Module 5 Flashcards
CNS Drugs Part 2
1
Q
Parkinson’s Disease Pathophysiology
A
progressive degeneration of neurons in the substantia nigra causing loss of DA transmission and reduced thalamic stimulation of the cortex
2
Q
Parkinson’s Disease sx
A
rest tremor, bradykinesia, rigidity, and postural defect causing a tendency to stoop
3
Q
effect of D1 receptors on neuronal activity
A
excitatory
4
Q
effect of D2 receptors on neuronal activity
A
inhibitory
5
Q
Levodopa (L-DOPA) MOA
A
dopamine precursor that crosses the blood-brain barrier and is converted to dopamine by dopamine decarboxylase
6
Q
Levodopa adverse effects
A
hallucinations/confusion, dyskinesia, peripheral effects including nausea (interaction with DA receptors in gut), hypotension, and arrhythmia
7
Q
Carbidopa MOA
A
peripheral inhibitor of DA decarboxylase (DDC) allowing Levodopa to make it to CNS without being metabolized in the periphery (does not cross the blood-brain barrier), reduces peripheral side effects of Levodopa
8
Q
Entacapone MOA
A
inhibits COMT (catechol-o-methyl transferase) enzyme mostly in the periphery preventing the degradation of Levodopa in the periphery
9
Q
Entacapone adverse effects
A
dyskinesia, nausea, and diarrhea
10
Q
Levodopa adjustment to reduce motor fluctuation
A
increase the number or frequency of Levodopa dosages
11
Q
Selegiline MOA
A
selectively inhibits MAO B in the striatum preventing the metabolism of DA, NE, and 5-HT (serotonin), reduces the dose of Levodopa needed
12
Q
Selegiline adverse effects
A
partly metabolized to amphetamine causing amphetamine-like side effects, serotonin syndrome can be induced by combining with tyramine-rich foods or SSRIs, can cause drug interactions due to metabolism by CYP450
13
Q
Bromocriptine MOA
A
Ergot alkaloid with more selective D2 receptor agonist activity but with some activity at D1, D3, and 5-HT receptors, does not rely on existing DA neurons
14
Q
Bromocriptine clinical use
A
used to delay the need for Levodopa and to treat advanced Parkinson’s disease
15
Q
Bromocriptine adverse effects
A
similar to levodopa but with more risk of psychotic effects, poses risk of cardiac valve fibrosis with long-term use
16
Q
Ropinirole MOA
A
less selective dopamine receptor agonist than Bromocriptine with D2, D3, and D4 receptor agonist activity
17
Q
Ropinirole clinical uses
A
Parkinson’s and restless leg syndrome
18
Q
Ropinirole adverse effects
A
reduced risk of cardiac valve fibrosis compared to Bromocriptine, can increase risky behavior due to D3 agonism, can cause drug interactions due to metabolism by CYP450
19
Q
Trihexyphenidyl MOA
A
muscarinic Ach receptor antagonist that is often given in combination with DA agonists, excreted in the urine unchanged
20
Q
Trihexyphenidyl clinical use
A
often given in combination with DA agonists effective at reducing dyskinetic movements and spastic contractions
21
Q
Trihexyphenidyl adverse effects
A
causes anticholinergic side effects including sedation, confusion, constipation, and urinary retention
22
Q
Amantadine MOA
A
antiviral drug that increases DA release and blocks NMDA glutamate receptors, has an anti-Parkinson’s affect
23
Q
Amantadine clinical use
A
less effective at treating Parkinson’s compared to Levodopa and used as last resort
24
Q
Amantadine adverse effects
A
causes confusion and psychosis
25
Huntington's disease pathophysiology
Inherited autosomal dominant disease characterized by involuntary movements (chorea), personality changes, and bradykinesia due to neuronal loss in the caudate nucleus/putamen and striatum and loss of GABA function
26
Deutetrabenazine MOA
inhibitor of VMAT-2 (vesicular monoamine transporter) which prevents the storage of neurotransmitters in vesicles and reduces involuntary hyperkinetic movements seen with Huntington's (longer half-life relative to tetrabenazine)
27
Deutetrabenazine adverse effects
similar to antipsychotics including akathisia, drowsiness, tremor, and depression, some patients are poor metabolizers due to the requirement of CYP450
28
Deutetrabenazine contraindications
contraindicated with MAO inhibitors and in uncontrolled depression with suicide risk
29
Deutetrabenazine clinical use
used to treat Huntington's, Tourette's, and Tardive dyskinesia (involuntary facial movements)
30
Alzheimer's Dementia pathophysiology
the accumulation of beta-amyloid plaques and neurofibrillary tangles in the hippocampus and cortex causing cholinergic damage, loss of enzymes for Ach synthesis, and loss of cholinergic neurons in the basal forebrain
31
Donepezil MOA
acetylcholinesterase inhibitor that readily enters the CNS and raises Ach levels in damaged areas of the brain and may also increase Ach synthesis and release
32
Donepezil clinical use
administered once daily (relatively long half-life) in the treatment of Alzheimer's Dementia
33
Donepezil adverse effects
overactive gut motility from cholinergic effects causing nausea, vomiting, and diarrhea, causes sleep disturbances - vivid dreams, no major drug interactions
34
Memantine MOA
NMDA receptor antagonist that blocks pathological activation of NMDA receptors and is thought to reduce excitotoxicity (noise which causes confusion)
35
Memantine clinical use
not as effective as monotherapy as Donepezil but useful for patients who do not respond or cannot tolerate Donepezil side effects, usually combined with Donepezil
36
Memantine adverse effects
dizziness, headache, constipation, and confusion
37
Epilepsy
An assortment of different seizure types and syndromes that have in common the sudden, excessive, and synchronous discharge of cerebral neurons causing abnormal electrical activity that can result in events including LOC, abnormal movements, atypical or odd behavior, and distorted perceptions of limited duration but that can recur if untreated.
38
Idiopathic epilepsy
seizures without specific anatomic cause, such as trauma or neoplasm, most cases of epilepsy are idiopathic
39
Symptomatic epilepsy
seizures caused by illicit drug use, tumor, head injury, hypoglycemia, meningeal infection, or alcohol withdrawal
40
Partial simple seizure
caused by a group of hyperactive neurons exhibiting abnormal electrical activity which are confined to a single locus in the brain, no LOC and often exhibit abnormal movement of a single limb or muscle group controlled by that area in the brain.
41
Partial complex seizure
exhibits complex sensory hallucinations and mental distortion, altered consciousness and memory
42
Generalized seizure
a complex seizure that involves both hemispheres of the brain and causes LOC and altered memory - include tonic-clonic, absence, and myoclonic seizures, infantile spasm, and status epilepticus
43
status epilepticus
two or more seizures that occur without full recovery of consciousness between them - life threatening
44
tonic-clonic seizure
LOC followed by tonic (continuous contraction) and clonic (rapid contraction and relaxation phases)
45
absence seizure
brief abrupt self-limiting loss of consciousness - may stare and exhibit rapid eye blinking lasting 3-5 seconds
46
myoclonic seizure
short episodes of muscle contractions that may recur within several minutes
47
General mechanism of antiseizure drugs (AEDs)
block Na+ or Ca2+ voltage-gated channels, enhance inhibitory GABA-ergic impulses, interfere with excitatory glutamate transmission
48
Benzodiazepines MOA
bind to GABA inhibitory receptors increasing the frequency of chloride channel opening
49
Benzo with shortest half-life but longest duration of action in the brain
Lorazepam
50
Diazepam admin
available for rectal admin to avoid or interrupt prolonged generalized tonic-clonic seizures or clusters (children and patients with AMS)
51
Benzodiazepine clinical use in seizures
diazepam and lorazepam are most often used as adjunctive therapy for myoclonic as well as partial and generalized tonic-clonic seizures
52
Carbamazepine MOA
blocks sodium channels reducing the propagation of abnormal impulses in the brain thereby inhibiting the generation of repetitive action potentials in the epileptic focus and preventing spread
53
Carbamazepine clinical use
used primarily prophylactically to treat partial seizures and secondarily generalized tonic-clonic seizures (DO NOT prescribe for patients with ABSENCE seizures because it could increase seizures)
54
Carbamazepine admin
administered orally and absorbed slowly and erratically resulting in large variations of serum concentrations, inducer of CYP and UGT enzymes
55
Carbamazepine contraindications
Do not prescribe to patients with ABSENCE seizures!! not well tolerated in the elderly
56
Ethosuximide MOA
most likely inhibits T-type calcium channels reducing the propagation of abnormal electrical activity in the brain
57
Ethosuximide clinical use
drug of choice for treating primary generalized absence seizures - "ET sux a mind" until all thoughts are absent!
58
Gabapentin MOA
analog of GABA but does not act on GABA receptors, enhance GABA actions, or become converted to GABA (unknown MOA)
59
Gabapentin clinical use
approved as adjunct therapy for partial seizures and for the treatment of postherpetic neuralgia
60
Gabapentin admin
requires dose reduction in renal disease but is well tolerated in the elderly, does not bind to plasma proteins and is excreted unchanged through the kidneys
61
Lamotrigine MOA
blocks sodium channels as well as high-voltage-dependent calcium channels
62
Lamotrigine clinical use
treatment for a wide variety of seizure types including partial, generalized, and absence seizures, Lennox-Gastaut Syndrome, and bipolar disorder, tolerated well in elderly
63
Lamotrigine pharmacokinetics
half-life is 24-35 hours which is shortened by CYP-inducing drugs like carbamazepine and phenytoin and increased by greater than 50% if given in combo with valproate (must reduce dose if given in combo), metabolized through the UGT pathway
64
Lamotrigine adverse effects
rapid titration can cause a rash which may progress to life-threatening Stevens-Johnson Syndrome
65
Levetiracetam/Keppra clinical use
approved for adjunct therapy of partial, myoclonic, and primary generalized tonic-clonic seizures in adults and children
66
Levetiracetam admin
administered orally and well absorbed, excreted in urine unchanged
67
Levetiracetam adverse effects
dizziness, sleep disturbances, headache, and weakness
68
Oxcarbazepine MOA
prodrug that is rapidly reduced to the 10-monohydroxy (MHD) metabolite which blocks sodium channels preventing the spread of abnormal discharge, thought to modulate calcium channels
69
Oxcarbazepine clinical use
used to treat partial onset seizures in adults and children
70
Oxcarbazepine adverse effects
hyponatremia
71
Phenobarbital MOA
a barbiturate that enhances the inhibitory effects of GABA-mediated neurons
72
Phenobarbital clinical use
used primarily in the abortive treatment of status epilepticus, levels must be monitored with continuous use and patients must be tapered off when stopped (being used more and more in hospital settings to sedate patients and to prevent seizures in alcohol withdrawal)
73
Phenytoin MOA
blocks voltage-gated sodium channels by selectively binding to the channel in the inactive state and slowing its rate of recovery, at high doses it can block voltage-depending calcium channels and interfere with release of monoaminergic neurotransmitters
74
Phenytoin clinical use
treatment of partial and generalized tonic-clonic seizures and for status epilepticus
75
Phenytoin pharmacokinetics
exhibits saturable enzyme metabolism at a low serum concentration where small increases in the daily dose can cause large increases in plasma concentration resulting in toxicity
76
Phenytoin toxicity
depression of the CNS in the cerebellum and vestibular system causing nystagmus and ataxia especially in the elderly
77
Phenytoin adverse effects
gingival hyperplasia causing the gums to grow over the teeth, peripheral neuropathies and osteoporosis can develop with long-term use, causes tissue damage and necrosis with IM use (DO NOT give IM!!)
78
Fosphenytoin MOA
prodrug that is rapidly converted to phenytoin in the blood reaching high levels within minutes (given IV or IM)
79
Pregabalin MOA
binds to the alpha-2-gamma site, a subunit of voltage-gated calcium channels in the CNS, inhibiting neurotransmitter release
80
Pregabalin clinical use
used to treat partial onset seizures, neuropathic pain, postherpetic neuralgia, and fibromyalgia
81
Pregabalin adverse effects
drowsiness, blurred vision, weight gain, and peripheral edema
82
Topiramate MOA
has a broad spectrum of antiseizure activity which includes blocking of voltage-dependent sodium channels, increasing the frequency of chloride channel opening by binding to GABA-A receptor, reducing high voltage calcium currents (L type), and inhibiting carbonic anhydrase
83
Topiramate clinical use
used to treat partial and primary generalized seizures and in migraine prevention
84
Topiramate pharmacokinetics
- inhibits CYP2C19 and is induced by phenytoin and carbamazepine
- lamotrigine causes an increase in topiramate concentration
- co-administration of topiramate with ethinyl estradiol reduces efficacy of the birth control
85
Topiramate adverse effects
- somnolence, weight loss, and paresthesia, and increased renal stones
- glaucoma, oligohidrosis, and hyperthermia have been reported related to carbonic anhydrase activity
86
Divalproex/Valproate MOA
combination of valproic acid and sodium valproate that is converted to valproate when it reaches the GI tract and is thought to block sodium channels, GABA transaminase, and action at the T-type calcium channels
87
Divalproex/Valproate clinical use
has a broad spectrum of activity against partial and primary generalized epilepsies
88
Valproate pharmacokinetics
inhibits CYP2C9, UGT, and epoxide hydrolase systems and can cause significant interactions with other highly protein-bound drugs due to it being 90% bound to albumin
89
Valproate adverse effects
may cause rare hepatic toxicity causing a rise in hepatic enzymes in plasma which should be monitored frequently, TERATOGENICITY is of great concern
90
Zonisamide MOA
a SULFONAMIDE derivative with a broad spectrum of action with multiple effects on neuronal systems thought to be involved in seizure generation, metabolized by CYP3A4
91
Zonisamide clinical use
used for treatment of patients with partial seizures
92
Zonisamide adverse effects
CNS effects, kidney stones, and oligohidrosis (patients should be monitored for increased body temp and decreased sweating)
93
Drugs contraindicated in pregnancy
Valproate and barbiturates (phenobarbital) are contraindicated, however, no antiepileptic drug has proven safe in pregnancy (drugs should be prescribed at lowest effective dose and drug levels monitored during pregnancy)
94
Migraine aura
spreading depression of neuronal activity accompanied by reduced blood flow in the most posterior part of the cerebral hemisphere which gradually spreads forward over the surface of the cortex to other contiguous areas of brain
95
Sumatriptan MOA
serotonin agonist which acts at a subgroup of serotonin receptors found on small peripheral nerves that innervate the intracranial vasculature
96
Sumatriptan admin
administered subcutaneously, intranasally, or orally with parental admin having the quickest onset (20 minutes)
97
Sumatriptan clinical use
Rapidly and effectively abort 70% of migraine headaches and can also be used for cluster headaches, DO NOT USE in patients with CAD
98
Sumatriptan adverse effects
elevation of blood pressure and cardiac events, pain and pressure in the chest, neck, throat, and jaw
99
Ergotamine MOA
complex binding to several receptors acting as an agonist and structurally similar to serotonin, dopamine, and epinephrine - causes vasoconstriction
100
Ergotamine admin
given IV with similar efficacy as sumatriptan, can cause nausea
101
Ondansetron MOA
selectively blocks the 5-HT3 receptors in the periphery and in the CNS
102
Ondansetron adverse effects
can cause headaches and cardiac arrhythmias (monitor for prolonged QT intervals)
103
Phenylzine MOA
irreversible nonselective MAO inhibitor (MAO-A and B) affecting NE, 5-HT, and DA transmission used as an antidepressant
104
Phenylzine adverse effects
- interacts with Tyramine-rich foods causing excess release of NE from adrenergic neurons and stimulation of the sympathetic nervous system resulting in hypertensive crisis (Tyramine is usually metabolized in the small intestine by MAO-A but if inhibited it can be taken up by adrenergic neurons in the ventrolateral medulla)
- weight gain, orthostatic hypotension, insomnia, hepatotoxicity, sexual dysfunction
- has narrow therapeutic index
105
Foods to avoid with MAOI antidepressants
aged cheese, draft beer, dried/aged food (smoked foods and tofu)
106
Phenylzine drug interactions
ephedrine/pseudoephedrine and amphetamine which can cause hypertensive crisis and antidepressants such as reuptake inhibitors which can cause hypertensive crisis and serotonin syndrome
107
Tricyclic antidepressants (TCAs) MOA
5-HT reuptake transporter (SERT) and NE transporter (NET) blockers which result in enhanced 5-HT and NE signaling
108
TCA adverse effects
- drowsiness, sedation, weight gain due to blockade of H1 receptors
- blurred vision, dry mouth, constipation, urinary retention, tachycardia, and cognitive dysfunction due to blockade of mAch receptors
- postural hypotension, dizziness, and reflex tachycardia due to alpha 1 and 2 partial block
- cardiac conduction delays dangerous in overdose due to Na+ channel block
- has a narrow therapeutic index
109
Secondary amine TCAs
Desipramine and Nortriptyline
110
Tertiary amine TCAs
Imipramine, Amitriptyline, and Clomipramine
111
What subgroup of TCAs have less side effects?
secondary amines (desipramine and nortriptyline)
112
What subgroup of TCAs have more anticholinergic effects?
tertiary amines (amitriptyline, imipramine, and clomipramine)
113
TCA drug interactions
other antidepressants, Na+ channel blockers, antimuscarinic drugs, and CYP450 substrates
114
SSRI adverse effects
serotonin syndrome, GI disturbances due to activation of 5-HT in the gut, weight gain, anxiety, agitation, insomnia, suicidal thoughts especially in children and adolescents, headache, sweating, and sexual dysfunction
115
SSRI with the lowest risk for children
Fluoxetine
116
Serotonin syndrome symptoms
hyperreflexia, CNS excitation, anxiety/agitation, autonomic excitation - hypertension and hyperthermia (usually only seen in SSRI overdose or SSRIs combined with other antidepressants)
117
Serotonin syndrome treatment
benzodiazepine sedation or cyproheptadine (anti-histamine)
118
SSRI with the most side effects
Paroxetine (Paxil)
119
Advantages of SNRIs over SSRIs
less likely to cause weight gain and possibly have greater efficacy than single-action agents like SSRIs
120
SNRI adverse effects
nausea is most common, can cause emergent hypertension with high doses, metabolized by CYP450 and can cause inhibition at high doses
121
SNRI most commonly prescribed due to lower cost
Venlafaxine, duloxetine, and desvenlafaxine
122
Duloxetine clinical use
used to treat major depression, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis
123
Venlafaxine clinical use
used to treat major depression, generalized anxiety disorder, panic disorder, and social phobia
124
Bupropion MOA
noradrenergic-dopaminergic reuptake inhibitor (NDRI) which has no effect on serotonin transmission
125
Bupropion clinical use
used to treat depression without sexual adverse effects (can increase libido) ADD, and nicotine dependence,
126
Bupropion adverse effects
lowers seizure threshold and can cause SEIZURES, metabolized by CYP450 and inhibits it at high doses, may cause anxiety - DO NOT prescribe for ANXIETY
127
Trazodone MOA
5-HT receptor antagonist
128
Trazodone clinical use
very sedating antidepressant and is commonly used as a hypnotic at low doses
129
Mirtazapine MOA
alpha-2 receptor antagonist which increases the release of NE and 5-HT from presynaptic neuron
130
Mirtazapine clinical use
used to treat patients who are "failing to thrive" and for whom weight gain is desirable or experience side effects with serotonergic agents
131
Mirtazapine adverse effects
weight gain and sedation due to anti-histamine effects
132
Main drug categories used to treat depression
serotonergic drugs (SSRIs, SNRIs, TCAs, and MAOIs) and bupropion
133
Main drugs used to treat OCD
SSRIs
134
Main drugs used to treat panic disorder
SNRIs, TCAs, and MAOIs for prevention (Paxil is the only SSRI that can be used safely for panic)
135
Main drugs used to treat PTSD
SSRIs
136
Main drugs used to treat insomnia and depression
trazodone and mirtazapine
137
Main drugs used to treat pain syndromes
TCAs and SNRIs
138
Main drug used to treat ADD and nicotine dependence
Bupropion
139
Main drugs used to treat eating disorders
SSRIs (fluoxetine) and mirtazapine
140
Class A mood stabilizers
stabilize mood from ABOVE baseline (mania) without causing depression (most treatments for bipolar are more effective at Class A than Class B)
141
Class B mood stabilizers
stabilize mood from BELOW baseline (depression) without accelerating mania
142
Lithium MOA
blocks the recycling of inositol phosphates desensitizing signaling through Gq-coupled receptors effecting 5-HT synthesis and release
143
Lithium pharmacokinetics
absorbed in GI tract and slowly passes through the blood-brain barrier, can also pass to unborn fetus and to milk, 95% eliminated in urine
144
Lithium adverse effects
weight gain, hypothyroidism, tremor, has a narrow therapeutic index and levels should be monitored in the blood
145
Lithium intoxication
vomiting, diarrhea, tremor, ataxia, coma (reversed by dialysis)
146
Lithium drug interactions
antidepressants and diuretics
147
Antiseizure drugs that also have antimanic properties
Valproate, carbamazepine, and lamotrigine (can use in Li+-refractory patients)
148
Benzodiazepine clinical use
short-term abortive treatment of anxiety, panic attacks, phobia, insomnia, alcohol withdrawal, agitation, sedation, status epilepticus, or as an adjunct to preventative treatment only when necessary (safer than barbiturates)
149
Benzo with the longest half-life
Clonazepam
150
Benzo adverse effects
sedation, ataxia/falls, impaired motor performance, impaired cognition, anterograde amnesia, and disinhibition of impulses
151
Treatment of benzo overdose
Flumazenil
152
Benzodiazepine of choice for sleep induction
Temazepam (half-life = 5 hours), next best is lorazepam (if CYP induction/inhibition is of great concern)
153
Buspirone MOA
partial agonist at pre and post-synaptic 5-HT A1 receptors and has some antagonist activity at D2 receptors
154
Buspirone clinical use
non-sedating anxiolytic with some antidepressant and antipsychotic activity most effective with chronic use not acute panic attacks (no abuse potential)
155
Buspirone adverse effects
dizziness, headaches, GI upset, and combination with MAOIs may cause tachycardia and hypertension
156
Zolpidem/Eszoplicone MOA
an agonist that binds similar to benzodiazepines but to only a subset of GABA receptors (alpha-1 sub-receptor) that are associated with sleep and produces pure sedation
157
Zolpidem/Eszoplicone adverse effects
high therapeutic index unless combined with other CNS depressants, can cause daytime drowsiness, complex sleep behaviors, similar abuse potential to benzos
158
Zolpidem/Eszoplicone pharmacokinetics
readily absorbed orally with short elimination half-lives, sublingual form for waking during the night (faster onset than oral), metabolized by CYP450 oxidation
159
Haloperidol MOA
antagonist of D2 receptors in the basal ganglia increasing inhibitory output and resulting in reduced psychotic symptoms by inhibition of corticothalamic circuits
160
Haloperidol adverse effects
sedation, hypotension, extrapyramidal symptoms (EPS), dystonic reactions, parkinsonian symptoms (tremor and rigidity), akathisia, and hyperprolactinemia causing gynecomastia
161
Neuroleptic Malignant Syndrome
life-threatening neurologic emergency associated with the use of antipsychotic agents with symptoms including autonomic instability, hyperpyrexia, elevated CK, and renal failure due to myoglobinuria
162
Drug used to treat neuroleptic malignant syndrome
IV Bromocriptine often in ICU
163
Risperidone MOA
high potency second-generation atypical antipsychotic that blocks D2 and 5-HT2 receptors with less EPS than Haloperidol
164
Quetiapine MOA
second-generation atypical antipsychotic that blocks D1, D2, 5-HT1A and 5-HT2 receptors with similar efficacy to Risperidone and even less EPS
165
Quetiapine adverse effects
very sedating with other D2-related side effects (useful in psychotic patients with sleep disorders)
166
Aripiprazole MOA
second-generation atypical antipsychotic that is a partial agonist/antagonist at D2 and 5-HT1 receptors
167
Aripiprazole clinical use
used to treat psychosis, mania, and major depression
168
Aripiprazole pharmacokinetics
can be given orally or IM and is metabolized by CYP450 so can cause drug interactions
169
Clozapine MOA
low potency second-generation atypical antipsychotic that blocks multiple receptors and is effective against positive and negative symptoms of schizophrenia
170
Clozapine adverse effects
increased risk of agranulocytosis and often reserved for patients with EPS of Haloperidol
171
Atypical antipsychotic adverse effects
metabolic side effects including diabetes, weight gain, and hyperglycemia
172
Morphine MOA
mu opioid receptor agonist that causes CNS effects
173
Effects of mu opioid receptor activation
analgesia, drowsiness, change in pain perception, euphoria, and cough suppression
174
Opioid adverse effects
nausea, constipation/vomiting, itching, respiratory depression
175
Codeine MOA
a low potency opioid agonist which is a prodrug that is converted to codeine-6-glucuronide and morphine by CYP450
176
Codeine clinical use
administered orally and used to treat pain (mixed with NSAIDS), cough, and diarrhea
177
Hydrocodone MOA
same as morphine but less subject to first-pass metabolism with more problems with drug interactions
178
Hydrocodone clinical use
typically combined with non-opioid painkillers such as acetaminophen or ibuprofen, prescribed as last resort
179
Oxycodone clinical use
administered as time-release tablets meant to extend its effectiveness and often combined with aspirin (Percodan) or acetaminophen (Percocet)
180
Opioid used to treat chronic pain in inpatient setting
morphine (half-life = 4 hours)
181
Opioid used to treat chronic pain in outpatient setting
methadone or time-release oxycodone (half-life = 15-40 hours)
182
Opioid used to treat short-term pain
codeine or oxycodone (half-life = 4-6 hours)
183
Morphine pharmacokinetics
metabolized by glucuronidation and first-pass metabolism leads to low oral bioavailability
184
Fentanyl pharmacokinetics
potent (50-100x more active than morphine), short-acting opioid agonist that is administered IV, metabolized by CYP3A, and excreted in urine (half-life = 2-4 hours)
185
Heroin MOA
opioid agonist that is highly lipid soluble (crosses the blood-brain barrier into CNS more readily) and is converted into morphine
186
Methadone MOA
a long-acting, orally active synthetic derivative of morphine that causes less euphoria
187
Methadone adverse effects
can cause prolongation of QT interval and arrhythmia
188
Buprenorphine MOA
nonselective partial opioid receptor agonist/antagonist with slow onset of action and slow departure from receptors, reduces craving and blocks effects of heroin
189
opioid overdose symptoms
stupor, coma, pinpoint pupils, depressed respiration, and needle marks
190
Dextromethorphan MOA
D isomer of morphine that doesn't cross the blood-brain barrier and is a centrally acting cough suppressant (does NOT act on known opioid receptors)
191
Loperamide MOA
agonist of opioid receptors in the gut achieving antidiarrheal activity (methadone skeleton), cannot cross the blood-brain barrier
192
Naloxone MOA
opioid receptor antagonist used to treat opioid overdose causing dramatic reversal
