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Drug Properties Flashcards

1
Q

Dantrolene presentation

A

20mg dantrolene sodium, orange powder
3g mannitol
recon with 60ml of sterile water
alkaline, highly irritant when extravasated

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2
Q

Dantrolene dose

A

2.5mg/kg IV up to 10mg/kg

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3
Q

Dantrolene protein binding

A

85%

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4
Q

Dantrolene metabolism

A

hepatic -> 5-hydroxy-dantrolene
50% active
Renal excretion

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5
Q

Dantrolene T1/2B

A

12 hours

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6
Q

Porphyria pathophysiology

A

defect in first step of haem synthesis + partial deficiency of enzymes subsequent to this process.

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7
Q

Drugs to trigger porphyria

A

barbiturates
ketamine
clonidine
ketorolac
phenytoin

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8
Q

plasma pseudocholinesterase deficiency

A

Genetic
Acquired - pregnancy, liver failure, renal failure, malignancy, malnutrition, burns, thyrotoxicosis

Post plasmapheresis

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9
Q

Excretion vs. elimination?

A

excretion is the removal of drugs from the body
elimination is removal of drugs from the plasma
- Can occur via distribution, metabolism, excretion

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10
Q

CSHT Remi

A

5 mins

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11
Q

CSHT Propofol

A

8 mins after 1 hour
40 mins after 8 hours

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12
Q

CSHT Fentanyl

A

at 2 hours = alfentanil at 50mins

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13
Q

CSHT Alfentanil

A

50 mins post 2 hours -> context insensitive

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14
Q

CSHT thiopental

A

150 mins post 8 hours (active pentobarbital, zero order kinetic)

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15
Q

Difference between iso and enflurane structures

A

positional isomers
3F on terminal carbon for iso, Cl + H on C2
End 2F on C2

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16
Q

changes to neonatal drug response - PO absorption

A

delayed GI emptying, prolonged contact with small bowel wall -> increased absorption of drugs

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17
Q

Neonatal NMJ changes

A

immature until 2 months of age
small reserve of Ach, more sensitive to NDMRs

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18
Q

Define shelf-life

A

length of time a drug can stay on the shelf without degrading to unacceptable level (minimum 90%)

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19
Q

What is sulphite addictive?

A

found in adrenaline (sodium meta-bisulfites)
antioxidants
can cause hypersensitivity, neurological damage from intrathecal administration

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20
Q

preservative in ketamine?

A

benzalkonium chloride

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21
Q

Side effect of benzalkonium?

A

histamine release -> hypotension

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22
Q

Class of agent - sevo

A

halogenated compound
poly-fluorinated isopropyl methyl ethers

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23
Q

Class of agent - des

A

halogenated, methyl ethyl ether

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24
Q

Difference between sevo and des structures?

A

2x CF3 on sevo while des has a fluoride instead.

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25
Structure-relationship of volatiles - purpose of low MW
reduce boiling point, increase SVP
26
Structure-relationship of volatiles - H+ vs F- side chain
H+ - increase flammability, increase potency F- - decrease flammability, C-F bond strong and resistant to oxidative metabolism, decrease potency
27
Structure-relationship of volatiles - CHF2 (di-fluor-methyl group)
interacts with soda lime to form CO -> increase carboxyhb
28
Metabolite of des / iso / halothane
TFA - trifluroacetate
29
Types of halothane hepatic toxicity
reversible - increase transaminase fulminant necrosis - TFA chloride + hepatic proteins -> antibody formation
30
pathophys of nephrotoxicity from methoxyflurane
extensive metabolism into inorganic fluoride -> accumulation
31
Factors to increase MAC
Children Hyperthermia Hyperthyroid Hypernatraemia Catecholamines Chronic opioid use, acute amphetamine use anxiety
32
Factors to decrease MAC
Elderly, pregnancy hypothermia hyponatraemia shocked state A2 agonist, acute opioid use Hypercapnic, hypoxia
33
MW of N2O
44g/mol
34
MW of O2
32
35
MW of sevo
200
36
MW of des
168
37
MW of xenon
130
38
Boiling point of des
23.5
39
Boiling point of sevo
60
40
Boiling point of N2O
-88
41
SVP at 20 degrees of N2O
50 bar
42
SVP at 20 degrees of des
600mmHg
43
SVP at 20 degrees of sevo
160mmHg
44
MAC of xenon
70%
45
Blood gas coefficient of xenon
0.14
46
Ranking of oil/gas coefficient of different agents
Halothane > iso > sevo > des > xenon > N2O
47
Resp effect of N2O
no blunting of laryngeal reflex. no change to minute ventilation increase pulmonary vascular resistance
48
Haem effect of N2O
oxidation of cobalt ion in B12 -> interferes with DNA synthesis -> megaloblastic anaemia, agranulocytosis, peripheral neuropathy, teratogenic
49
Cylinder pressure of O2
137 bar, white cylinder
50
How do volatiles cause tachycardia?
vagal inhibition
51
Indication of nitric oxide
severe ARDS pulmonary HTN severe right-sided heart failure
52
Effects of nitric oxide
reduce HPV -> reduce V/Q mismatch in ARDS increase cerebral blood flow inhibit PLT aggregation Methb
53
pKa of ketamine
7.5
54
Protein binding of thiopental
80%
55
Protein binding of propofol
>99%
56
Protein binding of ketamine
25%
57
Clearance of thiopental
3.5ml/kg/min
58
Clearance of propofol
30-60ml/kg/min
59
Clearance of ketamine
15ml/kg/min
60
Structure relationship Barbiturates - keto vs enol
keto active, lipid soluble enrol water soluble
61
Structure relationship Barbiturates - methohexital
methylation of nitrogen atom -R3 increase onset time, shorten duration increase excitatory phenomena
62
Content of thiopental
500mg sodium thiopental 6% sodium carbonate -> to make pH 10.5 fixed in nitrogen to prevent reaction with CO2 to reduce pH and reduce water solubility reconstitute in 20ml of H2O to make 2.5% solution
63
Metabolite of thio + fate
pentobarbital, active 30-50% hepatic saturable kinetics renally excreted
64
Propofol action aside from GABA A
glycine receptors nAchR D2 receptors
65
Characteristic of propofol infusion syndrome
in prolonged sedation in ICU, critically ill patients. metabolic acidosis rhabdomyolysis cardiac and renal failure
66
Benefit of S-ketamine
better analgesia more rapid metabolism better bronchodilator less intense emergence phenomena
67
Metabolite of ketamine
norketamine, 30% activity
68
Receptors ketamine acts on
NMDA mu and keppa Muscarinic Ach receptor antagonist Increase DA and Na release
69
Midaz PO bioavailability of
50%
70
Midaz pKa
6.5
71
Midaz protein binding
95%
72
Midaz Vd
1.5L/kg
73
Midaz Cl
5-10ml/kg/min
74
Midaz metabolite
1-a-hydroxy-midazolam, 50% activity Oxazepam
75
Flumazenil effect
competitive antagonist at the a/y interface receptor, competitively reverses effect of benzodiazepines
76
Flumazenil onset time
2 mins
77
Flumazenil dose
0.1mg increments up to 2mg
78
Flumazenil t1/2b
<1 hour, shorter than benzo
79
Flumazenil side effects
lower seizure threshold -> seizure N/V withdrawal symptoms if dependent on BDZ
80
A2 agonists - indications
HTN, sedation, premed, anxiolytics, intra-op haemodynamic stability, analgesia, post-op shivering
81
Protein binding clonidine
20%
82
Protein binding dexmedetomidine
90%
83
Metabolism of clonidine
50% metabolised, inactive metabolite 50% excreted unchanged
84
Metabolism of dexmed
almost complete metabolism to inactive compounds
85
T1/2b of dexmed
2 hours
86
Effect of A-agonist on coronary blood flow
direct vasoconstriction, offset by reduced SNS tone and local release of NO
87
Metabolic effect of A-agonist
Reduce ADH, reduce insulin from b-islet cells
88
Effect of A1 receptors
Gq GPCR -> increase [Ca] contraction of vascular SM, eye radial muscle, vas deferent, GIT sphincter Gluconeogenesis
89
Effect of B1 receptors - hormonal / renal
increase renin release from kidneys
90
Effect of B2 receptors
reduce histamine release from mask cells vascular smooth muscle relaxation Liver - glycogenolysis, gluconeogenesis
91
How is sedation / hypnosis mediated by dexmet
A2, Gi GPCR at locus cerulean in the medial dorsal pons
92
Dexmet analgesic mechanism
Reduce NA release -> reduce inhibition on the descending pathway At dorsal horn, inhibit release of substance P
93
Clinical uses of dexmed
Sedation, anxiolytics, reduced salivary secretion Maintain stable HD to stimulation Analgesia MAC sparring Prevents shivering Smooth induction and emergence, reduce delirium Reduce withdrawal Sx
94
Adult dose of dexmed
Loading 1microg/kg over 10mins then 0.6microg/kg/hr Reduced to 50% dose in elderly
95
CSHT of dexmed
stable at 2 hours, 70 mins
96
Contraindications of A2 agonist
Shock, bradycardia / heart block, allergy IHD, autonomic neuropathy
97
What are the components of accelero-myography?
Piezoelectric crystal attached to thumb measurement of acceleration of the crystal
98
Sux protein binding
30%
99
Sux Vd
0.2L/kg
100
Sux metabolites
succinyl-mono-choline + choline Succinct acid
101
Vec metabolism
hepatic de-acetylation, 60% activity, renal excreted
102
Roc metabolism
Minimally metabolised, mainly excreted unchanged in bile and less extent in urine
103
Intubating dose atracurium
0.5mg/kg
104
What physiological states affect Hoffman elimination
acidosis, hypothermia -> reduced reaction -> increase [atracurium]
105
ID cisatracurium
0.15mg/kg
106
ID mivacurium
0.2mg/kg
107
Neostigmine distribution facts
Low Vd Low protein binding

Definition Deck (5 decks)

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