Neurology- Pharmacology Flashcards
1
Q
What drug classes are used to tx glaucoma?
A
a-agonsts
BBs
diuretics (acetazolamide)
cholinomimetics
prostaglandins
2
Q
What is the purpose of glaucoma tx?
A
decreased IOP by decreasing the amount of aqueous humor (inhibit synthesis/secretion or increase drainage)
3
Q
What a-agonists are used to tx glaucoma?
A
epinephrine (a1)- decrease aqueous humor synthesis via vasoconstriction
brimonidine (a2)- decrease aqueous humor synthesis
4
Q
What are some AES of using a-agonists to tx glaucoma?
A
mydriasis (a1)- dont use in closed-angle glaucoma
blurry vision, ocular hyperemia, foreign body sensation, ocular allergic rxns, ocular pruritis
5
Q
What are some BBs used for glaucoma tx?
A
Timolol, betxaolol, and carteolol- all decrease aqueous humor synthesis
6
Q
How do diuretics (acetazolamide) help in glaucoma tx?
A
they decrease aqueous humor synthesis via inhbition of carbonic anhydrase
7
Q
What are some cholinomimetics used to tx glaucoma?
A
direct (pilocarpine, carbachol)
indirect (physostigmine, echothiophate)
8
Q
How do cholinomimetics help tx glaucoma?
A
they increase outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
use pilocaprine is emergencies (very effective at opening meshwork into the canal of Schlemm)
9
Q
What are some AEs of cholinomimetics?
A
miosis and cyclospams (contraction of the ciliary muscle)
10
Q
How do prostaglandins help tx glaucoma?
A
PGs like latanoprost (PGF2a) increase outflow of aqueous humor
11
Q
What is a major AE of latanoprost?
A
darkening of the iris color (browning)
12
Q
What are some opiods?
A
morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan,
diphenoxylate, pentazocine
13
Q
How do opiods work?
A
they act as agonists at opiod recepotrs (u= morphine, delta= enkepalin, kappa= dynorphin) to modulate synaptic transmission- open K+ channels, close Ca2+ channels to decrease synaptic transmission
Also inhibit the release of ACh, nor, 5-HT, glutamate, and substance P
14
Q
What are the clinical uses of opiods?
A
pain, cough suppresion (dextromethorphan), diarrhea (loperamide, diphenoxylate), acute pulmonary edema, maintenance for heroin addicts (methadone, naloxone)
15
Q
What are some common AEs of opiods?
A
addiction, respiratory depression, constipation, miosis, additive CNS depression with other drugs
tolerance does not develop to miosis and constipation
16
Q
Opiod toxicity/addiction is well tx with what?
A
naloxone or naltrexone (opiod receptor antagonist)
17
Q
What is Butorphanol?
A
k-opiod receptor agonist and u-opiod receptor partial agonist (produces analgesia) for tx of severe pain (e.g. migraine, labor)
18
Q
What is a major advantage of Butorphanol?
A
it causes less respiratory depression than full opiod agonists
19
Q
What are the AEs of Butorphanol?
A
can cause opiod withdrawal symptoms if pt is also taking a full opiod agonist (OD not easily reversed with naloxone)
20
Q
What is Tramadol?
A
a very weak opiod agonist (also inhibits 5-HT and nor reuptake) for tx of chronic pain
21
Q
What are the AEs of Tramadol?
A
decreased seizure threshold
serotonin syndrome
22
Q
What is the first line tx for simple, partial (focal) epilepsy?
A
carbamazepine
23
Q
What else is carbamazepine the first line tx for?
A
complex partial epilepsy
tonic-clonic, generalized epilepsy (can also use valproic acid or phenytoin first line)
24
Q
What are the other tx options for a simple, partial (focal) epilepsy?
A
pheyntoin
valproic acid
gabapentin
phenobarbital
topiramate
vigabatrin, tiagabine, lamotrigine, levetriacetam
25
What are the other tx options for a complex, partial (focal) epilepsy?
same as simple (again, dont use ethosuximide or benzodiazepines)
26
What are the other tx options for a tonic clonic, partial epilepsy between the first line options (pheyntoin, valproic acid, and carbamazapine)?
phenobarbital
topiramide
lamotrigine
levetiracetam
27
What is the first line for absence generalized epilepsy?
ethosuximide
28
What is the other tx options for absence generalized epilepsy?
valproic acid
lamotrigine
29
What are the tx options for ACUTE status epilepticus epilepsy?
benzodiazepines (diazepam and lorazepam)
30
What are the tx options for prophylaxis of status epilepticus epilepsy?
phenytoin
31
How does Ethosuximide work?
blocks thalamic T-type Ca2+ channels
| (Sux to have silent (absence) seizures)
32
What are the AEs of ethosuximide?
**EFGHIJ-** Ethosuximide causes fatigue, GI distress, HA, itching, and Steven-Johnson Syndrome
33
How do benzodiazepines work?
they increase GABAa action (also used for ecampsia seizures)
34
What are the AEs of benzodiazepines?
sedation, tolerance, dependence, and respiratory depression
35
How does pheyntoin work?
increased Na+ channel inactivation; zero-order kinetics
36
What are the AEs of phenytoin?
Nystagmus, diplopia
ataxia
sedation
gingival hyperplasia
hirsutism
peripheral neuropathy
megalobalstic anemia
teratotoxic (fetal hydantoin syndrome)
SLE- like syndrome
LAD
SJS
osteopenia
37
How does carbamazepine work?
increases Na+ channel inactivation
38
What are the AEs of carbamazepine?
diplopa, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia)
liver toxicity
teratogenesis
induction of CYP450
SIADH
SJS
39
carbamazepine is also first line for what?
trigeminal neuralgia
40
How does valproic acid work?
increases Na+ channel inactivation, and increases GABA concentration by inhibiting GABA transaminase
41
What are the AEs of valproic acid?
GI distress
rare but fatal liver toxicity
teratogenic- neural tube defects (spina bifida)
tremor
weight gain
42
What else is valproic acid used for?
myoclonic seizures and bipolar disorder
43
How does gabapentin work?
primarily inhibits Ca2+ channels (designed as a GABA analog)
44
What are the AEs of gabapentin?
sedation, ataxia
45
What are the other uses of gabapentin?
peripheral neuropathy
postherpetic neuralgia
fibromyalgia
46
How does phenobarbital work?
increases GABAa action
47
What are the AEs of phenobarbital?
sedation, tolerance
dependence
induction of CYP450
cardiorespiratory depression
48
Phenobarbital is first line in seizure tx in who?
neonates
49
How does Topiramate work?
blocks Na+ channels, increased GABA action
50
What are the AEs of Topiramate?
Sedation, mental dulling, kidney stones, weight loss
51
How does lamotrigine work?
blocks voltage-gated Na+ channels
52
What are the AEs of lamotrigine?
SJS (titrate slowly)
53
How does Levetriacetam work?
unknown but may modulate GABA and glutamate release
54
How does Tiagabine work?
increased GABA by inhibiting reuptake
55
How does Vigabatrin work?
increases GABA by irreversibly inhibiting GABA transaminase
56
What are some barbiturates?
Phenobarbital, pentobarbital, thipental, secobarbital
57
How do barbiturates work?
they facilitate GABAa action by increasing the duration of Cl- channel opening, thus decreasing neuron firing
58
barbiturates are contraindicated in what?
porphyria pts.
59
What are the main uses of barbiturates?
sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
60
What are the AEs of barbiturates?
```
respiratory and CV depression (can be fatal)
CNS depression (worse with EtOH use)
```
dependence
induces CYP450
61
How is barbiturate OD tx?
supportive (assist respiration and maintain BP)
62
What are the main benzodiazepines?
diazepam, lorazepam, triazolam, temazepam, ozazepam, modazolam, alprazolam
63
How do benzodiazepines work?
they facilitate GABAa action by icnreasing the frequency of Cl- channel opening
Also decrease REM sleep
64
Metabolism of benzodiazepines
Most have long half-lives and active metabolites (exceptions: **A**lprazolam, **T**riazolam, **O**xazepam, and **M**idazolam- **ATOM-** these have higher addiction potential due to short half-life)
65
What are the clinical uses of benzodiazepines?
anxiety, spasticity, status epilepticus (lorazepam and diazepam)
detox (especially EtOH withdrawal-DTs)
night terrors, sleepwalking
general anesthetic (amnesia, muscle relaxation)
hypnotic (insomnia)
66
What are the AEs of benzodiazepines?
dependence
additive CNS depression effects with alcohol
less risk of respiratory depression and coma than with barbiturates
67
How should benzodiazepines OD be tx?
**flumazenil** (competitive antagonist at GABA benzodiazepine receptors)
68
What are some nonbenzodiazepine hypnotics?
**Z**olpidem, **Z**aleplon, and es**Z**opiclone (Gives you the **ZZZ**s)
69
How do nonbenzodiazepine hypnotics work?
they act via the BZ1 subtype of the GABA receptor (effects reversed by flumazenil) for tx of insomnia
70
What are the AEs of nonbenzodiazepine hypnotics?
ataxia, HA, and confusion
71
What is the DOA of nonbenzodiazepine hypnotics?
short duration b/c of rapid metabolism by liver enzymes. Unlike older sedative-hyponotics, these only cause modest day-after psychomotor deression and a few amnestic effects (also less dependence risk than benzodiazepines)
72
What are some general principles of Anesthetics?
CNS drugs must be lipid soluble to cross the BBB or be actively-transported
73
What is MAC= Minimal Alveolar Conc (of inhaed anesthetics)?
requires to prevent 50% of subjects from moving in response to noxious stimulus (e.g. skin incision)
74
Exs of anesthetics: Nitrous oxide (N2) has lower blood and lipis solubility and this fast induction and low potency. Halothane, in constrat, has high lipid and blood solubility, and this high potency and slow induction
75
What are some inhaled anesthetics?
Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane
N2O
All mechanisms unknown
76
What are the effects of inhaled anesthetics?
myocardial depression, respiratory depression
N/V
increased cerebral blood flow (decreased cerebral metabolic demand)
77
What are the AEs of inhaled anesthetics?
hepatotoxicity (halothane)
nephrotoxicity (methoxyflurane)
proconvulsant (enflurane)
expansion of trapped gas in a body cavity (N2O)
malignant hyperthermia
78
How do inhaled anesthetics caused malignant hyperthermia?
they induce fever and severe muscle contraction
79
What is the tx for malignant hyperthermia?
dantrolene
80
What are some choices for IV anesthetics?
- Barbiturates
- Benzodiazepines
- Arylcyclohexylamines (Ketamine)
- Opiods
- Propofol
81
Describe the use of Barbiturates as IV anethetics
Thiopental- high potency, high lipid solubility, and rapid entry into the brain.
Used for induction of anestehsia and short surgical procedures.
Effect terminated by rapid redistribution into tissue (skeletal tissue and fat)
decreases cerebral blood flow
82
Describe the use of Benzodiazepines as IV anethetics
**Midazolam** most common drug used for endoscopy
used adjunctively with gaseos anesthetics and narcotics
may cause sever postoperative respiratory depression, decreased BP (tx with flumazenil), and/or anterograde amnesia
83
Describe the use of Ketamine as IV anethetics
PCP analogs that at as dissociative anesthetics.
They block NMDA receptors
CV stimulants
cause disorientation, bad dreams, and hallucinations
increased cerebral BF
84
Describe the use of Opiods as IV anethetics
Morphine, fentanyl used with other CNS depressents during general anesthesia
85
Describe the use of Propofol as IV anethetics
Used for sedation in the ICU, rapid anesthesia induction, and short procedures
Less postoperative neausea than thiopental
Potentiates GABAa
86
What are some local anesthetics?
Esters- procaine, cocaine, tetracaine
Amides- IIdocaine, Mepovacaine, Bupivacine
87
How do local anesthetics work?
they block Na+ channels by binding to specific receptors on the inner portion of the cell (preferentially bind to activated Na+ channels, so most effective in rapidly firing neurons)
tertiary amine local anesthetics penetrate membranes in their uncharged form, then bind to ion channels in their charged form
88
Principles of local anesthetics
- Can be given with vasoconstrictors (usually epi) to enhance local action- decreased bleeding, increases anesthesia by blocking systemic spread
- If used in infected (acidic) tissue, alkaline anesthetics are charged and cannot penetrate the membrane so more is needed
89
What is the order of nerve blockade produced by local anesthetics?
small diameter fibers \> large diameter
Myelinated fibers \> unmyelinated fibers
Overall, size factor predominates over myelination such that small myelinated fivers \> small unmyelinated fibers \> large myelinated fibers \> large unmyelinated fibers
90
Which sensations are lost first with local anesthetics?
pain \> temp \> touch \> pressure
91
What are the clinical uses of local anesthetics?
minor surgical procedures, spinal anesthesia. If allergic to esters, give amides
92
What are the AEs of local anesthetics?
CNS excitation, severe CV toxicity (Bupivacaine), HTN, hypotension, arrhythmias (cocaine), and methemoglobinemia (benzocaine)
93
What are the categories of neuromuscular blocking drugs used for muscle paralysis in surgery or mechanical ventilation? (Selective for motor nicotinic receptors)
depolarizing or non-depolarizing
94
What are some non-depolarizing NMJ blockers?
Tubocurarine, atracurium, pancuronium, vecuronium, rocuronium
all act as competitive antagonists that compete with ACh for binding
95
How can the effects of non-depolarizing NMJ blockers be reversed?
Neostigmine (must be given with atropine to prevent muscarinic effects such as bradycardia), edrophonum, and other cholinesterase inhibitors
96
What is the major depolarizing NMJ blockers
Succinylcholine
97
How does Succinylcholine act?
acts as a strong ACh receptor agonists to produce sustained depolarization initially and then prevents further muscle contraction
98
How are the effects of succinylcholine reversed?
Phase I (prolonged depolarization)- no antidote. Block potentiated by cholinesterase inhibitors
Phase II (repolarized but blocked; ACh receptors are available, but desensitized)- antidote is cholinesterase inhibitors
99
What are the main AEs of Succinylcholine?
hypercalcemia, hyperkalemia and malignant hyperthermia
100
What is Dantrolene?
prevents release of Ca2+ from the SR of skeletal muscle for tx of malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs)
101
How does Baclofen work?
It inhibits GABAb receptors at spinal cord level, inducing skeletal muscle relaxation for tx of muscle spasms (e.g. acute low back pain)
102
How does Cyclobenzaprine work?
centrally acting skeletal muscle relaxant, structurally related to TCAs, with similar anticholinergic side effects for tx of muscle spasms
103
What causes Parkinsonism?
loss of dopaminergic neurons and excess cholinergic activity
104
What are some strategies for tx Parkinson disease?
- Dopamine agonists (increase dopamine availability, increased L-DOPA availability, prevent doapmine breakdown)
- Decrease excess cholinergic activity
105
What are the major dopamine agonists?
Ergot- Bromocriptine
Non-ergot (preferred)- Pramipexole, and ropinirole
106
What are some drugs used to increase dopamine availability?
Amantadine (increase dopamine release and decrease uptake)
107
What else is Amantadine used for?
as an antiviral against influenza A and rubella
108
What are the major AEs of Amantadine?
ataxia and livedo reticularis
109
What drugs increase L-DOPA availability?
agents that prevent peripheral L-DOPA degradation to increase the amount of it entering the CNS (L-DOPA is converted to dopamine). These include:
- Levodopa/Carbidopa
- Entacapone/tolcapone
110
How does Carbidopa work?
it blocks peripheral conversion of L-DOPE to dopamine by inhibiting DOPA decarboxylase. It also reduces the side effects of peripheral L-DOPA conversion (e.g. N/V)
111
How do Entacapone and Tolcapone work?
they prevent peripheral L-DOPA degradation to 3-O-methyldopa (3-OMD) by inhibiting COMT
112
How can dopamine breakdown be prevented for Parkinson tx?
agents act centrally to block dopamine breakdown and include:
**Selegiline** (blocks conversion of dopamine into 3-MT by inhibiting MAO-B)
**Tolcapone** (blocks converison of dopamine to DOPAC by inhibiting central COMT)
113
What is an antimuscarinic used to tx Parkinson?
Benzotropine (improves tremor and rigidity but has little effect on bradykinesia)
114
Mnemonic for tx of Parkonsin's
**BALSA:**
**B**romocriptine
**A**mantadine
**L**evodopa (with carbidopa)
**S**elegiline
**A**ntimuscarinics
115
Mechanism of L-Dopa (levodopa)/carbidopa?
They increase the levels of dopamine in the brain. Unlike dopamine, L-DOPA can cross the BBB and is converted by doap decarboxylase in the CNS to dopamine
Carbidopa, a peripheral DOPA decarboxylase inhibitor, is given with L-DOPA to increase its bioavailability in the brain and to limit side effects
116
What are the AEs of L-Dopa (levodopa)/carbidopa?
arryhthmias from inrceased peripheral formation of catecholamines.
Long term use can lead to dyskinesia following administration ("on-off" phenomenon), akinesia between doses
117
How does Selegiline work?
Selectively inhibits MAO-B, which metabolizes dopamine over nor and 5-HT, thereby increasing the availabilty of dopamine (used with L-DOPA in Parkinson tx)
118
What are the main drugs for Alzheimer tx?
- Memantine
- Donepezil, galantamine, rivastigmine, tacrine
119
What is Memantine?
NMDA receptor antagonist that helps prevent excitability (mediated by calcium)
120
What are the AEs of Memantine?
dizziness, confusion, and hallucinations
121
What are Donepezil, galantamine, rivastigmine, and tacrine?
AChE inhibitors
122
What neurotransmitter changes are seen in Huntington's disease?
decreased GABA and ACh
increased dopamine
123
How is Huntington's disease tx?
**tetrabenazine and reserpine**- inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release
**Haloperidol**- D2 receptor antagonist
124
How do Triptans (e.g. Sumatriptan) work?
- 5-HT agonists
- Inhibit CN V activation
- prevent vasoactive peptide release
- induce vasoconstriction
125
What are Triptans used to tx?
acute migraine
cluster HA attacks
126
What are the AEs of triptans?
coronary vasospasm (contraindicated in pts with CAD or Prinzmetal angina)
mild paresthesia
