MOAs Flashcards
(147 cards)
1
Q
Alcohol MOA
A
Binds GABAa receptor→ increased Cl- influx→ enhanced inhibitor GABA transmission
Synergistic with drugs that bind GABA at different sites: barbiturates, benzos
Increases dopamine in mesolimbic pathway (addiction)
Inhibits effect of glutamate on NMDA receptor
2
Q
Naltrexone MOA for alcohol abuse
A
Blocks ability of alcohol to stimulate the reward pathway
3
Q
Acamprosate MOA
A
Structural analogue of GABA→ restores disturbed GABA/glutamate balance (alcoholism) to normal
4
Q
Disulfiram MOA
A
Inhibits aldehyde dehydrogenase→ aldehyde build up
5
Q
Normal alcohol metabolism
A
Alcohol→ alcohol dehydrogenase (ADH)→ acetaldehyde→ aldehyde dehydrogenase (ALDH) oxidizes using NAD+→ acetate
6
Q
Asians + Alcohol
A
lacking ALDH (aldehyde dehydrogenase)
7
Q
Women + Alcohol
A
Lower levels of ADH (alcohol dehydrogenase)
8
Q
Topiramate mechanism for alcoholism
A
Not understood, decreases craving and increases abstinence
9
Q
Fomepizole MOA
A
alcohol dehydrogenase inhibitor
10
Q
Barbiturates MOA
A
Bind GABA→ Cl- influx→ inhibitory
Produce inhibition independent of GABA: no ceiling effect
Hypnosis (CNS depressant)
Euphora→ abused
11
Q
Benzodiazepines MOA
A
Specific site on GABAa receptor→ prolonged action
GABA dependent effects→ Ceiling effect
12
Q
Flumazenil MOA
A
Benzodiazepine Antagonist→ competes for GABA receptor→ reverses effect of benzos and “z-drugs”
13
Q
Z drugs MOA
A
Bind to BZ1 subtype of GABA receptor→ increased GABA-mediated inhibition
14
Q
Suvorexant MOA
A
Antagonist at orexin receptors
15
Q
Ramelteon MOA
A
Melatonin analogue
16
Q
Chloral hydrate MOA
A
Converted to trichloroethanol→ similar effect as barbiturates on GABAa receptor→ sedation
17
Q
Buspirone MOA
A
Partial agonist at postsynaptic 5-HT1a receptor (serotonin) → inhibition of cell signaling
Full agonist for presynaptic 5-HT1a receptor→ decreased release of 5-HT
18
Q
Glutamate receptors are called
A
NMDA
also AMPA but never discussed
19
Q
Glutamate causes seizures….
A
By activating NMDA receptors
Goal: decrease glutamate
20
Q
GABA causes seizures
A
when GABA receptors are blocked
Goal: increase GABA
21
Q
Phenytoin / Fosphenytoin MOA
A
Prolong inactivation of Na+ channels→ decreased glutamate activity
22
Q
Carbamazepine MOA
A
Blocks Na+ channels→ decreased glutamate activity
Inhibits NE release + reuptake→ +/- potentiates GABA
23
Q
Lamotrigine MOA
A
Inactivation of Na+ channels→ decreased glutamate activity
+/- inhibition of Ca++ channels
24
Q
Topiramate MOA
A
Blocks Na+ channels→ decreased glutamate activity Some activity at Ca++ channels Potentiates GABA receptors Inhibits glutamate receptor (NMDA) \+/- Inhibits spread of seizures
25
Levetiracetam MOA
Binds SV2A→ apparent decrease in glutamate and increase in GABA release
26
Gabapentin MOA
```
GABA analog (but doesn’t act on receptor)
May augment GABA release
```
27
Pregabalin MOA
GABA analog→ binds to alpha-2-delta subunit of voltage-gated Ca++ channels inhibiting excitatory neurotransmitter release
28
Tiagabine MOA
Inhibits reuptake of GABA (GAT-1) → enhances GABA activity
29
Vigabatrin MOA
Irreversibly inhibits GABA transaminase (GABA-T) → decreased metabolism→ increased activity
30
Ethosuximide MOA
Inhibits low threshold (type T) Ca++ channels→ inhibits pacemaker for rhythmic cortical damage
31
Valproic acid MOA
Blocks Ca++ channels and Na+ channels
| +/- Enhances GABA activity
32
Synaptic vesicular protein (SV2A)
Binding SV2A increases GABA and decreases excitatory glutamate activity
33
Some glutamate targets that can be blocked
SV2A
Voltage-gated Na+ channels
Thalamic voltage gated-Ca++ channels
34
Increase GABA by....
Block GABA reuptake (tiagabine)
Inhibit GABA metabolism (vigabatrin)
Stimulate GABAa receptors (benzos, barbs)
Bind synaptic vesicular protein SV2A (levetiracetam)
35
Drugs that block Na+ Channels
Phenytoin
Lamotrigine
Carbamazepine
Valproate
Can cause SJS/TENS, screen for HLAB1502
36
Local Anesthetics MOA
Block Na+ channels and inhibit neuronal firing
Increase threshold for excitation and impulse conduction slows.
Binding increases→ rate of action potential declines→ complete block
37
A faster local anesthetic is
Smaller, lipophilic
38
A longer acting local anesthetic....
Binds more extensively to proteins
39
Elevated Ca++ makes local anesthetics
Less effective
Elevated Ca++ → hyperpolarize membrane → channels in resting state
40
Elevated K+ make local anesthetics
More effective
Elevated K+ → depolarizes membrane→ more channels inactivated state
41
Local anesthetics have a high affinity for the Na+ channel in the _______ states
Activated/open state
| Inactivated state
42
Local anesthetics have a low affinity for the Na+ channel in the _______ state
Resting/closed state
43
Esters cause allergic reactions by
the P-aminobenzoic acid (PABA) metabolite
44
A myelinated neuron is ______ to local anesthetics than an unmyelinated neuron
Less sensitive
45
A myelinated neuron is ______ to local anesthetics than an unmyelinated neuron
Less sensitive
46
Metabolism of ester local anesthetics
rapidly metabolized by plasma butyrylcholinesterase
Mutations affect metabolism
47
Metabolism of amide local anesthetics
CYP450s
48
Bupivacaine + Cardio MOA
more lipophilic: increased binding to cardiac Na+ channels, slower dissociative times
More toxic
49
Cardiac effects of local anesthetics
Inhibition of Na+ and Ca++ channels→ arrhythmias, vasodilation hypotension
50
Why won't sulfas work if you're taking procaine?
PABA metabolite inhibits sulfonamide action
51
Benzocaine MOA
Pka 3.5→ lipophilic, always non-ionized at physiological pH→ readily transported through membrane, minimal binding to Na+ channel
*topical OTC only*
52
Secondary mechanism of cocaine
Inhibits Na+ channels (local anesthetic)
53
Primary mechanism of cocaine
increasing dopamine in CNS and periphery
54
What does a lipid sink do?
IV lipids pull lipophilic local anesthetics out of cardiac tissue in toxicity
55
Ropivacaine is...
S-enantiomer of bupivacaine→ less lipid soluble and cleared more rapidly
56
Etidocaine effects
Inverse differential block→ causes motor block before or without sensory block
57
Articaine is....
an Amide with an additional ester→ metabolism by plasma esterases→ decreases half life and systemic toxicity
58
Baclofen MOA
Agonist at GABAb receptors (Gi/o protein coupled, metabotropic)
1. Open K+ channels→ hyper-polarization
2. Presynaptic inhibition of Ca++ influx→ decreased transmitter release
3. Inhibits adenylyl cyclase→ decrease cAMP→ decreased release of excitatory transmitters in brain and spinal cord
59
Tizanidine MOA
Alpha2 receptor agonist:
Pre and post-synaptic inhibition of spinal cord synaptic activity→ decreased glutamate→ decreased muscle spasticity
Inhibits pain transmission in dorsal horn
60
Dantrolene MOA
Blocking ryanodine receptor 1 (RyR1) channel→ inhibits Ca++ release from sarcoplasmic reticulum→ interferes with excitation-contraction coupling of actin and myosin in skeletal muscle fiber
61
Botulinum Toxin MOA
Inhibits SNAP-25 protein→ inhibition of ACh release from nerve at neuromuscular junction
62
What is the long term effect of reuptake inhibitors that has an effect on depression
Antidepressants down-regulate auto-receptors; increasing firing rate of 5-HT neurons
63
Initially when taking a reuptake inhibitor
5-HT levels in synapse will increase but so does feedback inhibition, thus balancing synaptic amine levels
64
TCA MOA
Inhibit reuptake of NE and 5-HT
Also block alpha-adrenergic, histamine, and muscarinic receptors
65
Tertiary amine TCAs....
primarily block 5-HT reuptake
66
Secondary amine TCAs....
primarily block NE reuptake
67
Side effects of TCAs are due to
Cholinergic blockade
Alpha 1 receptor blockade
Histamine receptor blockage
68
Analgesic effect of TCAs is due to
activation of descending NE pathways in spinal cord→ increase alpha 2 autoreceptor activation→ decreased glutamate input into pain pathway to brain
69
SSRIs MOA
Selectively inhibit 5-HT reuptake
70
SNRIs MOA
Inhibit NE and 5-HT reuptake
71
MAO-A
Metabolizes NE, DA, 5-HT in both CNS and periphery (GI tract, liver)
72
MAO-B
selectively metabolizes DA in CNS only
73
Phenelzine MOA
Inhibits MOA-A and B → increased NE, 5-HT, DA.
Also a substrate for MAO.
74
Selegiline MOA
selectively inhibits MAO-B→ increased DA
75
Tyramine
Accumulates if MAO-A is inhibited
Tyramine causes release of catecholamines, causing severe hypertensive crisis +/- intracranial bleeding
should be avoided while taking MAOIs
76
Bupropion MOA
Inhibits reuptake: DA, minimal of NE and 5 H-T
77
Mirtazapine MOA
Blocks presynaptic alpha 2 receptors→ decreased inhibition of NE and 5-HT release→ increased NE and 5-HT
78
Atomoxetine MOA
Selective inhibitor of norepinephrine reuptake
79
Trazodone MOA
5-HT2A receptor antagonist
80
Classical antipsychotics MOA
Block DA D2 receptor
Target mesolimbic system
Alleviate positive symptoms
81
Atypical antipsychotics MOA
Block 5-HT2A and DA receptors
Target mesocortical and mesolimbic system
Alleviate both negative and positive symptoms
82
All the receptors antipsychotics might act on
```
*D2* (higher affinity for D2=more potent)
alpha 1
D4
5-HT2A
D1
H1
```
83
Chlorpromazine MOA
Blocks DA D2 receptors + alpha adrenergic actions
84
Haloperidol MOA
Potent blocker of DA D2 receptors
Affinity for DA D1, 5-HT2, and H1 receptors
85
Clozapine MOA
Blocks 5-HT2A and DA D4 receptors
some DA D2 (least potent of all the antipsychotics)
86
Olanzapine MOA
Blocks
5-HT2A
DA D4
DA D2
"similar to clozapine"
87
Ziprasidone MOA
Blocks 5-HT2A, DA D2 receptors
Some antidepressant: 5-HT1a receptor agonist, inhibition of 5-HT reuptake
88
Risperidone
Blocks 5-HT2A, DA D2 receptors
No effect on DA in nigrostriatal pathway (EPS, TD rare)
89
Extrapyramidal symptoms from antipsychotics are due to
DA receptor antagonists block DA receptors in the nigrostriatal pathway
90
Quetiapine MOA
Blocks 5-HT2A, DA D2 receptors
“Similar to clozapine”
91
Aripiprazole MOA
“Dopamine system stabilizer”
Partial agonist for DA, 5-HT
Antagonist 5-HT2a, alpha 1, histamine receptors
92
Lurasidone MOA
Blocks D2, 5-HT2a receptors
Partial agonist 5-HT1a
No antihistamine or antimuscarinic
93
Lithium MOA
Suppress second messengers: IP3
| +/- increase ACh, NE, DA
94
Lithium in the kidney
Reabsorbed by proximal tubule of kidney
Competes with Na+ for reabsorption
Na+ decreases-->Li absorption increases→ Toxicity
Na+ increases→ Li absorption decreases and excretion increases
Li increases→ Na+ absorption decreases→ hyponatremia
95
Valproic acid MOA for bipolar
Mechanism unknown
96
Beta-endorphins
decrease pain transmission in spinal cord, facilitate dopamine in reward system→ euphoria
97
Enkephalins
decrease pain transmission in the spinal cord
98
Dynorphins
bind to kappa receptors→ analgesia and dysphoria
99
Mu receptor (MOR)
analgesia, euphoria, sedation, side effects
100
Kappa receptor
Analgesia or dysphoria
101
Delta receptor
Dysphoria
102
Opioids + GABA
GABA→ inhibits descending neuronal pain modulation pathways
Opioids→ decreased GABA release→ allow pathways to be activated→ decreased pain transmission in dorsal horn of spinal cord
103
Opioids + Glutamate
Decreasing glutamate release in the dorsal
| horn reduces activation of the ascending pathway.
104
Opioids MOA
Coupled to Gi/o → decrease cAMP
Close voltage gated Calcium channels on presynaptic nerve terminals→ decreased neurotransmitter release, decreased neuronal activity
Mu receptors open K+ channels→ hyperpolarization→ inhibition of nerve transmission→ difficult to respond to pain signals
105
3 opioids that paradoxically cause CNS excitement in overdose
Codeine
Meperidine
Proxyphene
106
Opioids and respiratory depression mechanism
Decreased response of brainstem to elevated CO2 +/- bronchoconstriction
107
Opioids and ICP mechanism
Increased CO2→ vasodilation→ increased cerebral blood flow→ increased intracranial pressure
108
Opioids and body temperature mechanism
Hypothermia, dysregulation in hypothalamus
109
Atropine
blocks parasympathomimetic effects
| Reverses opioid miosis
110
Opioid CV effects mechanism
CNS vasomotor depression and/or vasodilation via histamine release
111
Opioid GI effects mechanism
Decreased gastric activity: CNS and local effect inhibition of transmitter release
112
Opioids cause itching because
they cause histamine release
| *not an allergy*
113
Opioid tolerance mechanism
Due to receptor desensitization, down regulation and uncoupling from G- proteins in thalamus and spinal cord
114
Opioid physical dependence mechanism
Results from desensitization of mu receptors, or receptor uncoupling
115
Opioid hyperalgesia mechanism
Mediated by increases in spinal cord dynorphin→ more effective pain transmission
116
NMDA receptor antagonists + opioids
Decrease tolerance and hyperalgesia
117
Changes in the brain from addiction
Addictive drugs→ more dopamine release than normal rewards→ down regulation of dopamine receptors→ substance provides less pleasure but more craving
118
Morphine MOA
stimulates all opioid receptors, potent, produces all effects
119
Methadone MOA
Stimulates mu receptors
+/- block NMDA receptors
+/- inhibit NE/5-HT reuptake
120
Meperidine MOA
Mu agonist
121
Pentazocine MOA
Kappa receptor agonist
| Mu receptor partial agonist
122
Buprenorphine MOA
Partial agonist on mu +/- kappa
123
Tramadol MOA
Weak mu agonist
| Inhibits NE/5-HT→ contributes to analgesia
124
Dextrometorphan MOA
Blocks NMDA receptors→ abuse potential
125
L-dopa MOA
Dopamine does not cross blood brain barrier, but L-Dopa does→ converted into dopamine in neuron
126
Carbidopa MOA
inhibits dopa-decarboxylase in the periphery (doesn’t cross blood brain barrier) → Decreases the dose of l-dopa needed
127
Inhibition of MAO-B in the CNS
reduces striatal metabolism of DA
MAO inhibitors used for parkinsons
128
COMT...
Catechol-O-methyltransferase (COMT) metabolizes DA and l-dopa
COMT-I → Inhibit DA and l-dopa metabolism
129
Tocalpone MOA
COMT inhibitor in CNS and periphery
130
Entacopone MOA
COMT inhibitor in periphery only, inceases pool of l-dopa for transport into brain
131
Dopamine receptor antagonists primarily target
DA D2
132
Amantidine MOA
Increased dopamine neurotransmission
+/- increased release of dopamine
+/- inhibition of dopamine reuptake
133
Anticholinergics MOA
Muscarinic receptor antagonists→ restores DA/ACh balance in striatum
134
Galantamine MOA
inhibit metabolism of ACh by acetylcholinesterase
Increases the amount of ACh in the nerve terminal
AND
blocks presynaptic acetylcholine autoreceptor
135
Donepezil and rivastigmine MOA
Inhibit metabolism of AC by acetylcholinesterase Increase the amount of ACh in the nerve terminal
136
Memantine MOA
NMDA receptor antagonist (channel blocker)
Blocks pathological activation of NMDA receptors
Reduces excitotoxic effect of glutamate and slows degeneration
137
(meth)amphetamine MOA
Reverses dopamine transport through DAT (reuptake) → increased release of dopamine
138
Cocaine MOA
inhibits DA reuptake
139
Crack cocaine aka freebase cocaine
No HCl group on cocaine, can be inhaled for more rapid onset
140
Nicotine MOA
Activates nicotinic receptors in the CNS and periphery→ increases 5-HT and DA release
141
MDMA MOA
Increases 5-HT activity by blocking
| reuptake and stimulating 5-HT receptors
142
Marijuana (THC) MOA
Stimulates presynaptic CB1
| receptors to inhibit transmitter (ACh) release
143
LSD, Mescaline, Psilocybin MOA
Act on 5-HT receptors in the brain
144
PCP and Ketamine MOA
NMDA receptor antagonists
145
GHB MOA
GABA receptor weak agonist
146
MOA of inhalants
Mechanism unknown→ +/- alter
| ionotropic receptors and increase DA
147
Amyl and Butyl nitrite (poppers or snappers) MOA
Smooth muscle relaxants
