Neuro Drugs Flashcards
1
Q
tx for epilepsy
A
antiepileptics, surgical excision of foci, vagus nerve stimulation, removal of causative factors, regulation of physical and mental activity
2
Q
antiepiletic drugs
A
tx manifestation not cause of seizures, prevents spread of seizure from focus
3
Q
vagus nerve stimulation (VNS)
A
tx for partial seizures, for refractory cases or if anticonvulsants are poorly tolerated
4
Q
anticonvulsant drugs
A
used for partial / focal seizures and generalized tonic-clonic seizures
5
Q
phenytoin
A
for partial and general tonic-clonic seizures, anticonvulsant, non-sedating, target - voltage gated Na channels in presynaptic glutamatergic synapse, alters Na conductance, blocks high frequency repetitive action potentials, decreases glutamate, increases gaba
6
Q
phenytoin pharmacokinetics
A
well absorbed orally, binds to plasma proteins, need free conc. for clinical effect, excreted in urine, 1st order elimination - as dosage increases metabolism saturates increasing blood conc
7
Q
phenytoin toxicity
A
nystagmus (early, no need to decrease dosage), diplopia / ataxia (must adjust dose), sedation, gingival hyperplasia, hirsutism (hair growth), long term - coarse facial features, peripheral neuropathy (lessened deep tendon reflexes)
8
Q
carbamazepine
A
for partial and general tonic-clonic seizures, like tricyclic antidepressants, blocks presynaptic voltage gated sodium channels in glutamatergic neurons, inhibits high-freq repetitive firing, modulates voltage gated Ca channels, increases K conductance, interacts with adenosine receptors
9
Q
carbamazepine pharmacokinetics
A
slow oral absorption, after meals helps, to all tissues, 70% plasma protein binding, no competition with other protein binding drugs, completely metabolized, induces microsomal enzymes, carbamazepine-10,11 epoxide has anticonvulsant activity, low systemic clearance at first, alters clearance of other drugs, excreted in urine, t 1/2 = 36 hours after first dose / 8-12 hours with continuous tx -> needs adjustment early in tx
10
Q
carbamazepine drug interaction
A
induction of cytochrome p450, enhances biotransformation of phenytoin, lowers concentrations of valproate / lamotrigine / tiagabine / topiramate, metabolism increased by phenobarbital / phenytoin / valproate
11
Q
carbamazepine toxicity
A
acute - stupor, come, hyperirritability, convulsions, respiratory depression; long term - drowsiness, vertigo, ataxia, diplopia, blurred vision, more seizures, nausea, vomiting, hematological (aplastic anemia, agranulocytosis), hypersensitivities (skin, eosinophilia, lymphadenopathy, splenomegaly)
12
Q
oxcarbazepine
A
for partial and general tonic-clonic seizures, blocks presynaptic voltage gated Na channels in glutamatergic neurons, inhibits high-frequency firing, like carbamazepine with less toxicity, weaker inducer of P450, t 1/2 1-2 hours, active metabolite 10-hydroxy oxcarbazepine with t 1/2 8-12 hours
13
Q
phenobarbital
A
for partial and general tonic-clonic seizures, blocks postsynaptic AMPA receptors in glutamatergic neurons, oldest/safest anticonvulsant, limited sedative effect, barbiturates - choice for infant seizures
14
Q
phenobarbital mechanism I
A
suppresses abnormal neurons (inhibits spread from foci), inhibits high-freq firing at high conc, decreases Na conductance, blocks some Ca current, only at high conc, improves GABA inhibition and decreases glutamine excitation
15
Q
phenobarbital mechanism II
A
binds allosteric site for GABAa receptor -> prolongs opening of Cl channels; blocks AMPA receptors -> decreases glutamate release
16
Q
phenobarbital pharmacokinetics
A
complete oral absorption, slow peak conc, 40-60% bound to plasma protein, 25% pH dependent renal excretion of unchanged drug, 75% inactivated by hepatic microsomal enzymes, induces CYP2C and CYP3A - other drugs metabolized faster by them (oral contraceptive)
17
Q
phenobarbital toxicity
A
sedation (at first - disappears with chronic), nystagmus and ataxia (high doses), irritability / hyperactivity (children), agitation / confusion (elderly), induces hepatic CYPs, conc elevated by valproic acid
18
Q
vigabatrin
A
for partial and general tonic-clonic seizures, irreversibly binds GABA-transaminase in GABAergic neurons - prevents degradation of GABA, inhibits vesicular GABA transporter, increased EC GABA conc, desensitization of synaptic GABA receptors, activation of non-synaptic GABA receptors causes tonic inhibition, decreases brain glutamine synthetase, increases GABA conc
19
Q
lamotrigine
A
for partial and general tonic-clonic seizures, blocks postsynaptic AMPA receptors, suppresses rapid firing, inhibits voltage and use dependent Na channels (go for focal epil), inhibits voltage gated Ca channels (good for gen seizures), decreases synaptic release of glutamate
20
Q
felbamate
A
for partial and general tonic-clonic seizures, GABA receptors agonist in GABAergic neurons, use-dependent blockage of NMDA receptors in glutamatergic neurons
21
Q
felbamate drug interactions
A
increases plasma phenytoin and valproic acid leves, decreases carbamazepine
22
Q
felbamate toxicity
A
aplastic anemia and severe hepatitis
23
Q
gabapentin and pregabilin
A
for partial and general tonic-clonic seizures, GABA analogs, increase the synaptic / non-synpatic release of GABA, bind voltage gated Ca channels (main MOA), decreases synaptic release of glutamate
24
Q
gabapentin mechanism of action
A
increases GABA release, binds voltage gated Ca channels decreasing glutamate release in glutamatergic neurons
25
lacosamide
for partial and general tonic-clonic seizures, enhances slow inactivation of voltage gated Na channels, binds collapsin response mediator protein (CRMP2) in presynaptic glutamatergic neurons, blocks neurotrophic factors (BDNF, NT3), affects axonal / dendritic growth
26
levitiracetam
for partial and general tonic-clonic seizures, presynaptic target, binds synaptic vesicular protein SV2A modifying glutamate and GABA release, side effects - somnolence, asthenia, ataxia, dizziness, agitation, anxiety
27
tiagabine
for partial and general tonic-clonic seizures, targets GABA reuptake transporters (GAT-1) increasing GABA at synapse in forebrain and hippocampus, prolongs inhibitory action
28
topirimate
for general and tonic-clonic seizures, post synaptic target, blocks voltage gated Na channels, potentiates inhibitory effect of GABA, works at site different from benzodiazepine and barbiturates, weak carbonic anhydrase inhibitor
29
ethosuximide
for general seizures, presynaptic target, binds voltage gated Ca channels reducing low-threshold Ca (T type) current, pacemaker in thalamus where absence seizures are generated
30
ethosuximide toxicity
gastric distress (pain nausea, vomiting), lethargy, fatigue, headache, dizziness, hiccup, euphoria, improved behavior
31
valporic acid and sodium valproate
for general seizures, solvent for other seizure drugs, anticonvulsant, fully ionized in body
32
valporic acid and sodium valproate mechanism of action
blocks high frequency firing (Na currents), blocks NMDA glutamate receptor excitation, increases GABA levels in brain, faciliatates glutamic acid decarboxylase that synthesizes GABA, inhibits GABA transporter GAT-1, inhibits GABA transaminase that degrades GABA, inhibits histone deacetylase
33
benzodiazepines
for epilepsy, diazepam, lorazepam, clonazepam, nitrazepam, clorazepate, clobazam
34
diazepam
for epilepsy, banzodiazepine, IV or rectal, good at stopping continuous seizure activity (generalized status epilepticus), possibly oral but high tolerance
35
lorazepam
for epilepsy, benzodiazepine, more effective and longer acting than diazepam for status epilepticus, preferred
36
clonazepam
for epilepsy, benzodiazepine, long acting, good for absence seizures, one of most potent antiseizure agents, sedation common on initial therapy
37
nitrazepam
for epilepsy, benzodiazepine, not in US
38
clorazepate
for epilepsy, benzodiazepine, drowsiness, and lethargy common
39
clobazam
for epilepsy, benzodiazepine, not in US
40
acetazolamide
for epilepsy, inhibits carbonic anhydrase (diuretic)
41
acetazolamide mechanism of action
mild acidosis in the brain, diminished depolarizing action of bicarbonate ions moving out of neurons via GABA receptor ion channels
42
acetazolamide clinical uses
all types of seizures, rapid tolerance (return of seizures) in two weeks, may be useful in women who get seizures during their menses
43
tx tonic-clonic seizures
first line - carbamazepine, valproate, phenytoin; second line - lamotrigine, oxcarbazapine
44
tx myoclonic seizures
frist line - valproate; second line - topiramate, levetiracetam, zonisamide
45
tx partial seizures
first line - carbamazepine, phenytoin; second line - valproate, lamotrigine, oxcarbazine, levetiracetam
46
tx absence seizures
first line - valproate; second line - ethosuximide, lamotrigine
47
tx unclassified seizures
first line - valproate; second line - lamotrigine
48
ethosuximide
9 yr old, eyelid flutter every 5-10min, EEG 3Hz synchronously on all leads (generalized), ethosuximide - good tx without effect of excessive sedation / tolerance
49
lorazepam
generalized convulsions / seizure for 45 min in ER, tx IV lorazepam
50
phenytoin
tx for generalized tonic - clonic seizures, 10-20 mg/L plasma level is therapeutic, if inadequate seizure control -> could stop phenytoin and try different drug OR break into 3 daily doses OR increased dose slightly
51
carbamazepine
tx for tonic-clonic seizures, effective because decreases conduction of action potentials
52
complex partial seizure example
abnormal taste/olfaction/lip smacking/epigastric fullness/nausea AND transient loss of consciousness
53
case - 21 yr old female, lethargic, unresponsive (8 Glasglow Coma Scale), miosis, bradycardia, bradypnea, hypotension
methidion overdose, tx - IV fluids, feet in air, naloxone (narcan) pure opioid antagonist, put in floor bed / ICU will need another administration because methidone is long lasting
54
opioid toxidrome
miosis, bradycardia, bradypnea, hypotension, confirm with urine tox screen and responsiveness to naloxone (narcan)
55
narcan (naloxone)
pure opioid antagonist, reverses opioid toxidrome, has no activity when given alone, used in babies after delivery if opioid depression from pain killers given to mom
56
methadone
opioid, tx for opioid addiction, moderate to severe pain reliever, long acting opioid
57
classes of stimulants
sympathomimetics, xanthines, other
58
sympathomimetics stimulants
amphetamine, D- amphetamine, methamphetamine, methylphenidate, cocaine, MDMA - low dose increase release of NE / DA, medium dose blockes NE / DA reuptake, high dose inhibits monoamine oxidase that would break down NE / DA
59
xanthine stimulants
theobromine, theophylline, caffeine
60
other stimulants
nicotine, NE reuptake inhibitors, NE / DA reuptake inhibitors, modafinil, armodafinil
61
sympathomimetic CNS effects
wakeful, alert, increased confidence / motor / speech / accuracy / restless / tremor / respiration rate and depth, decreased eating / tolerance / weight
62
sympathomimetic non-CNS effects
increased systolic / diastolic BP, arrhythmia
63
acute sympathomimetic toxicity
CV headache / arrhythmia / palpitation / angina; CNS dizziness / agitation / confusion, tx antipsychotic, acidify urine so more of active drug is ionized in urine and can not be reabsorbed
64
chronic sympathomimetic toxicity
amphetamine psychosis - hallucinations, paranoid delusions, weight loss - looks like schizo must do urine tox to differentiate
65
sympathomimetics tolerance / dependence
tolerance to effects on appetite / mood, psychological dependence (more with cocaine than amphetamine), withdrawal craving, sleep, fatigue, eating, depression
66
sympathomimetic therapeutic uses
ADHD, narcolepsy, analeptic (reduces drug induced depression)
67
cocaine
alkaloid, crystalline hydrochloride salt, smoke faster pharmkin, injection faster pharmkin, snorting slower pharmkin, 10x potent than amphetamine,
68
amphetamine
>t1/2 than cocaine (slower acting, longer duration) - methamphetamine is the middle
69
fastest adminstration / pharmkin
IV, smoking
70
cocaine mechanism of action
blocks NE reuptake (motor), blocks DA reuptake motor (euphoria), local anesthetic
71
cocaine toxicity
cardiac arrhythmia, coronary / cerebral thrombosis, in utero - decreased brain size and neuro problems
72
cocaine tolerance / dependence
little tolerance, same daily dose gives same effect, possible physical withdrawal
73
methylenedioxymethamphetamine (MDMA)
from methamphetamine (extra methyl group increases lipophilicity and brain entry), releases and inhibits reuptake of epi / NE / DA, directly stimulates 5HT autoreceptor, stimulates release/inhibits reuptake of serotonin, also affecte histamine / GABA / ACh / DA receptors / NE transporters
74
bath salts
amphetamine-like, stimulants in the brain (cocaine substitute, high abuse / addiction), ingested or snorted, toxicity - chest pain / high BP / high HR / agitation / hallucination
75
caffiene
xanthine, most in starbucks, coffee, nodoz, energy drinks (ER visits)
76
theophylline
xanthine, H in place of R3 group, in tea
77
theobromine
xanthine, H in place of R1 group, in hot cocoa
78
low dose xanthine
clear thought, decreased reaction time, better idea association, less fatigue, improved dexterity for well learned tasks
79
medium dose xanthine
medullary centers affected - increased respiration, increased BP (vasomotor center)
80
high dose xanthine
spinal cord affected - hyperreflexia
81
other xanthine actions
heart stimulation (increased HR, force, output), increased skel muscle work capacity, diuretic, bronchial smooth muscle relaxant (theophylline tx for bronchial asthma), decreased vascular resistance, increased cerebral vascular resistance (tx some headaches)
82
xanthine mechanism of action
unclear, translocation of SR Ca, inhibition of phosphodiesterase - elevated cAMP, adenosine receptor antagonist (inhibits sleepiness adenosine)
83
xanthine toxicity
~ 1mg dose, CNS - insomnia, excitement, convulsions, clonic, death, LD50 150-200 mg/kg, CV - high HR, high resp, extra systoles, decreased clotting, GI - increased secretion
84
xanthine therapeutic uses
cardiac stim for CHF (dilates coronary arteries, increased inotropic forces), paroxysmal dyspnea (left heart failure), analeptic, bronchial asthma, ergot alkaloid (for migraines by vasoconstriction of cerebral arteries)
85
xanthine tolerance / dependence
tolerance to sleep disruption, withdrawal - headache / irritable / low concentration / drowsiness, insomnia, pain - 12-24 hours after not having caffeine
86
modafinil
stimulant, R-modafinil active, L-modafinil not active
87
modafinil theraputic uses
schedule IV controlled, tx - narcolepsy, shift work sleep disorder, daytime sleepiness from sleep apnea, ADHD (not in children - Stevens Johnson syndrome), off-label uses - depression, bipolar, parkinson, schizo, weight loss
88
modafinil mechanism of action
increased DA release in striatum / nucleus accumbens, increases NE release in hypothalamus - all like amphetamine; increased serotonin release in amygdala and frontal cortex, increase hypothalamic histamine, activates glutamatergic receptors, inhibits GABA transmission
89
modafinil adverse effects
headache, nausea, insomnia, low appetite, dizzy, anxiety, high BP --- serious dermatologic reaction (Stevens Johnson Syndrome)
90
cognitive enhancer uses
ADHD, alzheimer, smart drug
91
psychostimulants
methylphenidate, amphetamines - first line ADHD tx in children -
92
amphetamines, methylphenidate
psychostimulants, tx ADHD, immediate release and sustained release formulas (only AM administration)
93
amphetamine ADHD drug names
dexedrine, adderall - faster release, shorter acting
94
methylphenydate ADHD drug names
ritalin, concerta - slower release, longer acting
95
methylphenidate, d-amphetamine, d,l-amphetamine
increase DA release and block DA reuptake
96
d,l amphetamine
increases NE release
97
why stimulants work in tx for ADHD
stimulants affect inhibitory areas of the brain first - activation of inhibitory areas help block out other stimuli - low dose stimulants activate prefrontal / limbic inhibitory cortex, higher doses (toxic) - activate motor and euphoria pathways
98
increasing doses of stimulants (sympathomimetics)
low - increased DA / NE release, middle - blockage of NE / DA reuptake, high - inhibition of monoamine oxidase
99
ADHD tx and tolerance
tolerance development is lower in ADHD pt, no psychosis with chronic use
100
reverse tolerance
abuse of amphetamines and cocaine, same dose over long period becomes toxic - eventually become psychotic
101
atomoxetine (strattera)
NE reuptake inhibitor, increases DA in prefrontal cortex (not in nucleus accumbens or striatum - potential for abuse), increases ACh in cortical areas (increasing attention and working memory) tx for adult ADHD, no abuse potential
102
acetylcholinesterase inhibitors
tx for alzheimer, delay death of cholinergic neurons, adverse effects - nausea, anorexia, vomiting, diarrhea - limits max dose, includes donepezil, galanatamine, rivastigmine, tacrine, memantine - increase risk of stomach ulcers (use NSAIDs with caution)
103
rivastigmine (exelon)
acetylcholinesterase inhibitor, tx for alzheimer, 2x day, GI problems, muscle weakness
104
tacrine (cognex)
acetylcholinesterase inhibitor, tx alzheimer, short t1/2 (multiple administrations), many drugs interactions (NSAIDs), liver damage, second choice for AD
105
galantamine (razadyne)
acetylcholinesterase inhibitor, tx alzheimer, stimulates ACh release, do not take with antidepressants
106
memantine (namenda)
NMDA glutamate (GLU) receptor antagonist, tx moderate to severe alzheimer, adverse effects - dizzy, headache, constipation, confusion
107
other tx for alzheimer
vit E, selegiline, estrogen, NSAIDs, ginko biloba
108
nootropics
mind turning, smart drugs, memory enhancers
109
eugeroics
wakeful enhancers, modafinil, armodafinil, increase NE and DA release, increase hypothalamic histamine, lower abuse potential, tx for narcolepsy, shift work sleep disorder, daytime sleepiness from sleep apnea, off label uses - ADHD, depression, bipolar, parkinson, schizo, MS - performance enhancing drug at university
110
modafinil
eugeroic, wakeful enhancer
111
armodafinil
eugeroic, wakeful enhancer
112
general anesthesia
CNS depression, absence of sensation, unconscious, controlled, reversible, takes place in brain - equ fast vessel rish
113
stage I of anesthesia
analgesia, amnesia, induction, loss of consciousness, reflexes present, can respond to commands, voluntary resistance
114
stage II of anesthesia
delirium, loss of consciousness, agitated, combatitive, BP and resp fluctuation, rapid eye movement, breath holding, vomiting, laryngospasm, no memory of this, move through this stage FAST
115
stage III anesthesia
surgical anesthesia, regular resp, autonomics depressed due to increasing conc, four planes (light, moderate, deep, excessive)
116
stage IIII anesthesia
medullary depression, relative overdose, may result in CV collapse or resp depression
117
goals of general anesthesia
loss of consciousness, amnesia, analgesia, blunting of autonomic nervous system, skeletal muscle relaxation
118
balanced general anesthesia
general anesthetic -> loss of consciousness, bensodiazepine -> amnesia, opiod -> analgesia and blunting of autonimic system, neuromuscular blocker -> skeletal muscle relaxation
119
inhalation general anesthetics
anesthesia machine -> breathing circuit -> lungs -> blood -> brain -> blood -> lungs -> breathing circuit -> anesthesia machine
120
partial pressure
additive, P total = P anes + P O2 + P....dosage determined by partial pressure with inhalation, need to leave room for 20% O2
121
Henry's Law
drugs dissolved in fluid do not raise P anes, undissolved drug gives clinical effect, greater sol = slower acting, higher conc, lower sol = faster acting, lower conc
122
induction partial pressures
P delivered > P inspired > P alveolar > P arterial > P brain
123
at anesthesia partial pressures
P inspired = P alveolar = P arterial = P brain
124
recovery partial pressures
P delivered < P expired < P alveolar < P venous < P brain
125
affect P arterial
conc of anes in inspired air (higher = faster), pulmonary ventilation (higher = faster), sol of anes in blood (least sol reach equ fastest - N2O, most sol reaches equ slower - halothene)
126
inhalation anesthetics characteristics
diverse chem structures, do not interact with defined receptor (injection does), impact all systems, cause physical change (cell membrane?), all but N2O are vaporized (not gaseous)
127
minimum alvoelar concentration (MAC)
anes dose in 50% of pop, same as ED50, lowest MAC = most potent, surgical anes 1.3-1.5 MAC (2 MAC = deep anesthesia), effected by age / disease / depressants / ambient temp, MACs are additive leading with on drug can lower the needed MAC of a second drug
128
potency
amount to produce specific intensity, function of lipid solubility, correlates with anesthetic potency, more lipid sol = greater potency
129
aqueous solubility
determines onset and rate reaching equilibrium, the more soluble a drug the longer it takes to raise its partial pressure in the blood
130
halothene
high oil:gas partition coefficient = high potency, high blood:gas paritition coefficient = slow rate of induction
131
N2O
low oil:gas paritition coefficient = low potency, low blood:gas partition coefficient = fast induction
132
gas partition coefficient
at equilibrium.....blood conc / gas conc
133
second gas effect
rapid uptake of first anesthetic creates neg pressure in alveoli causing faster uptake of second anesthetic, ex: N2O rapidly taken up - used first to speed induction, N2O can cause diffusion hypoxia during recovery, lowers required MAC for second anesthetic
134
inhaled anesthetic elimination
low aqu sol - leave body fastest, high fat sol - leaves body slowest, lungs and skin/mucous membranes, liberation of halogen can cause kidney / liver / reproductive harm, halothane (poorly metab, consecutive surgery can cause hepatitis), N2O well metabolized
135
ideal inhalation anesthetic
stable, compatible, cheap, non-explosive, easily vaporized, low blood sol, potent, no CV depression / airway irritation, good muscle relaxation, minimal metabolism, not toxic to kidney / liver / GI
136
endotracheal intubation
may be done for mechanical ventilator, use short acting neuromuscular blocker to relax
137
effects of halogenated hydrocarbon inhalation anesthetics
CNS - lower brain metabolism, higher brain blood flow, high ICP; CV - lower contractility / stroke volume / BP (give epi - may increase automaticity), muscle relaxation, malignant hyperthermia (halothane and succinyl choline muscle relaxant)
138
halothane
inhalation anesthetic, Adv - potent (low MAC), fast induction / recovery, inexpensive, not irritant, Disadvan - inadequate analgesia / muscle relaxation, low cardiac output, low BP, sensitizes mycardium to catacholamines (give epi -> increased automaticity, cerebral blood flow, ICP), resp depression, heptic toxicity / liver metabolism, malignant hyperthermia (when given with succinyl choline muscle relaxant)
139
isoflurane
inhalant anesthetic, ADV - potent, fast induction, no mycardial senstization to catecholamines, less renal/hepatotoxicity; DISADV - rare arrhythmia, pungent odor, malignant hyperthermia
140
sevoflurane
high potency, low blood solubility, rapid onset 5-10min, rapid recovery (same day surgery), perfect inhalation anesthetic
141
nitrous oxide
only inhalation anesthetic that is gas, ADV - low blood sol, rapid onset, little CV effect, creates second gas effect, mild analgesic; DISADV - high MAC, can't use as sole anesthetic, no muscle relaxant, diffusion hypoxia if rapidly cut off during recovery
142
IV anesthetics
act faster, best for induction of anesthesia, good for short operations, not suitable as single anesthetic due to poor muscle relaxation
143
barbiturates
IV anesthetic, thiopental and methohexital, GABA induced Cl- entry into neurons that depresses CNS by hyperpolarizing cells, rapid onset, short action, toxicity - anesthetic dose 50-75% of LD50
144
benzodiazepines
IV anesthetic, midazolam (versed) and diazepam (valium), GABA induced entry of Cl- into neurons depressing CNS by hyperolarization, less CV and resp depression (safer), amnestic (memory loss - GOOD), insufficient anesthesia given alone, used as induction agent
145
propofol
IV anesthetic, rapid induction and recovery, induces anesthesia, maintains anesthesia alone, given as emulsion, apnea (22-45%) BAD, injection site pain, killed Micheal Jackson
146
ketamine
IV anesthetic, dissociative anesthetic (awake, unaware), rapid onset, short duration, emergence reactions (delirium, hallucinations), abused (vet clinics, special K), airway and resp maintained, CV stimulated (good for pt with unstable CV), analgesic, amnestic
147
opiods
IV anesthetic, high potency, short acting, fentanyl, sufentanyl, alfentanil, analgesia, hemodynamic stability (good for pt with myocardial dysfunction), depressed resp must be artificially maintained, supplemented with inhaled anesth / benzo / propofol
148
antidepressants
tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, dual mechanism drugs
149
mood stabilizers
lithium carbonate, anticonvulsants, atypical antipsychotics
150
tricyclic antidepressants
effect on normal - no stimulation (not abused), sleepiness (tx insomnia); effect in depressed - elevated mood 2-3 wks - in both cases antimuscarinic effects (dry mouth, blurred vision, constipation, urinary retention) - block NE and/or 5HT reuptake, tx depression/anxiety/chronic pain
151
adverse effects of tricyclic antidepressants
orthostatic hypotension (NE blocks alpha 1 receptors), antimuscarinic (blocks muscarinic receptor) effects (esp elderly, confusion / constipation / glaucoma), weight gain (block histamine receptor), tachycardia, arrhythmia (block Na channels)
152
tricyclic antidepressant toxicity
low therapeutic index 5-10, pts given no more than one week supply, easy to OD in since TI is so low
153
tricyclic antidepressant drug interactions
potentiates central depressants - alcohol, sedatives, hypnotics, opioids; decreased gastric emptying increases inactivation of L-DOPA and decreases effectiveness of parkinson tx
154
monoamine oxidase inhibitors
irreversibly blocks oxidative deamination of monoamines by monoamine oxidase, increases NT in synpase in 1-2 days, clinical effect 3 wks, tx depression and anxiety
155
MAOa
metabolizes NE and 5HT
156
MAOb
metabolizes DA
157
monoamine oxidase toxicity
low therapeutic index - 5, easy OD
158
monoamine oxidase drug interactions
potentiates sympathomimetic amines, esp indirect tyramine that is metabolized by monoamine oxidase in liver, release of NE/EPI/DA, tyramine + monoamine oxidase = hypertensive crisis via adrenergic stimulation
159
pt on monoamine oxidase inhibitor must avoid...
foods rich in tyramine - cheese, red wine, beer, broad beans, bananas, avocados, yogurt, sour cream, chocolate, OTC ephedrine / pseudoephedrine
160
selective / reversible monoamine oxidase inhibitors
not in US, moderate antidepressant, tyramine food reactions reduced
161
desipramine (norpramin)
tricyclic antidepressant, selective NE reuptake inhibitor
162
imipramine (tofranil)
tricyclic antidepressant, mixed action NE/5HT reuptake inhibitor
163
phenetzine (nardil)
monoamine oxidase inhibitor
164
selective serotonin reuptake inhibitors
block serotonin reuptake, not used alone with bipolar disorder - must use mood stabilzer first to prevent rapid mood switch, tx depression and anxiety
165
fluoxetine (prozac)
selective serotonin reuptake inhibitor
166
sertraline (zoloft)
selective serotonin reuptake inhibitor
167
citalopram (celexa)
selective serotonin reuptake inhibitor
168
escitalopram (lexapro)
selective serotonin reuptake inhibitor
169
selective serotonin reuptake inhibitor adverse effects
nausea, diarrhea, weight loss, stimulation - anxiety / nervousness / insomnia - not sedating like TCAs, risk of suicide because have energy to do so
170
selective serotonin reuptake inhibitor mechanism of action
inhibition of 5HT2a - downregulates other receptors, increases NE release, little muscarininic / histaminergic / andrenergic / serotonergic receptor effects (few adverse effects)
171
autoreceptor
presynaptic 5HT receptor that inhibits additional 5HT release
172
heteroreceptor
NE from neighboring neurons act on alpha2 receptors to inhibit presynaptic release of 5HT
173
atypical antidressants
dual/mixed action at 5HT / NE
174
venlafaxine (effexor)
selective serotonin and NE reuptake inhibitors, does not have adverse effects due to lack of activity at adrenergic / histaminergic / cholicergic, unlike most antidepressants - increasing dose of this drug increases efficacy due to secondary mechanisms of action (acts at 5HT first, NE second, DA third)
175
desvenlafaxine (pristiq)
active metabolite of venlafaxine - longer lasting, tx for adults with major depressive disorder
176
mirtazapine (remeron)
blocks presynaptic alpha 2 receptors - autoreceptor on andrenergic neurons increasing NE release and heteroreceptor on serotonergic neurons increasing 5HT release
177
buproprion (wellbutrin)
affects both NE and DA transport, adverse - stimulation/agitation/anorexia/insomnia, tx for smoking cessation
178
ketamine
IV anesthetic, NMDA receptor antagonist (glutamate), single dose significantly improves depressive symptoms for 2 hrs - 1 wk
179
lithium carbonate
tx manic bipolar phase and possible antidepressant, mood stabilizer, no effect in normal people, effect in manic subject, effect seen in 5-21 days, effective in 60-80%, well absorbed by GI, 95% excreted by kidneys - competes with Na reabsorption, Na deficiency increases lithium toxicity
180
lithium carbonate mechanism of action
unknown, most likely postsynaptic effect - interferes with production / release of phosphatdylinositol and diacyl glycerol
181
lithium adverse effects
fatigue, weakness, slurred speech, ataxia, hand tremor, thirst, urination - no tolerance to hand tremor / thirst / urination, doses >2 mEq/l causes impaired consciousness / coma / rigidity / hyperactive reflexes
182
anticonvulsants for bipolar disorder
valproic acid and sodium valproate - good for non-rapid cycling bipolar, better than lithium for rapid-cycling bipolar, carbamazepine aslo approved, phenytoin and phenobarbital no effective
183
atypical antipsychotics for bipolar disorder
quetiapine - blocks 5HT 2a receptor, DA antagonist? stabilizes mood
184
antidepressants and bipolar disorder
selective serotonin receptor inhibitors should never be used alone - may cause rapid onset mania, should be on mood stabilizer first
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wake therapy
keep pt awake for 24 hrs just starts antidepressant drugs effects, relapse in 24 hrs
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delay in clinical improvement following tx
neurotransmitter and receptor are at start of pathway, there are steps following that maintain mood, neurotransmitter acts through multiple second messangers increasing levels of BDNF which is neuroprotective (increases neuroplasticity, decreases apoptosis, increases neurogenesis)
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first generation antipsychotics
block D2 receptors in limbic system, may make neg symptoms worse, adverse affects due to action at muscarinic / adrenergic / histaminergic receptors
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first generation antipsychotic muscarinic receptor action adverse effect
dry mouth, blurred vision, racing heart, constipation, drowsiness
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first generation antipsychotics action at adrenergic receptor adverse effect
decreased BP, dizziness, drowsiness
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first generation antipsychotics action at histaminergic receptor adverse effect
weight gain, drowsiness
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first generation anti
chloropromazine (thorazine), fluphenazine (prolixin), thioridazine (mellaril), trifluperazine (stelazine), haloperidol (haldol)
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second generation antipsychotics
atypical antipsychotics, block D2 and 5HT receptors
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second generation antipsychotics
clozapine (clozaril), olanzapine (zyprexa), risperidone (risperdal), quetiapine (seroquel), ziprasidone (geodon), aripiprazole (abilify)
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clozapine
second gen antipsychotic, effective on positive and negative symptoms, no parkinsonism, life threatening agranularcytosis - need weekly blood test; ALL other SGA no life threatening effect but not as effective as clozapine, first drug of choice for schizo pt with mod-severe dyskinesia
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two receptors are better than one - second gen antipsychotics
presynaptic 5HT receptors regulate DA release, block presynaptic 5HT 2a receptors increase DA release, improves adverse effects by increasing DA levels, improves both negative and positive symptoms
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second gen antipsychotics adverse effects
weight gain (esp clozapine / olanzapine), type 2 diabetes mellitus, increased lipid levels leading to myocarditis / cardiomyopathy
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FGA and SGA adverse effect - tardive dyskinesia
late onset movement disorder, more with FGA, common in elderly, incidence with clozapine is zero
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FGS and SGA adverse effects - extrapyramidal side effects
seen more with FGA, due to DA receptor blockage, parkinsonism
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anxiolytic - sedative - hypnotic
dose related CNS depression - tranquilization, sedation, hypnosis, general anesthesia, death
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tranquilization / anxiolytic
relaxed, unconcerned with surroundings, fully functional - ideal tx for anxiety
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sedative
decreased activity, calms pt, pt is awake
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hypnotic
drowsiness, onset and maintenance of sleep, pt easily aroused
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general anesthesia
loss of consciousness, pt can't be aroused
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barbiturate
all similar, only differ on duration of action
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ultra-short acting barbiturate
t1/2 - minutes, very lipid soluble, tx conc reached quickly, redistribution to muscle and other sites causes termination of action
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thiopental and methohexital
ultra-short acting barbiturate
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short-intermediate action barbiturate
t1/2 - hours, depends on metabolism rate
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secobarbital and pentobarbital
short-intermediate acting barbiturate
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long acting barbiturate
t1/2 - days, slow metabolism or excreted uncharged
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phenobarbital
long acting barbituarte, slow and partial metabolism, selective anticonvulsant, less lipid soluble
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barbiturates action
reversible depression of all excitable tissues (skeletal/smooth/cardiac/CNS), skip tranquilization step of depression, like normal sleep, not analgesic until unconscious, paradoxical excitement
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barbiturates and analgesia
hyperalgesic until unconscious, will not sedate in presence of moderate pain
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barbiturates tolerance
tolerance faster - mood, sedation, hypnosis - need to keep increasing dose increasing chance of death, as use increases therapeutic index decreases, highest rate for accidental overdose
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barbiturates mechanism of action
facilitates GABA mediated neuronal hyperpolarization by inflow of Cl-
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barbiturate effect on organs
toxic doses - depresses resp and CV, liver - cytochrome p450 induced causing drug to be broken down faster
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barbiturate absorption
oral - sedative / hypnotic or anticonvulsant; IV - anesthetic induction; IM - not used, too alkaline
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barbiturate distribution
rate of brain up take depends on lipid solubility 30sec - 20min, redistribution causes termination of action for ultra-short acting barbs
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barbiturate metabolism
slower in geriatric and neonatal, decreased t1/2 with repeated administration
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barbiturate elimination
less lipid soluble barbs largely excreted unchanged and active, are weak acids that are reabsorbed at low urine pH
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tx phenobarbital OD
increase urinary pH to 8, causes more drug excreted, less drug reabsorbed, because weak acid drug is turned into ionized form - does not work with more lipid soluble drugs
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barbiturates adverse effects
hangover (extended depression) one day after use, paradoxical excitement (like intoxication) common in geriatric or weak pt
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barbiturate drug interactions
most with similar drugs, induce hepatic enzyme ctyo p450 effecting metabolism of other drugs, compete for metabolic pathways
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barbiturate clinical uses
hypnosis, seizure control, anesthesia induction
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benzodiazepines
tranquilization -> sedation -> hypnosis (no anesthesia step), awareness persists, not relaxed enough for surgery, anterograde amnesia occurs, some block seizures, some relax muscles - depends on partial / full agonist action at specific GABAa receptors
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benzodiazepine and sleep
decreases sleep latency (faster onset), diminished number of awakenings, increases total sleep time, increased REM sleep (fell well rested), partial tolerance develops
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benzodiazepine mechanism of action
facilitates GABA mediated neuronal hyperpolarization by allowing Cl- in
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benzodiazepine system effects
no resp effect unless taken with other depressant drugs, minor CV - decreased BP and increased HR, no liver metabolism effect --- little if any effect outside CNS / safer
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benzodiazepine pharm-kin
active metabolites, duration of behavior does not match plasma t1/2 of parent compound, ex: clorazepate decarboxylated in stomach to active metabolite
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benzodiazepine adverse effect
peak hypnotic effect - dizzy, increased reaction time, decreased coordination, confusion; anterograde amnesia at high dose or with alcohol
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flunitrazepam (rohypnol)
benzodiazepine, date rape drug, potent when combined with alcohol, memory loss
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benzodiazepine toxicity
relatively safe, high therapeutic indices, death by OD rare unless combined with other drugs, drug wears off with time, no OD tx needed
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benzodiazepine OD tx
flumazenil, benzo receptor antagonist, IV, reverses effect of benzos and z-sleep aids (zolpidem, zapelon)
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nezodiazepine clinical uses
anxiety, insomnia, seizures, muscle relaxation, preanesthetic med
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midazolam
benzodiazepine, lipid soluble, better sedation - more amnesia, anxiolytic, less pain on injection
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non-benzodiazepine benzodiazepine-receptor agonist
selectively bind benzodiazepine binding site on GABAa receptor, use for sleep, rapid onset, short duration, slow tolerance
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zolpindem (ambien)
non-benzodiazepine benzodiazepine-receptor agonist, sleep aid
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zaleplon (sonata)
non-benzodiazepine benzodiazepine-receptor agonist, sleep aid
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eszoplicone (lunesta)
non-benzodiazepine benzodiazepine-receptor agonist, sleep aid
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ramelteon (rozemrem)
works in suprachiasmatic nucleus, agonist for melatonin MT1 and MT2 receptors, decreased sleep onset time, does not increase total sleep time - longterm use in adults ok
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diphenydramine
OTC, "PM", for insomnia
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cholinesterase inhibitors
tx alzheimer/parkinson dementia/vascular dementia, alzheimer - reduced choline acetyl transferase = low acetylcholine, prevents breakdown of ACh at synapse, most effective as early tx
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cholinesterase inhibitors
donepezil, galantamine, rivastigmine, tacrine
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donepezil
AChase inhibitor, tx alzheimers/dementia, 1/day dosing, more commonly used, lower side effects
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galantamine
AChase inhibitor, tx alzheimer/dementia
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rivastigmine
AChase inhibitor, tx alzheimer/dementia, patch form
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tacrine
AChase inhibitor, tx alzheimer/dementia, hepatotxicity
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AChase inhibitor side effects
GI upset, rare manic episode
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memantine (namenda)
NMDA receptor antagonist, slows programmed cells death due to excitotoxicity, tx mod to severe dementia, slows decline, side effect - dizzy, BEST USED IN CONJUNCTION WITH ACH inhibitor
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dementia depression tx
SSRI, SNRI - avoid tricyclics with anti-ACh properties (worsen memory / balance)
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dementia agitation/hallucination tx
atypical antipsychotics - risk of mortality in elderly, quetiapine
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dementia sleep problem tx
behavior mod, OTC meds, trazodone or melatonin
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physical exercise
tx dementia, slows decline, less depression, improves functioning - improves cognition, larger hippocampus, less gray matter loss
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mental exercise
tx dementia, slows decline
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social support
tx dementia, greater and more varied social support is protective, less depression, stay in home longer, less hallucination/delusion/psychosis
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community support
tx dementia, help pt stay active and independent, assist with transportation, meds, meals, home help
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vascular dementia tx
prevent - stop risk factors smoking, BP, blood sugar, cholesterol, exercise, mental activity, social activity, fish oil; AChase inhibitors, NMDA antagonists, AND calcium channel blockers (nimodipine)
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lewy body dementia (parkinson) tx
AChase inhibitor, NMDA receptor antagonist, antipsychotics (CAUTION - may cause neuroleptic malignant syndrome), SSRI for depression, AVOID - OTC anticholinergic sleep meds and tricyclics, sleep clonazepam and melatonin
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frontal temporal dementia tx
SSRI - for disinhibition/implusivity (trazodone for aggression/agitation), antypical antipsychotics - olanzipine/quetiapine/abilify help with delusions/agitation (avoid - typical antipsychotics and risperdal), stimulants to increase frontal lobe activity - AChase inhibitors and NMDA receptor antagonists not as helpful
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dementia general tx tips
both behavioral / medical tx, start AChase inhibitor early, manage risk factors, healthy lifestyle, develop community supports, tx symptomatically, add memantine as disease progresses
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temozolamide (TMZ)
tx for gliobalstoma multiforme and melanoma, antineoplastic prodrug that methylates and damages DNA killing tumor cells, only effective if O-methylguanine methyltransferase gene is methylated or it will undo what drug does
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karnofsky performance scale index
classifies pt by functional impairment after tumor resection to determine if they are a good candidate for radiation/chemo, want balance between chemo side effects and benefit of symptom control gained, >80 = normal activity with some symptoms, 50-70 = unable to work can care for oneself with assistance, 0-40 = disabled, requiring increasing degrees of care
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O-methylguanine methyltransferase gene (MGMT)
fixes methylation of DNA, reverses what tx temozolamide does for gliobastoma multiforme does - it methylates tumor cell DNA killing cells
