Week 1 Flashcards
(186 cards)
1
Q
There are excitatory and inhibitory neuron terminals. Name one excitatory NT, two inhibitory NTs, and three NTs that can be excitatory or inhibitory
A
Excitatory: Glutamate
Inhibitory: dopamine, GABA
Both: Acetylcholine, serotonin, norepinephrine
2
Q
What is the difference between the direct and indirect actions of NTs?
A
Direct action - neurotransmitters bind to and open ion channels. Promotes rapid responses by altering membrane potential.
Indirect action - neurotransmitter acts through intracellular second messengers, usually G protein pathways. Broader, longer-lasting effects
3
Q
What are the two types of membrane channels? Describe them.
A
Voltage-gated: opens and closes in response to voltage changes across the membrane (voltage gated sodium channels; lidocaine)
Ligand-gated (ionotropic): a hormone, drug, or NT binds to the protein and the channel opens up (glutamate and ACh receptors)
4
Q
What are the two different types of receptors on neurons? Describe them.
A
Ligand gated (ionotropic) - action is immediate and brief. Some are excitatory and open channels for small cations. Some are inhibitory and allow Cl- influx or K+ efflux to cause hyperpolarization.
Metabotropic - Not directly linked to ion channels. Initiates biochemical processes (G-protein mechanisms) that mediate more long-term effects and modify the responsiveness of the neuron. NT acts as the first messengers which activates a second messenger that in turn changes the excitability of a neuron.
5
Q
What are the two types of metabotropic receptors? Describe them.
A
Membrane-delimited: occur entirely in plane of membrane. When G-proteins interact with Ca++ channels, they inhibit channel function (presynaptic inhibition). When G-proteins interact with K+ channels, they open (activate) channels causing postsynaptic inhibition.
Diffusible second messengers: beta-adrenergic receptors and cAMP . (This takes a lot more time to cause an effect than membrane-delimited)
6
Q
What’s the difference between an autoreceptor and a heteroreceptor?
A
Autoreceptor - receptors on an axon terminal through which the neuron’s own NT can influence the function of the terminal (usually inhibitory) (such as D2)
Heteroreceptor - receptors on an axon terminal through which NTs from other neuronal types can influence the function of the terminal.
7
Q
What does the chemical structure look like for dopamine, norepinephrine, and amphetamines?
A
Dopamine is a catecholamine that has an ethylamine group
Norepinephrine is a catecholamine with an ethyl group with a hydroxyl group and a terminal amine group
Amphetamine is a catecholamine with a site group with three carbons, one hydroxyl group, and a nonterminal amine group
8
Q
Dopamine is synthesized from what amino acid precursor?
A
tyrosine
9
Q
In order to produce dopamine.. once tyrosine is in the neuron, it is first converted to ___ by ____
A
DOPA (dihydroxyphenylalanine)
Tyrosine hydroxylase
Note that DOPA can be used to treat Parkinson’s
10
Q
Once DOPA is produced it is converted to ____ by ____
A
DA (dopamine)
AAD (aromatic amino acid decarboxylase)
11
Q
What happens once DA is produced in the neuron?
A
It is transported into vesicles via VMAT (vesicular monoamine transporter). It then can be released from the neuron
12
Q
Once DA is released from the terminal, what are three fates of DA?
A
Bind to autoreceptor D2 - this will lead to decreased release of DA and decreased activity of tyrosine hydroxylase
Bind to post synaptic neuron receptors (heteroreceptors)
Be reuptaken into the presynaptic neuron via DAT (dopamine transporter)
13
Q
What other molecules can go through the DAT?
A
Amphetamines can go through DAT. In this case, amphetamines enter the neuron while pumping out DA
14
Q
Once DA is reuptaken into the presynaptic neuron via DAT, DA is metabolized into DOPAC by what enzyme?
A
Monoamine oxidase (MAO)
15
Q
Describe the production of NE (norepinephrine)
A
Similar to production of DA. Once DA is produced and pumped into vesicles via VMAT, it is converted to NE by an intravesicular enzyme called DBH (dopamine beta hydroxylase)
16
Q
Once NE is released from the presynaptic neuron, it has three similar fates to DA. It can bind to its autoreceptor ___, it can bind to ___ or ___ heteroreceptors on other neurons, or it can be pumped back into the presynaptic neuron via ____. _____ metabolizes NE in the neuron (similar to DA).
A
Alpha 2
Alpha or beta
NET (norepinephrine transporter)
Monoamine oxidase
17
Q
What enzyme converts norepinephrine to epinephrine?
A
(PNMT) Phenylethenolamine-N-methyltransferase
18
Q
What is a chatechol? What is a catecholamine?
A
A catechol is a benzene ring with two hydroxyl groups on adjacent carbons
A catecholamine is a catechol with a side chain with an amine group in it.
19
Q
What cells mainly use epinephrine?
A
Adrenal medullary cells
Some CNS neurons
20
Q
What does the structure of serotonin look like? Is it a catecholamine?
A
Two rings (one 6 carbon ring, one 5 carbon ring) with one hydroxyl group, and two amine groups
It is NOT a catecholamine
21
Q
Serotonin is derived from what amino acid?
A
Tryptophan
22
Q
In order to synthesize serotonin, the amino acid precursor ___ is converted to ____ by _____. Then, it is converted to ____ by ____
A
Tryptophan
5-hydroxyltryptophan (5HTP)
Tryptophan hydroxylase
Serotonin (5-hydroxyltryptamine)
AADC (amino acid decarboxylase)
23
Q
What is the other name for serotonin?
A
5HT (5-hydroxyltryptamine)
24
Q
What happens once serotonin is produced in the neuron?
A
It is pumped into vesicles via VMAT (vesicular monoamine transporter). Then the vesicles fuse with the membrane for release of the NT.
25
Similar to other NTs, serotonin can bind to an autoreceptor (___), bind to heteroreceptors, or be pumped back into the neuron (by ____)
5HT/1B
SERT (serotonin transporter)
26
What are SSRIs?
Selective serotonin receptor inhibitors. These drugs work on SERTs (serotonin transporters)
27
What is the function of dopamine beta hydroxylase?
Converts DA to NE in vesicles
28
___ +___ will yield ACh through the action of what enzyme?
Choline
Acetyl coA
ChAT (choline acetyl transferase)
29
Once ACh is produced in the neuron it is stored into vesicles through what transporter?
Vesicular ACh transporter
| Note that it isn't VMAT
30
Once ACh is released from the neuron it is quickly metabolized by ___ back to choline.
Acetylcholinesterase
31
True or false... there is a plasma ACh transporter in neurons
False! Just a choline transporter to pump choline back into the neuron
32
ACh can bind to what kinds of post synaptic receptors?
Muscarinic and nicotinic
33
How does the botulinum toxin work?
It prevents the release of ACh from neurons
34
Once ACh is released from the neuron, it may bind to what autoreceptor to decrease the release of ACh?
A muscarinic autoreceptor
35
GABA is an inhibitory NT whereas glutamate is an excitatory NT. How are their molecular structures similar?
Both have four carbons and a carboxyl group, and amine group
36
What is the precursor for producing glutamate?
Alpha keto gluterate (from citric acid cycle)
37
Alpha keto gluterate is converted to glutamate by the action of the ___ enzyme
Aminotransferase
38
Once glutamate is produced in the neuron, it is transported into vesicles by ___
Vesicular glutamate transporter
39
Once glutamate is released from the neuron, it may re-enter the neuron by the ___ transporter
Glutamate transporter
40
Once released from the neuron, glutamate binds to ____ (autoreceptor )
Metabotropic glutamate
41
Name two post synaptic receptors that glutamate binds to
AMPA/kainate
NMDA
42
Glutamate enters astrocytes through the glutamate transporter. Once in the astrocytes, glutamate is converted to ___ via the action of ____.
Glutamine
Glutamine synthetase
43
Once glutamine is produced in astrocytes, glutamine may enter the neuron and be converted to ___ through the action of ___.
Glutamate
Glutaminase
44
In order to produce GABA, ___ must first be produced
Glutamate
45
In the production of GABA, glutamate is converted to ___ through the action of ___
GABA
GAD (glutamate decarboxylase)
46
Once GABA is produced in the neuron, how does it enter vesicles?
Vesicular GABA transporter
47
Once GABA is released from neurons, it may renter the neuron through ____. Or it may bind to ___ and ___ post synaptic receptors. Or it may bind to its autoreceptor ___. Or it may enter ___.
GABA transporter
GABA-A or GABA-B
GABA-B
Astrocytes
48
Which postsynaptic GABA receptor is involved with chloride channels?
GABA-B
49
Once GABA enters astrocytes, it is converted to ___ through the action of ____
Succinate
GABA transaminase
50
What is an endocannabinoid? Give an example
Anandamide (binds to CB1 receptors)
They are natural endogenous NTs
51
True or false... nitric oxide doesn't bind to receptors
True
52
Which histamine receptor is thought to function as an inhibitory heteroreceptor? Thus, activation of these receptors decreases the release of ACh, DA, NE, SER, and certain peptides?
H3
53
Endorphins bind to ___ receptors, causing a decrease in the release of ___. This mechanism can cause you to be happy.
Muscarinic
GABA
54
Name 7 neuropeptides
Neurotensin
Substance P
Somatostatin
Cholecystokinin
Vasoactive
Intestinal polypeptide
Neuropeptide Y
55
What does neurotensin do?
Acts as endogenous neuroleptic; regulates DA systems (inhibitory feedback)
56
What is nitric oxide? What does it do to vascular smooth muscle?
It is a gaseous signaling molecule
Relaxes vascular smooth muscle
57
In the autonomic nervous system, ACh binds to what kind of receptor on post ganglionic neurons
Nicotinic
58
True or false... ACh is used by both the sympathetic and parasympathetic pre-ganglionic fibers
True
59
True or false... drugs that alter ACh levels affect BOTH the sympathetic and parasympathetic systems
True
60
What other neurons act via nicotinic receptors?
Motor neurons innervating skeletal muscle
61
What types of NTs do post ganglionic sympathetic neurons use?
DA, NE, and EPI.
| Most use NE
62
NE and EPI act on __ and __ receptors. What about DA?
Alpha and beta
DA activates D1, alpha, and beta
63
What NTs do post-ganglionic parasympathetic neruons use?
ACh
64
What receptors does ACh (released from post-ganglionic parasympathetic) neruons bind to?
Muscarinic receptors in most effector tissues
Nicotinic in somatic muscles
65
Name 5 specific receptors that the parasympathetic nervous system acts on.
M1
M2
M3
Nm
Nn
66
Describe where each of the following parasympathetic receptors are found.
```
M1
M2
M3
Nm
Nn
```
M1 - Stomach
M2 - Heart (SA node, AV node, atria, ventricles)
M3 - GI tract (GI smooth muscle, secretory glands)
Nm- muscle (neuromuscular junction)
Nn - Neuronal (autonomic ganglia, adrenal medulla)
67
Name three agonists for parasympathetic muscarinic receptors
ACh
Bethanechol
Pilocarpine
68
If parasympathetic M1 receptors are activated by an agonist, what happens?
Acid secretion in the stomach increases
69
If M2 receptors are activated by an agonist, what happens?
SA node -> decrease HR
AV node -> decrease in conduction velocity
Atria -> decrease AP duration and contractility
Ventricles -> decrease in contractility
70
If M3 receptors are activated by an agonist, what happens?
GI smooth muscle - increase contractions (usually; except sphincters)
Secretory gland - increase secretions
71
Name two antagonists of the muscarinic receptors
Atropine
Scopolamine
72
Name two antagonists of Nm receptors
Succinylcholine***
D-tubocurarine
73
Name two antagonists of Nn receptors
Mecamylamine**
Trimethaphan
74
What are the two classes of neuromuscular blockers ? Describe them and give an example of each
Depolarizing (succinylcholine) - non-competitive. Acts as a nicotinic agonist and depolarizes/desensitizes the deuromuscualr endplate by opening up the NIC channels and keeps them open so that the neuron is depolarizer and unresponsive to another ACh challenge.
Non-depolarizing (tubucurare) - competitive. Competes with ACh at nicotinic receptors
75
What 3 things happen with the blockage of AChE? (Acetylcholinesterase)
Affects both sympathetic and parasympathetic systems
Affects tissues innervated by post ganglionic fibers
Affects signaling at the neuromuscular junction
76
Give an example of a cholinesterase inhibitor
Sarin
77
What may happen if you block AChE?
ACh will build up extraneuronally. This will lead to a decrease heart rate, stimulation of skeletal muscles to cause tetanus (prevents breathing), drooling, watery eyes, blurred vision, sweating, diarrhea.
78
What drug is used to counter the effects of Sarin?
Atropine because it is a muscarinic antagonist (competes with excess ACh)
79
Name three cholinesterase inhibitors and what they do.
Physostigmine - short duration of action, used for glaucoma, antidote for atropine
Donepezil (aricept)- extended duration of action, used to treat Alzheimer's
Sarin - irreversible, long duration of action, biological weapon nerve gas
80
how does botulinum toxin work? What does it do?
Prevents release of ACh
Relaxes intraocular muscles
Treats muscle dystonia (spasms)
Removes wrinkles
81
Name two cholinergic agents (cholinomemetics) used in dentistry and what they are used for
Cevimeline (Evoxac) - cholinergic agonist used to treat xerostomia in SS
Pilocarpine (salagen) - cholinergic agonist used to treat xerostomia after radiation therapy. (Mouthwash available)
82
What is a cholinomimetic?
An agent that mimics ACh
83
What is curare (tubocurarine) and how does it work? What is its antidote?
Used in poison darts. It competitively and reversibly inhibits nicotinic ACh receptors. This causes skeletal muscle weakness and even death by diaphragm paralysis.
Antidote - Acetylcholinesterase inhibitor
84
True or false... nicotine is a cholinesterase inhibitor
True
85
What is the indication for the use of bethanechol (urecholine)?
Increase urinary output to treat urinary retention
86
What is the indication for the use of pilocarpine?
Increases saliva secretion and treats glaucoma**
87
What is the indication for the use of succinylcholine?
It is an antagonist. Used in surgeries to relax muscles
88
The sphincter muscle in the iris has ___ receptors
Muscarinic
89
What is closed angle glaucoma?
Narrow angle between iris and cornea leads to fluid build up in the vitreous humor (increases intraocular pressure).
Develops very quickly and requires immediate medical attention
Signs and symptoms very noticeable
90
What do you use to treat angle closure glaucoma?
Pilocarpine to contract and pull iris to open trabecular meshwork
91
Name two anti muscarinic agents and some uses of them
Atropine (antidote for sarin gas)
Scopolamine (used for motion sickness)
Also can be used to treat Parkinson's, COPD, urinary urgency
92
What are the side effects of anti muscarinic agents? (5)
Anticholenergic effects...
```
Dry mouth
Constipation
Blurred vision
Sedation
Urinary retention
```
93
What is pralidoxime used to treat? How does it work?
Treats organophosphate poisoning
Organophosphates bind to acetylcholinesterase. Pralidoxime binds to acetylcholinesterase to kick of the organophosphates
94
Name two important synthetic anticholinergic agents. What are they used to treat?
Propantheline bromide (pro-banthine) - treats travelers diarrhea
Trihyxphenidyl HCl (artane) - anti-parkinsonism
95
Describe where the following sympathetic receptors are found...
```
Alpha 1
Alpha 2
Beta 1
Beta 2
Beta 3
```
Alpha 1 - radial muscle of iris, genitourinary sphincters
Alpha 2 - vasculature, NE terminals, brain stem
Beta 1 - heart
Beta 2 - ciliary muscle, vasculature, lungs, urinary bladder
Beta 3 - adipose tissue
96
Name two agonists of alpha 1 receptors
Epinephrine > NE
Phenylephrine
97
What happens to the radial muscle of the iris when alpha one receptors are activated by an agonist?
Contract. (Opens up pupil to cause dilation)
98
What happens to the genitourinary and GI sphincters when alpha 1 receptors are activated by an agonist?
Constrict (leads to retention)
99
Name two antagonists of alpha 1 receptors
Prazosin
Terazosin
100
True or false... phenylephrine is used as a decongestant because it causes vasoconstriction of the nasal passages
True
101
Name three agonists of alpha 2 receptors
Epi>NE
Clonidine
Guanfacine
102
What happens to the vasculature when an alpha 2 receptor is activated by an agonist?
Constricts (increases BP)
103
What happens to NE terminals when an alpha 2 receptor is activated by an agonist?
Decrease NE release. (Remember that alpha 2 is an autoreceptor in NE terminals)
104
What is the response of the brain stem when alpha 2 receptors are activated by an agonist?
The brain stem will decrease NE release (this will cause a reduction of BP)
105
What is guanfacine used to treat?
Treats ADD. It's mechanims are central.
The central signals will trump the peripheral signals to cause vasodilation leading to decease of BP.
106
What is an antagonist of alpha 2 receptors? (This antagonist isn't used for anything)
Yohimbine
107
Name two agonists of beta 1 receptors
Epi = NE
| Isoproterenol
Dobutamine
108
What tissues are Beta 1 receptors found in?
Cardiac tissue (SA node, AV node, Atria, ventricles, His-purkinje system)
109
What happens when the following tissues are Beta 1 activated by their agonist?
```
SA node
AV node
Atria
Ventricles
His-purkinje system
```
SA node - increase HR
AV node - increase automaticity and conduction velocity
Atria - increase conduction velocity and contractitliy
Ventricles - increase automaticity, conduction velocity and contractility
His-purknje system - increase automaticity and conduction velocity
110
Name one antagonist of beta 1 receptors. What are they used to treat?
PropranOLOL
(Also atenolol, metoprolol)
Betablockers are used to treat hypertension.
111
What types of tissues are beta 2 receptors found in?
Ciliary muscle
Vasculature
Lungs (tracheal and bronchial smooth muscle)
Urinary bladder, uterine wall
112
Name 4 beta2 agonists. Which is better epi or NE?
Epi>>>NE***
Isoproterenol
Albuterol
Terbutaline
113
What happens to the following tissues when beta 2 receptors are activated by an agonist?
Ciliary muscle
Vasculature
Lungs (trancheal/bronchial smooth muscle)
Urinary bladder/uterine wall
Ciliary muscle - relaxation (for far vision)
Vasculature - relaxation, especially in skeletal muscle (vasodilation)
Smooth muscle in lungs - relaxation for opening of airways
Urinary bladder - relaxation
Uterine wall - relaxation
114
In adipose tissue, are beta 3 receptors activated more easily by NE or EPI?
NE
115
When B1 receptors are stimulated in the heart, the increase in HR is a positive ___ effect. The increase strength of ventricular contraction is a positive ___ effect.
Chronotropic
Ionotropic
116
When epinephrine binds to alpha 1 receptors of the bladder sphincter, what happens? What about when epi binds to Beta 2 receptors of the muscle of the urinary bladder?
Constricts
Relaxes
*this leads to urinary retention
117
Name 5 therapeutic uses of epinephrine
Broncospasm
Anaphylaxis
Restore function in cardiac arrest
Treat open-angle glaucoma
Prolong action of local anesthetics
118
Describe open-angle glaucoma
Most common type of glaucoma
Imbalance in the production and drainage of aqueous humor that fills the anterior chamber (leading to build up of fluid)
Wide angle between iris and cornea
Develops over lifetime
119
How do you treat open-angle glaucoma?
Treat with epinephrine to decrease production of aqueous humor
120
Name three side-effects of epinephrine
Cardiac - increased HR, palpitations, arrhythmias, angina
Vascular - increased TPR (total peripheral resistance ) leading to increased BP and pallor (pale face due to less blood flow in face due to vasoconstriction)
Respiratory - increased TPR can lead to pulmonary edema
121
True or false. Epinephrine easily crosses the BBB
False. CNS effects are negligible
122
What receptors does NE bind to?
Alpha and beta
B1 >>> B2
123
What are some physiological effects of NE?
Vasoconstriction, increased TPR, increased BP. (Things get complicated with baroreceptor involvement)
124
What is a therapeutic use for NE?
Shock
125
What are some side effects of NE?
Slow heartbeat if BP increased (due to baroreceptors), forceful beat (B1), vasoconstriction (decrease blood flow to vital organs; alpha 1)
126
Which, epi or NE is used as an emergency hormone secreted in response to stress?
Epinephrine
Note that A1=A2, B1=B2 in regards to affinity
127
Is this a description of epinephrine or NE?
Increases HR
Redistributes blood to skeletal muscles by dilating pre-capillary resistance vessels in skeletal muscles (B2)
If "high and fast" -> increased TPR (alpha-1)
Epinephrine
128
Is this a description of epi or NE?
Increases HR if released by cardiac neurons (beta1) however, decreases HR when infused because vagaries stimulation overrides beta-1 mediated increase in HR
Maintains peripheral resistance by constricting pre-capillary resistance vesicles (alpha-1; alpha-1 trump beta 2)
NE
129
Name in order, the affinity of receptors that DA binds to
DA > beta > alpha
Primarily alpha 1 and beta 1
130
What is a therapeutic use for DA?
Used to treat shock and heart failure (at high doses, increased BP and TPR (alpha 1), increased HR (B1), increased organ perfusion (D1)
131
Name some effects of alpha 1 agonists such as phenylephrine
Vasoconstriction and increased TPR (used as nasal decongestant (PE))
Change in HR
Constricts sphincter muscle of bladder
132
What are some effects and uses of alpha 2 agonists?
Effects: Bradycardia, dry mouth
Used to treat HTN and ADHD (stimulation of CNS alpha2 receptors decreases sympathetic output
133
What are some uses of B agonists?
Asthma
Bronchospasm
COPD
OBGYN (relaxes smooth muscle of uterus during labor to slow contractions)
134
True or false... Isoproterenol is non selective for beta 1 or beta 2. However albuterol and terbutaline are Beta 2 selective
True
135
What are some mixed agonists? (Act on alpha and beta, but also cause release of NE)
Ephedrine
Ephedra
Pseudophedrine
136
What are some uses of mixed agonists? What are some side effects?
Decongestant, dietary supplements
Side effects: increase HR, vasoconstriction, dilation of airways, stimulant (if penetrates CNS)
137
Name 5 other "indirect" adrenergic agents (not sympathemimics)
Amphetamine
Cocaine
Methylphenidate
NNRIs
TCAs
138
How does cocaine work?
Blocks the reuptake of DA, NE, and Seratonin reuptake
139
What are NNRIs?
NE reuptake inhibitors
140
Tyramine is an indirect agonist with the action of a monoamine oxidase inhibitor. Describe its mechanism.
Tyramine is usually metabolized by MAO. If taking a MAOI, tyramine concentrations will increase. When neuron terminal vesicles fill with tyramine, NE goes out so you end up with a lot more NE.
141
Name two examples of non-selective alpha antagonists
Phenoxybenzamine
Phentolamine
142
What are the uses, effects, and side effects of non-selective alpha antagonists?
Uses: treatment of pheochromaocytoma (NE secreting tumor), hypertensive emergencies
Effects - decreased TPR (alpha 1) and decreased BP. Increased HR (baroreceptor response to decreased BP)
Side effects: orthostatic hypotension, nasal stuffiness
143
Name two examples of alpha 1 antagonists. What are their uses, effects, and side effects.
Prazosin
Terazosin
Uses: treat hypertension, benign prostatic hypertrophy (tamsulosin)
Effects - vasodilation and thus decreased TPR and decreased BP
Side effects: orthostatic hypotension, nasal congestion
144
What drug is used to treat benign prostatic hypertrophy?
Tamsulosin
145
Name four beta antagonists
What are the uses of beta blockers?
Propranolol (beta 1 and beta 2)
Atenolol (beta 1)
Metoprolol (beta 1)
Treatment of HTN, angina, open-angle glaucoma
146
What are the effects that beta antagonists have on the following tissues?
```
Cardiac
Vascular
Renal
Respiratory
Metabolic
Eyes
```
Cardiac: decreased HR and contractility
Vascular: increased TPR (blockade of B2 in skeletal muscle)
Renal: decreased renin release
Respiratory: bronchial constriction
Metabolic: decreased glycogenolysis in response to hypoglycemia
Eyes: decreased aqueous humor production
147
Epilepsy is a neurological disorder affecting __% of the population. __-__% of patients with epilepsy are therapy-resistant
1.2
25-40
148
What is the difference between a seizure and epilepsy?
Seizure = a finite clinical manifestation of abnormal and excessive excitation of a population of cortical neurons.
Epilepsy = a syndrome characterized by 2 or more* recurrent seizures that are unprovoked* by systemic or neurological insults
149
What is epileptogenesis?
A sequence of events that convert normal neuronal networks into a hyperexcitable network
150
What is status epilepticus (SE)?
Continuous seizure lasting more than 30 minutes or 2 or more seizures without full recovery of consciousness between them.
- any seizure lasting >5 minutes is treated clinically as SE due to the high risk of morbidity and mortality
- most patients in status epilepticus for 30 minutes will die
151
What percentage of the population will have at least one seizure in their lifetime?
10%
152
Over a lifetime, 1 in ___ people will be diagnosed with epilepsy
1/26
153
What is the main inherited etiology factor for epilepsy
Mutations in ion channels
154
What are some common seizure precipitants?
```
Metabolic imbalance
Stimulate intoxication
Depressant withdrawal
Sleep deprivation
Reduction of ASD treatment
Hormonal variations
Stress
Hypoxia
High fever
CNS infection
Concussion and/or closed head injury
```
155
What are the different seizure classifications?
Partial seizures: simple partial, complex partial, secondarily generalized
Generalized seizures: tonic-clonic, absence, atonic
156
What is a simple partial seizure?
Single focus
Patient is fully aware and responsive
Shortest duration (<90s)
Phenotype depends on areas of focal cortical involvement. (Focus is confirmed via EEG).
157
What is a complex partial seizure?
Focal onset with local spread.
Initially aware and responsive, but may develop some memory impairment if limbic system involved.
A complex partial seizure does not fully generalize, if it does it is considered a secondarily generalized seizure
Clinical manifestations vary with site of origin and degree of spread
Slightly longer duration (<120s)
158
What is a secondarily generalized seizure?
May begin as either simple or as complex partial seizures
Seizure activity fully generalizes with variable symmetry, intensity, and duration before evolving to tonic and/or clonic phases
Usually lasts <240s
159
What is the postictal phase of generalized seizures?
Confusion, somnolence, with or without transient focal deficit can last minutes - hours
160
What are generalized absence seizures?
Impaired awareness and responsiveness for 2-15 seconds. Patient stares off into space
161
Generalized absence seizures represent abnormal interactions between what parts of the brain?
Abnormal interactions between cortical and thalamic transmissions
The spike and wave pattern is a hallmark of absence epilepsy
162
Describe generalized tonic-clonic seizures
Progresses from tonic (rigid) to clonic (movement). Patient may scream as lungs constrict.
Then the patient enters the postictal phase where the patient is lethargic and confused.
163
What is the problem with ASD (anti seizure disorder) medication?
Approximately 1/3rd of all patients with epilepsy remain refractory to all treatments
164
What is the therapeutic (protective) index?
Safety margin between the effective dose and toxic dose. Calculated as...
Toxic dose/efficacious dose
Larger the number the better
165
What are three mechanisms of action for most commonly used ASDs?
1) enhancement of GABA-mediated inhibition
2) reduction of excitatory transmission (i.e. Glutamate)
3) modification of ionic conductance (i.e. sodium, calcium, potassium ions)
166
Carbamazepine
Indicated in partial simple or partial complex, and generalized tonic-clonic seizures
Common side effects: impaired vision, cognitive impairment.
Rare side effects: Stevens-Johnson syndrome
AVOID IN ABSENCE!! (May aggravate spike wave seizures)
Active metabolite
Potent CYP3A4 inducer
167
True or false.. carbamazepine is a great drug for partial epilepsy but the potential for drug-drug interactions is high.
True
168
What is the mechanism of carbamazepine?
Blocks voltage gated Na+ channels to inhibit repetitive firing neurons (this blocks the onset and spread of seizures)
169
What is Stevens-Johnson syndrome?
Toxic epidermal necrolysis - Skin becomes inflamed and sloughes off.
Symptoms: fever, sore throat, fatigue, painful mucosal lesions.
Patients on sodium channel blocker ASDs are at most risk
170
True or false... carbamazepine inhibits CYP3A4 enzyme in gut/liver, decreasing carbamazepine' metabolism and increases its plasma levels.
True.. note that grapefruit juice also raises CBZ plasma levels by inhibiting its breakdown by CYP3A4
171
What drug is used to treat uncomplicated absence only?
Ethosuximide
172
What are the indications, common side effects, and other special comments of ethosuximide?
Indication: uncomplicated absence only
Common side effects: drowsiness, dizziness, headache, minor weight loss,....**may worsen partial and tonic-clonic seizures
Special comments: narrow clinical spectrum (for absence only). *very long half life (40 hours)
173
What is the mechanism of ethosuximide?
Reduces T-type calcium channel currents in thalamic pacemaker neurons
174
What are the indications, common side effects and special comments of phenytoin?
Indication: partial simple or complex. Generalized tonic-clonic
Common side effects: nystagmus, cognitive impairment, fetal drug effects
Non-dose related: ***gingival hyperplasia
Special comments: **contraindicated for absence seizures (may aggravate absence spike-wave seizures. Zero-ordered kinetics at high doses; must check plasma levels often and titrate dose as needed
175
What is the mechanism of phenytoin?
Blockade of sodium channels during repetitive firing
176
Which ASD causes severe gingival hyperplasia?
Phenytoin
177
Why must you monitor plasma levels often and titrate the dosage of phenytoin?
Because it has zero order elimination kinetics
178
What are the indications, common side effects, and special comments of topiramate?
Indications: simple and complex partial. Generalized tonic-clonic and Lennox-gastuat syndrome
Common side effects: somnolence, **word recall problems, weight loss. (Rare but may also cause open-angle glaucoma)
Special comments: weight loss can be an advantage. Increases metabolism of estrogen so can reduce oral contraceptive efficacy (must use secondary means of birth control)
179
What is the mechanims of topiramate?
Broad spectrum
Blocks repetitive firing of voltage gated sodium channels, inhibits calcium currents, inhibits AMPA/kainate recpetors and potentials GABA currents
180
What are the indications, common side effects, and special comments for valproic acid?
Indications: atypical absence, absence, myoclonic, tonic-clonic. Partial simple and partial complex
Common side effects: weight gain. Toxic doses may cause reye-like syndrome and hepatic failure
Special comments: **contraindicated in patients with hepatic disease or significant hepatic dysfunction. Increased teratogenicity and neural tube defects such as spina bifida
181
What is the mechanism of valproic acid?
Broad spectrum
Blocks voltage gated sodium channels (main mechanism), reduces NMDA currents, increases GABA-mediated chloride currents
182
Why do you want to avoid valproate (valproic acid) during pregnancy?
Category D risk for birth defects including spinal bifida and other birth defects
183
What are the drugs of choice for partial seizures?
Carbamazepine
Phenytoin
Topiramate (if secondarily generalized)
184
What are the drugs of choice for generalized onset tonic-clonic seizures?
Valproate (valproic acid)
Topiramate
185
What are the drugs of choice for absence seizures?
Ethosuximide (uncomplicated)
Valproate (complicated)
186
What are the four principles of ASD treatment?
Match appropriate ASD to the seizure type confirmed by EEG
Try mono therapy first
Monitor plasma levels of drugs
Tailor therapy to individual patient
