Neuropharm- Comp 1 Flashcards
1
Q
A1 Receptor binding effects
A
- increased vascular smooth muscle contraction
- mydriasis (increased contraction of pupillary sphincter m.)
- increased intestinal and bladder spincter contraction
Gq protein class
2
Q
a2 R binding effects
A
- inhibition of NT release ( - NE from nerve endings, Ach from adjacent PS neurons)
- decreased sympathetic outflow
- increased platelet aggregation
- decreased lipolysis
- decreased insulin release
- decreased aqueous humor production
Gi protein class
3
Q
B1 R effects
A
- increased hr, contractility
- increased renin release –> which increases BP
- increased lipolysis
Gs protein class
4
Q
B2 R effects
A
- Smooth m. Relaxation (vasodilation in skeletal m., bronchodilation, uterine smooth m., GI smooth m.)
- CNS: presynaptic Rs stimulate NT release
- increased aqueous humor production
- increased HEart contraction
- increased platelet aggregation
- increased insulin secretion, increased lipolysis, increased glycogenolysis
- increased K+ uptake
Gs protein class
5
Q
NSAIDs
(Aspirin, ibuprofen, naproxen)
Mechanism of Action
A
Cox inhibition
Aspirin is irreversible, others are reversible
6
Q
NSAIDs
(Aspirin, ibuprofen, naproxen)
Use
A
- Decrease PGE2 synthesis, stops pain nerve sensitization
- Early intervention
against platelet action.
Acute pain suppression.
Tension headache & Migrane Acute action
7
Q
NSAIDs
(Aspirin, ibuprofen, naproxen)
Toxicity
A
Bleeding, GI irritation, erosions, and ulcers
- salicyclism, increased leukotrienes (asthma, allergies) with aspirin
- -> with allergy to ASA, avoid NSAIDs
8
Q
Acetaminophen
Mechanism of action
A
Weak COX inhibition
9
Q
Acetaminophen
Use
A
- Decease PGE2 synthesis
- Stops pain nerve sensitization
- Less GI effects than NSAIDs
Tension headaches
10
Q
Acetaminophen
Toxicity
A
Liver toxicity at high doses Or EtOH consumption
N-acetylcysteine is the antidote
11
Q
Benzodiazepines
Examples and Mechanism
A
Estazolam, Flurazepam. Temazepam
Potentiate GABA
at Cl-channel (increase frequency)
12
Q
Benzodiazepines
Use
A
Muscle relaxant; Anxiolytic
Status epilepticus seizures
Tension headaches
EtOH withdrawal, muscle relaxant, sedative, preop-sedation/induction of mechanically ventillation
13
Q
Benzodiazepines
Toxicity
A
- Drowsiness
- Impaired judgement
- Depressed motor skills
- Anterograde amnesia
- Tolerance
- Dependence
14
Q
Antimuscarinics
Examples and MOA
A
Cyclobenzaprine
Methocarbamol
Orphenadrine
Amitriptyline
M3 Block; Amitriptyline (tricyclic antidepressant) inhibits reuptake of 5HT and NE
15
Q
Antimuscarinics
Use
A
Local Strain, muscle spasm
Tension headaches
16
Q
Tizanidine
Mechanism of Action
A
Centrally acting α2 adrenergic agonist (reduced norepinephrine outflow)
17
Q
Tizanidine
Use
A
Muscle relaxant
-Migraine prophylaxis
Multiple sclerosis, amyotrophic lateral sclerosis (ALS)
Also for tension headaches
18
Q
Tizanidine
Toxicity
A
Drug interactions (fluoroquinolones) with CYP1A2 raises tizanadine levels
Results in enhanced CNS effects
19
Q
“Ergots”
Mechanism of Action, Drugs
A
- Ergotamine
- Ergotamine Tartrate and Caffeine (Cafergot)
- Dihydroergotamine
Vasoconstrictor at
5-HT1B/1D receptor
20
Q
“Ergots”
Toxicity
A
Vasoconstriction in
coronary arteries. Avoid coronary artery disease, atherosclerosis
21
Q
“Ergots”
Use
A
Counteracts the early
vasodilating phase of Acute Migrane
22
Q
“Triptans”
MOA, Drugs
A
- Sumatriptan
- Almotriptan
- Rizatriptan
- Zolmitriptan
- Naratriptan
- Eletriptan
- Partial Agonist at
5HT1D/1B receptors - Vasoconstriction to reverse vasodilatory phase
23
Q
“Triptans”
Use
A
Migraine (acute) and cluster
headaches
Oral, Nasal, SQ administration; short duration requires multi-dose, but must limit daily dosing
24
Q
“Triptans”
Toxicity
A
All Drugs:
Paresthesias, dizziness, muscle weakness, coronary vasoconstriction, chest pain. Not for coronary artery disease patients.
Serotonin syndrome: SSRIs, MAOIs, tricyclic antidepressants, St John’s Wort, linezolid
25
Propranolol
MOA
Nonselective Beta
| Blocker
26
Propanolol
Use
Prevents trigeminal
nerve excitement
Migrane Prophylaxis
27
Propanolol
Toxicity
- Hypoglycemia
- Bronchoconstriction via beta2 blockade
- Vasoconstriction
28
Amitriptyline
MOA
Tricyclic blocks
| reuptake of 5-HT
29
Amitriptyline
Use
Maintains serotonin
against vasodilating phase
Migrane prophylaxis
30
Amitriptyline
Toxicity
- Anticholinergic (M3) effects
- Alpha1 block (orthostasis)
- H1 block (sedation)
31
Calcium channel Blockers
Examples and MOA
E.g. Verapamil
Diltiazem
Block vascular calcium channels; Vasodilation
32
Calcium channel Blockers
Use
Prevent onset of vasoconstrictive
ischemic phase
Migrane prophylaxis
33
Ca2+ Channel blockers
Toxicity
Hypotension
Constipation
Gingival hyperplasia
34
Valproic Acid and Valproate
MOA
- Mixed action:
1. Sodium and calcium channel blocker
2. Increase GABA synthesis
3. Reduce GABA degradation
4. Decreases glutamate at NMDA receptor
35
Valproic Acid and Valproate
Use
Migrane Prophylaxis
Absence Seizures, Myoclonic Seizures, Specific Myoclonic Seizures, Generalized Tonic- Clonic Seizures.
Manic phase of bipolar disorder
36
Valproic Acid and Valproate
Toxicity
```
Birth defects (blocks
folate absorption), severe hepatitis, weight gain, GI upset
```
Inhibitor of CYP
37
Topiramate
MOA
Potentiate GABA
Blocks sodium channels and Glutamate
38
Topiramate
Use
Migrane prophylaxis
Partial Seizures,
Generalized Tonic- Clonic Seizures
Adjunct therapy for headache
39
Topiramate
Toxicity
- CNS effect
- Teratogen
- Reduced oral contraceptive effect
40
Phenothiazines
Prochlorperazine
MOA
Dopamine receptor antagonists. Also M3 and histamine H1 blockade.
41
Phenothiazines
Prochlorperazine
Use
Antiemetic
Used in migrane prophylaxis
42
Phenothiazines
Prochlorperazine
Toxicity
EPS symptoms and Parkinson’s like effects, increase in prolactin, muscarinic (M3) and histamine (H1) blockade.
Elevated QT interval.
43
Botulinum toxin
MOA
Cleavage of Snap-25 protein, which prevents vesicle fusion, release of Ach vesicles
44
Botulinum toxin
Use
Migraine prophylaxis
Blepharospasm
Focal hand dystonia
Cervical dystonia
45
Botulinum toxin
Toxicity
Absence of muscarinic actions, loss of muscle tone, fatigue, paralysis, respiratory arrest
46
Carbamazepine
Oxcarbazepine (prodrug)
MOA
Sodium channel blockade
47
Carbamazepine
Oxcarbazepine (prodrug)
Use
Trigeminal neuralgia
Partial Seizures,
Generalized Tonic-Clonic Seizures, Manic episodes
48
Carbamazepine
Oxcarbazepine (prodrug)
Toxicity
Drowsiness, Ataxia, Agranulocytosis, SIADH (hyponatremia), Teratogen, Nausea, diplopia, headache
Potent inducers of CYP isoenzymes (e.g. CYP3A4); induces own metabolism
49
```
Lorazepam
Diazepam
Midazolam
Clorazepate
Clobazam
```
Use
Status epilepticus initial treatment, anxiolytic, EtOH withdrawal, muscle relaxant, sedative, preop-sedation/induction of mechanically ventillation, tension headaches
50
```
Lorazepam
Diazepam
Midazolam
Clorazepate
Clobazam
```
MOA
Enhance GABA-mediated Cl- influx, increased membrane polarization
51
```
Lorazepam
Diazepam
Midazolam
Clorazepate
Clobazam
```
Adverse effects
Sedation
Tolerance can occur with chronic use
Interactions minimal
52
Ethosuximide
| Use
Absence seizures
53
Ethosuximide
| MOA
Blocks T-type (low-threshold) Ca2+ channels thus reducing pacemaker current underlying thalamic rhythm in spikes and waves seen in generalized seizures.
54
Ethosuximide
| Adverse effects
Nausea, headache, dizziness, hyperactivity
55
Felbamate
| Use
Refractory to other seizure treatments; typically used for partial and Lennox-Gastault syndrome
56
Felbamate
| MOA
- Blocks glycine activation of NMDA-type glutamate receptors
| - GABAa receptor potentiation
57
Felbamate
| Adverse effects
Aplastic anemia and hepatotoxicity limit its use (must obtain informed consent)
Also: Nausea, vomiting, headache, dizziness, somnolence, insomnia
58
Gabapentin,
Pregabalin
MOA
Blocks presynaptic voltage-gated Ca2+ channels possessing α2δ subunit
May may modulate the release of excitatory neurotransmitters that participate in epileptogenensis and nociception
59
Gabapentin,
Pregabalin
Use
Adjunct therapy for partial seizures, also for neuropathic pain & bipolar disorder
60
Gabapentin,
Pregabalin
ADEs
Somnolence, dizziness, ataxia;
Favorable pharmacokinetic profile; dosage adjustment necessary in renal impairment
- Interactions are minimal
61
Lamotrigine
| MOA
Prolong inactivation of voltage-gated Na+ channels, decreases ability of neurons to fire at high frequency
Acts on voltage-gated presynaptic Ca2+ channels-- decreases glutamate release
62
Lamotrigine
| Use
Partial seizures, primary general epilepsy, Lennox-Gestault Syndrome (can be adjunct or monotherapy)
Also for bipolar disorder maintenance
63
Lamotrigine
| ADEs
Dizziness, headache, diplopia, rash including potentially life-threatening Stevens-Johnson syndrome
Slow dose titration required to reduce risk of rash (over 6-8 weeks)
64
Levetiracetam
| MOA
Assumed to act on synaptic protein SV2A, a/w antiseizure activity in mice
65
Levetiracetam
| Use
Broad spectrum drug, focal seizures, primary general tonic/clonic seizures; off label for status epilepticus
66
Levetiracetam
| ADEs
Nervousness, dizziness, depression, seizures
Pregnancy: animal studies show teratogenic effects
**No CYP or UGT metabolism
67
Phenobarbital
(Barbituates)
MOA
Enhances GABA-mediated Cl- influx
68
Phenobarbital
(Barbituates)
Use
Partial seizures, primary general tonic/clonic seizures; Status epilepticus alternative
69
Phenobarbital
(Barbituates)
ADEs
Sedation, decreased cognition, ataxia, hyperactivity
**Potent inducer of CYP isoenzymes
t½ 75-110h
70
Phenytoin, Fosphenytoin
| MOA
Prolong inactivation of voltage-gated Na+ channels , decreased glutamate release
71
Phenytoin, Fosphenytoin
| Use
Complex partial seizures, general tonic/clonic seizures, status epilepticus, prevention or treatment of seizures during neurosurgery
Nonseizure: ventricular arrythmias, sometimes from digitalis intodication
72
Phenytoin, Fosphenytoin
| ADEs
Diplopia, ataxia, hypotension, bradycardia, gingival hyperplasia, hirsutism, neuropathy, nystagmus, jaundice, osteomalacia, skin coarsening, purple glove syndrome (IV), SJS/TEN/DRESS
- Teratogenic (interference with folic acid absorption)
* Nonlinear elimination kinetics at therapeutic doses;
* Potent inducer of CYP isoenzymes
73
Topiramate
| MOA
Likely:
Prolonged inactivation of voltage-gated Na+ channels
Increased GABA synthesis and decreased GABA degradation
Blocks kainite and AMPA glutamate receptors
Weakly inhibits carbonic anhydrase
74
Topiramate
| Use
Partial seizures, Primary General Tonic/Clonic seizures, Lennox-Gestalt syndrome (adjunctive)
Nonseizure: Migrane prophylaxis, cluster headaches, neuropathy, weight loss with phenteramine
75
Topiramate
| ADEs
- Somnolence
- cognitive slowing
- confusion
- paresthesias
- Hyperthermia most commonly in children; metabolic acidosis; renal calculus
Use with caution in patients with renal impairment and those with hepatic impairment
-Inhibits CYP2C19 and a weak inducer of CYP3A4
76
Valproate
| MOA
increased GABA synthesis, increased GABA transport from synapse, and decreased GABA degradation, or may mimic GABA actions at postsynaptic receptor sites
Possibly blocks voltage-gated Na+ channels
Possibly blocks T-type Ca2+ channels thus reducing pacemaker current underlying thalamic rhythm in spike and waves seen in generalized seizures
Possible histone deacetylation
Possible block of NMDA receptors
77
Valproate
| Use
Generalized tonic/clonic seizures,
Focal seizures,
Absence seizures,
Status Epilepticus (off-label)
Nonseizure: Acute mania with bipolar disorder, migrane prophylaxis, diabetic neuropathy
78
Valproate
| ADEs
Nausea, tremor, weight gain, hair loss, teratogenic, thrombocytopenia, hyperammonia, hepatotoxic, rare acute pancreatitis (Boxed warning)
Inhibits CYP isoenzymes
79
Aspirin
| MOA
Irreversible acetylation of serine on COX-1and 2. Blocks Thromboxane (TXA2)
80
ASA
| Use
Analgesic, Antipyretic, Anti-inflammatory, Low dose antiplatelet
81
ASA
| Toxicity
- Bleeding, GI irritation, erosion, ulceration, allergic reactions (leukotriene mediated)
- Compensated resp. alkalosis. (Manage by ion trapping)
- salicylism (ringing ears), Reye’s syndrome
82
Dipyridamole
| MOA
- Phosphodiesterase inhibitor -blogs PGI2 binding (increases cAMP, cGMP, and NO
- -->Vasodilator (PGI2).
- Inhibits TXA2 synthesis and receptors; Antiplatelet
83
Dipyridamole
| Use
Combine with aspirin for stroke and TIA prevention
84
Dipyridamole
| Toxicity
Bleeding, hypotension, vasodilation
85
Cilostasol
| MOA
Phosphodiesterase inhibitor (increases cAMP). Acts to stabilize platelets; Antiplatelet
86
Cilostasol
| Use
Intermittent claudication.
Thrombosis in peripheral vascular disease.
Prevents stroke.
87
Cilostasol
| Toxicity
Vascular headache, tachycardia (secondary to vasodilation)
88
Clopidogrel
| MOA
Irreversible ADP receptor blocker. Stops expression of surface GPIIb/IIIa.
Prodrug; Antiplatelet
89
Clopidogrel
| Use
Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.
90
Clopidogrel
| Toxicity
Bleeding.
Alternative if patient has aspirin contraindication.
Safer than Ticlopidine.
May lose effect due to inactive CYP2C19.
14% of population is variant and cannot convert clopidogrel to active form. These patients are at risk for MI stroke and death.
91
Ticlopidine
| MOA
Irreversible ADP receptor blocker. Stops expression of surface GPIIb/IIIa.
Prodrug; Antiplatelet
92
Ticlopidine
| Use
Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.
93
Ticlopidine
| Toxicity
Bleeding.
**Neutropenia,
agranulocytosis, thrombotic thrombocytopenic purpura (TTP) and aplastic anemia
94
Prasugrel
| MOA
Irreversible ADP receptor blocker. Stops expression of surface GPIIb/IIIa.
Prodrug; Antiplatelet
95
Prasugrel
| Use
Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.
Faster onset, more consistent action than clopidogrel.
96
Prasugrel
| Toxicity
Multi-enzyme conversion to active metabolite, therefore less problems with enzyme inactivity.
Conversion by CYP3A4 and CYP2B6; not CYP2C19.
Bleeding.
97
Ticagrelor
| MOA
Reversible ADP receptor blocker
Direct acting; Antiplatelet
98
Ticagrelor
| Use
Angioplasty, stent, CAD, Stroke
vascular ischemia with atherosclerosis.
Acute coronary syndrome.
Faster action than clopidogrel
Prevents thrombotic events
99
Ticagrelor
| Toxicity
Drug inhibits CYP3A4 (so will increase concentrations of drugs such as statins).
Bleeding
100
Abciximab
| MOA
High affinity for GPIIb/IIIa receptors
Blocks the glycoprotein IIb/IIIa pathway involved in cross-linking platelets
Long-acting (7-10 days)
101
Abciximab
| Use
Angioplasty, stent, CAD, Stroke
102
Abciximab
| Toxicity
Bleeding
103
Eptifibatide
Tirofiban
MOA
Short-acting,
reversible, binds GPIIb/IIIa receptors
Antiplatelet
104
Eptifibatide
Tirofiban
Use
Angioplasty, stent, CAD, Stroke
105
Eptifibatide
Tirofiban
Toxicity
Bleeding
106
Heparin
Unfractionated
MOA
Binds Antithrombin III to reduce active clotting factors (II and Xa)
107
Heparin
Unfractionated
Use
IV anticoagulant.
Rapid acting, t1/2 1.5 hrs.
Does not cross placenta (safe in pregnancy)
108
Heparin
Unfractionated
Toxicity
```
Bleeding
- Use protamine to bind heparin (antidote).
Thrombocytopenia
Osteoporosis
Hyperkalemia
Hypersensitivity
```
109
Low Molecular Weight Heparins
| MOA
Enoxaparin, Dalteparin, Tinzaparin
Binds Antithrombin III to reduce active clotting factors
110
Low Molecular Weight Heparins
| Use
SQ anticoagulant. Rapid acting t1/2 4-6 hrs
111
Low Molecular Weight Heparins
| Toxicity
Bleeding, less thrombocytopenia
112
Fondaparinux
Idraparinux
MOA
Synthetic pentasaccharide of heparin which binds to antithrombin III.
Selective for factor Xa vs II
113
Fondaparinux
Idraparinux
Use
Anticoagulant
Fondaparinux: s.c., t1/2 17-21 hrs (dosed once daily)
Idraparinux: s.c., t1/2 80 hrs (dosed once per week)
114
Fondaparinux
Idraparinux
Toxicity
Bleeding, but minimal thrombocytopenia
115
Warfarin
| MOA
Blocks vitamin K epoxide reductase. Stops clotting factor synthesis.
116
Warfarin
| Use
Delay of 4-5 days for anticoagulant benefit. - Check INRs
Hypercoagulopathy, vascular necrosis, and protein C deficiency can be controlled by heparin.
Crosses placenta (teratogen)
117
Warfarin
| Toxicity
Bleeding.
Add vitamin K or replace clotting factors (severe bleed).
```
Drug interactions (protein
binding and CYP mediated)
```
118
Bivalirudin
Argatroban
Dabigatran
MOA
Hirudin-like Direct Thrombin Inhibitors (DTI)
119
Bivalirudin
Argatroban
Dabigatran
Use
Alternative to heparin in HIT. Rapid injectable, short-acting. Angioplasty, stent.
Dabigatran to prevent stroke in nonvalvular atrial fibrillation--Oral formulation
120
Bivalirudin
Argatroban
Dabigatran
Toxicity
Bleeding, but no thrombocytopenia.
Idarucizumab is the antidote.
All require dose adjustment in renal impairment.
121
Rivaroxaban
Apixaban
Edoxaban
MOA
Direct factor Xa inhibitor
(oral drugs)
Rapid onset
122
Rivaroxaban
Apixaban
Edoxaban
Use
DVT, prevent strokes in patients with atrial fibrillation
VTE prophylaxis and treatment
Little monitoring, unlike warfarin
123
Rivaroxaban
Apixaban
Edoxaban
Toxicity
Bleeding risk especially with drugs that inhibit CYP3A4.
No antidote, use antifibrinolytics for severe bleed
Impaired renal or hepatic function result in increased drug effect.
124
Streptokinase
Urokinase
MOA
Natural tissue plasminogen activator (tPA); a protease which targets plasminogen to plasmin
125
Streptokinase
Urokinase
Use
Infused in thrombosed vessel to lyse clot. (Fibrinolytic)
Streptokinase is a bacterial protein, can induce allergic reactions.
Replaced with newer drugs (alteplase)
126
Streptokinase
Urokinase
Toxicity
All drugs increase bleeding.
Contraindications: Prior intracranial hemorrhage and malignant intracranial neoplasms
Reversed by aminocaproic acid tranexamic acid.
Block plasmin interaction with fibrin
127
Anistreplase
| MOA
(Streptokinase
plus plasminogen)
Activates plasminogen to plasmin
128
Anistreplase
| Use
Infused in thrombosed vessel to lyse clot.
129
Anistreplase
| Toxicity
All drugs increase bleeding.
Contraindications: Prior intracranial hemorrhage and malignant intracranial neoplasms
Reversed by aminocaproic acid tranexamic acid.
Block plasmin interaction with fibrin
130
Alteplase
Reteplase
Tenecteplase
MOA
Human Recombinant tissue plasminogen activators tPA
Faster onset of action than alteplase
Longer t1/2 than alteplase or reteplase
131
Alteplase
Reteplase
Tenecteplase
Use
Infused in thrombosed vessel to lyse clot.
Use IV asap, within 3 hrs for optimal benefit
Use: MI, acute ischemic stroke, pulmonary embolism, central venous catheterization.
132
Alteplase
Reteplase
Tenecteplase
Toxicity
All drugs increase bleeding.
Contraindications: Prior intracranial hemorrhage and malignant intracranial neoplasms
Reversed by aminocaproic acid tranexamic acid.
Block plasmin interaction with fibrin
133
Nifedipine
| MOA
Calcium channel blocker
134
Nifedipine
| Use
Common to all CCBs; antianginal, antihypertensive
Arterioles relax, TPR and afterload decrease.
BP falls, heart works less for systole.
Stroke prevention
135
Nifedipine
| Toxicity
Arteriole action only
Decreases TPR, BP.
May elicit the SANS reflex and tachycardia.
Common to all “dipines”
136
Labetalol
| MOA
Alpha and Beta 1,2 antagonist, antioxidant potential
137
Labetalol
| Use
Hypertensive crisis, congestive heart failure, cocaine withdrawal
138
Labetalol
| Toxicity
Bronchoconstriction, masking hypoglycemia (beta-2), orthostasis (alpha-1)
139
```
“Statin” drugs MOA
Lovastatin
Atorvastatin
Pravastatin
Simvastatin
Rosuvastatin
```
Competitively inhibit HMG CoA reductase.
140
```
“Statin” drugs use
Lovastatin
Atorvastatin
Pravastatin
Simvastatin
Rosuvastatin
```
There is an increase in the number of LDL receptors
LDL decreases 25-45%.
Stroke prevention
141
```
“Statin” drugs Toxicity
Lovastatin
Atorvastatin
Pravastatin
Simvastatin
Rosuvastatin
```
Hepatic toxicity, Myopathy, rhabdomyolysis
Drug interactions: enzyme inhibitors
142
Cytochrome P450 Enzyme inhibitors
- grapefruit juice
- protease inhibitors,
- amiodarone
- cimetidine
- azole antifungals (e.g. ketoconazole)
- erythromycin
- sulfonamides
- isoniazid
- valproic acid
- quinidine
- acute alcohol abuse
143
Cytochrome P450 Enzyme inducers
- St John’s wort
- phenytoin, phenobarbital, carbamazepine
- griseofulvin
- rifampin
- chronic alcohol abuse
- nevirapine
144
B3 R effects
Gs
Increased lipolysis, increased thermogenesis, increased bladder relaxation
