)
taking the natural logswill give a linear graph
InC=InC0-kt. The gradient of the slope represents -k
Vd=X/C0
what is time constant (T)= 1/k
time constant is the time taken for plasma conc to fall by a factor of e (or to 37% of its value).
this can be extrapolated from gradient of curve giving e. and using the equation:
C=C0.e-kt
- what is half life (t1/2)
- What is larger… time constant or half life?
3.how many half lives to be close to completion
how many time constants
time it takes for plasma conc to fall by 1/2
t1/2= T x In2
t1/2=T x 0.693
In2 is 0.693 and therefore time constant is always larger than half life
- it takes 5 half lives to be close to completion
it takes 3 time constants to be close to completion
