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83 Cards in this Set
- Front
- Back
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Dopamine and Dopamine Agonist: Types
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Dopamine- levodopa (L-dopa)
Dopamine Agonists Ergot derivatives- bromocriptine, pergolide, cabergoline Non ergot- pramipexole, ropinirole A class consisting of dopamine itself and agents that mimic the actions of dopamine as agonists at dopamine receptors. |
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Dopamine and Dopamine Agonist: MOA
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Parkinson's is characterized by progressive loss of dopaminergic neurons in the substantia nigra.
Dopamine is a catecholamine that is synthesized in these dopaminergic neurons and is released onto tow pathways to regulate coordinated movement. Direct pathway via the D1 receptor enables movement Indirect pathway via the D2 receptor inhibits movement Balance of input between excitatory glutamate (Glu) (+) and inhibitory GABA (-) is required for normal movement to be maintained. Mimic the effects of dopamine |
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Dopamine and Dopamine Agonist: Pharm
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Levodopa has short half-line of 1-3 hours
Dopamine is metabolized/inactivated by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) Cabergoline has longer half-life 100 days |
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Dopamine and Dopamine Agonist: Indications
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Parkinson’s disease (L-dopa, ropinirole, pergolide, pramipexole)
Restless legs syndrome (pramipexole) Endocrine (bromocriptine, cabergoline) -Acromegaly -Amenorrhea- galactorrhea -Prevention of lactation -Prolactin secreting adenoma |
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Dopamine and Dopamine Agonist: Contraindications
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(Pramipexole, ropinirole)
Caution should be exercised when driving or engaging in other activities that require alertness, because of potential for sudden sleep |
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Dopamine and Dopamine Agonist: SE
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Numerous side effects related to dopamine agonism:
Nausea Peripheral edema Hypotension Hallucinations, vivid dreams Serious SE: Sudden sleep onset has occurred without warning and poses a potential risk for activities requiring attention, such as driving. This may be a class effect but has been confirmed with ropinirole and pramipexole |
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Dopamine and Dopamine Agonist: Notes
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L-dopa is administered with peripheral decarboxylase inhibitor to prevents its breakdown to dopamine in the periphery. Decarboxylase inhibitor cannot cross into CNA, so L-dopa can be converted to dopamine in the CNS
Therapeutic effects of dopamine appear to extend beyonedits short half-life, a result of lost parkinson's, doses of L-dopa begin to wear off quickly Benefits of dopamine over L-dopa for treatment of parkinsons: -Do not require enzymatic conversion for activity -Have longer duration of action -Avoid potential neurodegeneration associated with conversion of L-dopa to free radicles -START LOW GO SLOW |
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Catechol-O-methyl Transferase (COMT)
inhibitors: Types |
Entacapone
Tocapone |
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Catechol-O-methyl Transferase (COMT)
inhibitors: MOA |
COMT inhibitors inhibit COMT; which is the enzyme that breaks down levodopa
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Catechol-O-methyl Transferase (COMT)
inhibitors: Pharm |
Inhibits breakdown of catecholamines (epinephrine, norepinephrine, dopamine); increase amount of catecholamines available in synaptic cleft
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Catechol-O-methyl Transferase (COMT)
inhibitors: Indications |
Parkinson's Disease
As an adjunct to levodopa- carbidopa in patients who experience “wearing off”. Wearing off is a phenomenon resulting in immobility. |
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Catechol-O-methyl Transferase (COMT)
inhibitors: Contraindications |
Concomitant use with nonselective MAOIs; give a 2 week washout period before initiation of COMT treatment
The MAO pathway becomes the key metabolic route for epinephrine and norepinephrine in the presence of COMT blockade. Caution with use in patients on MAO-B selective inhibitors, as these become nonselective at higher doses History of neuroleptic malignant syndrome and/or non-traumatic rhabdomyolysis Liver impairment Pheochromocytoma because of increased risk of hypertensive crisis. |
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Catechol-O-methyl Transferase (COMT)
inhibitors: SE |
Dopamine related- dyskinesia, vivid dreams, hallucinations, nausea, hypOtension
Abdominal pain Diarrhea Discoloration of urine (dark yellow/reddish brown) Serious: hepatotoxicity |
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Catechol-O-methyl Transferase (COMT)
inhibitors: Notes |
Parkinson's syndrome is characertized by the progressive loss of dopaminergic neruons in the substantia nigra
Dopamine is a catecholamine synthesized by these neurons It works on D1 (direct) pathey to enable movement adn on D2 (indirect) pathway to inhibit movement Entacapone doesn't cross the BBB so is only peripheral COMT inhibitor Tolcapone does cross the BBB do is central and peripheral inhibitor |
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Cholinesterase Inhibitors: Types
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Reversible
Donepezil Collection of agents that increase acetylcholine levels. |
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Cholinesterase Inhibitors: MOA
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Acetylcholine is the main neurotransmitter in the parasympathetic arm of the ANS and is a major neurotransmitter in the CNS
Acetyl cholinesterase is the key enzyme involved in the breakdown of acetylcholine in the synapse Acetyl cholinesterase inhibitors bind to this enzyme, inhibiting its activity and leading to an increase in acetylcholine in the synapse, thus enhancing cholinergic transmission |
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Cholinesterase Inhibitors: Pharm
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Neostigmine and pyridostigmine are eleminated by kidney; elimination half-life is 1-2 hours
Rivastigmine is available as a patch (improves compliance) |
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Cholinesterase Inhibitors: Indications
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Alzheimer's disease
Myasthenia gravis Reversal of nondepolarizing neuromuscular blockers Postoperative intestinal ileus Urinary retention |
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Cholinesterase Inhibitors: Contraindications
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Contra:
Neostigmine, pyridostigmine, physostigmine, edrophoium- bronchial asthma, urinary obstruction, gastrointestinal obstruction |
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Cholinesterase Inhibitors: SE
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SE:
• Nausea, vomiting • Increased urination • Intestinal cramping, diarrhea • Increased secretions (bronchial, salivary) Acronym to remember the effects of cholinergic overload is SLUDGE: Salivation Lacrimation Urination Defecation GI distress emesis |
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Cholinesterase Inhibitors: Notes
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Alzheimer's is characterized by profound death cell death in the brain. The death of neurons leads to a reduction in the amount of acetylcholine released into the synapse as well as amount of postsynaptic receptors on which acetylcholine acts.
Cholinesterase inhibitors are not felt to be disease modifying. Once cell death has reached a certain threshold, their effects begin to wane as there are too few remaining synapses for cognition to be significantly affected. Cholinesterase inhibitors used to treat Alzheimer's disease are reversible. Irreversible cholinesterase inhibitors lead to profound increase in cholinergic neurotransmission, which in turn leads to convulsions, thick secretions that block airways, cardiac rrhythmias, and death. Irreversible cholinesterase inhibitors have been used as nerve gases in warfare (sarin gas) for decades and are also used in pesticides |
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Ergot Alkaloids: Types
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Ergots are naturally derived agents that are primarily vasoconstrictors, although they do possess other properties
Ergotamine Dihydroergotamine Methylergonovine |
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Ergot Alkaloids: MOA
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Agonists at serotonin 1B and 1D receptors; partial agonists of alpha-1 adrenergic receptors
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Ergot Alkaloids: Pharm
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Biologic activity (24hr+) of ergotamine extends well beyond its own half-life of 2 hours
Effects: causes vasoconstriction of cerebral blood vessels, utrine contractions |
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Ergot Alkaloids: Indications
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Migraine
Acute- ergotamine, dihydroergotamine Prevention- methysergide Postpartum Hemorrhage |
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Ergot Alkaloids: Contraindications
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Coronary artery disease
Hypertension Peripheral vascular disease Avoid using within 24 hours of triptans or other vasoconstrictors; due to additive vasoconstrictive effects Pregnancy- can cause fetal distress and, or miscarriage; they are used during labor to control hemorrhage |
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Ergot Alkaloids: SE
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• Nausea, vomiting
• Diarrhea • Numbness and tingling of extremities • Angina • Hypertension |
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Ergot Alkaloids: Notes
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Caffeine is added to some ergot preparations to both facilitate absorption and potentiate the analgesic effects.
Ergot is derived from fungus |
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Triptans: Types
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Serotonin (5-HT) agonists used for treating migraines
Sumatriptan Naratriptan Rizatriptan Zolmitriptan |
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Triptans: MOA
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Triptans are agonists of 5-HT1B and 5-HT1D receptors, leading to vasoconstriction of cerebral blood vessels.
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Triptans: Pharm
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Triptans are intended to be used acutely and are characterized by a rapid onset and short half-life.
All are available as tablets Sumatriptan (injection and nasal spray) Zolmitriptan) (nasal spray and orally disintegrating tablet) Rizatriptan (orally disintegrating tablet) |
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Triptans: Indications
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Acute Migrane
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Triptans: Contraindications
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Ischemic or vasospastic coronary artery disease
Uncontrolled hypertension MAOIs Severe hepatic or renal impairment is a contraindication for naratriptan only |
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Triptans: SE
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SE:
cardiac events- rare but serious: -Coronary artery vasospasm -Transient myocardial ischemia -Atrial or ventricular arrhythmias -Myocardial infarction Pressure, tightness or pain chest, neck or jaw |
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Triptans: Notes
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Triptans should be taken AT ONSET of migraine attack
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Topiramate: Type
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Topiramate
Inhibits several carbonic anhydrase isoenzymes |
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Topiramate: MOA
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Thought to have multiple mechanisms of action
Potentiation of GABA (GABA is major inhibitory neurotransmitter in CNS, enhancing its effects should have further inhibitory effect) Na+ channel blockade Glutamate antagonist (Glutamate is a major excitatory neurotransmitter so blocking it should have antiexcitatory effect Calcium channel blockade |
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Topiramate: Pharm
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Topiramate is rapidly and well absorbed
topiramate may reduce levels of estrogen component of oral contraceptives |
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Topiramate: Indication
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Seizure disorders
Migraine |
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Topiramate: Contraindication
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Contra:
None |
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Topiramate: SE
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SE:
Serious Cognitive impairment-relatively common with antiseizure drugs Renal calculi-likely related to drugs effects on carbonic anhydrase Other: Parasthesia Fatigue and sedation Dizziness Weight loss |
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Phenytoin: Type
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Phenytoin
Fosphenytonin Antiseizure drug |
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Phenytoin: MOA
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Sodium channel inhibitor:
Sodium channels exist in three conformations -Closed-before activation -Open-during depolarization -Inactivated- shortly after the peak of de polarization |
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Phenytoin: Pharm
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Phenytoin exhibits saturation kinetics, meaning at lower doses metabolism is first order, then at higher doses the enzymes responsible for metabolizing phenytoin become saturated and metabolism switches to zero order.
Toxicity can be reached quickly at higher doses Phenytoin is a CYP450 enzyme inducer. |
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Phenytoin: Indication
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Seizure prophylaxis in patients with head injuries
Partial seizures Generalized tonic- clonic seizures |
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Phenytoin: Contraindication
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Cardiac conduction abnormalities
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Phenytoin: SE
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-CNS- diplopia, ataxia, nystagmus
-Gingival hyperplasia -Hirsuitism -Bone deficiencies (rickets, osteomalacia)- may be caused by abnormal vitamin D metabolism -Decreased levels of consciousness -IV use-hypotension -Phenytoin induces the metabolism of oral contraceptives |
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Phenytoin: Notes
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Lamotrigine is increasingly being used for psychiatric indications, including bipolar disorder.
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Lamotrigine: Type
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Lamotrigine
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Lamotrigine: MOA
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Works primarily by inhibiting sodium channels
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Lamotrigine: Pharm
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Phenytoin, carbamazepine, and phenobarbital are all CYP450 enzyme inducers and all reduce the half life of lamotrigine, where as valproate increased plasma levels of lamotrigine by inhibiting its metabolism
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Lamotrigine: Indications
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Seizure disorders
Partial seizures Secondarily generalized seizures (these are seizures that precede a generalized tonic-clonic seizure) Bipolar disorder |
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Lamotrigine: Contraindication
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None
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Lamotrigine: SE
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SE:
CNS- dizziness, ataxia, blurred vision and double vision Nausea, vomiting Serious: -Rash- ranging from mild to severe including Stevens Johnsons syndrome and toxic epidermal necrolysis. -These rashes can be fatal in patients who are otherwise compromised or if treatment is not discontinued and/or if the rash is not treated. |
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Lamotrigine: Notes
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Several commonly used antiseizure medications interact with lamotrigine.
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GABA (gamma- aminobutyric acid) analogues: Type
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Gabapentin
Pregabalin |
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GABA (gamma- aminobutyric acid) analogues: MOA
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Used for treatment of seizures and neuropathic pain
Binds to subunit of Ca+2 channel |
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GABA (gamma- aminobutyric acid) analogues: Pharm
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Neither drug is metabolized to an appreciable extent; pharmacokinetic drug interactions are not an issue
The clearance of pregabalin and gabapentin is reduced in patients with impaired renal function |
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GABA (gamma- aminobutyric acid) analogues: Indication
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Seizure disorders (adjunctive)
Management of neuropathic pain |
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GABA (gamma- aminobutyric acid) analogues: Contraindication
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None
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GABA (gamma- aminobutyric acid) analogues: SE
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Fatigue
Dizziness Ataxia- due to disruption of the cerebellum |
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GABA (gamma- aminobutyric acid) analogues: Notes
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Gabapentin has a very wide dosage range. Recommended dosage range begins at 300mg goes up to 1800mg per day. Patients have taken up to 3600mg per day (divided dose)
**1200-1600mg is most that is absorbed at one time; so if patient dose is increased, should be given as divided dose (i.e. for 2400mg per day; divided dose of 1200mg twice a day OR 800mg 3x per day…) |
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Carbamazepine: Type
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Carbamazepine
Oxcarbazepine |
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Carbamazepine: MOA
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Commonly referred to as a sodium channel blocker
Carbamazepine is chemically related to the tricyclic antidepressants Carbamazepine stabilizes the inactive form of the sodium channel. |
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Carbamazepine: Pharm
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Carbamazepine is slowly and erratically absorbed, with peak plasma concentrations occurring anywhere from 4 to 24 hours after an oral dose.
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Carbamazepine: Indications
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Partial seizures
Generalized tonic- clonic (carbamazepine) Trigeminal neuralgia Neuropathic pain-usually in the facial areas, arising from trigeminal nerves Bipolar disorder (carbamazepine) |
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Carbamazepine: Contraindications
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• Hepatic disease
• Bone marrow suppression • Atrioventricular heart block • MAOIs |
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Carbamazepine: SE
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• Drowsiness
• Dizziness • Ataxia • Blurred vision • Nausea, vomiting Serious Side effects • Dermatologic reactions including Stevens Johnson syndrome and toxic epidermal necrolysis • Hematologic • Hepatic- cholestatic jaundice and hepatitis |
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Carbamazepine: Notes
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Carbamazepine is also an auto inducer meaning that its half life can decrease after prolonged therapy.
Once its half life becomes shorter, maintaining stable plasma levels can be a challenge; therefore controlled release formulation can be useful for obtaining stable levels. Oxcarbazepine is better tolerated than carbamazepine Carbamazepine is use more in psychiatry as mood stabilizer in acute mania, prophylaxis in bipolar disorder |
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Barbiturates: Types
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Phenobarbital
Other- butabarbital Ending: -barbital Anesthetics: thiopental, methohexital |
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Barbiturates: MOA
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CNS depressant
Barbiturates are auto inducers. A drug that induces the same enzymes that metabolize it. This results in increased dose requirements over time, compared with initial dose requirements. |
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Barbiturates: Pharm
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Narrow therapeutic index between anti seizure activity and sedation, most anti seizure medication are commonly measured in the blood to ensure that the target concentrations are appropriate
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Barbiturates: Indications
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Seizure disorders
Sedation- benzodiazepines have mostly replace barbiturates for sedation and treatment of anxiety and sleep disorders |
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Barbiturates: Contraindications
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Porphyria
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Barbiturates: SE
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SE:
• Sedation • Addiction • Hypotension Overtime chronic use will lead to addiction and tolerance Barbiturate toxicity closely resembles alcohol toxicity Sedation Slurred speech Ataxia Nystagmus Depressed level of consciousness Hypotension Respiratory depression |
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Barbiturates: Notes
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Phenobarbital has more selective anti seizure properties relative to its sedative properties. As a result, it is the most commonly used barbiturate for treatment of seizures
Ultimate goal of therapy should be suppression of seizure activity and the absence of sedation Barbiturate withdrawal closely resembles alcohol withdrawal: -Increased CNS activity Agitation, sleep Disturbance, seizures -Increased sympathetic nervous system activity: Tachycardia, hypertension sweating |
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Valproate: Types
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Valproic acid
Divalproex sodium |
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Valproate: MOA
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Acts as a sodium channel blocker
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Valproate: Pharm
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Eliminated by hepatic metabolism
It can interfere with metabolism of other antiseizure medications such as phenytoin and Phenobarbital Valproate is more commonly used as a sustained release formulation, divalproex sodium Sustained release formula has a lower incidence of side effects |
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Valproate: Indications
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Absence seizures
Partial seizures Generalized tonic- clonic seizures Bipolar disorder Migraine prophylaxis |
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Valproate: Contraindications
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Contra:
Significant hepatic disease or dysfunction Pregnancy |
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Valproate: SE
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SE:
GI- nausea, vomiting, Other Tremor Decrease mental clarity Weight gain May worsen symptoms of PCOS |
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Valproate: Notes
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Serious, rare side effects
-Hepatotoxicity -Elevations in liver enzymes and bilirubin are relatively common, however severe hepatotoxicity leading to liver failure and death are rare. Infants are at the greatest risk for developing severe hepatotoxicity |
