Exam 3 Flashcards
Dopamine, epinephrine, norepinephrine, and serotonin are all what?
monoamines (NT of the CNS)
Aspartate, GABA, Glutamate, and Glycine are all what?
amino acid (NT of the CNS)
Adenosine, adenosine monophosphate, and adenosine triphosphate are all what?
purines (NT of the CNS)
Dynorphins, endorphins, and enkephalins are all what?
opioid peptides (NT of the CNS)
Neurotensin, oxytocin, somatostatin, substance P, and vasopressin are all what?
nonopioid peptides (NT of the CNS)
Name two “other” neurotransmitters of the CNS?
Acetylcholine, Histamine
Which will pass through the blood brain barrier easier, lipid soluble molecules or charged/protein bound molecules and why?
lipid soluble because of the tight junctions that make up the BBB.
What are some possible adaptations of the CNS to prolonged drug exposure?
increased therapeutic effects due to adaptive changes (antipsychotics and antidepressants), decreased side effects (phenobarbital and sedation, morphine and nausea), tolerance and physical dependence
Dyskinesias such as tremor at rest, rigidity, postural instability, gait issues, bradykinesia, akinesia, autonomic disturbances, depression, psychosis, and dementia are all symptoms of what neurodegenerative disorder?
Parkinson’s Disease
Describe the pathology and cause of Parkinson’s Disease?
There is a degeneration of the neurons that supply dopamine to the striatum causing an imbalance between dopamine and acetylcholine. Excess ACh promotes GABA transmission to the globus pallidus and causes excess movement.
Recent evidence suggests which three proteins play a role in Parkinson’s Disease? Which one is toxic to dopaminergic neurons?
alpha-synuclein is the one that is toxic to dopaminergic neurons. Parkin and ubiquitin are the two proteins that are involved in breaking down alpha-synuclein. If any of these three proteins are defective then alpha-synuclein accumulates in the cell forming neurotoxic fibrils called lewy bodies.
What are the two major categories of drugs used to treat Parkinson’s disease?
dopaminergic agents and anticholinergic agents
This dopaminergic agent is used to treat PD and promotes dopamine synthesis, often given in combination with carbidopa.
levodopa
These dopaminergic agents stimulate dopamine receptors directly, examples include Pramipexal (Mirapax) and Apomorphine.
dopamine agonists
This dopaminergic agent inhibits dopamine breakdown, Selegine (Eldepryl and Carbex) are examples.
MAO-B inhibitor
This dopaminergic agent promotes dopamine release.
Amantadine
These dopaminergic agents block the degradation of levadopa, an example is Entacapone (Comtan).
COMT inhibitors
This drug used for PD crosses the blood brain barrier and is then converted to dopamine by the enzyme decarboxylase pyridone. It can be degraded in the brain, liver, and intestine.
Levodopa
Nausea and vomiting due to the presence of DA-R in the CTZ, Dyskinesia, dysrhythmias, hypotension, psychosis in 20% of patients, dark urine and sweat, malignant melanoma, and the need for drug holidays are all adverse reactions of which PD med?
Levodopa
Why are Carbidopa and Levodopa often given together and what are the advantages and disadvantages of this?
The Carbidopa prevents decarboxylation of Levodopa in the periphery, making more of it available in the brain. this decreases the amount of levodopa needed for a therapeutic response. The disadvantage is that abnormal movements and psychiatric disturbances appear sooner.
How do Carbidopa, Tolcapone, and Entacapone increase the effects of Levadopa?
By inhibiting its metabolism.
How do Bromocriptine and Pramipexole increase the effects of Levadopa?
By directly stimulating dopamine receptors.
How does Amantadine increase the effects of Levadopa?
By promoting the release of dopamine.
How do anticholinergic drugs increase the effects of Levadopa?
By blocking CNS acetylcholine receptors.
Name 2 drugs that decrease the effects of Levadopa?
vitamin B6 which enhances its destruction by decarboxylases, and antipsychotics which block CNS dopamine receptors.
Name a class of drugs that increase Levodopa toxicity.
MAO inhibitors can cause a hypertensive crisis when combined with Levodopa.
What are the effects of high protein meals on Levodopa?
It decreases the absorption of Levodopa because the amino acids compete for absorption in the brain and intestine.
This non ergot derivative dopamine agonist can be used alone in early PD treatment, and with Levodopa in late stage treatment. It is also approved for restless legs syndrome. Side effects include “sleepy attacks”, nausea, dizziness and insomnia.
Pramipexole (Mirapex)
This COMT inhibitor is used with levadopa and prolongs the halflife of the drug. It is a reversible drug that inhibits levodopa metabolism in the periphery. Adverse effects are due to levodopa levels and include hallucinations, dyskinesias, nausea, and hypotension.
Entacapone (Comtan)
Another COMT inhibitor that functions similar to Entacapone. It has more serious adverse effects including liver failure, dyskinesias, and nausea.
Tolcapone (Tasmar)
This drug used in treating PD possibly increases dopamine release, decreases dopamine reuptake, creates cholinergic blockade and glutamate receptor blockade. It has less of a response than levodopa but is the drug of choice for dyskinesias. This drug is a second line treatment. Adverse effects include CNS effects and peripheral effects due to muscarinic block, also, livedo reticularis (skin discoloration).
Amantadine (Symmetrel)
This irreversible MAO-B inhibitor is used to treat PD. It is a second or third line treatment that inhibits MAO-B in the striatum and may delay the disease. May be used alone or with levodopa. May have interactions with various drugs like meperidine and fluoxetine and can be fatal.
Selegiline (Eldepryl, Carbex)
These two anticholinergic agents are a second line treatment for PD and addresses tremors. They are more commonly used in younger patients with mild symptoms. These drugs work by blocking muscarinic receptors in the striatum. Side effects include delusion, confusion, and hallucinations (CNS effects). If they block receptors in the periphery they can cause dry mouth, blurred vision, photophobia, urinary retention, constipation and tachycardia.
Trihexyphenidyl (Artane) and Benztropine (Cogentin)
What are the two major risk factors for Alzheimer’s disease?
advancing age and family history
Being female, have a head injury, low educational level, production of apoE4, high levels of homocysteine, and nicotine in cigarette smoke are all possible risk factors for which disease?
Alzheimer’s Disease
Thia disease involves the degeneration of neurons in the hippocampus first and then the cerebral cortex. There is reduced cholinergic transmission and the formation of beta-amyloid and neuritic plaques. Neurofibrillary tangles and tau protein are also present. Apolipoprotein E4 (ApoE4) binds to beta amyloid and renders it insoluble. Endoplasmic Reticulum-associated binding protein (ERAB) enhances neurotoxicity to beta amyloid. Elevation of homocysteine also blocks neural blood vessels.
Alzheimer’s Disease
Symptoms of this disease include memory loss, confusion, disorientation, impaired judgment, personality changes, difficulty with self-care, behavior problems such as wandering, pacing, agitation, screaming - sun downing, an inability to recognize family members, and an inability to communicate.
Alzheimer’s Disease
This classification of drugs is used to treat Alzheimer’s Disease and prevents the breakdown of Acetylcholine and helps to slow the progression of the disease. Adverse effects include cholinergic side effects, GI issues, dizziness, headache, bronchoconstriction, and liver injury.
Cholinesterase inhibitors
This reversible cholinesterase inhibitor is rarely used due to the fact that it is hepatotoxic. It has a short half life and requires dosing 4 times a day.
Tacrine (Cognex)
This reversible cholinesterase inhibitor is selective to acting on cholinesterase in the brain. It has a 60 hour half life and requires once a day dosing. It is the drug of choice for Alzheimer’s Disease.
Doneprazil (Aricept)
This “irreversible” cholinesterase inhibitor has modest benefits and no significant drug interactions.
Rivastigamine (Excelon)
This reversible cholinesterase inhibitor is used for mild to moderate Alzheimer’s Disease. It can cause GI complaints.
Galantamine (Reminyl or Razadine)
This drug is an NMDA receptor antagonist used to treat Alzheimer’s Disease. It is indicated for moderate to severe AD and is better tolerated than cholinesterase inhibitors. Adverse effects include dizziness, headache, confusion, and constipation. When combined with doneprazil there is less of a decline in cognitive and day to day function.
Memantine (Namenda)
Name the 2 atypical antipsychotics and the SSRI that are used to treat neuropsychiatric symptoms associated with Alzheimer’s disease.
Risperidone (Risperdal), Olanzapine (Zyprexa), and Prozac
This disease is a chronic, inflammatory autoimmune disorder that attacks the myelin sheath of neurons in the CNS. It causes a wide variety of motor and sensory deficits. Symptoms usually grow progressively worse and the patients may experience periods or complete or partial recovery or remission. It is more common in countries with cold climates and Caucasians of Northern Europe descent are at high risk.
Multiple Sclerosis
This type of MS is recurrent with partial or full recovery. 80-90% of patients have this type initially.
relapsing-remitting MS
This type of MS is steady, worsening with minor remissions. 50% of patients have this version within 10-20 years.
secondary progressive MS
This type of MS affects 10% of patients and clear remissions doesn’t occur.
primary progressive MS
This is the rarest type of MS.
progressive-relapsing MS
These drugs are all used to treat MS and are given via injection. Their MOA is unknown but they reduce the frequency and severity of attacks and the number and size of lesions. They delay the progression of disability of MS. Adverse effects include flu-like reactions, hepatotoxicity (increase in liver enzymes), myelosuppression, injection site reactions, depression.
interferon beta
These two interferon beta drugs are injected subQ and have more benefit than Avonex.
Rebif and Betaseron
This drug is used for long term therapy of relapsing-remitting MS. It is a polypeptide referred to as copolymer-1. It inhibits immune response to myelin basic protein. This drug promotes T cell shift (TH2>TH1). It increases inflammatory cells and inhibits inflammatory attack on myelin sheath. This drug is well tolerated but adverse effects include injection site reactions and post injection reactions such as flushing, palpitations, severe chest pain, anxiety, laryngeal constriction, and urticaria in 10% of people.
Glatiramer Acetate (Copaxone)
This MS medication was approved in 2004 and then withdrawn from the market due to progressive multifocal leukoencephalopathy before being reintroduced in 2006. It is used for relapsing forms of MS and Crohn’s disease. It acts by preventing activated leukocytes from crossing the blood brain barrier. Leukocytes must bind to vascular endothelium before they exit the blood vessels. This drug binds to integrin molecules on leukocytes and prevents binding and thus stops them from leaving the blood vessels. Adverse reactions include hepatotoxicity, hypersensitivity, and neutralizing antibodies.
Natalizumab (Tysabri)
This MS drug is the first oral disease modifying drug. It is more effective than interferon beta but has more adverse effects. It’s MOA is that is binds to SIP receptors and sequesters lymphocytes in lymph nodes. Fewer lymphocytes in blood then less enter the brain thus less inflammation and less nerve damage. Adverse effects include bradycardia, macular edema, liver injury and reduced lung function and fetal harm.
Fingolimod (Gilneya)
This immunosuppressant is more toxic than immunomodulators and is used to decrease neurologic disability and clinical relapses, and to treat worsening relapsing-remitting MS, secondary progressive MS, and progressive-relapsing MS. It works by suppressing production of T and B cells and reducing cytokine production. Adverse effects include myelosuppression, cardiotoxicity, fetal harm, also it is toxic to any tissues with rapidly producing cells like bone marrow and hair follicles. Also tints urine a blue green color.
Mitoxantrone
This type of seizure begins focally in the cerebral cortex and has a limited spread to adjacent cortical areas.
partial (focus) seizures
This type of seizure lasts 20-60 seconds and involves no loss of consciousness.
simple partial seizure
This type of seizure lasts 45-90 seconds and involves the person becoming partially unresponsive and automatism.
complex partial seizure
This type of seizure lasts 1-2 minutes and is a mix of simple and complex.
secondarily generalized seizure
This type of seizure can be convulsive or nonconvulsive and effects both hemispheres with immediate loss of consciousness.
generalized seizures
This type of seizure has a loss of consciousness of 10-30 seconds and can occur almost 100 times a day. It is usually seen in children.
absence/petit mal seizure
This type of seizure involves a loss of muscle tone and is seen in children. The head may drop and the person might collapse.
atonic seizure
This type of seizure involves muscle contractions that last about a second. It can be one limb or the entire body.
myoclonic seizure
This condition is marked by seizure activity lasting 30 minutes or longer.
status epilepticus
This type of seizure is fever related and occurs most often in kids aged 6 months to 5 years.
febrile seizures
This condition is marked by severe epilepsy in the preschool years, developmental delays, and a mix of partial and generalized seizures.
Lennox Gastaut syndrome
List three non pharmacological treatments for epilepsy.
neurosurgery of the temporal lobe, vagal nerve stimulator, and ketogenic diet
This anti-epileptic drug is used for all types of seizures except absence. It is specifically used for tonic-clonic seizures. It works by selective inhibition of sodium channels. Adverse effects include nystagmus (back and forth eye movement), sedation, ataxia, diplopia, cognitive impairment, gingival hyperplasia, skin rash (2-5%), defects in pregnancy, hypotension and cardiac dysrhythmias. There are many drug interactions with this medication. It increases liver enzymes and can interfere with oral contraceptives, warfarin, and glucocorticoids. Diazepam, isoniazid, cimetidine, acute alcohol use, and valproic acid reduce the metabolism of this drug. Chronic alcohol, carbamazepine, and phenobarbital increase the metabolism of this drug.
Phenytoin (Dilantin)
This anti-epileptic is the first choice drug for partial seizures, it is also used for tonic clonic seizures. It is not used for absence seizures.
Carbamazepine (Tegretol)
This anti-epileptic drug works by delaying the recovery of sodium channels and suppresses high frequency neuronal discharge. It has adverse reactions like visual disturbances, ataxia, vertigo, unsteadiness, leukopenia, anemia, thrombocytopenia, neural tube defects, it increases ADH and water retention, rash, photosensitivity reactions, and sometimes Steven Johnson’s syndrome and toxic epidermal necrolysis. Drug interactions include that it induces liver enzymes so it interferes with warfarin and birth control. Drugs like phenytoin and phenobarbital can increase the metabolism of this drug, and grapefruit juice can decrease the metabolism of this drug causing higher blood levels.
Carbamazepine (Tegretol)
This anti-epileptic drug is the first line treatment for all seizure disorders. It is also used for bipolar disorder and migraines. It acts through inhibition of Na and Ca influx and GABA enhancement. Adverse effects include nausea, vomiting, indigestion, hepatotoxicity and liver failure, pancreatitis, teratogenic effects, neural tube defects and hyperammonemia when combined with topiramate.
valproic acid (depakene, depakote, depacon)
This anti-epileptic drug is the drug of choice for absence seizures and is indicated only for this type of seizure. It works by suppressing neurons in the thalamus that are responsible for absence seizures. It also inhibits low threshold Ca currents. No significant adverse effects but may have some drowsiness dizziness, and lethargy. Rarely can have SLE, leukopenia, and steven johnson syndrome.
ethosuximide (Zarontin)
This is the oldest anti-epileptic drug and it is used for partial and generalized tonic-clonic seizures. It can also be used for sedation and the induction of sleep. It works by enhancing GABA response. Adverse reactions include sedation, depression, agitation, confusion, physical dependence, exacerbation of intermittent porphyria, and fetal deformations and neonatal bleeding.
Phenobarbital
Name the three newer anti-epileptic drugs that are used as monotherapy for epilepsy.
Oxcarbazepine (Trileptal), Lamotrigine (Lamictal) and Topiramate (Topamax).
an involuntary contraction of muscle or a muscle group.
muscle spasm
Name the four causes of muscle spasm.
epilepsy, hypocalcemia, pain syndromes, trauma
This condition is a group of muscle disorders of CNS origins. It is most commonly caused by MS and cerebral palsy, and can be caused by traumatic spinal cord lesions and stroke. Characteristics include heightened muscle tone, spasm, and loss of dexterity.
spasticity
This centrally acting muscle relaxant works through enhancing the effects of GABA.
Diazepam (Valium)
This centrally acting muscle relaxant works through agonist action at pre-synaptic alpha 2 receptors.
Tizanidine (Zanaflex)
This classification of drugs is used to relieve local muscle spasm, decrease local muscle pain, and increase range of motion. Adverse effects include CNS depression (drowsiness, dizziness, light headedness), hepatic toxicity (with zanaflex and skelaxin), hepatitis and fatal hepatic necrosis (with paraflex), physical dependence, and life threatening abstinence syndrome upon abrupt withdrawal.
centrally acting muscle relaxants
This drug is used to treat the spasticity with MS, spinal cord injury, and cerebral palsy, it decreases spasms with flexor and extensor muscles. Its MOA is that it acts in the spinal cord and suppresses hyperactive reflexes. It may mimic GABA on spinal neurons. Adverse effects include no antidote for overdose, CNS depression, nausea and constipation, urinary retention, and the need for gradual withdrawal over 1-2 weeks.
Baclofen (Lioresal)
This drug acts directly on skeletal muscle and suppresses the release of calcium from the sarcoplasmic reticulum (SR). It has a minimal effect on cardiac and smooth muscle at a therapeutic concentration. It is used to treat spasticity associated with multiple sclerosis, cerebral palsy, and spinal cord injury, as well as malignant hyperthermia. Adverse effects include hepatic toxicity, muscle weakness, drowsiness, diarrhea, anorexia, nausea, vomiting, and an acne like rash.
Dantrolene (Dantrium)
These symptoms of schizophrenia include hallucinations, delusions, agitation, and paranoia.
positive symptoms of schizophrenia
These symptoms of schizophrenia include lack of motivation, social and emotional withdrawal, poor judgment and self care.
negative symptoms of schizophrenia
These symptoms of schizophrenia include disordered thinking, less focus and learning, memory difficulties.
cognitive symptoms of schizophrenia
These medications block receptors for dopamine in the CNS, and can cause serious movement disorders (EPS). Positive symptoms of schizophrenia respond better to these medications and they are classified into six chemical groups.
first generation (conventional) antipsychotics
These medications only produce moderate blockade of dopamine receptors and produce a stronger blockade for serotonin. They cause fewer extrapyramidal symptoms (EPS). Clinically they are superior for positive and negative symptoms of schizophrenia. Cognitive symptoms also respond better to these drugs.
second generation (atypical) antipsychotics
This class of drugs act by blocking dopamine receptors and also by blocking ACh, Histamine, and NE receptors to varying degrees. They suppress psychosis by blocking DA2 receptors in the mesolimbic area of the brain. Incidence of side effects are based on potency but include EPS, anticholinergic effects, sedation, orthostatic hypotension, and weight gain.
conventional antipsychotic agents
Name two low potency conventional antipsychotic agents.
chlorpromazine (Thorazine), phenothiazine
Name a medium potency conventional antipsychotic.
Loxapine (loxitane)
Name a high potency conventional antipsychotic.
Haloperidol (Haldol)
Name three drugs that have depot preparations available.
haloperidol decanoate (Haldol decanoate), Fluphenazine decanoate (Prolixin decanoate), Risperidone microspheres (Risperdal Consta)
Give three differences between conventional antipsychotics and atypical antipsychotics.
less risk of EPS with the atypicals but more risk of weight gain, diabetes, and dyslipidemia. They have different mechanisms of action.
This atypical antipsychotic blocks dopamine and serotonin receptors but has a low affinity for DA2 receptors meaning there are fewer EPS symptoms. It is used for schizophrenia and levodopa induced psychosis. Adverse effects include agranulocytosis, tonic-clonic seizures, diabetes, weight gain, dyslipidemia, myocarditis, anticholinergic effects, orthostatic hypotension, and effects in elderly dementia patients leading to double the rate of mortality. It shouldn’t be used with drugs that cause agranulocytosis and anti cancer drugs that suppress bone marrow.
Clozapine (Clozaril, Fazaclo)
This atypical antipsychotic binds to multiple receptors specifically 5HT and DA. Side effects are infequent and generally mild. There is a long term variant that utilizes microspheres.
Risperidone (Risperdal)
This atypical antipsychotic blocks multiple receptors - DA, 5HT, Histamine, ACh, and NE.
Olanzapine (Zyprexa)
This atypical antipsychotic is in a new class of drugs. It acts at multiple receptor sites and is a dopamine system stabilizer. Its actions depend on neurotransmitter levels. If low levels of dopamine then it activates dopamine receptors, if high levels then it blocks dopamine receptor action. Partial agonist of DA2 receptors and 5HT-1 receptors, complete antagonist of 5HT2 receptors. This drug has minimal EPS and side effects and treats both positive and negative symptoms.
Aripiprazole (Abilify)
This class of drugs can be used as an adjunct to treat anxiety and sleep issues associated with schizophrenia.
benzodiazipines
This class of drugs can be used as an adjunct to treat depressive symptoms of schizophrenia.
antidepressants
This disorder has the following clinical features: depressed mood, loss of pleasure or interest, insomnia or hypersomnia, anorexia or hyperphagia, mental slowing and loss of concentration, guilt, worthlessness, helplessness, thoughts of death and suicide, and overt suicidal behavior.
Depression
The pathogenesis of this disease is complex and incomplete. Possible contributing factors include genetic heritage, difficult childhood, and chronic low self esteem. One hypothesis is that it is caused by a lack of monoamine neurotransmitters like NE or 5HT.
Depression
List 4 different types of antidepressant medications.
tricyclic antidepressants, selective serotonin or serotonin norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, atypical antidepressants
This class of antidepressants work by blocking the reuptake of norepinephrine and serotonin, but this doesn’t account for the therapeutic action. They are used to treat depression, bipolar disorder, ADHD, OCD, panic disorders, chronic insomnia, and neuropathic pain. Adverse effects include orthostatic hypotension, anticholinergic effects, diaphoresis, sedation, cardiac toxicities, seizures, hypomania, and yawngasms.
Tricyclic antidepressants
Name two prototype TCAs.
Imipramine (Tofranil) and Chlomipramine (Anafranil)
When a patient is to be taking TCAs and they have insomnia, which ones would be appropriate?
the ones with sedating properties (amitriptaline) (Doxepin)
When a patient is to be taking TCAs during the daytime, which ones would be appropriate?
less sedating ones (desipramine/ Protriptaline)
When an elderly patient is to be taking TCAs and they have glaucoma or constipation, which ones would be appropriate?
TCAs with weak anticholinergic effects (Desipramine, Nortriptyline)
This class of antidepressants work by selectively inhibiting serotonin reuptake (no effects on DA or NE). They produce CNS excitation and then sedation and are used to treat major depression, OCD, bulemia, panic disorders, and premenstrual dysphoric disorder. Adverse effects include sexual dysfunction, weight gain, serotonin syndrome, withdrawal syndrome, neonatal withdrawal syndrome, EPS, bruxism, bleeding disorders, and hyponatremia. Drug interactions exist with MAOIs (serotonin syndrome more likely), warfarin (displaces warfarin), TCAs and Lithium cause elevated levels.
Selective Serotonin Reuptake Inhibitors (SSRIs)
Name the prototypical SSRI.
Fluoxetine (Prozac)
This SSRI blocks DA and serotonin.
Sertralin (Zoloft)
Name three other SSRIs that function very similar to Prozac.
Fluvoxamine (Luvox), Paroxetine (Paxil, Paxil CR, Pexeva), Citalopam (Celexa)
This SSRI is the S-isomer of Celexa and is better tolerated.
Escitalopram (Lexapro)
This class of antidepressants work by inhibiting the reuptake of 5HT and NE with weak inhibition of DA reuptake. They are used for depression and to relieve the pain of diabetic peripheral neuropathy. Adverse effects include nausea, somnolence, dry mouth, sweating, insomnia, and blurred vision. Liver toxicity is also a concern. These drugs shouldn’t be taken with alcohol due to the risk of liver damage or MAOIs due to the risk of serotonin syndrome. Drugs that inhibit CYP1A2 or CYP2D6 increase drug level.
Serotonin Norepinephrin Reuptake Inhibitors (SNRIs)
Name two SNRIs that were mentioned in class.
Duloxetine (Cymbalta) and Venlafaxine (Effexor)
These antidepressants are a second or third lie treatment and cause irreversible inhibition of MAO-A in the nerve terminals. They cause antidepressant effects though MAO-A block and are used to treat depression, bulimia, OCD, and panic attacks. Adverse effects include CNS stimulation, orthostatic hypotension, hypertensive crisis due to dietary tyramine, and multiple drug drug interactions.
MAO Inhibitors
List some dietary restrictions when taking MAOIs.
caffeine, chocolate, fava beans, and tyramine rich foods like yeast extracts (baked goods), most cheeses and milk, aged fish or meat, overripe figs, bananas, chianti wine, and imported beer.
This class of antidepressants isn’t well understood and is to work by possibly blocking DA reuptake. It has a structure similar to amphetamines and acts as a stimulant and is used to treat major depresion, seasonal affective disorder, and sexual dysfunction (investigational). It is well tolerated but adverse effects include seizures, agitation, tremor, tachycardia, blurred vision, dizziness, headache, and insomnia. MAOI’s increase toxicity.
Bupropion (Wellbutrin)
This cyclic mental disorder is marked by abnormal elevation or depression separated by periods in which mood is relatively normal. Recurrent fluctuations in mood. Episodes of mania and depression.
Bipolar Disorder
Imbalance in neurotransmitters was thought to be the etiology of this disorder historically. Presently a disruption of neuronal growth and survival and atrophy of specific brain regions is thought to be the cause. The region of interest is the subgenual prefrontal cortex.
Bipolar Disorder
What three types of drugs are used in the treatment of bipolar disorder?
mood stabilizers, antipsychotics, and antidepressants
These drugs are used during manic and depressive episodes and relieve symptoms and prevent recurrence. They do not worsen symptoms of mania or depression.
mood stabilizers
These drugs are used to treat severe manic episodes.
antipsychotics
These drugs are used during a depressive episode of bipolar disorder, with mood stabilizers but never alone.
antidepressants
This drug is a mood stabilizer used to treat bipolar disorder and sometimes alcoholism, bulimia, schizophrenia, and glucocorticoid induced psychosis. It is a simple inorganic ion and has a low TI. There are many proposed MOAs including altered distribution of certian ions (Ca, Na, and Mg), altered synthesis and release of NE, 5HT, and DA, altered glutamate uptake/release, block 5HT binding to receptor, inhibiting glycogen synthase kinase-3 beta, and promoting neurotropic proteins such as Bcl-2.
Lithium (lithobit, lithonate, lithotabs)
If the following signs of toxicity are observed what is the likely plasma level of Lithium? - nausea, vomiting, diarrhea, thirst, polyuria, lethargy, slurred speech, muscle weakness, and fine hand tremor.
If the following signs of toxicity are observed what is the likely plasma level of Lithium? - persistent GI upset, coarse hand tremor, confusion, hyperirritability of muscles, EKG changes, sedation, incoordination
1.5-2.0 mEq/L
If the following signs of toxicity are observed what is the likely plasma level of Lithium? - ataxia, giddiness, high output of dilute urine, serious EKG changes, fasciculations, tinnitus, blurred vision, clonic movements, seizures, stupor, severe hypotension, coma, death (secondary to pulmonary complications)
2.0-2.5 mEq/L
If the following signs of toxicity are observed what is the likely plasma level of Lithium? - symptoms may progress rapidly to generalized convulsions, oliguria, and death.
> 2.5 mEq/L
This antiepileptic drug is used to treat bipolar disorder, it is an alternative to Lithium and reduces symptoms. It protects against the recurrence of mania and depression.
Carbamazepine
This anti-epileptic is a first line treatment for its mood stabilizing effects. It works faster and has a higher TI than lithium. It is useful for rapid cycling bipolar disorders, acute manic episodes, and prophylaxis. It is well tolerated but has rare side effects like thrombocytopenia, liver failure, pancreatitis, and is teratogenic.
Valproic acid (depakote, depakene, depakot)
These drugs are sometimes given with mood stabilizers to control symptoms of manic episodes. They benefit patients with positive and negative psychotic symptoms. Mostly the atypical variant are given.
antipsychotic drugs (Zyprexa, Risperdal, Abilify)
This class of drugs causes its effects by potentiating the effects of GABA. It is the drug of choice for anxiety and is also used for insomnia, seizure disorder, muscle spasms, alcohol withdrawal, panic disorder, and perioperative applications. Adverse effects include CNS depression, anterograde amnesia, paradoxical effects such as insomnia euphoria, anxiety and rage, respiratory depression, abuse, congenital malformations when usd during pregnancy, weakness, headache, vertigo, blurred vision, vomiting, sleep driving.
Benzodiazepines
What drug can be given is toxicity or overdose of benzodiazepines occurs?
Flumazenil (Romazicon) - it is a competetive receptor antagonist. Also gastric lavage, activated charcoal, and dialysis are options.
Name some drugs that would cause greater CNS depression when taken with benzodiazepines.
barbiturates, opioids, and alcohol
This type of drug is structurally different from benzodiazapines, but have the same MOA. They have low tolerance and abuse potential and are used only for insomina, not anxiety.
benzodiazepine like drugs
This benzodiazepine like drug is a rapid onset sedative-hypnotic. It is used for the short term management of insomnia.
Zolpidem (Ambien)
This benzodiazepine like drug belongs to a new class of hypnotics, pyrazolopyrimidines and is used for the short term management of insomnia. Prolonged use doesn’t appear to cause tolerance.
Zaleplon (Sonata)
This benzodiazepine like drug is the S-isomer of Zopiclone and is used for treating insomnia. There is no limitation on how long it can be used.
Eszopiclone (Lunesta)
This class of drugs is further divided based on how long they act. They work by binding to the GABA receptor chloride channel complex. At low doses they enhance GABA, and at high doses they mimic GABA. They cause CNS depression, low blood pressure, and lower heart rate. They also induce hepatic enzymes. They are used to treat seizure disorders, insomnia, acute mania and delirium, and to induce anesthesia. Adverse effects include respiratory depression, suicide and abuse potential, teratogenic effects, exacerbation of intermittent porphyria, hangover effects, paradoxical excitement (esp. in elderly), and hyperalgesia.
Barbiturates
Name the ultrashort acting barbiturate that is used in he induction of anesthesia.
Thiopental
Name the short to intermediate acting barbiturate used as a sedative hypnotic.
secobarbital
Name a long acting barbiturate that is used as a sedative hypnotic.
phenobarbital
Name the classic triad of symptoms that mark acute toxicity of barbiturates.
respiratory depression, coma, pinpoint pupils
This is a new hypnotic drug that works by activating melatonin receptors (MT1 and MT2), which mediate the sleep wake cycle. It is used for the rapid onset of sleep and has no residual effects/rebound insomnia. It is generally well tolerated but adverse effects include dizziness, fatigue, amenorrhea, galactorrhea, reduced libido and fertility. It is contraindicated for pregnant and nursing mothers. It shouldn’t be taken with alcohol which intensifies the sedation, or Fluvoxamine (Luvox) due to this med inhibiting CYPIA2 and increasing the blood levl of Luvox.
Ramelteon (Rozerem)
Signs and symptoms of this disorder in children include inattention, hyperactivity, impulsivity, fidgety, unable to concentrate, unable to wait their turn, switching excessively from one activity to another, calling out excessively in class. Over 2 million kids are affected.
Attention Deficit Hyperactivity Disorder
What are the mainstay drug treatments for ADHD?
CNS stimulants
What is the second line treatment of ADHD?
Atomoxetine (a non stimulant)
What other drugs are used to treat ADHD?
antidepressants, TCAs and Wellbutrin primarily.
Signs and symptoms of this disorder in adults include poor concentration, stress intolerance, antisocial behavior, outbursts of anger, and inability to maintain a routine.
ADHD
This drug is a CNS stimulant that works by releasing NE and DA and partly inhibits the reuptake of NE and DA> This takes place both in the CNS and the periphery. It is used to treat narcolepsy, ADHD, and obesity. Adverse effects include CNS stimulation (insomnia, restlessness), weight loss, psychosis (hallucinations and paranoid delusions), cardiovascular effects. Acute toxicity is marked by dizziness, confusion, hallucinations, and delusions, rarely death. A fatal OD will cause coma, convulsions, and cerebral hemorrhage.
Amphetamines
Name the 4 amphetamines in use.
Dextroamphetamine sulfate, Amphetamine/Dextroamphetamine mixture (Adderall), Lisdexamfetamine (Vyvanse), Methamphetamine (Desoxyn)
This drug is a CNS stimulant that is used for narcolepsy and ADHD. It consists of a 50:50 mix of D and L isomers and is the most commonly used drug for ADHD. It has several formulations.
methyphenidate (ritalin)
This CNS stimulant is the dextra-isomer of methylphenidate and is identical in structure and pharmacologic effects to methyphenidate.
dexmethylphenidate (Focalin)
The short duration preparation of methylphenidate.
Ritalin or Methylin
The intermediate preparation of methylphenidate.
Ritalin SR, Metadate ER, Methylin ER
The long duration preparation of methylphenidate.
Concerta, Metadate CD, Ritalin LA
These stimulant medications work by reversibly blocking adenosine receptors and enhance calcium permeability in SR. The inhibition of phosphodiesterase leads to accumulation of cAMP. It is used for neonatal apnea, promoting wakefulness, headaches, enhancing opioids. Adverse effects are common and include CNS stimulation, insomnia, and restlessness. Acute toxicity is marked by restlessness, insomnia, and convulsions, tachycardia, respiratory stimulation, sensory phenomena.
methylxanthines
This drug is the first nonstimulant medication approved for ADHD. It is a selective NE reuptake inhibitor. The reuptake of NE is immediate but the full therapeutic effects come on later. The side effects in children include weight loss and growth retardation.
Atomoxetine (Strattera)
