Module D Flashcards
(104 cards)
1
Q
Signalling in the CNS is ________ (electrical / chemical / both)
A
Both
neurotransmitters and neuromodulators act at synapses, but there is also direct voltage signalling at electrotonic gap junctions
2
Q
Most neurotransmitters are ________ (inhibitory / excitatory / either) with the exception of ______, which is only inhibitory
A
either, GABA
3
Q
The only purely inhibitory CNS neurotransmitter is ________
A
GABA
4
Q
Excitatory effects promote:
A
release of NTs from the neruronal terminal
5
Q
inhibitory effects cause _________ and inhibit release of _________
A
hyperpolarization, neurotransmitters
6
Q
Fast NTs act on what kind of receptors?
A
ligand-gated ion channels
7
Q
Slow NTs act on which kinds of receptors
A
GPCRs
8
Q
GABA is a _____ (fast / slow) NT
A
Fast
it acts on ligand-gated ion chanels
9
Q
CNS agents act in the following 4 ways:
A
- Altering synthesis, storage, or release of an NT
- Inhibiting reuptake of an NT
- Inhibiting degredation of an NT
- Activating or blocking the receptor
10
Q
receptors respond to long-term drug treatments by which two processes?
A
- sensitization (up-regulation)
- desentization/tolerance (down-regulation)
11
Q
Delirium is a disorder of ________, as seen in _________
A
cognitive processing, schizophrenia
12
Q
Dementia is a disorder of _________, as seen in __________ and ________
A
memory, alzheimers and parkinson
13
Q
emotional disorders arise from the ________ system
A
limbic
14
Q
Three classes of drugs used in the management of delirium are:
A
- antipsychotics
- CNS stimulants
- Sedative-hypnotics
15
Q
Sedative-hypnotic drugs tend to have dose-dependent effects, first causing ________ and then ________
A
sedation/anxiolysis first, and then hypnosis (drowsiness, then sleep)
16
Q
contrast the common anxiety disorders and their common pharmacological treatments
A
- Acute Anxiety: self-limiting acute arousal, may be treated with benzodiazepines
- Panic Disorder: recurrent, acute periods of anxiety with marked psychological and physiological manifestations. May be treated acutely with benzodiazepines and chronically with an SSRI
- Phobic Disorders: panic diorder with specific triggers. managment is similar to panic disorder, but performance anxiety may be managed with a beta-blocker like propranolol
- OCD: marked by compulsions, best treated with an antidepressant
- Generalized anxiety disorder: chronic worry and apprehension, best managed acutely with benzodiazepines and chronically with an SSRI
- PTSD: similar treatment to panic disorder, GAD, etc.
17
Q
Generally, treatment for anxiety disorder involves:
A
treatment of acute episodes with a benzodiazepine and chronic managment with an SSRI antidepressent.
18
Q
There are ___ stages of sleep which tend to occur in ___ minute cycles in healthy individuals. The REM stage is stage ___ and is critical for stable emotional status
A
5, 90, 5
19
Q
The clinical term for difficulty falling asleep is
A
sleep latency
20
Q
Benzodiazepines and antidepressants may decrease sleep latency, but have the adverse effect of:
A
changing sleep architecture, reducing REM sleep, and causing emotional disturbance
21
Q
The advantage of modern sleep agents like sublinox (zolpidem) is:
A
they have a minimal effect on sleep architecture
22
Q
A disadvantage of all sleep agents is that they may cause:
A
tolerance and dependence
23
Q
Compare and contrast physical and psychological dependence
A
both manifest as continued seeking of exposure to a drug. Physical dependence is continued use to avoid unpleasant physical withdrawal symptoms. Psychological dependence is continued use to receive the pleasurable effects of the drug or escape reality
24
Q
Sedative drugs are also called:
A
anxiolytics
25
The main advantage of benzodiazepines over other sedative-hypnotics is
very broad therapeutic index
26
Explain why some patients taking benzodiazepines may experience increased sedation after a high-fat meal
this is due to enterohepatic cycling (active metabolites are reabsorbed from the gut after biliary excretion)
27
Describe the MOA of benzodiazepine drugs
* bind to an allosteric site on the GABA-gated chloride channel receptor, increasing GABA activity
* this increases duration and frequency of opening of the chloride channel
* cause post-synaptic hyper-polarization (puts on the brakes)
* also inhibit neuronal reuptake of adenosine
28
Benzodiazepines _____ (can / can not) produce sedation sufficient for general anesthesia
can not!
29
Most BZ drugs are metabolized by the liver to produce _________ and are therefore classified as \_\_\_\_\_\_\_\_\_
active metabolites, prodrugs
30
Benzodiazepines have a ________ (fast / slow / etc.) onset
fast or very fast
31
A benefit of BZs like midazolam is that they prodruce \_\_\_\_\_\_\_\_\_\_, limiting unpleasant memories of procedures
anterograde amnesia
32
Five pharmacological effects of BZ drugs are:
* anxiolyis (sedation)
* amnesia (anterograde)
* hypnosis
* skeletal muscle relaxation
* anticonvulsant
33
Whereas _________ sedative-hypnotics have a strong ceiling effect, ____________ do not
benzodiazepine, barbiturates
## Footnote
*this is due to the dependence of BZs on already-existing GABA for their MOA*
34
List advantages and disadvantages of BZ drugs
Advantages: Little respiratory/cardiac depression, large therapeutic index, very dose-dependent response (can produce sedation without hypnosis)
Disadvantages: Cause physical and cognitive impairment, rebound effect if discontinued suddenly, physical dependence which may result in delirium
35
**Valium** (Diazepam)
* Benzodiazepine, sedative-hypnotic
* Lipid-soluble GABA agonist, causes CNS depression due to potentiation of GABA receptors and post-synaptic hyperpolarization
* **Fast onset with long duration of action**
* Dose dependent effects with ceiling effect: at low doses sedation only, at higher doses hypnosis and anterograde amnesia
36
**Ativan** (Lorazepam)
* Benzodiazepine, sedative-hypnotic
* Lipid-soluble GABA agonist, causes CNS depression due to potentiation of GABA receptors and post-synaptic hyperpolarization
* **Fast onset with medium duration of action and no active metabolites**
* Dose dependent effects with ceiling effect: at low doses sedation only, at higher doses hypnosis and anterograde amnesia
37
Versed (Midazolam)
* Benzodiazepine, sedative-hypnotic
* Lipid-soluble GABA agonist, causes CNS depression due to potentiation of GABA receptors and post-synaptic hyperpolarization
* **Fast onset with short duration of action, generally only given IV (or IM)**
* Dose dependent effects with ceiling effect: at low doses sedation only, at higher doses hypnosis and anterograde amnesia
* **used in acute settings for induction of anaesthesia, termination of seizures, and delirium**
38
Barbiturates are recognized by their names ending in \_\_\_\_
-tal
39
**Anexate** (Flumazenil)
* Benzodiazepine antagonist, reversal agent
* Competitive BZ receptor antagonist
* used to reverse BZ overdose and BZ sedation
* short half-life (7-15 minutes) with unpredictable effects that may potentiate seizures. Rarely indicated due to low mortality with benzo overdose
40
Briefly describe the MOA of barbiturates and explain why they do not demonstrate a ceiling effect
* Bind to an allosteric site on the GABA-gated chloride gate (different from BZ site) which increases GABA affinity
* unlike BZs, also increases chloride gate activity in absence of GABA, explaining the lack of a ceiling effect
41
Explain some disadvantages of barbiturates
* high risk of physical dependency (unpleasant withdrawal)
* low therapeutic index
* less dose-dependent, cause simultaneous sedation, anxiolysis, and hypnosis
42
describe benefits of modern sedative-hypnotics used for non-acute insomnia (zopiclone, zaleplon, eszoplicone) vs BZs
* less effect on sleep archtecture (protection of REM sleep)
* lower risk of dependence/tolerance
* shorter duration of action for less daytime effects
43
**Imovane** (Zopiclone)
* non-BZ sedative-hypnotic
* used in management of sleep disorders
* increases GABA activity in CNS
* less tolerance and dependence forming than the BZ drugs
* preserves sleep architecture
44
**Sublinox** (Zolpidem)
* non-BZ sedative-hypnotic
* used in management of sleep disorders
* increases GABA activity in CNS
* less tolerance and dependence forming than the BZ drugs
* preserves sleep architecture, less effect on next-day cognitive performance and coordination
45
**Sotacor** (Zaleplon)
* non-BZ sedative-hypnotic
* used in management of sleep disorders
* increases GABA activity in CNS
* less tolerance and dependence forming than the BZ drugs
* preserves sleep architecture
46
**Noctec** (Chloral hydrate)
* Non-BZ sedative hypnotic
* given as a prodrug
* generally only given as preanesthetic sedation in **pediatric patients**
47
**Precidex** (Dexmetetomidine)
* alpha-2 agonist
* used in treatment of hypertension and for sedation in anaesthetized/intubated patients in an ICU setting
* used due to lack of respiratory depression
48
contrast analgesia and anaesthesia
analgesia is the blockage or reduction of only pain sensation. Anaesthesia is the blockage of all sensation
49
The two major classes of local anaesthetics and the prototype drugs of each are:
Ester-type (procaine/cocaine) and Amide-type (lidocaine)
50
Describe the MOA of local anaesthetics
they bind to sodium channels and prolong the inactivated state, reducing excitability.
51
Describe the methods of administration of local anaesthetics
Topical: may reduce pruritis or pain of IV placement. May be given as a eutectic mixture of agents
Infiltration: most common, injected into SC tissue. Duration depends on local blood flow (slow flow prolongs duration) so sometimes given with epinephrine (**but never at terminal arterioles in digits**)
Iontophoreis: delivery using small electric current, mainly in dentistry
Nerve block and field block
Intrathecal and epidural
52
Describe the effects of size-dependent and use-dependent blockade in local anaesthetics
Local anaesthetics have greatest effect on small, unmyelinated fibres (size-dependent) and on fibres that are actively firing frequently (use-dependent).
53
**Xylocaine** (Lidocaine)
* Amide-type local anaesthetic
* sodium channel blocker that produces use-dpendent and size-dependent blockade
* may be given with epi to induce vasoconstriction and prolong duration of action
* relatively strong local anaesthetic effect
54
Cocaine
* Ester-type local anaesthetic
* Sodium channel blocker
* causes local vasoconstriction, prolonging duration of action
* relatively weak anaesthetic effect and high risk of abuse, so rarely used
55
Adverse effects of local aneasthetics include:
* CNS effects (stimulation, then inhibition)
* Cardiovascular effects (hypotension and arrhythmogenesis)
* NMBA potentiation
* Allergic reactions (especially ester-type)
56
The 4 stages of general anaesthesia are:
1. Analgesia and **conscious sedation**
2. **Paradoxical excitation** (not commonly seen with modern, balanced anaesthesia)
3. **Surgical anaesthesia** (desired state)
4. Vasomotor and respiratory depression with **cardiovascular collapse** (not desired!)
57
Factors that effect the rate of induction when using inhalational anaesthetics are: (list 4)
1. Solubility of the gas
2. Alveolar partial pressure of the anaesthetic
3. Pulmonary ventilation
4. Pulmonary blood flow
58
Inhalational anaesthetics with _______ (high / low) blood:gas partition coefficient will have a rapid onset
Low
## Footnote
*gasses with a high BG partition require high concentrations to achieve saturation of blood proteins and exist as free gas at tissue beds*
59
Decribe the MOA of inhalational anaesthetics
the free gas form of these drugs binds to GABA receptors and increases chloride influx, leading to cell hyperpolarization
60
inhalational anaesthetics with a _________ (high / low) oil:gas partition coefficient have the highest efficacy
high
61
give examples of halogenated and non-halogenated inhalational anaesthetics
halogenated: Halothane, desflurane, isoflurane, sevoflurane
non-halogenated: nitrous oxide
62
describe why sevoflurane is considered a near-ideal inhalational anaesthetic
* it has a relatively low blood:gas partition coefficient and high oil:gas partition coefficient leading to rapid induction and high efficacy
* it provides smooth induction and emergence
* it has very little CV or other toxicity
63
A rare but important adverse effect of inhaled halogenated anaesthetics is:
malignant hyperthermia
64
explain why inhalational anaesthetics should be used with caution in patients with low cardiac output
these patients may have pulmonary arterial hypertension which will increase pulmonary bloodflow and potentiate the rate and depth of induction
65
the value used to measure the potency of inhalational anaesthetics is the:
minimum alveolar concentration
## Footnote
*this is the partial pressure in the lungs required to produce desired anaesthesia in 50% of patients*
66
The inhalational anaesthetic which provides the most potent analgesia is:
nitrous oxide
67
All halogenated anaesthetics cause _______ (CP effects)
cardiovascular and respiratory depression (decreased cardiac ouput, decreased resp rate and tidal volume)
68
What are three advantages of parenteral (IV) anaesthetics over inhalational ones?
* they have a rapid onset
* they do not require specialized equipment
* they have fast recovery/emergence rates
## Footnote
*Fast on, fast off, and easy*
69
Outline popular parenteral anaesthetic agents
Benzodiazepines: especially midazolam, used as a sedative-hypnotic for premedication and during surgical procedures. Amnesic properties useful
Opioids: especially Fentanyl, for analgesia and combined with sedatives to provide general anaesthesia without CV depression
Propofol: Rapid on, rapid off sedation and amnesia which **reduces ICP and BP**. Ideal for head injury, caution in hypotension.
Etomidate: Rapid induction with minimal CV effects, but causes long term inhibition of steroid synthesis so only useful in acute setting (RSI)
Ketamine: Rapid induction, strong analgesia, minimal CV effects, but unpleasant emergence. Useful in children since emergence effects are less pronounced
70
**Diprivan** (Propofol)
* Parenteral, non-opioid anaesthetic
* Cause GABA potentiation (similar to BZs) to produce sedation and anaesthesia
* generally used to induce anaesthesia which is maintained by an inhalational anaesthetic, except in short, minor procedures. (20s onset, 5-10 min duration)
* **Reduces ICP and BP**, so near ideal for head injury management
* prolonged use potentiates cardiovascular depression
71
**Amidate** (Etomidate)
* Parenteral anaesthetic
* Acts on GABA receptors to produce anaesthesia/sedation
* **Rapid onset and very few cardiovascular side effects**, so ideal for hyperacute situations
* used in RSI and conscious sedation
* Prolonged use inhibits steroid synthesis
72
**Ketamar** (Ketamine)
* Non-opioid parenteral anaesthetic, sedative, dissociative
* Blocks excitatory NTs at NMDA receptors. Produces **dissociative anaesthesia**
* Anaesthesia characterized by analgesia, reduced sensory perception, incomplete loss of consciousness, immobility, and amnesia
* Causes increased BP and no respiratory depression (great for trauma)
* produces unpleasent emergence including hallucinations and delirium; **less common in pediatric patients!**
73
Typical and atypical antipsychotics are also known as _________ and are differentiated based on \_\_\_\_\_\_\_\_\_
first and second generation anipsychotics; differentiated based on D2 to 5-HT2 receptor specificity (second-generation have greater 5-HT2 specificity)
74
Common drug name endings for atypical (2nd gen) antipsychotics are:
* **-Pine** (Cloza**pine**, Olanza**pine**, Quetia**pine**)
* -**Idone** (Respir**idone**, Paliper**idone**)
* Apripirazole (gets its own darn name!)
## Footnote
*The schizoprenic pt, afraid his penis had disappeared, shouted "help, my **ole** **peen** **i**s **done**!" for -ole, -pine, -idone.*
75
The advantages of 2nd generation antipsychotics are:
effective in management of positive symptoms (hallucinations, delusions, agitation) with fewer extrapyramidal symptoms (EPSs) and less exacerbation of negative symptoms (social withdrawal, anhedonia)
76
Long term treatment with antiphsychotics may lead to \_\_\_\_\_\_\_\_\_\_, an irreversible disorder of movement that includes involuntary repetitive movements of the perioral and ocular muscles
tardive dyskinesia
77
the ________ hypothesis is an attempt to explain the underlying cause of schizophrenia and states:
dopamine; schizophrenia is caused by imbalances in dopamine trasnmission in the mesolimbic and mesocortical pathways.
78
**Haldol** (Haloperidol)
* first generation, typical antipsychotic
* blocks D2 receptors in the mesocortical, mesolimbic and other pathways
* high potency, very high risks of extrapyramidal side effects
* generally only useful in treatment of **positive** symptoms of schizophrenia.
* prolonged use may lead to tardive dyskinesia or neuroleptic malignant syndrome
79
**Clozaril** (Clozapine)
* second generation, atypical antipsychotic
* blocks 5-HT and D2 receptors in the mesocortical, mesolimbic and other pathways
* high potency, low risk of EPSs, but many other systemic side effects stemming from alpha blockade and anticholinergic effects
* useful in treating both positive and negative symptoms of schizophrenia
* prolonged use may lead to tardive dyskinesia or neuroleptic malignant syndrome
80
The two types of affective disorder are:
depressive and bipolar
81
Affective disorders are thought to be rooted in imbalance of \_\_\_\_\_\_\_, \_\_\_\_\_\_\_, and _________ as stated by the ___________ hypothesis
norepinephrine, serotonin (5-HT), and dopamine; biogenic amine hypothesis
82
The most commonly used, and first-line anti-depressants are _________ due to \_\_\_\_\_\_\_
SSRIs due to good effectiveness and lower risk of adverse effects than other antidepressents
83
TCAs ______ (are / are not) highly effective in treating depression and have many potentially severe side effects, including:
* They are very effective
* Side effects include; sedation, anticholinergic effects, orthostatic hypotension, and cardiac conduction disturbances
* prolonged use and overdose may cause serotonin syndrome and wide-QRS tachycardia with seizures, respectively
84
**Elavil** (amitryptiline)
* tricycylic antidepressent (TCA)
* inhibits reuptake of serotonin and norepinephrine, increasing synaptic concentration
* highly effective in treatment of depression, but with many adverse effects
* onset of 2-4 weeks
* adverse effects include; sedation, anticholinergic effects, orthostatic hypotension, and cardiac dysrhythmia. OD may cause wide-QRS tachy. Prolonged use may lead to serotonin syndrome
85
serotonin syndrome, which may be caused by TCA, MAOI, SSRI, or SNRI antidepressents as well as other drugs, manifests as:
* flushing
* tremor and hyperreflexia
* diaphoresis
* hyperthermia
* agitation
* dilated pupils
* diarrhea
86
Because many antidepressants are biogenic amine analogues, they end their names in \_\_\_\_\_
-ine
## Footnote
*ex: amitryptil**ine** (TCA), fluoxet**ine** (SSRI), sertral**ine** (SSRI), venlafax**ine** (SNRI), selegil**ine** (MAOI)*
87
**Prozac** (fluoxetine)
* SSRI antidepressent
* selectively blocks reuptake of serotonin, increasing serotonin concentration in the synaptic cleft
* highly effective with a low rate of adverse effects (e.g. sedation, anticholinergic effects, ortho hypo, dysrhythmia)
* most common and first line drug in treatment of depression
88
Compare and contrast TCA and SNRI antidepressants
* both inhibit the reuptake of serotonin and norepinephrine
* SNRIs are much more selective for these two NTs, whereas TCAs have far more broad systemic effects, and therefore more adverse effects
89
**Cymbalta** (duloxetine)
* SNRI antidepressant
* Inhibits reuptake of Serotonin and Norep with few other NT interactions
* Used in treatment of affective and anxiety disorders
* Fewer adverse effects than TCAs
90
The major potential adverse effect of MAOIs is:
Hypertensive Crisis
91
Identify three common classifications of pain
Somatic, visceral, and neuropathic
92
Identify neurotransmitters that are important to the neurotransmission and modulation of pain
**Substance P** and **glutamate** are important in the ascending transmission of pain
**Serotonin** and **norep** are important in downregulation of the pain cascade
**Enkephalins** inhibit pain transmission and the release of substance P
93
The three common classifications of opioids based on efficacy are:
full agonists, partial agonists, and mixed agonists/antagonists
94
Common pharmacologic effects of opioids include:
* analgesia
* sedation
* euphoria/dysphoria
* miosis
* nausea/vomiting
* cough supression
* Constipation
* respiratory depression
* vasodilation and decreased HR
* pruritis and flushing
95
Describe the general mechanism of action of opioid analgesics
* primarily bind to mu-opioid receptors (along with delta and kappa) in the CNS and descending inhibitory pathways of pain
* opioid receptors are Gi GPCRs and their activation decreased cAMP and decreases Ca2+ transmission, leading to decreased activation of pain pathways
96
Give examples of common opioid full agonists, partial agonists, and mixed agonists/antagonists
* Full: Morphine, hydromorphone, fentanyl, meperidine, methadone, oxycodone
* Partial: Codeine, hydrocodone
* Mixed: Buprenorphine (with naloxone = suboxone)
97
**Dilaudid** (Hydromorphone)
* Strong, semi-synthetic opioid, full opioid agonist
* 10x potency relative to morphine with fewer CNS, GI, and CV effects than morphine
* powerful analgesic for acute and chronic pain
* adverse effects include sedation, respiratory depression, constipation, miosis, N/V
98
Morphine
* Strong, natural opioid, full opioid agonist
* considered the prototype opioid
* powerful analgesic for acute and chronic pain
* adverse effects include sedation, respiratory depression, constipation, miosis, N/V
* hydromorphone preferred for chronic pain management due to fewer adverse effects
99
describe benefits of morphine in MI management
* decreased pain and agitation due to analgesic and sedative effects
* vasodilation and negative chronotropy reduce myocardial workload and oxygen demand
100
**Sublimaze** (Fentanyl)
* Strong, synthetic opioid, full opioid agonist
* 100x potency relative to morphine with fewer CV effects, faster onset, and less hangover than morphine
* powerful analgesic for acute and chronic pain
* adverse effects include sedation, respiratory depression, constipation, miosis, N/V
101
**Sufenta** (Sufentanil)
* Strong, synthetic opioid, full opioid agonist
* 1000x potency relative to morphine with fewer CV effects, faster onset, and less hangover than morphine
* powerful analgesic for acute and chronic pain
* adverse effects include sedation, respiratory depression, constipation, miosis, N/V
102
**Demerol** (Meperidine)
* Strong synthetic full opioid analgesic
* 0.1X potency relative to Morphine
* Less smooth muscle effects less pronounced than with other opioids. Fewer GI, biliary, and uterine side effects
* Safer for pregnant patients, or those with cholecystitis
103
**Dolophine** (Methadone)
* Long-acting synthetic full opioid agonist
* Does not tend to produce euphoria or other reinforcing effects
* Used in management of chronic pain and in opioid addiction treatment
104
The 6 modes of brain function that neuropharmacological agents can act on are:
1. Cognitive Processing
2. Memory
3. Emotional Processing
4. Sensory Processing
5. Motor Processing
6. Autonomic Processing
