Pharm exam II- CNS depressants Flashcards
1
Q
What NT is found in cell bodies at all neuro levels and causes EPSP at the muscarinic receptors?
A
Acetylcholine
2
Q
What are some drugs acting at Ach receptors?
A
Atropine
Antiparkinsons drugs
Alzheimers drugs
3
Q
The NT dopamine binds to which receptors (blank1) and causes what effect (blank 2)?
A
- Dopanergic receptors
2. IPSP
4
Q
Drugs that work at Dopanergic receptors include?
A
Antipsychotic
Antiparkison
5
Q
If a barbiturate is given to a patient who is acidotic what will it do to the drugs effects?
A
potentiate the effects because the active portion of barbs are weak acids even though they are alkalotic in solution. So acid in an acid will be unionized and can cross membranes more easily
6
Q
What is important about when drawing up concentrations of barbs (thiopental and Brevitol)?
A
Should not be higher than recommended concentration or can cause tissue damage
Thio concentration = 2.5%
Metho concentration = 1%
7
Q
Are barbs compatible with other drugs?
A
not very many. Will cause precipitation and sludge if combined with other acidic meds
8
Q
What solution should barbs not be reconstituted with?
A
LR will precipitate
9
Q
With oxybarbiturates what will a substitution at carbon 2 of a O2 with sulfur create?
A
Thiobarbital
Sulfarization= increased potentancy and increases lipid solubility
10
Q
What will a branched chain on C5 do to barbs characteristics?
A
More hypnotic activity compared to a straight chain
11
Q
A barb with a phenyl group on C5 will enhance what effects?
A
Anticonvulsant effects
12
Q
Adding a methyl group to the N atom on barbs will do what?
A
Will impart convulsant effects and result in shorter duration = Methohexital (Brevial)
Brevital used in ECT therapy because does not prevent siezure activity while causing sedation
13
Q
What is the MOA of barbs?
A
decreases rate of dissociation of GABA from receptor which depresses RAS by opening Cl- channels longer (enhances GABA)
14
Q
Barbs and propofol both will have decreases in BP but what is different in each?
A
Barbs decrease in BP due to SNS depression= vasodilation
Propofol decrease in BP due to Myocardial depression
15
Q
Rapid awakening from Thiopental is result of what?
A
Redistribution out of brain (very lipid soluble)
16
Q
Is Thiopental and other barbs good drugs for IV infusions?
A
No because of accumulation effects that can linger in fat and muscle tissue
17
Q
What is the pKa of Thiopental and what is the pH of the solution after reconstituting?
A
pKa= 7.5 (close to normal physiologic pH) pH= 10.5 very alkalotic can cause tissue damage
18
Q
When considering kinetics what is important to know about Thiopental?
A
It is highly lipid soluble and protein bound so drug will be enhanced from displacement from proteins from other drugs or low albumin states.
19
Q
How quick does Thiopental and Methohexital reach reach equilibrium (max brain uptake)?
A
within 60 secs
20
Q
If patient has low cardiac output how can this affect an induction dose?
A
May take longer than normal to circulate to brain so be patient and don’t redose to quickly or may drop bp too much
21
Q
How should you calculate most induction doses?
A
Lean body mass
women= 105 + (5lbs for each in over 5ft) men= 106 + (6lbs for each in over 5ft)
22
Q
Who would wake up quicker after giving a barb, an enzyme induced drug abuser or renal failure patient?
A
Both will wake up about same time because context sensitive time is based off redistribution not elimination.
23
Q
What are some clinical uses for Barbs?
A
- induction of Anesthesia
- sedation
- **tx of increased intracranial pressure related to decreased CBF
- anticonvulsant
24
Q
In higher doses barbs will do what to an EEG in comparison to versed?
A
- barbs will produce isoelectric line in EEG in high doses
- versed decreases CMR02 and CBF but has ceiling effect and will not produce isoelectric EEG like barbs
25
What do barbs do to hepatic enzymes?
Will cause enzyme induction after prolonged use of barbs
26
Drugs that increase activity of the hepatic CP-450 system such as barbs can cause what in certain populations?
Acute Intermittent Porphyria= genetic disorder found more in northern European women that accelerates heme production and is often manifested as abdominal pain, peripheral neuropathies, and psychiatric symptoms
27
What will happen if a barb is injected into an artery?
- intense vasoconstriction and pain
| - tissue damage and loss of pulse
28
How would you manage intra-arterial injection of barbs are caustic drugs?
- dilute to avoid spasm and maintain flow
- Give lidocaine
- Give alpha blocker (phenoxybenzamine)= vasodilator
- Give Urokinase to break up clots
- Possible Stellate ganglion block to manage vasoconstriction
29
What is the concentration of propofol?
1%= 10mg/ml
30
What food allergies might be a concern when giving propofol?
Eggs and soy because propofol made from egg and soybean solutions
31
What is important to note about length of administration when giving propofol?
- supports bacteria growth
- should be refrigerated
- can be at room temp for 12 hrs**
- can also cause Propofol infusion syndrome >5hrs (more to come)
32
How does propofol cause its effect at the receptor binding site?
- Decreases rate of dissociation of GABA from receptor (Same as barbs) therefore increases duration of opening of Cl- channels (IPSP) causing hyperpolarization of cell membranes
33
Propofol is almost ideal infusion agent when considering kinetics why?
- undergoes rapid hepatic metabolism
- short duration of action
- **rapid wake up time** (context sensitive time)
- highly lipid soluble so rapid brain uptake (equilibration)
- ** decreased NV**
- **less hangover effects**
34
What are other uses for propofol other than sedation and anesthesia?
1. Antiemetic 10mg bolus
2. Antipruritic 10mg
3. Anticonvulsant
35
CNS effects of Propofol?
- decreased CMRO2, CBF, and ICP (good neuro)
- May decreased CPP as result of bp drop
- Decreases SSEP's as seen in barbs
36
What can propofol do to sense of well-being?
Can make you feel amorous (sexy)
37
Propofol cardiovascular effects?
- **Inhibits baroreceptor reflex**
- decrease BP (> than thiopental) due to myocardial depression
- Decreased *CO and SVR
- May decrease HR
- Blunts CV effects of laryngoscopy (reduces increases in HR, BP, ICP)
38
What drugs are better to blunt CV effects of laryngoscopy?
- Fentanyl
- Lidocaine IV bolus or topical spray (Laryngeal tracheal Anesthesia kit (LTA))
- Esmolol
*Not in kids though because HR decreases so atropine given to blunt*
39
Rapid and shallow breathing could be sign of what drug on board?
Muscle relaxants
40
Slow and deep breathing is result of what type of drug?
Opioids
41
Slow and Shallow breathing could be caused by what drug?
Propofol
42
What is the most common complaint about propofol?
Pain on injection (give in large vein or give lidocaine prior)
43
What is Propofol Infusion syndrome?
Impaired oxidation of fatty acids and oxidative phosphorylation in mitochondria leading to lactic acidosis and muscular necrosis after using propofol for extended periods of time (seen after 5 hrs but usually recommended to limit <48hrs)
44
What are clinical effects of propofol infusion syndrom?
- hyperkalemia
- hepatomeglia
- lipidemia
- metabolic acidosis
- myocardial failure
- rhabdo
45
What is fospropofol (Lusedra)?
- Prodrug that is water soluble and is hydrolyzed into propofol
- Its onset is slowed and has a prolonged duration in comparison to propofol (*may lead to more abuse*)
46
What is the major side effect of fospropofol?
Perineal itching
47
Does fospropofol cause pain on injection like propofol?
No
48
What are some of the characteristics of Etomidate?
- carboxylated imidazole ring which gives with lipid solubility
- May cause pain on injection if contains propylene glycol
- Large Vd
- rapid brain uptake (equilibration)
- Highly protein bound (76%)
- fast awakening
49
How is Etomidate metabolized?
Rapidly metabolized by liver and plasma by ester hydrolysis to inactive metabolites
50
What is Etomidate mostly used for?
- Induction agent (**drug of choice for myocardial depressed inductions**)
- Infusion (rare)
51
What makes Etomidate a relative contraindications for neuro patients?
EEG changes similar to thiopental except excitatory spikes suggests possible seizure activity
52
What is one of the most common effects seen with Etomidate inductions?
Myoclonus (or muscle tensing) (87%) another reason why contraindicated in seizure patients
53
If a patient is immunocompromised or has adrenocortical suppression should you give Etomidate?
No can cause effects to last as long as 4-8hrs in these groups
54
What is the MOA of Etomidate?
enhances effect of GABA
55
How does Dexmedetomidine (Precedex) cause its effects at receptors?
- It is a Alpha agonist pre and post
| - manly Alpha 2 presynaptic
56
What is Dexmedetomidine (Precedex) mostly used for?
Ventilator sedation
57
How is Precedex respiratory effects different from most other sedation meds?
Minimal respiratory depression (Ketamine also doesn't depress resp)
58
What are the effects seen with Dexmedetomine (Precedex)?
- Sedation
- Analgesia
- Anxiolysis
- blunts CV effects of intubation
59
When is Precedex contraindicated?
- hypovolemia
- hypotension
- Cardiac conduction defects
60
What is Ketamine a derivative of?
Phencyclidine
| "PCP = Angel dust"
61
Why is Ketamine considered a "dissociative" anesthetic?
-Causes crazy feelings and hallucination (EEG dissociation between limbic and thalamocortical systems)
62
Which receptors do Ketamine cause its effects?
- antagonist of NMDA receptors (blocks glutamate)
| - also interacts with opioid receptors to give it some analgesic effects
63
What causes Ketamine to be rapidly distributed?
- It is not highly protein bound
| - highly lipid soluble (not as lipid soluble as other CNS depressants though)
64
What should be noted about Ketamine metabolism?
- High hepatic extraction (fast metabolism)
| - Metabolized by demethylation by CP-450 into active metabolite norketamine
65
Which CNS depressants does not cause enzyme induction after repeated use?
Benzo's ( but barbs and ketamine do cause enzyme induction)
66
What situations would you use and not use Ketamines?
- Wouldn't use with:
1. Cardiac- increased HR, PAP, Myocardial O2 consumption
2. Neuro- seizure like activity, myoclonus, increased ICP, CBF
- Would be used with:
1. Trauma to support Bp
2. OB (minimal neonate depression)
3. burn drsg changes (repeated procedures)
67
Why is it important to read Ketamine label especially?
Supplied in multiple vials with different doses (higher potential for drug error)
68
What med should you consider giving prior to Ketamine?
Benzo's versed to prevent CNS/Delirium effects
69
What effects does Ketamines have on airway?
- no resp depression unless given rapidly
- upper airway reflexes maintained
- Cholinergic (salivary response)
- bronchodilator (Good for asthma pt)
70
What med can be given to decrease cholinergic (salivary) effects of ketamine?
robinul
71
Droperidol (Inapsine) is related to what drug?
Haldol
72
How does Droperidol (Inapsine) work at receptors?
Interferes with CNS transmission at dopamine, NE, GABA, and 5-ht sites to cause tranquilization/sedation and detachment while maintaining a state of reflex alertness
73
How does Inapsine cause its antiemetic effect?
receptor blockade at CRTZ (chemoreceptor zone)
74
What cardiac side effect is commonly seen with Droperidol (Inapsine)?
Prolonged QT interval (black box warning requires EKG monitoring)
75
What is "neurolept" anesthesia?
Combo of (opioid) Fentanyl and (neuroleptic) Inapsine into drug called Innovar
76
What CNS side effects are seen with Droperidol (Inapsine)?
Extrapyramidal reactions (dystonia, parkonsonian symptoms)
77
What is the antiemetic dose for Droperidol (Inapsine)
0.625mg
78
Generic Propofol may cause bronchoconstriction due to what?
Metabisulfites found in it
79
What are some of the main effects of Benzo's?
Sedation
Anxiolysis
Anticonvulsant
Muscle relaxant (ex. back pain from stress)
80
What type of amnesia does Benzo's cause?
Anterograde= forget everything after
81
What are the main uses for Benzo's?
- IV sedation
- preoperative anxiolysis
(no usually used for induction because other meds better)
82
Can benzo's be antagonized?
Yes- Flumazenil (Romazicon)
83
Does Benzo's have active metabolites?
Yes
84
Do Benzo's cause enzyme induction?
NO (but barbs and ketamine do)
85
How does Benzo's cause its effects at receptors?
Enhances or boosts GABA effects by increasing frequency of Cl- channel openings to negatively "supercharge" the neuron making it less responsive to other neurotransmitters that would excite it.
(different than MOA of Barbs, prop, and etomidate)
86
Benzo Alpha 1 receptor is responsible for what effects?
Sedative effects
87
Benzo Alpha 2 receptor is responsible for what effects?
Anti-anxiety
88
Benzo Alpha 1, Alpha 2, and Alpha 5 cause what effects?
Anticonvulsant effects
89
What type of effect occurs when benzo's and other CNS drugs bind to different GABA binding sites?
Synergistic effects
90
Can tolerance to Benzo's occur from other CNS depressant that work on GABA site?
Yes
91
Barbs do what in large doses?
has GABA-mimetic effects (direct action) but Benzo's don't
92
Benzo's are more selective than barbs, what does this do to CNS effects?
Less profound CNS effect and gives benzo's higher margin of safety
93
What is the occupancy effects of benzo's at 20%, 30-50%, and >60% receptor saturation?
```
20%= Anxiolysis
30-50%= sedation
>60%= loss of consciousness
```
94
Why is Diazepam (Valium) have a prolonged duration?
It is highly lipid soluble so even though it is rapidly equilibrated in the brain it is also rapidly redistributed into fat which gives prolonged effects.
95
Does Diazepam (Valium) cause venous irritation?
- It does if it is dissolved in organic salts (propylene glycol) to improve water solubility
- Less irritation though if in soybean formulation
96
What Valium's absorption like when given PO?
Rapid
97
Does Valium cross the placenta?
Yes
98
What medication can cause inhibition of enzyme activity and cause a prolonged duration of Valium?
Cimetidine (histamine h2 blocker for GERD and ucler tx)
99
Is Valium protein bound?
yes highly protein bound
100
How is Valium metabolized?
In the liver, oxidation through N-demethylation
101
Does Diazepam (Valium) have active metabolites?
Yes Oxazepam, and desmethyldiazepam which contribute also to prolonged effects
102
How is Valium excreted?
By kidney
103
Active metabolite desmethyldiazepam elimination half-life is how long?
48-96hrs so accumulation can be a problem
104
What drugs have involvement with the NT GABA?
- Barbs
- Propofol
- Benzos
- Etomidate
105
What does the high pH of Barb solutions do to shelf life?
Increases gives it Bacteriostatic qualities
106
Barbs are incompatible with many other drugs that are what in solution?
Acidic (will cause precipitation) ex:opiates, muscle relaxants, LR
107
Which meds may be contraindicated in astmatics?
- Tordal (COX-1, COX-2 imbalance)
- Barbs (histamine release)
- Propofol (generic has metabisulfites cause bronchoconstriciton)
- Morphine (histamine release?)
108
Which med group in the notes that causes enzyme induction can cause Acute Intermittent Porphyria?
Barbiturates
109
What solutions make up propofol?
It is a 1% solution (10mg/ml) in aqueous solution of 10% soybean, 2.25% glycerol, 1.2% egg phosphatide
110
Which meds are contraindicated in patients with history of seizures?
- Etomidate (myoclonus side effects 87%)
- Ketamine (myoclonus, (seizure-like activity)
- Demerol + MOA (not good)
- Romazicon (reverese benzo to quick)
111
What is important about the structure of Midazolam (Versed)?
it is a Imidazole ring in structure which allows for water solubility (more hydrophilic = metabolize quicker)
112
What drug is more potent Valium or Versed?
Versed 2-3x's more potent
113
Which drug's Hepatic clearance is faster Valium or Versed?
Versed is cleared 10x faster
114
Drugs that inhibit or compete for CP-450 enzymes may do what to Versed?
decrease metabolism of Versed
115
Diazepam does what to MAC doses?
decreases
116
Do benzo's (Versed) reduce increases in HR and BP from intubation?
No
117
What are the main uses for versed?
- Pre-op anxiolytic & Conscious sedation (0.5-5mg)
- Induction (approx 10mg for 70kg pt)
- Seizures (2-5mg)
118
Lorazepam (Ativan) is a potent what?
Amnestic
119
What is Ativan conjugated to by the liver?
** Inactive metabolites**
120
Which is more lipid soluble diazepam or lorazepam?
diazepam is more lipid soluble
121
Why are the clinical effects of Lorazepam seen longer than Diazepam even though the elimination half time of Lorazepam is shorter?
Possibly due to slower rate of dissociation from GABA receptors
122
What has a longer duration Versed or Ativan?
Ativan= 6-10 hrs
123
Why is Ativan not good for induction or seizure control?
Slow onset = 1-5 minutes
124
What is Oxazepam used for?
Insomnia (it is an active metabolite of valium)
125
What is Flumazenil (Romazicon) used for and what dose would you give?
Benzo reversal
| 0.2-1mg give slowly 0.2mg/min
126
What are some side effects of Romazicon?
- Seizures
- arrhythmia's
- N&V
- pain at IV site
127
What is Physostigmine used for?
It is an antichoinesterase (increases Ach and crosses BBB) that reverses Benzo's and possibly other CNS depressants
