Module 5 Flashcards
CNS Drugs Part 2
Parkinson’s Disease Pathophysiology
progressive degeneration of neurons in the substantia nigra causing loss of DA transmission and reduced thalamic stimulation of the cortex
Parkinson’s Disease sx
rest tremor, bradykinesia, rigidity, and postural defect causing a tendency to stoop
effect of D1 receptors on neuronal activity
excitatory
effect of D2 receptors on neuronal activity
inhibitory
Levodopa (L-DOPA) MOA
dopamine precursor that crosses the blood-brain barrier and is converted to dopamine by dopamine decarboxylase
Levodopa adverse effects
hallucinations/confusion, dyskinesia, peripheral effects including nausea (interaction with DA receptors in gut), hypotension, and arrhythmia
Carbidopa MOA
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
Entacapone MOA
inhibits COMT (catechol-o-methyl transferase) enzyme mostly in the periphery preventing the degradation of Levodopa in the periphery
Entacapone adverse effects
dyskinesia, nausea, and diarrhea
Levodopa adjustment to reduce motor fluctuation
increase the number or frequency of Levodopa dosages
Selegiline MOA
selectively inhibits MAO B in the striatum preventing the metabolism of DA, NE, and 5-HT (serotonin), reduces the dose of Levodopa needed
Selegiline adverse effects
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
Bromocriptine MOA
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
Bromocriptine clinical use
used to delay the need for Levodopa and to treat advanced Parkinson’s disease
Bromocriptine adverse effects
similar to levodopa but with more risk of psychotic effects, poses risk of cardiac valve fibrosis with long-term use
Ropinirole MOA
less selective dopamine receptor agonist than Bromocriptine with D2, D3, and D4 receptor agonist activity
Ropinirole clinical uses
Parkinson’s and restless leg syndrome
Ropinirole adverse effects
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
Trihexyphenidyl MOA
muscarinic Ach receptor antagonist that is often given in combination with DA agonists, excreted in the urine unchanged
Trihexyphenidyl clinical use
often given in combination with DA agonists effective at reducing dyskinetic movements and spastic contractions
Trihexyphenidyl adverse effects
causes anticholinergic side effects including sedation, confusion, constipation, and urinary retention
Amantadine MOA
antiviral drug that increases DA release and blocks NMDA glutamate receptors, has an anti-Parkinson’s affect
Amantadine clinical use
less effective at treating Parkinson’s compared to Levodopa and used as last resort
Amantadine adverse effects
causes confusion and psychosis
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
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)
Deutetrabenazine adverse effects
similar to antipsychotics including akathisia, drowsiness, tremor, and depression, some patients are poor metabolizers due to the requirement of CYP450
Deutetrabenazine contraindications
contraindicated with MAO inhibitors and in uncontrolled depression with suicide risk
Deutetrabenazine clinical use
used to treat Huntington’s, Tourette’s, and Tardive dyskinesia (involuntary facial movements)
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
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
Donepezil clinical use
administered once daily (relatively long half-life) in the treatment of Alzheimer’s Dementia
Donepezil adverse effects
overactive gut motility from cholinergic effects causing nausea, vomiting, and diarrhea, causes sleep disturbances - vivid dreams, no major drug interactions
Memantine MOA
NMDA receptor antagonist that blocks pathological activation of NMDA receptors and is thought to reduce excitotoxicity (noise which causes confusion)
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
Memantine adverse effects
dizziness, headache, constipation, and confusion
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.
Idiopathic epilepsy
seizures without specific anatomic cause, such as trauma or neoplasm, most cases of epilepsy are idiopathic
Symptomatic epilepsy
seizures caused by illicit drug use, tumor, head injury, hypoglycemia, meningeal infection, or alcohol withdrawal
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.
Partial complex seizure
exhibits complex sensory hallucinations and mental distortion, altered consciousness and memory
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
status epilepticus
two or more seizures that occur without full recovery of consciousness between them - life threatening
tonic-clonic seizure
LOC followed by tonic (continuous contraction) and clonic (rapid contraction and relaxation phases)
absence seizure
brief abrupt self-limiting loss of consciousness - may stare and exhibit rapid eye blinking lasting 3-5 seconds
myoclonic seizure
short episodes of muscle contractions that may recur within several minutes
General mechanism of antiseizure drugs (AEDs)
block Na+ or Ca2+ voltage-gated channels, enhance inhibitory GABA-ergic impulses, interfere with excitatory glutamate transmission
Benzodiazepines MOA
bind to GABA inhibitory receptors increasing the frequency of chloride channel opening
Benzo with shortest half-life but longest duration of action in the brain
Lorazepam
Diazepam admin
available for rectal admin to avoid or interrupt prolonged generalized tonic-clonic seizures or clusters (children and patients with AMS)
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
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
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)
Carbamazepine admin
administered orally and absorbed slowly and erratically resulting in large variations of serum concentrations, inducer of CYP and UGT enzymes
Carbamazepine contraindications
Do not prescribe to patients with ABSENCE seizures!! not well tolerated in the elderly
Ethosuximide MOA
most likely inhibits T-type calcium channels reducing the propagation of abnormal electrical activity in the brain
Ethosuximide clinical use
drug of choice for treating primary generalized absence seizures - “ET sux a mind” until all thoughts are absent!
Gabapentin MOA
analog of GABA but does not act on GABA receptors, enhance GABA actions, or become converted to GABA (unknown MOA)
Gabapentin clinical use
approved as adjunct therapy for partial seizures and for the treatment of postherpetic neuralgia
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
Lamotrigine MOA
blocks sodium channels as well as high-voltage-dependent calcium channels
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
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
Lamotrigine adverse effects
rapid titration can cause a rash which may progress to life-threatening Stevens-Johnson Syndrome
Levetiracetam/Keppra clinical use
approved for adjunct therapy of partial, myoclonic, and primary generalized tonic-clonic seizures in adults and children
Levetiracetam admin
administered orally and well absorbed, excreted in urine unchanged
Levetiracetam adverse effects
dizziness, sleep disturbances, headache, and weakness
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
Oxcarbazepine clinical use
used to treat partial onset seizures in adults and children
Oxcarbazepine adverse effects
hyponatremia
Phenobarbital MOA
a barbiturate that enhances the inhibitory effects of GABA-mediated neurons
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)
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
Phenytoin clinical use
treatment of partial and generalized tonic-clonic seizures and for status epilepticus
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
Phenytoin toxicity
depression of the CNS in the cerebellum and vestibular system causing nystagmus and ataxia especially in the elderly
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!!)
Fosphenytoin MOA
prodrug that is rapidly converted to phenytoin in the blood reaching high levels within minutes (given IV or IM)
Pregabalin MOA
binds to the alpha-2-gamma site, a subunit of voltage-gated calcium channels in the CNS, inhibiting neurotransmitter release
Pregabalin clinical use
used to treat partial onset seizures, neuropathic pain, postherpetic neuralgia, and fibromyalgia
Pregabalin adverse effects
drowsiness, blurred vision, weight gain, and peripheral edema
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
Topiramate clinical use
used to treat partial and primary generalized seizures and in migraine prevention
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
Topiramate adverse effects
- somnolence, weight loss, and paresthesia, and increased renal stones
- glaucoma, oligohidrosis, and hyperthermia have been reported related to carbonic anhydrase activity
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
Divalproex/Valproate clinical use
has a broad spectrum of activity against partial and primary generalized epilepsies
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
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
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
Zonisamide clinical use
used for treatment of patients with partial seizures
Zonisamide adverse effects
CNS effects, kidney stones, and oligohidrosis (patients should be monitored for increased body temp and decreased sweating)
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)
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
Sumatriptan MOA
serotonin agonist which acts at a subgroup of serotonin receptors found on small peripheral nerves that innervate the intracranial vasculature
Sumatriptan admin
administered subcutaneously, intranasally, or orally with parental admin having the quickest onset (20 minutes)
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
Sumatriptan adverse effects
elevation of blood pressure and cardiac events, pain and pressure in the chest, neck, throat, and jaw
Ergotamine MOA
complex binding to several receptors acting as an agonist and structurally similar to serotonin, dopamine, and epinephrine - causes vasoconstriction
Ergotamine admin
given IV with similar efficacy as sumatriptan, can cause nausea
Ondansetron MOA
selectively blocks the 5-HT3 receptors in the periphery and in the CNS
Ondansetron adverse effects
can cause headaches and cardiac arrhythmias (monitor for prolonged QT intervals)
Phenylzine MOA
irreversible nonselective MAO inhibitor (MAO-A and B) affecting NE, 5-HT, and DA transmission used as an antidepressant
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
Foods to avoid with MAOI antidepressants
aged cheese, draft beer, dried/aged food (smoked foods and tofu)
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
Tricyclic antidepressants (TCAs) MOA
5-HT reuptake transporter (SERT) and NE transporter (NET) blockers which result in enhanced 5-HT and NE signaling
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
Secondary amine TCAs
Desipramine and Nortriptyline
Tertiary amine TCAs
Imipramine, Amitriptyline, and Clomipramine
What subgroup of TCAs have less side effects?
secondary amines (desipramine and nortriptyline)
What subgroup of TCAs have more anticholinergic effects?
tertiary amines (amitriptyline, imipramine, and clomipramine)
TCA drug interactions
other antidepressants, Na+ channel blockers, antimuscarinic drugs, and CYP450 substrates
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
SSRI with the lowest risk for children
Fluoxetine
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)
Serotonin syndrome treatment
benzodiazepine sedation or cyproheptadine (anti-histamine)
SSRI with the most side effects
Paroxetine (Paxil)
Advantages of SNRIs over SSRIs
less likely to cause weight gain and possibly have greater efficacy than single-action agents like SSRIs
SNRI adverse effects
nausea is most common, can cause emergent hypertension with high doses, metabolized by CYP450 and can cause inhibition at high doses
SNRI most commonly prescribed due to lower cost
Venlafaxine, duloxetine, and desvenlafaxine
Duloxetine clinical use
used to treat major depression, generalized anxiety disorder, diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis
Venlafaxine clinical use
used to treat major depression, generalized anxiety disorder, panic disorder, and social phobia
Bupropion MOA
noradrenergic-dopaminergic reuptake inhibitor (NDRI) which has no effect on serotonin transmission
Bupropion clinical use
used to treat depression without sexual adverse effects (can increase libido) ADD, and nicotine dependence,
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
Trazodone MOA
5-HT receptor antagonist
Trazodone clinical use
very sedating antidepressant and is commonly used as a hypnotic at low doses
Mirtazapine MOA
alpha-2 receptor antagonist which increases the release of NE and 5-HT from presynaptic neuron
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
Mirtazapine adverse effects
weight gain and sedation due to anti-histamine effects
Main drug categories used to treat depression
serotonergic drugs (SSRIs, SNRIs, TCAs, and MAOIs) and bupropion
Main drugs used to treat OCD
SSRIs
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)
Main drugs used to treat PTSD
SSRIs
Main drugs used to treat insomnia and depression
trazodone and mirtazapine
Main drugs used to treat pain syndromes
TCAs and SNRIs
Main drug used to treat ADD and nicotine dependence
Bupropion
Main drugs used to treat eating disorders
SSRIs (fluoxetine) and mirtazapine
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)
Class B mood stabilizers
stabilize mood from BELOW baseline (depression) without accelerating mania
Lithium MOA
blocks the recycling of inositol phosphates desensitizing signaling through Gq-coupled receptors effecting 5-HT synthesis and release
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
Lithium adverse effects
weight gain, hypothyroidism, tremor, has a narrow therapeutic index and levels should be monitored in the blood
Lithium intoxication
vomiting, diarrhea, tremor, ataxia, coma (reversed by dialysis)
Lithium drug interactions
antidepressants and diuretics
Antiseizure drugs that also have antimanic properties
Valproate, carbamazepine, and lamotrigine (can use in Li+-refractory patients)
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)
Benzo with the longest half-life
Clonazepam
Benzo adverse effects
sedation, ataxia/falls, impaired motor performance, impaired cognition, anterograde amnesia, and disinhibition of impulses
Treatment of benzo overdose
Flumazenil
Benzodiazepine of choice for sleep induction
Temazepam (half-life = 5 hours), next best is lorazepam (if CYP induction/inhibition is of great concern)
Buspirone MOA
partial agonist at pre and post-synaptic 5-HT A1 receptors and has some antagonist activity at D2 receptors
Buspirone clinical use
non-sedating anxiolytic with some antidepressant and antipsychotic activity most effective with chronic use not acute panic attacks (no abuse potential)
Buspirone adverse effects
dizziness, headaches, GI upset, and combination with MAOIs may cause tachycardia and hypertension
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
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
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
Haloperidol MOA
antagonist of D2 receptors in the basal ganglia increasing inhibitory output and resulting in reduced psychotic symptoms by inhibition of corticothalamic circuits
Haloperidol adverse effects
sedation, hypotension, extrapyramidal symptoms (EPS), dystonic reactions, parkinsonian symptoms (tremor and rigidity), akathisia, and hyperprolactinemia causing gynecomastia
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
Drug used to treat neuroleptic malignant syndrome
IV Bromocriptine often in ICU
Risperidone MOA
high potency second-generation atypical antipsychotic that blocks D2 and 5-HT2 receptors with less EPS than Haloperidol
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
Quetiapine adverse effects
very sedating with other D2-related side effects (useful in psychotic patients with sleep disorders)
Aripiprazole MOA
second-generation atypical antipsychotic that is a partial agonist/antagonist at D2 and 5-HT1 receptors
Aripiprazole clinical use
used to treat psychosis, mania, and major depression
Aripiprazole pharmacokinetics
can be given orally or IM and is metabolized by CYP450 so can cause drug interactions
Clozapine MOA
low potency second-generation atypical antipsychotic that blocks multiple receptors and is effective against positive and negative symptoms of schizophrenia
Clozapine adverse effects
increased risk of agranulocytosis and often reserved for patients with EPS of Haloperidol
Atypical antipsychotic adverse effects
metabolic side effects including diabetes, weight gain, and hyperglycemia
Morphine MOA
mu opioid receptor agonist that causes CNS effects
Effects of mu opioid receptor activation
analgesia, drowsiness, change in pain perception, euphoria, and cough suppression
Opioid adverse effects
nausea, constipation/vomiting, itching, respiratory depression
Codeine MOA
a low potency opioid agonist which is a prodrug that is converted to codeine-6-glucuronide and morphine by CYP450
Codeine clinical use
administered orally and used to treat pain (mixed with NSAIDS), cough, and diarrhea
Hydrocodone MOA
same as morphine but less subject to first-pass metabolism with more problems with drug interactions
Hydrocodone clinical use
typically combined with non-opioid painkillers such as acetaminophen or ibuprofen, prescribed as last resort
Oxycodone clinical use
administered as time-release tablets meant to extend its effectiveness and often combined with aspirin (Percodan) or acetaminophen (Percocet)
Opioid used to treat chronic pain in inpatient setting
morphine (half-life = 4 hours)
Opioid used to treat chronic pain in outpatient setting
methadone or time-release oxycodone (half-life = 15-40 hours)
Opioid used to treat short-term pain
codeine or oxycodone (half-life = 4-6 hours)
Morphine pharmacokinetics
metabolized by glucuronidation and first-pass metabolism leads to low oral bioavailability
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)
Heroin MOA
opioid agonist that is highly lipid soluble (crosses the blood-brain barrier into CNS more readily) and is converted into morphine
Methadone MOA
a long-acting, orally active synthetic derivative of morphine that causes less euphoria
Methadone adverse effects
can cause prolongation of QT interval and arrhythmia
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
opioid overdose symptoms
stupor, coma, pinpoint pupils, depressed respiration, and needle marks
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)
Loperamide MOA
agonist of opioid receptors in the gut achieving antidiarrheal activity (methadone skeleton), cannot cross the blood-brain barrier
Naloxone MOA
opioid receptor antagonist used to treat opioid overdose causing dramatic reversal
