Term
| anticonvulsant drugs that work by prolonging the rate of recovery of voltage-gated Na+ channels from inactivation |
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Definition
| carbamazepine, valproic acid, Lamotrigine phenytoin, oxycarbazepine |
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Term
| anticonvulsant drugs that block T-type calcium channels located on the postsynaptic membrane |
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Definition
| ethosuximide and valproic acid |
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Term
| Use, MOA, Pharmacokinetics, Side Effects: Phenobarbitol |
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Definition
| Barbiturate, first anti-seizure drug, still used today (cheap, effective) Use - monotherapy generalized tonic-clonic and partial seizures Mechanism of Action – potentiation of synaptic inhibition via GABAA receptor Pharmacokinetics – 40-60% bound to plasma proteins, 25% eliminated unchanged in urine, rest is metabolized in liver (CYP2C9) Side effects – Sedation in adults, irritability/ hyperactivity in children (why pheno. is not first line medication). Induction of CYP3A4 resulting in increased drug metabolism (e.g. oral contraceptives). |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Phenytoin |
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Definition
Use - monotherapy generalized tonic-clonic and partial seizures
Mechanism of Action – prolong rate of recovery of voltage-gated Na+ channels from inactivation
Pharmacokinetics – 90% bound to plasma proteins (albumin) t1/2 6 – 24hrs @ 10 μg/ml but t1/2 increases at higher concentrations (drug concentration increases disproportionately as dosage is increased), 95% metabolized in liver (CYP2C9/10/19)
Side effects – Because CYP2C9/10/19 are saturable enzymes, concentrations of other drugs metabolized by CYP2C9/10/19 will be affected e.g. warfarin. Induction of CYP3A4 resulting in increased drug metabolism (e.g. oral contraceptives). Gingival hyperplasia (20%). Minor rash (2 - 5%) occasionally Stevens-Johnson Syndrome (SJS). |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Carbamazepine |
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Definition
Use - monotherapy generalized tonic-clonic and partial seizures (also used in manic-depressive patients)
Mechanism of Action – prolong rate of recovery of voltage-gated Na+ channels from inactivation
Pharmacokinetics – metabolized to 10,11 epoxide (just as effective as carbamazepine), induces own metabolism, difficult to maintain constant plasma concen. Phenobarbital, phenytoin, valproic acid increase metabolism of crabamazepine
Side effects – Acute: stupor, coma, hyperirritability convulsions. Chronic: drowsiness, vertigo, ataxia, blurred vision. Induces CYP3A4 resulting in increased drug metabolism (e.g. oral contraceptives). |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Oxcarbazepine |
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Definition
became generic Oct 2007, structurally similar to carbamazepine
a)
Use – monotherapy/adjunctive treatment partial seizures, in 2003 approved for monotherapy partial seizures 4 - 16 yr olds
b)
Mechanism of Action – prolong rate of recovery of voltage-gated Na+ channels from inactivation
c)
Pharmacokinetics – Acts as prodrug that is converted to active metabolite in liver; inactivated by glucuronide conjugation and eliminated by renal excretion, does not autoinduce like carbamazepine
d)
Side effects – Dizziness, nausea, somnolence, ataxia. Less of a drug metabolizing enzyme inducer as carbamazepine. However, it still induces CYP3A4 resulting in increased drug metabolism (e.g. oral contraceptives). |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Ethosuximide |
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Definition
Use – monotherapy absence seizures
Mechanism of Action – inhibit T-type Ca channels
Pharmacokinetics – Not bound to plasma proteins, few drug-drug interactions. 25% excreted in urine
Side effects – Nausea, vomiting, anorexia. CNS drowsiness, lethargy, euphoria. SJS, aplastic anemia |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Valproic Acid |
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Definition
Use – monotherapy absence, myoclonic, partial and tonic/clonic seizures
Mechanism of Action – inhibit T-type Ca channels, prolong inactivation of Na channels, increase GABA synthesis (in vitro)
Pharmacokinetics – 90% bound to plasma proteins, t1/2 = 15 hrs but is reduced with other anticonvulsants
Side effects – GI nausea, anorexia. CNS sedation, ataxia, tremor. Increase in hepatic blood enzymes (40%). Hepatic toxicity in patients < 2 yrs old on multiple AEDs including valproic acid. Inhibits CYP2C9 resulting in increased concentrations of phenytoin, phenobarbital, also displaces phenytoin from plasma binding proteins |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Gabapentin |
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Definition
Fun Fact!
GABA molecule bound to lipophillic hexane ring – does not appear to interact with GABA receptors, but it does suppress neuronal acitivity
Use – Adjunctive treatment partial with and without generalized secondary seizures; neuropathic pain (2002) fibromyalgia.
Mechanism of Action – ?? Binds to L-type Ca channel, no change in Ca conductance
Pharmacokinetics –Not metabolized, excreted unchanged in urine. Renal function must be determined.
Side effects – Fatigue, ataxia |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Lamotrigine |
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Definition
Use – Monotherapy and adjunctive treatment partial- and generalized tonic/clonic seizures; LGS
Mechanism of Action – prolong rate of recovery of voltage-gated Na+ channels from inactivation, inhibit Ca to lesser extent
Pharmacokinetics –T1/2 = 24 – 35 hrs phenytoin, carbamazepine, phenobarbital, primidone reduce t1/2 to 15hrs. Reduces valproate by 25%.
Side effects – dizziness, ataxia, blurred vision, nausea. Rash and SJS when in addition to other AEDs |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Topiramate |
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Definition
Use – Adjunctive treatment for partial with and without generalized tonic/clonic seizures, LGS
Mechanism of Action – Inhibit Na channels and AMPA-kainate receptors enhance GABA receptors
Pharmacokinetics – mostly (~ 85%) excreted unchanged in urine
Side effects – Ataxia, fatigue, somnolence, weight loss. Reduces plasma levels of oral contraceptives |
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Term
Use, MOA, Pharmacokinetics, Side Effects:
Levetiracetam |
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Definition
Use – Adjunctive treatment for partial and tonic-clonic seizures in adults and myoclonic seizures in kids...IV prep for status epilepticus
Mechanism of Action – ??
Pharmacokinetics –65% excreted unchanged in urine, no liver enzyme induction, highest safety margin in animal studies, rapid dose titration
Side effects – somnolence, dizziness, asthenia , no drug-drug interactions |
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Term
| Drugs of choice (2) and alternative drugs (2) for the treatment of partial seizures--secondarily generalized |
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Definition
drugs of choice: carbamazepine and phenytoin
alternative drugs: lamotrigine and valproic acid |
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Term
| drugs of choice (2) and alternative drug (1) for treatment of generalized absence seizures |
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Definition
drugs of choice: ethosuximide and valproic acid
alternative drug: clonazepam |
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Term
| drugs of choice (3) and alternative drugs (2) for treatment of generalized tonic-clonic seizures |
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Definition
drugs of choice: carbamazepine, phenytoin, and valproic acid
alternative drugs: lamotrigine and topiramate |
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Term
| 3 types of analgesics used in the treatment of mild to moderate migrane |
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Definition
| NSAIDS, Midrin, and opiates |
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Term
use of NSAIDS for treating migraines:
Efficacy, MOA, use with caution in who? |
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Definition
Relative efficacy of the different NSAIDS for treating migraine has not been clearly established
Mechanism of action appears to be related to the ability to block prostaglandin synthesis and prevent inflammation in the trigeminovascular system
Use with caution in patients with peptic ulcer disease, renal disease or hypersensitivity to aspirin |
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Term
Use of Midrin for the treatment of migraines
efficacy, MOA, |
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Definition
(isometheptene 65 mg + dichloralphenazone 100 mg + acetaminophen 325 mg)
As effective as oral ergotamine in some patients with fewer side-effects
Isometheptene is a synthetic sympathomimetic and is included in Midrin due to its mild vasoconstrictor activity
Dichloralphenazone is included due to its sedative actions
Isometheptene containing products are contraindicated in glaucoma, renal disease, hypertension, heart and liver disease and with concurrent use of MAO inhibitors |
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Term
Use of opiates for treatment of migraines
Efficacy, side effects |
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Definition
(e.g. Butorphanol)
Reserved for severe infrequent headaches where conventional therapies are contraindicated or when rescue medication is needed.
Nasal administration of butorphanol can provide an alternative to frequent visits to the hospital for injectable migraine therapies.
Butorphanol is a controlled substance and can be addictive, long term therapy should be closely monitored.
Adverse effects include dizziness, nausea/vomiting, drowsiness, bad taste |
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Term
Use, chemistry, an history:
Ergotamine Tartrate |
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Definition
Historically drug of choice for acute migraine attacks that are unresponsive to non-narcotic analgesics
Ergot alkaloids are compounds that occur naturally in rye contaminated with the fungus Claviceps purperea
Epidemics of “ERGOTISM” have been reported throughout history |
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Term
Pharmacodynamics:
Ergotamine Tartrate |
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Definition
Ergotamine is a dirty drug and interacts with serotonin, dopamine and adrenergic receptors.
The effectiveness of ergotamine for migraine can be seen in figure 1 of the handout
Activation of 5-HT1B receptors and vasoconstriction
Reduce neurogenic inflammation by decreasing the release of vasodilator/proinflammatory neuropeptide transmitters (e.g. substance P, neurokinin A, CGRP) |
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Term
Contraindications and side effects:
Ergotamine Tartrate |
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Definition
Powerful vasoconstrictor –
Partial agonist at alpha-adrenoceptors and 5-HT2 receptors, contraindicated in patients with peripheral vascular disease.
Beta-blockers may potentiate vasoconstriction caused by ergotamine. Patients on both medications should be closely monitored
The Macrolide antibiotic erythromycin can interfere with the liver metabolism of ergotamine and may cause ergot toxicity (severe peripheral vasospasm, ischemia, cyanosis, numbness)
Contraindications – Cardiovascular disease, sepsis, liver and kidney disease and pregnancy/breast feeding
Side effects:
GI upset – nausea, vomiting, anorexia
Occurs in ~10% of patients due to activation of central dopamine receptors in the chemoreceptor trigger zone.
This side-effect may require adjunct therapy with an antiemetic e.g. 10 mg oral Metoclopramide (e.g. Reglan). |
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Term
Chemistry and Pharmacokinetics:
Dihydroergotamine |
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Definition
it is a semisynthetic alkaloid
Incompletely absorbed form the GI tract and is administered parenterally (IM,SQ) or via a nasal spray (Migranol) |
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Term
Pharmacodynamics:
Dihydroergotamine |
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Definition
similar to ergotamine tartrate (stim of 5HT1 receptors)...probably involves direct vasoconstriction of the dilated intracranial arteries leading to decreased pulsations, and reduced neurogenic inflammation by decreasing the release of vasodilator/proinflammatory neuropeptide transmitters
like E.T. is a dirty drug |
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Term
side effects
dihydroergotamine |
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Definition
GI upset
transient bradycardia, weakness in legs...vasospasm less than in ergotamine tartrate though |
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Term
contraindications
dihydroergotamine |
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Definition
| CV disease, sepsis, liver or kidney disease, arterial insufficiency, pregnancy/ breast feeding |
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Term
|
Definition
| Sumatriptan (Imitrex) – Triptans are used for the acute treatment of moderate to severe migraines |
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Term
Chemistry and Pharmacokinetics:
Sumatriptan |
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Definition
Chemistry and Pharmacokinetics
subcutaneous injection, oral tablets or by nasal spray
Metabolized by MAO-A/Contraindicated with the use of a MAO inhibitor W/I a 2 week time span after discontinuing MAO therapy
Triptans can be administered up to 4 hrs after the onset of a headache and still be effective |
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Term
Pharmacodynamics:
Sumatriptan |
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Definition
Pharmacodynamics
Sumatriptan is an agonist at type 1 serotonin receptors, similar action as the ergot alkaloids
Relieves nausea/vomiting and photophobia/phonophobia |
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Term
Toxicity, adverse reactions, and contraindications:
Sumatriptan |
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Definition
Toxicity, adverse reactions, and contraindications
Cardiovascular (coronary spasm, myocardial infarction, ventricular arrhythmias)
Several fatalities reported with subcutaneous sumatriptan due to myocardial infarction
Do not give by IV due to due to the risk of vasospasm
Use of sumatriptan is contraindicated within 24 hrs of treatment with an ergot due to the risk of additive vasospastic effects.
Triptan Symptoms:
Common with Sumatriptan and newer triptans, chest and throat tightness, difficulty breathing, panic/anxiety, parathesias, feeling of heaviness |
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Term
Use
Prochlorperazine (Compazine) |
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Definition
These dopamine antagonists are useful for the treatment of acute migraine attacks that are unresponsive to Sumatriptan, DHE or oral analgesics
Relieve headache pain and have anti-emetic activity |
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Term
|
Definition
| effective for the treatment of prophylactic management of migrane and cluster HA |
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Term
Chemistry and Pharmacokinetics
Methysergide |
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Definition
Chemistry – semisynthetic ergot alkaloid
Pharmacokinetics – Oral administration, metabolized in the liver to an active metabolite (Methylergometrine) |
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Term
Pharmacodynamics
Methysergide |
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Definition
Antagonist at 5-HT2 receptors but also an agonist at 5HT1 receptors
The protective effect of methysergide takes 1-2 days to develop and may be due to the generation of the active agent methylergometrine |
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Term
Toxicity, Adverse reactions, and contraindications
Methysergide |
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Definition
Fibrosis and fibrotic complications, retroperitoneal fibrosis (obstruction of the urinary tract), pleuropulmonary fibrosis, and fibrosis of cardiac tissues (vascular shutdown)
Toxicity
To prevent the serious side effect of fibrosis stop the usage of the drug for 3-4 weeks every 6 months (drug holiday)
Cardiovascular – vasoconstriction and coronary insufficiency can lead to myocardial infarction
Contraindicated in patients with cardiovascular disease, fibrotic disease, pregnant women and children |
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Term
Use for headaches:
Beta Blockers |
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Definition
| first choice drug for migraine prophylaxis |
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Term
| Pharmacodynamics, what ones to use and not to use: Beta Blockers |
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Definition
MOA of beta blockers is not well understood
beta blockers which lack partial agonist activity (intrinsic sympathomimetic activity) are the most effective in the prophylaxis of migraine (propanolol, nadolol, timolol, aternolol, metropolol)
So beta blockers with partial agonist activity like acebutolol, pindolol, and penbutolol will NOT be effective for migraine prophylaxis |
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Term
Side effects:
beta blockers |
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Definition
fatigue, cold extremities, dizziness, CNS side effects (vivid dreams, nightmares, insomnia, depression)
Beta blockers may augment the vasoconstriction caused by ergotamine
Should be used with caution in pts with conditions such as asthma and diabetes mellitus |
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Term
|
Definition
Use: prophylaxis of migraine
Mechanism of action of Amitriptyline is unknown, independent of antidepressant action, may involve down-regulation of central 5-HT2 and adrenergic receptors |
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Term
Side effects
Amitriptyline |
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Definition
| Anticholinergic side-effects (dry mouth, blurred vision, urinary retention, cardiac arrhythmia) |
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Term
Use for treatment of headaches and MOA:
Valproic acid (Valproate), Topiramate, Gabapentin |
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Definition
Use: prophylaxis of migraines
MOA: unclear, may involve facilitating GABA neurotransmission, modulating glutamate and inhibiting sodium and calcium channel activity |
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Term
Adverse effects
Valproic acid (Valproate) |
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Definition
| Valproic acid:Valproate Sodium: nausea/vomiting, weight gain, tremor, hair loss, hepatic toxicity, teratogenic (neural tube defects) |
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Term
Adverse effects
Topiramate |
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Definition
| paresthesia, fatique, anorexia/nausea, diarrhea, weight loss, memory problems (cognitive slowness) |
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Term
Adverse Effects
Gabapentin |
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Definition
| somnolence, asthenia (weakness), dizziness, ataxia |
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Term
| chemical classification and active moiety of Morphine |
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Definition
Morphine is a phenanthrene alkaloid
phenyl-N-methyl piperidine is active moiety |
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Term
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Definition
| are located primarily in the brainstem, spinal cord, and limbic areas and are thought to mediate suprespinal analgesia, some spinal analgesia, sedation, respiratory depression, euphoria, and dependence. There is solid evidence that they are also located in the periphery and modulate the sensitivity of nociceptors |
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Term
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Definition
| located mainly in the brainstem and spinal cord, and to a lesser extent the limbic system. They are thought to mediate some spinal analgesia, some supraspinal analgesia, meiosis sedation, and dysphoria |
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Term
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Definition
| are located in the brainstem and limbic system, and mediate dysphoria and hallucinations. They also appear to play a role in the development of tolerance to μ opioid receptor agonists |
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Term
|
Definition
| A pro-drug of phenytoin used for treating status epilepticus |
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Term
Current medical use and route of administration
Morphine (sulfate salt) |
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Definition
route of administration - absorbed from GI tract, but not as effective orally because of first pass metabolism; however, oral forms are available. Morphine can be given subcutaneously, IM or IV. In addition it is now widely used for various types of spinal analgesia.
***usual dose is 10 mg SC or IM***
used for more severe pain |
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Term
Use, route of administration, and pharmacokinetics
Codiene |
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Definition
analgesic for mild-moderate pain
–
antitussive
route of administration - orally effective
codeine molecule is only a weak opioid agonist, but in most patients codeine is metabolized to morphine; genetic differences in metabolism may explain individual differences in sensitivity to codeine
– |
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Term
| significance of Hydromorphone |
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Definition
| similar to morphine but more potent |
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Term
is a cross between what? Use, administration, common example of it
Oxycodone |
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Definition
similar to both morphine and codeine, but used orally (usually in combinations with acetaminophen) for mild-moderate pain.
OxyContin is a sustained release oral preparation for the management of severe chronic pain |
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Term
Similar to what? use?
hydrocodone |
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Definition
| similar both to morphine and codeine; used orally for mild-moderate pain and as an antitussive; is currently one of the most widely prescribed opioids |
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Term
Use, route of administration, pharmacokinetics
Meperidine |
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Definition
synthetic drug
route of administration - oral and parenteral
1/10 the potency of morphine
reputed to have weaker effects on smooth muscle than morphine - less constipation and urine retention, although the evidence to support this is weak.
has been used for moderate to severe pain
has been commonly used in obstetrics - may cause less respiratory depression in the newborn than morphine
relatively short acting 1-3 hours; not appropriate for chronic pain because of the buildup of an active metabolite (normeperidine) that can cause seizures.
falling into disfavor in many circles |
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Term
Use, effects, route of administration
Heroin |
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Definition
more potent and more euphoric than morphine; duration of action about 4-6 hours.
available for medical use in some countries, but not in the US
abuse
commonly taken by injection, snorting or smoking |
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Term
Use, pharmacokinetics
Methadone |
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Definition
less euphoric and longer duration of action (12-24 hours) than heroin (4-6 hours) or morphine (4-6 hours)
used as an analgesic and in treating opioid addiction
dosing can be tricky and needs to be done carefully, with close monitoring of the patient.
–
Note: When used acutely as an analgesic, methadone has a duration of action of 4-6 hours. However, when used chronically (as in methadone maintenance for the treatment of opioid dependence, or for the management of chronic pain), it has a duration of action of 12-24 hours. |
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Term
Use and side effects
Propoxyphene |
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Definition
–
much less potent than other opioid agents; has little analgesic activity at therapeutic doses; it does have potential for serious toxicity at high doses. Although has been widely used, it is not a particularly good drug.
–
Was withdrawn from the US market in 2010.
–
Still mentioned here because there is still a lot of the stuff sitting in medicine cabinets across the US!!!! |
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Term
Use and mode of administration
Fentanyl |
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Definition
| very potent mu agonist (about 100 x more potent than morphine) - given parenterally to supplement surgical anesthesia. A transdermal preparation (Duragesic) is available for the management of chronic pain. A combination preparation containing fentanyl plus droperidol (Innovar) can induce a state called neuroleptic analgesia. In this state, various diagnostic (e.g. endoscopies, etc..) or minor surgical procedures may be carried out even though the patient might not completely lose consciousness. Administering nitrous oxide in conjunction with Innovar will produce a state called neuroleptic anesthesia. |
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Term
Significance and administration
Butorphanol |
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Definition
similar to pentazocine
must be given perenterally although can be given intranasally |
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Term
Type of Drug, pharmacodynamics, use
Pentazocine |
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Definition
Pentazocine is a mixed agonist-antagonist opioid drug
agonist effects are dominant - acts as an agonist at κ (kappa) receptors, but only as a partial agonist at μ (mu) receptors; it acts as a μ antagonist at high doses.
–
less effective than morphine for severe pain
–
sedation and respiratory depression are less than with morphine
–
CNS stimulation and hallucinations are more common than with morphine
–
with chronic use, the potential for physical dependence is less than morphine, but still significant
–
can precipitate withdrawal syndrome in opioid addicts
–
Talwin Nx is a preparation that contains petazocine and naloxone. The latter is included to reduce the potential for IV abuse. |
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Term
Type of drug, use, pharmacodynamics
Buprenorphine |
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Definition
–
acts as a partial agonist at μ-receptors and possibly κ-receptors.
–
Although its analgesic effects may be slightly less than that of morphine, its abuse potential is reported to be much lower.
–
It has been reported to reduce drug craving in heroin addicts and is being used in the treatment of heroin addiction. Suboxone is a new combination product containing buprenorphine plus nalaxone designed for sublingual use. When taken as directed, the naloxone does not reach a therapeutic blood level and the buprenorphine can produce its effects. However, if the user tries to inject the drug to achieve a high, the naloxone will block the effects of the buprenorphine.
–
Although it is usually given by injection, it is also effective when administered sublingually, intranasally, or transdermally.
–
Buprenorphine is the primary agent used for the so-called “office based” treatment of opioid addiction. |
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Term
Type of drug, Use, pharmacodynamics, side effects
Tramadol |
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Definition
And opioid mixed agonist-antagonist
newer drug for use in mild-moderate pain.
It supposedly is a weak mu agonist. In addition, it inhibits the synaptic reuptake of norepinephrine and serotonin, much like the tricyclic antidepressants.
It supposedly produces good analgesia, with only mild side effects. In general, the side effects resemble those of other opioids (dizziness, sedation, nausea, constipation).
The manufacturer has claimed that the drug has a very low abuse and addiction potential. However, there are a significant number of reports indicating that the drug has opioid-like abuse potential. |
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Term
Type of drug, use, administration, side effects
Naloxone |
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Definition
a "pure" opioid antagonist...drug of choice for opioid poisoning, can reverse respiratory depressant effects of opioids
not effective orally, because of first pass metabolism, must be given parenterally
–
sometimes included in combination with oral narcotic analgesics (eg. Talwin NX) to prevent abuse (i.e. injection of the drug)
–
relatively short duration of action (i.e. only about 1-2 hours)
–
can precipitate withdrawal in addicts
–
has been tried for a variety of conditions (eg. prevention of post traumatic neuronal injury, shock.) |
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Term
Type of Drug, Use, route of administration
Naltrexone |
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Definition
Naltrexone is a "pure" opioid antagonist
orally effective, long acting antagonist (24 hours)
used in "immunizing" addicts (ie. preventing the high produced by opioid agonists)
risk of hepatotoxicity is a serious drawback
its effectiveness in the long-term treatment of opioid dependence is not clear
patient compliance is a major problem
Keep in mid that an opioid addict must first be detoxified (ie. brought through withdrawal) before naltrexone therapy can be initiated.
It has recently been shown to decrease the craving for alcohol in alcoholics. It is now approved for use in the treatment of alcoholism |
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Term
type of drug, use, mode of administration
Methylnaltrexone |
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Definition
Methylnaltrexone is a "pure" opioid antagonist
orally effective, long acting antagonist (24 hours)
used in "immunizing" addicts (ie. preventing the high produced by opioid agonists)
risk of hepatotoxicity is a serious drawback
its effectiveness in the long-term treatment of opioid dependence is not clear
patient compliance is a major problem
Keep in mid that an opioid addict must first be detoxified (ie. brought through withdrawal) before naltrexone therapy can be initiated.
It has recently been shown to decrease the craving for alcohol in alcoholics. It is now approved for use in the treatment of alcoholism |
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Term
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Definition
a similar to methylnaterxone but better oral efficacy Quaternary analog of naloxone recently approved for the treatment/prevention of opioid-induced constipation.
Must be given parenterally, usually SC
Only appropriate for serious constipation resulting from use higher doses of opiods for more severe pain and from treatment of post-operative paralytic ileus |
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Term
NSAIDS used for the treatment of gout
how/when are they used? MOA, Side effects/toxicities, administration |
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Definition
NSAIDS used: indomethacin, Ibuprofen, and ketorolac
When used: can be used to STOP an acute gout attack and have good antiinflammatory activity..IM ketoralac can be useful in treating severe, acute, gout attacks
MOA: inhibit prostaglandin synthesis
Side effects: GI irritation; so contraindicated in pts with peptic ulcer disease...indomethacin causes CNS effects in many pts
Administration: oral...also Ketoralac is injectable |
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Term
Colchicine
Use, MOA, Side effects, route of administration, place in therapy |
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Definition
Colchicine has a unique antiinflammatory activity aspecific for gout
MOA: binds to tubulin and prevents its polymerization to microtubules...this leads to a reduction in leukocyte migration, phagocytosis and mitosis ..in addition it inhibits the production and release of proinflammatory glycoproteins from neutrophils
Side effects: diarrhea and GI upset (nausea, vomiting, etc)
Route of administration: usually administered orally although it can be given IV for acute attack
Place in therapy: traditionally has been the preferred drug for alleviating acute gout attack...however, because the side effects can be quite severe, most physicians first try to treat an acute attack with NSAIDS and corticosteroids in 2010, FDA ordered withdrawl from the market of all non-approved colchicine drugs...at present, the only colchicine product sanctioned by the FDA is Colcrys...very expensive!! |
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Term
Allopurinol
Use, MOA, Side Effects and toxicities, drug interactions |
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Definition
Used to prevent gout attacks--Allopurinol does not stop a gout attack, but over time it can greatly reduce the potential for future attacks
MOA: Allopurinol acts by inhibiting the enzyme xanthine oxidase and reducing the formation of uric acid...by lowering the level of uric acid below its limit of solubility, allopurinol can keep sodium urate crystals from forming and facilitate the dissolution of existing crystals
Side effects/toxicities:generally well tolerated, can increase the frequency of gout attacks during early stages of therapy, increased frequency of gout attacks during early stages of therapy...probably due to breakdown of crystals as the uric acid levels fall, elevation of liver enzymes, allergic reactions
Drug interactions:
increases the half life and uricose uric effect of probenacid
inhibits the hepatic metabolism of many drugs
increases the half life of theophylline |
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Term
Use, MOA, Side effects, big drawback?
Febuxostat |
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Definition
a newer drug used for the treatment of gout...is generally similar to allopurinol, but is touted as causing fewet skin problems and allergic reactions..some studies suggest might be beneficial in patients who dont respond to allopurinol
MOA: xanthine oxidase inhibitor
Side effects: elevation of liver enzymes as will allopurinol
High cost is a drawback |
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Term
Probenacid
Type of drug, MOA, administration,side effects/toxicities, What do pts taking this need to do? when used? |
|
Definition
Probenacid is a "Uricosuric Agent": inhibits the anion eschange transporter int the kidney tubule
MOA: inhibits the anion exchange transporter in the kidney microtubule that allows for uric acid to be reabsorbed into the body ..it also inhibits the secretio of uric acid but because more uric acid is reabsorbed than secreted, the net effect of probenecid is to increase uric acid excretion
Side effects/toxicities: can cause increased risk of kidney stone formation as the concentration of urate in the tubular fluid/urine rises...it is contraindicated in patients with kidney stones
Administration: given orally
Pts need to consume adequate amounts of fluids to maintain urine flow and prevent the formation of urate crystals in the kidney
use: for patients with hyperuricemia and that are prone to gout...DO NOT use for treating acute gout attacks...may trigger gout attacks |
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Term
| Treatment of status epilepticus |
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Definition
Rapid AED effects are needed so IV drugs are given during initial treatment
--give IV diazepam initially (IV loazepam is preferable to diazepam because it acts longer)
--Once seizures controlled give IV fosphenytoin (dont give IV phenytoin bc this will irritate veins)
Alternatives to IV fosphenytoin: levetiracetam, phenobarbital and valproic acid |
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Term
| Steps to manage a pregnant epileptic patient |
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Definition
1. Reduce patient to monotherapy
2. Administer Folate to decrease neural tube defect likelihood
3. Administer Vitamin K during last month of gestation to reduce blood coagulation problems that might be associated with AEDs |
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